Conditions: COVID-19
Keywords: COVID-19 MP1032
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 132
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the efficacy and safety of MP1032 with standard of care (SoC) verses placebo with SoC in hospitalized adults participants with moderate to severe coronavirus disease 2019 (COVID-19).

Detailed description:

Arms:
arm 1: Participants will receive MP1032 300 milligrams (mg) twice daily (BID) with hospital selected SoC for 28 days. arm 2: Participants will receive placebo matched to MP1032 with hospital selected SoC for 28 days.

Interventions: intervention 1: MP1032 intervention 2: Placebo
Intervention descriptions: intervention 1: Hard gelatin capsules for oral administration. intervention 2: Placebo capsules matched to MP1032 for oral administration.

Protocol document:
Prot_000.pdf: 
16.1.1 
Study Protocol 
The latest version of the protocol used during the study is provided in this section. Previous 
versions of the protocol are available on request. 
Clinical Study Protocol (MP1032-CT05) version 2.0 dated 31-January-2022 
Clinical Study Protocol (MP1032-CT05) version 2.0 Bulgaria dated 31-January-2022 
Clinical Study Protocol (MP1032-CT05) version 2.0 France dated 31-January-2022 
Protocol Clarification Memo #2 (Protocol MP1032-CT05) 
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1 
CLINICAL STUDY PROTOCOL 
 
Protocol Title: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF MP1032 PLUS 
STANDARD OF CARE VS STANDARD OF CARE IN THE TREATMENT OF 
HOSPITALIZED PATIENTS WITH MODERATE TO SEVERE COVID-19 
Protocol Number: MP1032-CT05 
Short Title: MP1032 Treatment in Patients with Moderate to Severe COVID-19 
Investigational New Drug Number: 
153604 
Name of Investigational Product: 
MP1032 hard gelatin capsules 50 mg  
Phase of Development: 
IIa 
Indication: 
Treatment of symptomatic patients with moderate to severe 
coronavirus disease 2019 (COVID-19) disease  
EudraCT Number: 
2021-000344-21 
Sponsor’s EU Representative: 
 
MetrioPharm Deutschland GmbH 
Am Borsigturm 100 
13507 Berlin 
Germany 
Sponsor: 
MetrioPharm AG 
Bleicherweg 10 
8002 Zürich 
Switzerland 
Protocol Version:  
2.0 
Protocol Date: 
31-Jan-2022 
 
-CONFIDENTIAL- 
This document and its contents are the property of and confidential to MetrioPharm AG. Any unauthorized 
copying or use of this document is prohibited. 
 
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PROTOCOL APPROVAL SIGNATURES 
Protocol Title: 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF 
MP1032 PLUS STANDARD OF CARE VS STANDARD OF CARE IN 
THE TREATMENT OF HOSPITALIZED PATIENTS WITH 
MODERATE TO SEVERE COVID-19 
Protocol Number: 
MP1032-CT05 
This study will be conducted in compliance with the clinical study protocol (and 
amendments), International Council for Harmonisation guidelines for current Good 
Clinical Practice (GCP), and applicable regulatory requirements. 
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INVESTIGATOR SIGNATURE PAGE 
Protocol Title: 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF MP1032 
PLUS STANDARD OF CARE VS STANDARD OF CARE IN THE 
TREATMENT OF HOSPITALIZED PATIENTS WITH MODERATE TO 
SEVERE COVID-19 
Protocol Number: 
MP1032-CT05 
Confidentiality and Current Good Clinical Practice (GCP)/E6(R2)/Compliance Statement 
x 
I, the undersigned, have reviewed this protocol (and any amendments), including appendices, and I 
will conduct the study as described in compliance with this protocol (and any amendments), GCP, 
and relevant International Council for Harmonisation guidelines. 
x 
I am thoroughly familiar with the appropriate use of the study drug, as described in this protocol and 
any other information provided MetrioPharm AG including, but not limited to, the current 
investigator’s brochure. 
x 
Once the protocol has been approved by the institutional review board (IRB)/independent ethics 
committee (IEC), I will not modify this protocol without obtaining prior approval of 
MetrioPharm AG and of the IRB/IEC. I will submit the protocol amendments and/or any informed 
consent form (ICF) modifications to MetrioPharm AG and the IRB/IEC, and approval will be 
obtained before any amendments are implemented. 
x 
I ensure that all persons or parties assisting me with the study are adequately qualified and informed 
about the MetrioPharm AG study drug and of their delegated study-related duties and functions as 
described in the protocol. 
x 
I ensure that source documents and study records that include all pertinent observations on each of the 
site’s patients will be attributable, legible, contemporaneous, original, accurate, and complete.  
x 
I understand that all information obtained during the conduct of the study with regard to the patients’ 
state of health will be regarded as confidential. No patients’ names will be disclosed. All patients 
will be identified by assigned numbers on all case report forms, laboratory samples, or source 
documents forwarded to the sponsor. Clinical information may be reviewed by the sponsor or its 
agents or regulatory agencies. Agreement must be obtained from the patient before disclosure of 
patient information to a third party. 
x 
Information developed in this clinical study may be disclosed by MetrioPharm AG to other clinical 
investigators, regulatory agencies, or other health authority or government agencies as required. 
 
 
 
 
 
 
Printed Name  
 
Investigator Signature 
 
 
 
Title  
 
Date (DD-Mmm-YYYY) 
 
 
 
Institution 
 
 
 
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2 
SYNOPSIS 
Title of Study: 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF MP1032 
PLUS STANDARD OF CARE VS STANDARD OF CARE IN THE 
TREATMENT OF HOSPITALIZED PATIENTS WITH MODERATE TO 
SEVERE COVID-19 
Protocol Number: 
MP1032-CT05 
Investigators/Study Sites: 
Approximately 40 sites worldwide will participate in this study. 
Phase of Development: 
Phase IIa 
Study Objectives: 
 
The primary objective of this study is: 
x 
To measure the effect of MP1032 plus standard of care (SoC) versus 
placebo plus SoC on Day 14 on disease progression in patients with 
moderate to severe coronavirus disease 2019 (COVID-19)  
 
The secondary objectives of this study are: 
x 
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
Day 28 on disease progression in patients with moderate to severe 
COVID-19 
x 
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
disease resolution on Day 14 and Day 28  
x 
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
the mortality rate and other specific COVID-19 related characteristics 
x 
To assess the safety of MP1032 (eg, adverse events [AEs] and laboratory 
abnormalities) 
x 
To assess the pharmacokinetics (PK) of MP1032 on Day 1 (single dose) 
and Day 7 (steady state) in a PK subset of patients 
 
The exploratory objectives of this study are: 
x 
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
some additional COVID-19 related characteristics 
x 
To evaluate the health-related quality of life (HRQoL) of patients treated 
MP1032 plus SoC compared with placebo plus SoC 
x 
To evaluate biomarker levels 
Study Endpoints: 
The primary efficacy endpoint of this study is: 
x 
Proportion of patients with disease progression on Day 14. Disease 
progression is defined as the proportion of patients who are not alive or who 
have respiratory failure. Respiratory failure is defined as patients who have a 
score of 2, 3, or 4 on the National Institute of Allergy and Infectious Diseases 
(NIAID) 8-point ordinal scale (see below).  
 
The key secondary efficacy endpoints of this study are: 
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x 
Proportion of patients with disease progression on Day 28. Disease 
progression is defined as the proportion of patients who are not alive or who 
have respiratory failure. Respiratory failure is defined as patients who have a 
score of 2, 3, or 4 on the NIAID 8-point ordinal scale (see below).  
x 
Proportion of patients with disease resolution on Day 28. Disease resolution 
is defined as patients who are alive and have a score of 6, 7, or 8 on the 
NIAID 8-point ordinal scale.  
x 
All-cause mortality rate at Day 28  
x 
Change of clinical status related to COVID-19 on Day 28 compared with 
baseline according to the following NIAID 8-point ordinal scale: 
1. Death 
2. Hospitalized, on invasive ventilation (mechanical ventilator and/or 
extracorporeal membrane oxygenation [ECMO]) 
3. Hospitalized, on non-invasive ventilation or high-flow oxygen devices 
4. Hospitalized, requiring supplemental oxygen 
5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing 
medical care (COVID-19 related or otherwise) 
6. Hospitalized, not requiring supplemental oxygen and no longer requires 
ongoing medical care (used if hospitalization was extended for 
infection-control reasons) 
7. Not hospitalized, limitation on activities, and/or requiring home oxygen 
8. Not hospitalized, no limitations on activities 
Please note: Patients requiring oxygen before COVID-19 and returning to 
baseline oxygen use will be considered improved (ie, not requiring supplemental 
oxygen). Patients with a limitation on activities before COVID-19 and returning 
to baseline activity will be considered improved. In case of death before Day 14 
or Day 28, the patient will be considered with the NIAID score for death (score of 
1) on the date of death in the analysis. 
 
The other secondary endpoints of this study are: 
x 
Proportion of patients with disease resolution on Day 14. Disease resolution 
is defined as patients who are alive and have a score of 6, 7, or 8 on the 
NIAID 8-point ordinal scale.  
x 
All-cause mortality rate at Day 14 and Day 60 
x 
Change of clinical status related to COVID-19 on Day 14 compared with 
baseline according to the NIAID 8-point ordinal scale as listed above. 
x 
Proportion of patients requiring invasive ventilation (mechanical ventilator 
and/or ECMO), or who are not alive on Day 14 or Day 28  
x 
Proportion of patients in each category of the NIAID 8-point ordinal scale 
x 
Time to (first) improvement of at least 1 category on the NIAID 8-point 
ordinal scale (until Day 28). Patients who did not improve at least 1 category 
on the NIAID scale or die before Day 28 will be censored at Day 28. 
x 
The odds ratio between MP1032 and SoC and placebo and SoC for the 
number of patients with clinical status improvement from baseline on the 
NIAID 8-point ordinal scale (ie, an improvement of at least 1 category) at 
Day 14 and Day 28  
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x 
Total duration of hospitalization on Day 28 and Day 60 (from baseline to 
discharge; with death censored on the last day of the observed period – at 
Day 28 or Day 60, respectively) 
x 
Proportion of patients alive and testing negative for COVID-19 on Day 14, 
Day 28, and Day 60 
x 
Safety and tolerability assessed by: 
o 
Cumulative incidence of treatment-emergent AEs (summarized by 
seriousness, severity, relationship to the study medication, outcome, 
and duration)  
o 
Vital sign parameters  
o 
Clinical laboratory parameters 
o 
Physical examination findings 
x 
MP1032 plasma concentrations and PK parameters (if possible) including 
maximum observed plasma concentration, area under the concentration-time 
curve, elimination parameters, apparent body clearance, apparent volume of 
distribution, trough concentration, average observed plasma concentration at 
steady state, and other relevant PK parameters assessed via MP1032 plasma 
exposure on Day 1 and Day 7 in a PK subset of patients 
 
Exploratory endpoints of this study are: 
x 
Change in saturation of oxygen (SpO2)/fraction of inspired oxygen (FiO2) 
ratio (for patients alive) on Day 14 or Day 28 compared with baseline 
x 
Total number of days in the intensive care unit (ICU) 
x 
Duration of invasive mechanical ventilation  
x 
Duration of ECMO 
x 
Time to recovery from COVID-19 symptoms (stuffy or runny nose, sore 
throat, red or irritated eyes, shortness of breath, cough, low energy or 
tiredness, muscle or body aches, headache, chills or shivering, feeling hot or 
feverish, nausea, and number of times of vomit, times of diarrhea, sense of 
smell, sense of taste in the last 24 hours) at Day 14, Day 28, and Day 60 
x 
Change from discharge in the EuroQol (EQ) index value and EQ visual 
analog scale (VAS) based on the EuroQol-5D-5L (EQ-5D-5L) questionnaire 
at Day 60 
x 
Change from baseline in biomarker levels potentially including, but not 
limited to, cytokines (eg, C-reactive protein, interleukin [IL]-1E, IL-6, tumor 
necrosis factor-Į, and interferon-J), and other coagulation/inflammatory 
biomarkers (eg, D-dimer and ferritin) 
Study Design: 
This is a Phase IIa, randomized, double-blind, placebo-controlled, multicenter, 
proof-of-concept study designed to assess the efficacy and safety of 300 mg 
MP1032 twice daily (BID) plus SoC versus placebo plus SoC in hospitalized 
adults with moderate to severe COVID-19. 
Approximately 140 patients will be screened to randomize approximately 
120 patients in 2:1 ratio as follows:  
x 
Arm A (300 mg MP1032 BID plus SoC): approximately 80 patients 
x 
Arm B (placebo BID plus SoC): approximately 40 patients 
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The stratification factor for randomization will include baseline COVID-19 
severity (moderate versus severe) and age-class (aged 65 years versus 
>65 years). COVID-19 severity will be determined using the following criteria: 
x 
Moderate COVID-19:  
o 
Positive severe acute respiratory syndrome coronavirus type 2 
(SARS-CoV-2) testing by standard reverse 
transcription-polymerase chain reaction (RT-PCR) assay or 
equivalent test  
o 
Symptoms of moderate illness with COVID-19, which could 
include any symptom of mild illness or shortness of breath with 
exertion 
o 
Clinical signs suggestive of moderate illness with COVID-19, 
such as respiratory rate 20 breaths per minute, SpO2 >93% (on 
room air at sea level, if possible), heart rate 90 beats per 
minute  
o 
No clinical signs indicative of severe or critical COVID-19 
x 
Severe COVID-19:  
o 
Positive SARS-CoV-2 testing by standard RT-PCR assay or 
equivalent test  
o 
Symptoms suggestive of severe systemic illness with 
COVID-19, which could include any symptom of moderate 
illness or shortness of breath at rest, or respiratory distress 
o 
Clinical signs suggestive of severe systemic illness with 
COVID-19, such as respiratory rate 30 breaths per minute, 
heart rate 125 beats per minute, SpO2 93% (on room air at 
sea level, if possible), partial pressure of oxygen/FiO2 <300, or 
diagnosed with acute respiratory distress syndrome (according 
to the Berlin definition) 
o 
No criteria met for critical COVID-19 
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and 
heart rate will be measured when the patient is on room air at sea level (ie, no 
supplemental oxygen) and at rest for at least 5 minutes. If possible, the site should 
collect the information from each patient at the same time each day (±1 hour).  
Please note: Patients who are receiving oxygen therapy at baseline for a chronic 
condition (eg, emphysema, chronic obstructive pulmonary disease [COPD], 
pulmonary arterial hypertension [PAH], idiopathic pulmonary fibrosis [IPF], etc) 
must be considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19 severity, 
the investigator should contact the medical monitor. 
Each site will treat all patients with SoC for the duration of the study. The 
selected SoC will be used in accordance with the hospital’s SoC procedures and 
may include drugs under an emergency use authorization. 
This study consists of 3 periods: (1) screening, (2) treatment, and (3) follow-up. 
During the screening period, each potential patient (or patient’s legally acceptable 
representative) will provide informed consent before starting any study-specific 
procedures. The randomization of patients to treatment groups will be performed 
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centrally by an interactive web-response system (IWRS) using a randomization 
scheme that will be developed by an unblinded, independent statistician. During 
the treatment period, randomized patients will be provided their assigned 
treatment and assessments according to the protocol. All patients will be treated 
for 28 days unless the study drug is discontinued for safety reasons. Patients who 
progress to the use of an invasive ventilation (mechanical ventilator and/or 
ECMO) or who can no longer swallow the study drug (>2 days [ie, 2-day 
interruption is acceptable]) must discontinue the study drug; but whenever 
possible, the study assessments will be performed on Day 14, Day 21, Day 28, 
and Day 60. If the patient is discharged home before Day 28, the study team will 
provide the patient with the remainder of the assigned blinded study drug kit(s) to 
take home along with instructions on how to continue treatment at home on the 
day-of-discharge; for these patients, treatment compliance will be conducted via a 
diary. If the patient does not feel comfortable to complete the diary, the site will 
alternatively provide the patient with the option to be called, twice a day, to 
confirm that the study drug is taken as instructed. The treatment period will end 
with the Day 28 (End of Treatment Visit) assessments. The follow-up period will 
consist of Day 60 (Follow-up Visit) assessments. 
Selection of Patients: 
Inclusion Criteria: 
Individuals must meet all of the following criteria to be included in the study: 
1. The patient must be willing and able to give informed consent to 
participate in the study and to adhere to the procedures stated in the 
protocol or, for adults incapable of consenting due to their medical 
condition (eg, too weak or debilitated, severe shortness of breath) or due 
to literacy issues, the patient’s legally authorized representative must be 
willing and able to give informed consent on behalf of the patient to 
participate in the study as permitted by local regulatory authorities, 
institutional review boards (IRBs)/independent ethics committees 
(IECs), or local laws. 
2. The patient is male or female adult aged 18 years (as per local laws) at 
the time of giving informed consent. 
3. The patient is admitted to a hospital and has a positive SARS-CoV-2 test 
by standard RT-PCR assay or equivalent test. Please note: If the patient 
has a previous confirmation of SARS-CoV-2 (within 7 days of Day 1), 
the SARS-CoV-2 test at screening is not required.  
4. The patient has the presence of any symptom(s) suggestive of moderate 
or severe systemic illness with COVID-19 on Day 1, such as presence of 
fever (38.0ιC [100.4ιF] by any route), loss of smell or taste, cough, 
sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, 
shortness of breath upon exertion and/or at rest, or respiratory distress. 
5. The patient has the presence of moderate to severe clinical signs 
indicative of moderate or severe illness with COVID-19 on Day 1:  
a) Moderate:  
i. Clinical signs suggestive of moderate illness with 
COVID-19, such as respiratory rate 20 breaths per 
minute, SpO2 >93% (on room air at sea level, if 
possible), heart rate 90 beats per minute  
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ii. No clinical signs indicative of severe or critical 
COVID-19 
b) Severe:  
i. Clinical signs suggestive of severe systemic illness 
with COVID-19, such as respiratory rate 30 breaths 
per minute, heart rate 125 beats per minute, SpO2 
93% (on room air at sea level, if possible), partial 
pressure of oxygen/FiO2 <300, or diagnosed with acute 
respiratory distress syndrome (according to the Berlin 
definition) 
ii. No criteria met for critical COVID-19 
Please note: Patients who are receiving oxygen therapy at baseline for a 
chronic condition (eg, emphysema, COPD, PAH, IPF, etc) must be 
considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19 
severity, the investigator should contact the medical monitor. 
6. The patient does not require hemodialysis (chronic) or any renal 
replacement therapies at screening or Day 1. 
7. The patient is able to swallow the study drug (hard gelatin capsules).  
8. The patient agrees to minimize strong sun exposure (sunbathing) and 
strong ultraviolet exposure during the course of the study. Additionally, 
during the study, patients must agree to use sunscreen when spending an 
extended period outdoors. 
9. Men whose sexual partners are women of childbearing potential 
(WOCBP) must agree to comply with 1 of the following contraception 
requirements from the time of first dose of study medication (Day 1) 
until at least 30 days after the last dose of study medication: 
a) Vasectomy with documentation of azoospermia.  
b) Sexual abstinence (defined as refraining from heterosexual 
intercourse from the time of first dose of study medication until 
at least 30 days after the last dose of study medication) 
c) Male condom plus partner use of 1 of the contraceptive options 
below: contraceptive subdermal implant; intrauterine device or 
intrauterine system; oral contraceptive, either combined or 
progestogen alone; injectable progestogen; contraceptive 
vaginal ring; percutaneous contraceptive patches.  
The above is an all-inclusive list of those methods that meet the 
following definition of highly effective: having a failure rate of <1% per 
year when used consistently and correctly and, when applicable, in 
accordance with the product label. For non-product methods (eg, male 
sterility), the investigator will determine what is consistent and correct 
use. The investigator is responsible for ensuring that patients understand 
how to properly use these methods of contraception.  
10. WOCBP must agree to comply with 1 of the following contraception 
requirements from the time of first dose of study medication (Day 1) 
until at least 30 days after the last dose of study medication: 
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a) Sexual abstinence (defined as refraining from heterosexual 
intercourse from the time of first dose of study medication until 
at least 30 days after the last dose of study medication) 
b) Use of 1 of the contraceptive options below plus use of a 
condom by male partner: contraceptive subdermal implant; 
intrauterine device or intrauterine system; oral contraceptive, 
either combined or progestogen alone; injectable progestogen; 
contraceptive vaginal ring; percutaneous contraceptive patches.  
c) Vasectomy of male partner with documentation of azoospermia.  
The above is an all-inclusive list of those methods that meet the 
following definition of highly effective: having a failure rate of <1% per 
year when used consistently and correctly and, when applicable, in 
accordance with the product label. The investigator is responsible for 
ensuring that patients understand how to properly use these methods of 
contraception. Women of non-reproductive potential are defined as:  
a) Premenopausal females with 1 of the following: documented 
tubal ligation; documented hysteroscopic tubal occlusion 
procedure with follow-up confirmation of bilateral tubal 
occlusion; hysterectomy; documented bilateral oophorectomy. 
b) Postmenopausal defined as 12 months of spontaneous 
amenorrhea [in questionable cases a blood sample with 
simultaneous follicle stimulating hormone and estradiol levels 
consistent with menopause (refer to laboratory reference ranges 
for confirmatory levels)]. Women on hormone replacement 
therapy (HRT) and whose menopausal status is in doubt will be 
required to use 1 of the highly effective contraception methods 
listed above if they wish to continue their HRT during the 
study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before randomization.  
Exclusion Criteria: 
Individuals meeting any of the following criteria are ineligible to participate in 
this study:  
1. The patient, in the opinion of the investigator, is not likely to survive for 
48 hours beyond Day 1.  
2. The patient has a diagnosis of asymptomatic COVID-19, mild 
COVID-19, or critical COVID-19 on Day 1.  
a) Asymptomatic COVID-19 is defined as a patient with a positive 
SARS-CoV-2 test by standard RT-PCR assay or equivalent test 
but not experiencing symptoms.  
b) Mild COVID-19 is defined as a patient with a positive SARS-
CoV-2 test by standard RT-PCR assay or equivalent test and 
experiencing symptoms of mild illness but no clinical signs 
indicative of moderate, severe, or critical COVID-19.  
c) Critical COVID-19 is defined as a patient with a positive 
SARS-CoV-2 test by standard RT-PCR assay or equivalent test 
and experiencing at least 1 of the following: shock defined by 
systolic blood pressure <90 mm Hg or diastolic blood pressure 
<60 mm Hg, or requiring vasopressors; respiratory failure 
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requiring endotracheal intubation and invasive mechanical 
ventilation, oxygen delivered by high-flow nasal cannula 
(heated, humidified, oxygen delivered via reinforced nasal 
cannula at flow rates >20 L/min with fraction of delivered 
oxygen 0.5), non-invasive positive pressure ventilation, 
ECMO, or clinical diagnosis of respiratory failure (ie, clinical 
need for 1 of the preceding therapies, but preceding therapies 
not able to be administered in setting of resource limitation), 
and/or multi-organ dysfunction/failure. 
Please note: Patients who are receiving oxygen therapy at baseline for a 
chronic condition (eg, emphysema, COPD, PAH, IPF, etc) must be 
considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19 
severity, the investigator should contact the medical monitor. 
3. The patient has a Child Pugh score  C. 
4. The patient has a documented medical history of infection with hepatitis 
A, B, or C at screening or Day 1. 
5. The patient has a documented medical history of infection with human 
immunodeficiency virus and has a detectable viral load and CD4 count 
<500 cells/L.  
6. The patient has a documented active infection with tuberculosis at 
screening or Day 1. 
7. The patient has clinically significant electrocardiogram abnormalities at 
screening. 
8. A female patient who is pregnant, planning to become pregnant during 
the study, breastfeeding, or has a positive pregnancy test at screening (by 
serum) and before dosing on Day 1 (by urine) as determined by human 
chorionic gonadotrophin tests. 
9. The patient is planning to donate or bank ova or sperm from Day 1 until 
30 days after the last dose of study drug. 
10. The patient has a known history of drug or alcohol abuse within 
6 months of study start that would interfere with the patient’s 
participation in the study. 
11. The patient has a history of sensitivity to any of the study medications, 
components thereof (eg, mannitol or gelatin), or a history of drug or 
other allergy that, in the opinion of the investigator or medical monitor, 
would contraindicate their participation. 
12. The patient has participated in and/or plans to participate in another 
clinical study using an investigational product within the following 
period before the first dosing day in the current study: 30 days, 5 half-
lives, or twice the duration of the biological effect of the investigational 
product (whichever is longer). 
13. The patient will be transferred to another hospital that is not a study site 
within 72 hours. Please note: If the investigator has admitting privileges 
to the transfer hospital, the patient may be considered for randomization. 
14. The patient is employed by MetrioPharm, the contract research 
organization or clinical site involved in the clinical study. 
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15. The investigator makes a decision that study involvement is not in 
patient’s best interest, or the patient has any condition or critical illness, 
in the opinion of the investigator, that will not allow the protocol to be 
followed safely. 
Planned Sample Size: 
The primary efficacy endpoint “proportion of patients with disease progression on 
Day 14” is assumed to be 10% in the 300 mg MP1032 BID plus SoC treatment 
group (Arm A) and 30% in the placebo plus SoC treatment group (Arm B). Using 
the Chi-square test with type I error alpha=10% two-sided for this proof-of-
concept study and 2:1 randomization ratio, with 114 randomized patients (76 in 
Arm A and 38 in Arm B) a statistical power of 83% can be achieved. Considering 
about 5% early study terminations, the necessary sample size to randomize results 
is 120 patients in total (80 in Arm A and 40 in Arm B). If during the conduct of 
the study the early study termination rate is higher than the estimated 5%, then an 
increase in the randomized number of patients may be necessary.  
Sample size estimation was performed using nQuery 8, Version 8.6.1.0. 
A subset of randomized patients will be consented for the collection of blood 
samples for PK measurements. The PK subset consists of approximately 
20 patients from the 300 mg MP1032 BID plus SoC group and approximately 
10 patients from the placebo plus SoC group, up to a total of approximately 
30 patients. 
Study Drug, Dose, and 
Mode of Administration: 
All randomized patients will receive study drug from Day 1 to Day 28 according 
to their assigned treatment and according to the randomization scheme. Patients 
will receive 6 capsules in the morning and 6 capsules in the evening (ie, 
approximately every 12 hours, approximately at the same time every day, and at 
least 8 hours apart) according to their randomized treatment arm assignment as 
described below:  
x 
Arm A: MP1032 (300 mg [6 × MP1032 hard gelatin capsules 50 mg] 
BID) for oral administration 
x 
Arm B: 6 × placebo capsules (ie, matching MP1032 hard gelatin 
capsules 50 mg) BID for oral administration 
Standard of Care 
Each site will treat all patients with SoC for the duration of the study. The 
selected SoC will be used in accordance with the hospital’s SoC procedures and 
may include drugs under an emergency use authorization. 
Treatment Duration: 
Patients will be treated with study drug for 28 consecutive days (unless study drug 
is discontinued for safety reasons) to provide a fixed duration of treatment across 
all patients. Patients who progress to the use of an invasive ventilation 
(mechanical ventilator and/or ECMO) or who can no longer swallow the study 
drug (>2 days [ie, 2-day interruption is acceptable]) must discontinue the study 
drug; but whenever possible, the study assessments will be performed on Day 14, 
Day 21, Day 28, and Day 60. If the patient is discharged home before Day 28, the 
study team will provide the patient with the remainder of the assigned blinded 
study drug kit(s) to take home along with instructions on how to continue 
treatment at home on the day-of-discharge; for these patients, treatment 
compliance will be conducted via a diary. If the patient does not feel comfortable 
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to complete the diary, the site will alternatively provide the patient with the option 
to be called, twice a day, to confirm that the study drug is taken as instructed. 
The study duration for an individual patient will be as follows: 
x 
Screening period: up to 7 days  
x 
Treatment period: 28 consecutive days (ie, Day 1 to Day 28) 
x 
Follow-up period: 32 days after Day 28 (ie, Day 60) 
As such, the approximate study duration (including screening and the follow-up 
period) for an individual patient is up to 67 days (±3 days). 
Please note: Patients who remain hospitalized after 28 days of consecutive 
treatment with study drug are not eligible for additional treatments with study 
drug.  
Any patient who is discharged during the study should complete the day-of-
discharge assessments before release from the hospital. 
Efficacy Assessments: 
The following efficacy assessments will be collected: 
x 
COVID-19 symptoms 
x 
COVID-19 severity 
x 
Clinical status related to COVID-19 on the NIAID 8-point ordinal scale, 
as well as, each individual component of the NIAID 8-point ordinal scale 
x 
HRQoL assessed by the EQ-5D-5L questionnaire 
x 
COVID-19 testing  
Safety Assessments: 
The following safety assessments will be collected: 
x 
Medical/surgical history 
x 
Demographics 
x 
Prior and concomitant medications 
x 
Vital signs  
x 
Physical examinations 
x 
Electrocardiograms 
x 
Clinical laboratory assessments  
x 
AEs  
Pharmacokinetic 
Assessments: 
PK samples will be collected via sparse sampling from a subset of approximately 
30 patients (who give optional consent) in a 2:1 ratio (approximately 20 patients 
from the 300 mg MP1032 BID plus SoC group and approximately 10 patients 
from the placebo group plus SoC group) to assess the PK of MP1032 on Day 1 
(single dose) and Day 7 (steady state). A total of 16 samples will be collected 
relative to the first dose on Day 1 and the first dose on Day 7. Samples on Day 1 
and Day 7 will be collected predose (within 10 minutes before the first daily dose) 
and postdose at 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 
8 hours (before next dose), and 24 hours before the next morning dose (if 
applicable), if possible. Patients who provide consent for the PK sampling, but are 
no longer hospitalized on Day 7, will not have Day 7 PK samples collected.  
Other Assessments: 
Blood samples will be obtained on Day 1 (before the first study drug 
administration) and Days 7, 14, 21, 28, and 60 (when possible) to measure 
biomarker levels. Biomarkers will potentially include but will not be limited to 
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cytokines (eg, C-reactive protein, IL-1E, IL-6, tumor necrosis factor-Į, and IFN-J) 
and other coagulation/inflammatory biomarkers (eg, D-dimer and ferritin). 
Statistical Methods and 
Planned Analyses: 
Analysis Sets: 
Intention-to-Treat Set 
The Intention-to-Treat (ITT) set, correspond with randomized set, will include all 
randomized patients irrespective of any deviation from the protocol or premature 
discontinuation from study drug/withdrawal from study. The treatment group 
assignment will be designated according to initial randomization. The ITT will 
serve as the basis for the analysis of efficacy and summary of demographics and 
baseline characteristics. 
Per Protocol Set 
The Per Protocol Set (PPS) will include all patients from ITT who received at 
least 1 dose of study drug and who do not have any major protocol deviations 
impacting the efficacy assessments. The PPS will be used for supportive analyses 
of efficacy. 
Safety Set 
The Safety Set (SS) will include all randomized patients who received at least 
1 dose of study drug. The treatment group assignment in the SS will be defined by 
the treatment actually received. The SS will be used for the analysis of safety. 
PK Analysis Set 
The PK Analysis Set (PKS) will include all the patients who have been 
administered active study drug and have at least 1 postdose evaluable plasma 
concentration after Day 1 dose. 
Analyses:  
The estimands for the primary efficacy endpoint and for the 4 key secondary 
endpoints comparing the 2 treatment groups will be tested with consideration of a 
two-sided alpha of 10% on each test-level on the ITT. Additionally, 95% 
confidence intervals will be provided. Also, the treatment comparison with 
regards to the other efficacy endpoints will be performed using a two-sided alpha 
level of 10%.  
The main estimand for the primary efficacy endpoint is defined as a binary 
variable indicating disease progression (death or respiratory failure) at Day 14. 
Intercurrent events that lead to study drug discontinuation and/or switch to other 
treatment before Day 14 will be handled using the treatment-policy strategy (ie, 
the NIAID score at Day 14 will be used for definition of the failure in such 
patients). Missing data on Day 14 resulting from study termination before Day 14 
are not expected. However, in case they happen, such monotone missings will be 
imputed by multiple imputation using information from similar patients of the 
same treatment group. Missing post-baseline data for patients randomized but not 
treated will be imputed by the respective baseline value (baseline observation 
carried forward, BOCF). The comparison between the treatment groups 
considering all randomized patients after having imputed missing values will be 
performed using Mantel-Haenszel (MH) test for risk difference considering the 4 
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strata resulting from the 2 randomization stratification factors disease severity 
(moderate versus severe) and age-class (aged 65 years versus >65 years) at 
baseline. 
Similar MH analyses will be conducted for the main estimand of the first key 
secondary efficacy endpoint, which is defined as a binary variable indicating 
disease progression (death or respiratory failure) at Day 28, and the main 
estimand for the second key secondary efficacy endpoint, which is defined as a 
binary variable indicating disease resolution (alive and have a score of 6, 7 or 8 
on NIAID) at Day 28. Intercurrent events that lead to study drug discontinuation 
and/or switch to other treatment before Day 28 will be handled using the 
treatment-policy strategy for these estimands (ie, the NIAID score at Day 28 will 
be used for definition of the failure or response, respectively) in such patients. 
Missing data on Day 28 will be imputed by multiple imputation using information 
from similar patients of the same treatment group.  
A similar MH approach as described above will be applied also to the main 
estimand of the third key secondary efficacy endpoint, which is the all-cause 
mortality at Day 28. Intercurrent events that lead to study drug discontinuation 
and/or switch to other treatment before Day 28, will be handled using the 
treatment-policy strategy (ie, the life status at Day 28 will be considered). No 
missing data of life status on Day 28 is expected.  
The main estimand of the fourth key secondary efficacy endpoint, change of 
clinical status related to COVID-19 on Day 28 compared with baseline according 
to the NIAID 8-point ordinal scale, will be compared using the risk difference 
from the analysis of covariance model with treatment and the 2 binary 
stratification factors (ie, severity and age-class) as independent factors and the 
baseline value of NIAID as independent covariate. Intercurrent events that lead to 
study drug discontinuation and/or switch to other treatment before Day 28 will be 
handled using the treatment-policy strategy for these estimands (ie, the NIAID 
score at Day 28 will be used). Missing data on Day 28 will be imputed by 
multiple imputation using information from similar patients of the same treatment 
group.  
Sensitivity analyses for the main estimands of the primary and key efficacy 
estimands will be performed by assuming missing data at Day 14 or Day 28 as 
failure or non-resolution for the binary endpoints, and by multiple imputation 
using information from similar patients of the placebo group for the NIAID 8-
point ordinal scale. 
All above analyses for the main estimands of the primary efficacy and key 
secondary efficacy endpoints will be repeated on PPS as supportive analysis. 
Additionally, for the primary efficacy and binary key secondary efficacy 
endpoints, logistic regression model with treatment and the 2 stratification factors 
as covariables will be performed on the ITT. 
The proportion of patients with disease resolution at Day 14 and the all-cause 
mortality rate at Day 14 and Day 60 will be analyzed using similar MH methods 
as described above for Day 28. Cumulative proportion of patients with disease 
resolution will be plotted by time. 
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A similar analysis of covariance approach as described above for Day 28 will be 
applied for the analysis of the change of clinical status related to COVID-19 on 
Day 14 compared with baseline on the NIAID 8-point ordinal scale. The endpoint 
considering the proportion of patients requiring invasive ventilation (mechanical 
ventilator and/or ECMO) or who are not alive, the proportion of patients in each 
NIAID category, and the proportion of patients alive and testing negative for 
COVID-19 on Day 14, Day 28, and Day 60, respectively, will be compared 
between the treatment groups using MH test. Overall survival, time to (first) 
improvement of at least 1 category on the NIAID scale and total hospitalization 
duration (from baseline to discharge; with death censored on last day of the 
observed period - at Day 28 or Day 60, respectively - depending on the analyses) 
will be summarized using the Kaplan-Meier method and will be compared 
between treatment groups using log-rank tests. Additionally, Cox proportional 
hazards model will be applied with treatment and the 2 stratification factors as 
covariables. 
The odds ratio between MP1032 and SoC and placebo and SoC for the number of 
patients with clinical status improvement from baseline on the NIAID 8-point 
ordinal scale (ie, an improvement of at least 1 category) at Day 14 and Day 28 
will be analyzed using a logistic regression with consideration of the 
2 stratification factors. 
The time to recovery of all at baseline present COVID-19 symptoms (stuffy or 
runny nose, sore throat, red or irritated eyes, shortness of breath, cough, low 
energy or tiredness, muscle or body aches, headache, chills or shivering, feeling 
hot or feverish, nausea, and number of times of vomit, times of diarrhea, sense of 
smell, sense of taste in the last 24 hours) will be presented by Kaplan-Meier 
estimates and figure. The change from baseline will be presented in shift tables 
for each single symptom, with the number and percentage of subjects in each 
category at postbaseline assessment time-point compared to baseline for each 
treatment group.  
Total number of days in ICU, duration of invasive mechanical ventilation, and 
duration of ECMO will be descriptively summarized by treatment group using 
mean days with 90% confidence intervals and additionally by median days and 
quartiles. To consider death sufficiently unfavorable in these measures, in case of 
death the duration of the respective measure will be considered with the longest 
duration possible (eg, if a summary of the first 28 days is presented, then death 
before Day 28 will be considered as duration 28 days, and if the summary also 
includes follow-up period until Day 60, then death before Day 60 will be 
considered as duration of 60 days). Both summaries (up to Day 28 and up to Day 
60) will be provided.   
For HRQoL assessments at discharge and Day 60, the EQ index value and the EQ 
VAS, both based on the EQ-5D-5L questionnaire will be calculated and 
summarized by visit and treatment group. Additionally, change at Day 60 from 
discharge by treatment group. 
All efficacy endpoints will be summarized using descriptive statistics by 
treatment group and by visit, as appropriate: Binary and categorical endpoints will 
be summarized by treatment group by presenting the number and percentage of 
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patients in the categories. Continuous and ordinal endpoints will be described by 
mean, standard deviation, median, minimum, and maximum for actual values and 
change from baseline. Additionally, for ordinal data, the number and percentage 
of patients in each category will be presented. 
The PK parameters (such as Cmax, Tmax, AUC0-t, and others) of MP1032 on Day 1 
(single dose) and Day 7 (steady state; if available), using up to 8 hours postdose, 
will be derived applying non-compartmental analysis. PK parameters will be 
summarized along with plasma concentrations at various time points. Individual 
and mean plasma concentration versus time will be presented on linear, and semi-
log scales. Further details of the PK analysis will be described in the statistical 
analysis plan (SAP). Any possible correlation between plasma exposure and 
biomarkers (eg, change from baseline in cytokines, or other 
coagulation/inflammatory biomarkers) or efficacy measures can be explored by 
appropriate regression analysis methods during the final data analysis.  
The change from baseline biomarker levels will be summarized descriptively by 
treatment group and visit. The change in biomarker levels will also be evaluated 
with any change of COVID-19 clinical status. 
All safety parameters will be summarized descriptively by treatment group for the 
entire study period.  
Study drug duration and SoC therapies will be described for each treatment group. 
The SAP will present further estimands for the primary and key secondary 
endpoints and will describe the statistical analyses in detail. 
Independent Data 
Monitoring Committee: 
An independent data monitoring committee (DMC) will be established by the 
sponsor or designee to review accumulating study data at regular intervals (as per 
the DMC charter) throughout the study to ensure the safety of patients and review 
overall study conduct. Additional data may be reviewed that are related to 
efficacy, but the DMC will only be reviewing data for risk-benefit purposes. 
Members will include experts in drug safety and/or medical specialist and 
biostatistics, who are not participating in this study and do not have affiliation 
with the investigators or the sponsor. The DMC can recommend in writing to the 
sponsor whether to continue, modify, or stop the clinical study on the basis of 
safety considerations. The DMC’s specific duties will be fully described in a 
DMC charter. 
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3
TABLE OF CONTENTS
1
CLINICAL STUDY PROTOCOL....................................................................................1
2
SYNOPSIS ........................................................................................................................4
3
TABLE OF CONTENTS ................................................................................................18
3.1
List of In-text Tables ..................................................................................................21
4
LIST OF ABBREVIATIONS .........................................................................................22
5
INTRODUCTION...........................................................................................................24
5.1
Background on COVID-19.........................................................................................24
5.2
Background on MP1032, Including Benefit Risk Assessment ..................................25
Nonclinical Studies ............................................................................................26
Clinical Studies ..................................................................................................27
5.3
Risk Management of MP1032....................................................................................29
5.4
Study Rationale ..........................................................................................................29
6
STUDY OBJECTIVES AND ENDPOINTS ..................................................................31
6.1
Study Objectives.........................................................................................................31
6.2
Study Endpoints..........................................................................................................31
7
INVESTIGATIONAL PLAN .........................................................................................33
7.1
Description of Overall Study Design and Plan...........................................................33
7.2
Discussion of Study Design........................................................................................36
7.3
End of Study...............................................................................................................37
8
SELECTION OF STUDY POPULATION.....................................................................37
8.1
Inclusion Criteria........................................................................................................37
8.2
Exclusion Criteria.......................................................................................................39
8.3
Rescreening ................................................................................................................41
8.4
Study Withdrawal, Removal, and Replacement of Patients.......................................41
9
TREATMENTS...............................................................................................................42
9.1
Details of Study Drugs ...............................................................................................42
9.2
Dosage Schedule ........................................................................................................42
9.3
Measures to Minimize Bias: Randomization and Blinding........................................43
Randomization ...................................................................................................43
Blinding44
9.4
Treatment Modifications and Discontinuations .........................................................45
9.5
Treatment Accountability and Compliance................................................................46
9.6
Prior and Concomitant Medications...........................................................................46
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10
STUDY PROCEDURES.................................................................................................47
10.1
Informed Consent .......................................................................................................53
10.2
Study Procedures........................................................................................................53
11
EFFICACY ASSESSMENTS.........................................................................................53
11.1
COVID-19 Symptoms................................................................................................54
11.2
COVID-19 Severity....................................................................................................54
11.3
Clinical Status Related to COVID-19 on the National Institute of Allergy and Infectious 
Diseases 8-Point Ordinal Scale ..................................................................................56
11.4
Health-related Quality of Life Assessment ................................................................58
11.5
COVID-19 Testing .....................................................................................................58
12
SAFETY ASSESSMENTS .............................................................................................58
12.1
Medical/Surgical History and Demographics ............................................................58
12.2
Vital Signs ..................................................................................................................59
12.3
Physical Examinations................................................................................................60
12.4
Electrocardiograms.....................................................................................................60
12.5
Clinical Laboratory Assessments ...............................................................................60
12.6
Adverse Events...........................................................................................................62
Adverse Events ..................................................................................................62
Serious Adverse Events .....................................................................................64
Serious Adverse Event Reporting......................................................................65
Suspected Unexpected Serious Adverse Reactions ...........................................66
Pregnancy...........................................................................................................66
Overdose ............................................................................................................67
13
PHARMACOKINETICS ................................................................................................67
13.1
Pharmacokinetic Sampling.........................................................................................67
13.2
Pharmacokinetic Analytical Methodology.................................................................68
14
OTHER ASSESSMENTS...............................................................................................68
14.1
Biomarkers .................................................................................................................68
15
STATISTICAL ANALYSIS...........................................................................................69
15.1
Determination of Sample Size....................................................................................69
15.2
Analysis Sets ..............................................................................................................70
15.3
Efficacy Analysis........................................................................................................70
15.4
Safety Analysis...........................................................................................................73
15.5
Pharmacokinetic Analysis ..........................................................................................74
15.6
Biomarker Analysis....................................................................................................75
15.7
Interim Analysis .........................................................................................................75
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15.8
Data Monitoring Committee.......................................................................................75
16
STUDY MANAGEMENT..............................................................................................75
16.1
Approval and Consent ................................................................................................75
Regulatory Guidelines........................................................................................75
Institutional Review Board/Independent Ethics Committee..............................76
Informed Consent...............................................................................................76
16.2
Data Handling.............................................................................................................76
16.3
Source Documents......................................................................................................76
16.4
Record Retention........................................................................................................77
16.5
Monitoring..................................................................................................................77
16.6
Quality Control and Quality Assurance .....................................................................77
16.7
Protocol Amendment and Protocol Deviation............................................................78
Protocol Amendment .........................................................................................78
Protocol Deviations............................................................................................78
16.8
Ethical Considerations................................................................................................78
16.9
Financing and Insurance.............................................................................................78
16.10 Publication Policy/Disclosure of Data........................................................................79
17
REFERENCES................................................................................................................80
18
APPENDICES.................................................................................................................82
APPENDIX 1.
CHARLSON COMORBIDITY INDEX......................................................83
APPENDIX 2.
EUROQOL-5D-5L (EQ-5D-5L) QUESTIONNAIRE.................................84
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3.1 
List of In-text Tables 
Table 1: Schedule of Assessments ........................................................................................48 
Table 2 
COVID-19 Symptoms .............................................................................................54 
Table 3: Acute Respiratory Distress Syndrome – Berlin Definition .....................................56 
Table 4 
Standard Conversion for Liter Flow Oxygen ..........................................................57 
Table 5: Clinical Laboratory Assessments ............................................................................61 
Table 6: Classification of Adverse Events by Severity .........................................................63 
Table 7: Classification of Adverse Events by Relationship to Study Drug ..........................64 
 
 
 
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4 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
ARDS 
acute respiratory distress syndrome 
AUC0-t 
area under the concentration-time curve from time zero to the last non-zero 
concentration 
BID 
twice daily 
BOCF 
baseline observation carried forward 
CFR 
Code of Federal Regulations 
Cmax 
maximum plasma concentration 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
CSR 
clinical study report 
DMC 
data monitoring committee 
ECG 
electrocardiogram 
ECMO 
extracorporeal membrane oxygenation 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EQ 
EuroQol 
EQ-5D-5L 
EuroQol-5D-5L 
FiO2 
fraction of inspired oxygen 
GCP 
good clinical practice 
hCG 
human chorionic gonadotropin 
HRQoL 
health-related quality of life 
HRT 
hormone replacement therapy 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICU 
intensive care unit 
IEC 
independent ethics committee 
IL 
interleukin 
IMP 
investigational medicinal product 
IPF 
idiopathic pulmonary fibrosis 
IRB 
institutional review board 
ITT 
Intention-to-Treat 
IWRS 
interactive web-response system 
LAR 
legally authorized representative 
MH 
Mantel-Haenszel 
NIAID 
National Institute of Allergy and Infectious Diseases 
PAH 
pulmonary arterial hypertension 
PaO2 
partial pressure of oxygen 
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Abbreviation 
Definition 
PARP1 
poly-ADP-ribose-polymerase 1 
PASI 
Psoriasis Area and Severity Index 
PI 
principal investigator 
PK 
pharmacokinetic 
PKS 
PK Analysis Set 
PPS 
Per Protocol Set 
PT 
preferred term 
ROS 
reactive oxygen species 
RT-PCR 
reverse transcription-polymerase chain reaction 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus type 2 
SoC 
standard of care 
SOC 
system organ class 
SpO2 
saturation of oxygen 
SS 
Safety Set 
SUSAR 
suspected unexpected serious adverse reactions 
TEAE 
treatment-emergent adverse events 
Tmax 
time of observed Cmax 
TNF 
tumor necrosis factor 
VAS 
visual analog scale 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
 
 
 
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5 
INTRODUCTION 
5.1 
Background on COVID-19 
On 31 December 2019, the World Health Organization (WHO) was informed of a cluster of 
cases of pneumonia of unknown cause detected in 
. Severe 
acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) was identified as the causative 
virus by Chinese authorities on 07 January 2020 (WHO 2020a). Coronavirus disease 2019 
(COVID-19) was identified as the disease caused by SARS-CoV-2 infection. In March 2020, the 
COVID-19 outbreak was declared as a pandemic by the WHO. The disease resulting from 
SARS-CoV-2 led to shutdowns and social measures in great parts of the world, particularly to 
slow down the transmission of the virus and thereby avoiding the overburden of health care 
systems.  
The pandemic is still ongoing. Estimates of actual morbidity, mortality, and lethality are highly 
variable and depend on factors such as the time of analysis, region analyzed, and surveillance 
methods. As of 04 August 2020, the WHO estimated the case fatality ratio, which estimates the 
proportion of deaths among confirmed cases, to vary from 0.1% to >25%. Whereas, the true 
severity of COVID-19 as measured by the infection fatality ratio, which estimates the proportion 
of deaths among all infected individuals, is estimated to be approximately 0.5% to 1% 
(WHO 2020b). In a more recent summary of Levin et al (2020) it could be clearly shown that the 
infection fatality ratio is highly age dependent, being in average as low as 0.004% for patients 
younger than 35 and as high as 28.3% in patients at the age of 85 and older. 
Presentations of COVID-19 range from an asymptomatic course or mild symptoms to severe 
illness and mortality. Common symptoms include fever or chills, cough, shortness of breath or 
difficulty breathing, fatigue, muscle or body aches, headache, loss of taste or smell, sore throat, 
congestion or runny nose, nausea or vomiting, and diarrhea (Cennimo 2021). Less common 
symptoms are sputum production, malaise, respiratory distress, and neurologic symptoms, such 
as altered mental state. While most patients with COVID-19 seem to show mild respiratory 
symptoms only, some of them develop pneumonia, shortness of breath and hypoxia, or other 
serious conditions that require hospitalization. Generally, pneumonia seems to be the most 
common serious manifestation of COVID-19. Further, major deterioration such as an acute 
respiratory distress syndrome (ARDS) can lead to the imperative need of an intensive care unit 
(ICU) and might even require mechanical ventilation via intubation. Other complications that 
might occur during the course of the disease include sepsis, acute kidney injury, thyrotoxicosis, 
and neurologic manifestations such as myasthenia gravis. The elderly, as well as patients with 
pre-existing chronic conditions (eg, asthma, chronic obstructive pulmonary disease [COPD], 
diabetes mellitus, chronic kidney disease, immune system deficiencies, liver disease, and cardiac 
diseases, etc), seem to be more vulnerable to a severe disease course. 
Although, to date, knowledge about SARS-CoV-2 and corresponding COVID-19 is still limited, 
it seems to be clear that the course of the disease, and particularly severe complications, are 
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based on an overshooting immune response. Details on and a deeper understanding of how the 
virus causes such a reaction will be a central part of future investigations (Hillienhof 2020). 
Patients with COVID-19 show increased levels of plasma pro-inflammatory cytokines (Rothan 
and Byrareddy 2020). From a pathophysiological point of view, in severe cases the viral 
infection seems to trigger an excessive immune reaction in the host, a so-called cytokine storm, 
leading to extensive tissue damage. A key player of this mechanism is interleukin (IL)-6. IL-6 
inhibitors, as well as other immune modulators, must thus be considered a potential treatment 
approach. This approach seems to be particularly promising, as recent postmortem findings show 
direct viral infection of the endothelial cells and diffuse endothelial inflammation in the whole 
body (Varga et al 2020). 
Recently the first vaccines to prevent COVID-19 have been approved by authorities, including 
the Food and Drug Administration in the United States and the European Medicines Agency in 
Europe, and numerous further vaccine projects are still under development. Nonetheless, it will 
take years until the majority of people will be vaccinated and the epidemiological situation can 
be considered as under control. Hence, there is still an urgent need for therapeutic agents to cure 
COVID-19 and/or ameliorate its symptoms. Among the antiviral treatment options, remdesivir 
has shown to be effective in reducing hospitalization time when administered early in the course 
of the disease (Beigel et al 2020); however, in the meantime the WHO has issued a conditional 
recommendation against the use of remdesivir in hospitalized patients regardless of disease 
severity (WHO 2020c) Among immune modulating drugs low-dosed dexamethasone could 
significantly lower the incidence of deaths when applied at a later time point of the disease 
course (WHO-REACT 2020) but is not recommended early in disease or in patients with mild 
symptoms only (WHO 2020c). Hence, there is still no antiviral treatment or otherwise effective 
curative agent that could really lower the burden of this pandemic. Thus, COVID-19 still 
presents an urgent unmet medical need. 
5.2 
Background on MP1032, Including Benefit Risk Assessment 
MP1032 is a purely synthetic, new chemical entity. MP1032 is a mono sodium salt derived from 
the aromatic system phthalazinedione, containing an additional amino group. MP1032 is 
water-soluble and hydrophilic. 
The primary mechanism of action of MP1032 is assumed to be a reactive oxygen species (ROS) 
scavenging action in inflamed tissues (ie, tissues that experience oxidative stress). A unique 
pharmacologic property of MP1032 is that the ROS-scavenging function of the molecule is only 
activated in tissues with pathologically high ROS concentrations (oxidative stress), which is the 
case in inflamed tissue. By re-establishing a physiologic redox balance in activated immune 
cells, MP1032 is putatively inhibiting nuclear factor-kappa B activation. Inhibition of nuclear 
factor-kappa B is expected to lead to inhibition of pro-inflammatory cytokines (eg, IL-6 and 
TNF-Į) (Gloire et al 2006). In addition, MP1032 is a specific inhibitor of poly-ADP-ribose-
polymerase 1 (PARP1). PARP1 is a nuclear enzyme involved in inflammation (Ke et al 2019). 
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Further identified potential targets are the kinases human Aurora-B, human Aurora-C, 
serine/threonine-protein kinase, tyrosine kinase, and the metalloprotease TNF-Į-converting 
enzyme—however, at relatively high molarity only. Therefore, the administration of MP1032 (as 
shown nonclinically, both in vitro and in vivo), in pathological conditions only, leads to a 
reduced concentration of pro-inflammatory cytokines without completely blocking them. In 
addition to this broadly anti-inflammatory potential, MP1032 exhibits direct antiviral activity 
against SARS-CoV-2 that could be shown by a clear and dose-dependent inhibition of SARS-
CoV-2 reproduction in Vero B4 cells (African green monkey [Chlorocebus aethiops] kidney 
epithelium cells) (Schumann et al 2020).
MP1032 could attenuate prolonged virus replication by preventing oxidative stress 
(Khomich et al 2018) and/or by limiting ADP-ribosylation of the viral nucleocapsid protein via 
PARP1 inhibition (Grunewald et al 2018). PARP1 inhibitors also have been suggested for the 
treatment of COVID-19 (Curtin et al 2020).
Based on the basic chemical mechanism of MP1032 as an electron donor to ROS, the molecule 
acts similarly across a wide range of species and is thus not an agent with a high degree of 
species specificity. Further, MP1032 has no specific immune-system targets as known from 
various biologicals. MP1032 is not expressed by using mammalian systems (cells) or using raw 
materials of human or animal origin.
Nonclinical Studies
In vivo safety studies showed no evidence of neurotoxic potential or negative 
cardiohemodynamic effects; no local intolerance was observed. There was no dose-limiting or 
target organ toxicity and no substance-related findings in histopathology in rats or dogs. 
However, after 6 months of long-term treatment in rats receiving the highest dose 
(1000 mg/kg/d), liver organ weight was elevated compared with that of controls and 
histopathologically associated with hepatocellular hypertrophy. This finding was not considered 
adverse because of its adaptive character, as histopathological changes were not present at the 
end of the recovery period (ie, effect was reversible after 8 weeks).
In reproduction toxicity studies on fertility, early embryonic, and embryo-fetal development, no 
pathological effects were found. On the basis of results from 4 different test systems, mutagenic 
or clastogenic effects are not considered to be a potential risk for volunteers and patients.
Transient effects on some pulmonary parameters have been observed in rats following a single 
intravenous bolus injection of the highest dose (300 mg/kg) of MP1032. No pulmonary effects 
have been observed in any of the long-term animal toxicity studies. The maximum plasma levels 
reached in humans are over 1000 times (oral) lower than for the abovementioned dose. Thus, 
pulmonary effects are not considered a potential risk for patients and volunteers.
Emesis sporadically occurred in various repeat-dose toxicology studies in dogs; the emesis was 
present in the dogs more often at the high doses of 150 mg/kg twice daily (BID) intravenous than 
at 125 mg/kg BID (oral). The lowest experimental oral dose inducing emesis was 25 mg/kg BID 
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(oral) in dogs, corresponding to 1.8 g (oral; conversion based on human-equivalent dose) for a 
65-kg human. Dogs are well known to be susceptible to emesis; in addition, the maximum doses 
administered in humans are 6 to 30 times below the converted human-equivalent doses. 
Therefore, emesis is not considered a potential risk for patients and volunteers.
Transient liquid feces were sporadically observed in various repeat-dose toxicology studies in 
dogs of all dose groups treated with MP1032. However, these gastrointestinal irritations could 
not be attributed to specific animals and thus did not have an observable effect on their 
wellbeing. Further, no such observations were made in any of the other species investigated. 
Also, in the clinical studies completed so far, no cases of diarrhea have been reported as adverse 
drug reactions by the respective investigators. Gastrointestinal irritations are therefore not 
considered a potential risk for patients and volunteers.
A potential phototoxic risk cannot be excluded from the in vitro 3T3 neutral red uptake and the 
distribution quantitative whole-body autoradiography test. In the clinical studies completed so far 
with MP1032, mean maximum plasma concentrations and calculated maximum skin 
concentrations were all below the half maximal effective concentration in the 3T3 neutral red 
uptake test with safety margins between 2 to 20 times. Therefore, a phototoxic risk for patients 
seems to be unlikely.
Further, a slight to moderate increase in serum creatinine level combined with a slight decrease 
of kidney weights was observed after a 90-day treatment period in male mice in a dose-range 
finding, repeated dose (oral) toxicity study at high dosed animals. However, as there were no 
associated histopathological findings in kidneys of the respective animals, this effect is also not 
considered to be adverse in nature. In the scope of extensive laboratory controls in the clinical 
studies completed so far, no respective treatment-emergent adverse events (TEAEs) have been 
reported. 
The probability of pharmacokinetic interactions of MP1032 regarding the inhibition or induction 
of Cytochrome P450 or inhibition of well-known drug transporters is rather low. However, based 
on in vitro experiments there are hints that a combination of MP1032 and dexamethasone might 
act (supra-)additive regarding the inhibition of proinflammatory cytokines (ie, IL-6). Thus, 
currently, a potential drug-drug interaction of MP1032 and dexamethasone regarding their anti-
inflammatory action cannot be excluded.
For further details of the completed nonclinical studies conducted with MP1032, readers are 
referred to the current version of the investigator’s brochure (IB).
Clinical Studies
MP1032 so far has been investigated in 3 clinical studies, including a first-in-human study 
(MP1032-CT01; EudraCT-No.: 2014-004606-15) with a single ascending dose and a multiple 
ascending dose part, as well as 2 studies in patients with moderate-to-severe psoriasis: a 6-week,
Phase IIa, pilot study (MP1032-CT02; EudraCT-No.: 2015-005159-28) and a 3-month, Phase II
study (MP1032-CT04; EudraCT-No.: 2017-003484-36).
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Among the subjects enrolled in MP1032 studies, 146 subjects were administered MP1032 orally. 
Among them, 24 male subjects participated as healthy volunteers in the Phase I study, while both 
male (n=89) and female (n=33) patients with psoriasis participated in the Phase II studies. The 
age of participants administered MP1032 ranged from 18 to 68 years. Pregnant and breastfeeding 
women, as well as children and adolescents have not been included in the studies. 
The highest single dose of MP1032 administered was 600 mg, applied to healthy volunteers. The 
highest repeated dose was 300 mg MP1032 BID, applied to both healthy volunteers (7 days) and 
patients with psoriasis (3 months). 
No serious adverse events (SAEs) occurred in any of the subjects administered MP1032. 
No deaths occurred in the scope of the MP1032 clinical development program. 
MP1032 was well tolerated in all studies, and safety analyses did not reveal any clinically 
important safety issues. In general, incidence, intensity, causality, and spreading of TEAEs over 
system organ classes (SOCs) were comparable between groups. In the recent Phase II study, the 
incidence, intensity, relationship to investigational medicinal product (IMP), and causality to 
IMP for adverse events (AEs) were even lower for both MP1032 dose groups compared with 
those of the placebo group and statistically significantly lower for the 300 mg MP1032 group 
compared with the placebo group. 
None of the potential risks arising from preclinical data could be confirmed with clinical data.  
From the TEAEs that occurred in the MP1032 groups and were regarded as at least possibly 
related by the investigator, nasopharyngitis, pruritus, and psoriasis must be considered as 
common (1/100 to <1/10); while neutropenia, palpitations, abdominal pain upper, fatigue, 
feeling drunk, influenza-like illness, cystitis, and headache can be regarded as uncommon 
(1/1,000 to <1/100). Regarding the general spreading of AEs over SOCs and the comparison 
between groups, currently none of them can be considered a significant clinical risk. 
Regarding efficacy in the treatment of moderate to severe psoriasis, the MP1032-CT02 study 
showed that after only 6 weeks of treatment, there was a clinically meaningful response in 
patients who entered the study with moderate to severe psoriasis with a Psoriasis Area and 
Severity Index (PASI) score of 10 to 20 and achieved the appropriate drug-exposure levels. 
Hence, only patients with a PASI score of 10 to 20 at baseline were randomized to the 
MP1032-CT04 study. After 12 weeks, a significant PASI reduction could be shown in the 
300 mg MP1032 BID group compared with those in the placebo group; however, this only 
occurred in a prespecified subgroup of patients with PASI 15 at baseline. 
Further details of the completed clinical studies conducted with MP1032 may be found in the 
current version of the IB. 
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5.3 
Risk Management of MP1032 
In the scope of planning and conducting future clinical studies, all potential risks associated with 
MP1032 will be considered, and measures will be taken as applicable.  
On the basis of limitations in the amount of preclinical and clinical data available so far, MP1032 
shall not be administered to patients for >3 months, and it will generally not be administered to 
children or pregnant women.  
Adverse drug reactions that have already been described in the clinical program so far, as well as 
any suspected AEs arising from risks associated with preclinical data will be evaluated 
extensively on a case-by-case base during ongoing and/or upcoming studies. 
Because of potential phototoxicity, patients in upcoming studies will be advised to avoid strong 
sun exposure (sunbathing) and strong ultraviolet exposure. Furthermore, the use of sunscreen 
will be recommended when spending an extended period outdoors. It should be ensured that 
exposure to ultraviolet light (eg, from lasers in procedures) is limited while the patient is 
hospitalized. 
To avoid risks associated with potential low efficacy in serious and life-threatening conditions, 
such as COVID-19, MP1032 is only recommended to be used as add-on to standard of 
care (SoC) until a respective proof-of-concept is demonstrated. 
As dexamethasone is expected to be part of SoC in most institutions treating patients with 
COVID-19 investigators should be aware that a (supra-)additive synergism between MP1032 
and dexamethasone regarding their anti-inflammatory activity cannot be excluded. 
Further details regarding known or anticipated risks, as well as reasonably anticipated AEs for 
MP1032 may be found in the current version of the IB. 
5.4 
Study Rationale  
MP1032 is a small molecule that combines localized, auto-regulated ROS-scavenging and 
immune-modulating effects with potential antiviral properties against SARS-CoV-2. MP1032 
leads to a reduced concentration of pathologically increased pro-inflammatory cytokines without 
completely blocking them. This downregulation to physiologic levels was shown in vivo and in 
vitro for IL-1ȕ, IL-6, IL-12, IL-23, and TNF-Į in activated macrophages/neutrophils; most data 
are available on the downregulation of IL-6 and TNF-Į. Once physiologic ROS levels have been 
reached, concurrent with down-modulated cytokine levels, the drug activation stops. Further, 
MP1032 might suppress virus replication in patients with COVID-19 dose-dependently like it 
has been shown in vitro with no effect on cell viability. 
On the basis of this mechanism of action, MP1032 does not carry the risk of developing 
opportunistic infections, such as with IL-6 or TNF-Į inhibitors. On the contrary, an in vivo study 
on polymicrobial abdominal sepsis in mice showed a decrease of bacterial burden in animals 
treated with MP1032, although a direct antibacterial effect for MP1032 could not be shown. 
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MP1032 has also been investigated in a small exploratory hemagglutinin type 5 neuraminidase 
type 1 virus infection model in mice, wherein animals treated with MP1032 showed a 
significantly improved clinical score on Days 6 and 7 after infection, combined with a clear trend 
of prolonged survival compared with that of the mice receiving placebo. 
In summary, when administered in combination with or as add-on to standard treatments, 
MP1032 may prevent and/or ameliorate any overstimulation of the immune system in the course 
of a COVID-19, thereby reducing the danger of opportunistic infections and helping to reduce 
the severity of general inflammatory symptoms. At the same time, the probability of a severe 
course of the disease is reduced because of a potential direct antiviral capacity of MP1032. This 
combinative approach makes MP1032 a promising candidate for the treatment of COVID-19. In 
addition, synergistic effects may be obtained when using MP1032 as an add-on to other 
medicinal products currently under investigation for treating patients with COVID-19. 
There is a substantial medical need for preventive and/or therapeutic options for the COVID-19 
pandemic. COVID-19 is a viral disease with a considerable mortality rate that is not yet 
completely determined, and it significantly affects healthcare systems. Considering the strong 
safety profile and good tolerability of MP1032 based on both preclinical and clinical data, 
combined with the signals of meaningful therapeutic effects of MP1032, it is justified that a 
proof-of-concept for MP1032 in the treatment of patients with COVID-19 is started. 
As such, this proof-of-concept study is designed to investigate the efficacy and safety of MP1032 
plus SoC versus placebo plus SoC treatment in hospitalized adults with confirmed moderate to 
severe COVID-19, the disease caused by SARS-CoV-2 infection. Additional exploratory 
objectives include pharmacokinetics (PK) of MP1032 in a PK subset of patients and the effect of 
MP1032 on biomarker levels. 
This study will be executed during a worldwide outbreak of COVID-19, resulting in capacity 
issues at many medical facilities and concerns about the safety of healthcare providers caring for 
these seriously sick patients. Consequently, this study is designed to minimize the burden on 
clinical sites, including minimizing the number of required assessments and interventions. To 
allow close monitoring and oral administration, the intended patient population shall include 
only hospitalized patients with COVID-19 that do not require intubation at the time of screening 
and/or randomization. Only adults shall be included. Additionally, pregnant and breastfeeding 
women shall be excluded. 
The study drugs will be indistinguishable to blinded study personnel to limit bias in study 
assessments. Most interventions and assessments may be accomplished in conjunction with the 
schedule dictated by SoC. An independent data monitoring committee (DMC) will be established 
by the sponsor or designee to review accumulating study data at regular intervals (as per the 
DMC charter) throughout the study to ensure the safety of patients and review overall study 
conduct. 
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6 
STUDY OBJECTIVES AND ENDPOINTS 
6.1 
Study Objectives 
The primary objective of this study is: 
x To measure the effect of MP1032 plus SoC versus placebo plus SoC on Day 14 on 
disease progression in patients with moderate to severe COVID-19  
The secondary objectives of this study are: 
x To measure the effect of MP1032 plus SoC versus placebo plus SoC on Day 28 on 
disease progression in patients with moderate to severe COVID-19  
x To measure the effect of MP1032 plus SoC versus placebo plus SoC on disease 
resolution on Day 14 and Day 28  
x To measure the effect of MP1032 plus SoC versus placebo plus SoC on the mortality rate 
and other specific COVID-19 related characteristics 
x To assess the safety of MP1032 (eg, AEs and laboratory abnormalities) 
x To assess the PK of MP1032 on Day 1 (single dose) and Day 7 (steady state) in a PK 
subset of patients 
The exploratory objectives of this study are: 
x To measure the effect of MP1032 plus SoC versus placebo plus SoC on some additional 
COVID-19 related characteristics 
x To evaluate the health-related quality of life (HRQoL) of patients treated MP1032 plus 
SoC compared with placebo plus SoC 
x To evaluate biomarker levels 
6.2 
Study Endpoints 
The primary efficacy endpoint of this study is: 
x Proportion of patients with disease progression on Day 14. Disease progression is defined 
as the proportion of patients who are not alive or who have respiratory failure. 
Respiratory failure is defined as patients who have a score of 2, 3, or 4 on the National 
Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale (see below).  
The key secondary efficacy endpoints of this study are: 
x Proportion of patients with disease progression on Day 28. Disease progression is defined 
as the proportion of patients who are not alive or who have respiratory failure. 
Respiratory failure is defined as patients who have a score of 2, 3, or 4 on the NIAID 8-
point ordinal scale (see below).  
x Proportion of patients with disease resolution on Day 28. Disease resolution is defined as 
patients who are alive and have a score of 6, 7, or 8 on the NIAID 8-point ordinal scale.  
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x All-cause mortality rate at Day 28  
x Change of clinical status related to COVID-19 on Day 28 compared with baseline 
according to the following NIAID 8-point ordinal scale: 
1. Death 
2. Hospitalized, on invasive ventilation (mechanical ventilator and/or extracorporeal 
membrane oxygenation [ECMO]) 
3. Hospitalized, on non-invasive ventilation or high-flow oxygen devices 
4. Hospitalized, requiring supplemental oxygen 
5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 
(COVID-19 related or otherwise) 
6. Hospitalized, not requiring supplemental oxygen and no longer requires ongoing 
medical care (used if hospitalization was extended for infection-control reasons) 
7. Not hospitalized, limitation on activities, and/or requiring home oxygen 
8. Not hospitalized, no limitations on activities 
Please note: Patients requiring oxygen before COVID-19 and returning to baseline oxygen use 
will be considered improved (ie, not requiring supplemental oxygen). Patients with a limitation 
on activities before COVID-19 and returning to baseline activity will be considered improved. In 
case of death before Day 14 or Day 28, the patient will be considered with the NIAID score for 
death (score of 1) on the date of death in the analysis. 
 
The other secondary endpoints of this study are: 
x Proportion of patients with disease resolution on Day 14. Disease resolution is defined as 
patients who are alive and have a score of 6, 7, or 8 on the NIAID 8-point ordinal scale.  
x All-cause mortality rate at Day 14 and Day 60 
x Change of clinical status related to COVID-19 on Day 14 compared with baseline 
according to the NIAID 8-point ordinal scale as listed above 
x Proportion of patients requiring invasive ventilation (mechanical ventilator and/or 
ECMO), or who are not alive on Day 14 or Day 28  
x Proportion of patients in each category of the NIAID 8-point ordinal scale 
x Time to (first) improvement of at least 1 category on the NIAID 8-point ordinal scale 
(until Day 28). Patients who did not improve at least 1 category on the NIAID scale or 
die before Day 28 will be censored at Day 28. 
x The odds ratio between MP1032 and SoC and placebo and SoC for the number of 
patients with clinical status improvement from baseline on the NIAID 8-point ordinal 
scale (ie, an improvement of at least 1 category) at Day 14 and Day 28  
x Total duration of hospitalization on Day 28 and Day 60 (from baseline to discharge; with 
death censored on the last day of the observed period – at Day 28 or Day 60, 
respectively) 
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x Proportion of patients alive and testing negative for COVID-19 on Day 14, Day 28, and 
Day 60 
x Safety and tolerability assessed by: 
o Cumulative incidence of TEAEs (summarized by seriousness, severity, 
relationship to the study medication, outcome, and duration)  
o Vital sign parameters  
o Clinical laboratory parameters 
o Physical examination findings 
x MP1032 plasma concentrations and PK parameters (if possible) including maximum 
observed plasma concentration, area under the concentration-time curve, elimination 
parameters, apparent body clearance, apparent volume of distribution, trough 
concentration, average observed plasma concentration at steady state, and other relevant 
PK parameters assessed via MP1032 plasma exposure on Day 1 and Day 7 in a PK subset 
of patients 
 
Exploratory endpoints of this study are: 
x Change in saturation of oxygen (SpO2)/fraction of inspired oxygen (FiO2) ratio (for 
patients alive) on Day 14 or Day 28 compared with baseline 
x Total number of days in the intensive care unit (ICU) 
x Duration of invasive mechanical ventilation  
x Duration of ECMO 
x Time to recovery from COVID-19 symptoms (stuffy or runny nose, sore throat, red or 
irritated eyes, shortness of breath, cough, low energy or tiredness, muscle or body aches, 
headache, chills or shivering, feeling hot or feverish, nausea, and number of times of 
vomit, times of diarrhea, sense of smell, sense of taste in the last 24 hours) at Day 14, 
Day 28, and Day 60 
x Change from discharge in the EuroQol (EQ) index value and EQ visual analog scale 
(VAS) based on the EuroQol-5D-5L (EQ-5D-5L) questionnaire (Appendix 2) at Day 60 
x Change from baseline in biomarker levels potentially including, but not limited to, 
cytokines (eg, C-reactive protein, interleukin [IL]-1E, IL-6, TNF-Į, and IFN-J), and other 
coagulation/inflammatory biomarkers (eg, D-dimer and ferritin)  
7 
INVESTIGATIONAL PLAN 
7.1 
Description of Overall Study Design and Plan 
This is a Phase IIa, randomized, double-blind, placebo-controlled, multicenter, proof-of-concept 
study designed to assess the efficacy and safety of 300 mg MP1032 BID plus SoC versus 
placebo plus SoC in hospitalized adults with moderate to severe COVID-19. 
Approximately 40 sites worldwide will participate in this study. 
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Approximately 140 patients will be screened to randomize approximately 120 patients (see 
Section 15.1 for determination of sample size) in 2:1 ratio as follows:  
x Arm A (300 mg MP1032 BID plus SoC): approximately 80 patients 
x Arm B (placebo BID plus SoC): approximately 40 patients 
The stratification factor for randomization will include baseline COVID-19 severity (moderate 
versus severe) and age-class (aged 65 years versus >65 years). COVID-19 severity will be 
determined using the following criteria: 
x Moderate COVID-19:  
o Positive SARS-CoV-2 testing by standard reverse-transcription polymerase 
chain reaction (RT-PCR) assay or equivalent test  
o Symptoms of moderate illness with COVID-19, which could include any 
symptom of mild illness or shortness of breath with exertion 
o Clinical signs suggestive of moderate illness with COVID-19, such as 
respiratory rate 20 breaths per minute, SpO2 >93% (on room air at sea level, 
if possible), heart rate 90 beats per minute  
o No clinical signs indicative of severe or critical COVID-19 
x Severe COVID-19:  
o Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test  
o Symptoms suggestive of severe systemic illness with COVID-19, which could 
include any symptom of moderate illness or shortness of breath at rest, or 
respiratory distress 
o Clinical signs indicative of severe systemic illness with COVID-19, such as 
respiratory rate 30 breaths per minute, heart rate 125 beats per minute, 
SpO2 93% (on room air at sea level, if possible), partial pressure of oxygen 
(PaO2)/FiO2 <300, or diagnosed with ARDS (according to the Berlin 
definition; see Table 3 
o No criteria met for critical COVID-19 
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will 
be measured when the patient is on room air at sea level (ie, no supplemental oxygen, if possible) 
and at rest for at least 5 minutes. If possible, the site should collect the information from each 
patient at the same time each day (±1 hour).  
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition (eg, 
emphysema, COPD, pulmonary arterial hypertension [PAH], idiopathic pulmonary 
fibrosis [IPF], etc) must be considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19 severity, the investigator 
should contact the medical monitor. 
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Each site will treat all patients with SoC for the duration of the study. The selected SoC will be 
used in accordance with the hospital’s SoC procedures and may include drugs under an 
emergency use authorization. 
This study consists of 3 periods: (1) screening, (2) treatment, and (3) follow-up. During the 
screening period, each potential patient (or patient’s legally acceptable representative) will 
provide informed consent before starting any study-specific procedures. The randomization of 
patients to treatment groups will be performed centrally by an interactive web-response 
system (IWRS) using a randomization scheme that will be developed by an unblinded, 
independent statistician. During the treatment period, randomized patients will be provided their 
assigned treatment and assessments according to the protocol. All patients will be treated for 
28 days unless the study drug is discontinued for safety reasons. If the patient is discharged home 
before Day 28, the study team will provide the patient with the remainder of the assigned blinded 
study drug kit(s) to take home along with instructions on how to continue treatment at home on 
the day-of-discharge; for these patients, treatment compliance will be conducted via a diary. If 
the patient does not feel comfortable to complete the diary, the site will alternatively provide the 
patient with the option to be called, twice a day, to confirm that the study drug is taken as 
instructed. The treatment period will end with the Day 28 (End of Treatment Visit) assessments. 
The follow-up period will consist of Day 60 (Follow-up Visit) assessments. 
Please note: Patients will be assessed while hospitalized. If patients are discharged from the 
hospital, they can have study visits at Day 14, Day 21, Day 28, and Day 60 as an outpatient visit. 
Patients discharged early will continue to receive study drug through Day 28. For discharged 
patients, Day 14 and Day 28 visits are preferred to be conducted in person at the study site. If 
restrictions limit the ability of the patient to return to the study site, these visits may be 
conducted by home healthcare visit or by telephone/virtual call (the patient’s caregiver may 
assist during the telephone/virtual call). For discharged patients, it is sufficient to conduct the 
Day 60 Follow-up Visit as a telephone/virtual call (the patient’s caregiver may assist during the 
telephone/virtual call) or an outpatient or home healthcare visit is also allowed. 
Note: Home healthcare visits are only allowed in countries where home healthcare visits are 
explicitly permitted by regulatory requirements. 
The study duration for an individual patient will be as follows: 
x Screening period: up to 7 days  
x Treatment period: 28 consecutive days (ie, Day 1 to Day 28) 
x Follow-up period: 32 days after Day 28 (ie, Day 60) 
As such, the approximate study duration (including screening and the follow-up period) for an 
individual patient is up to 67 days (±3 days). 
An independent DMC will be established by the sponsor or designee to review accumulating 
study data at regular intervals (as per the DMC charter) throughout the study to ensure the safety 
of patients and review overall study conduct. The DMC can recommend in writing to the sponsor 
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whether to continue, modify, or stop the clinical study on the basis of safety considerations (see 
Section 15.8 for further details). 
No interim analysis is planned. 
7.2 
Discussion of Study Design 
This study is designed to investigate the efficacy and safety of 300 mg MP1032 BID plus SoC 
versus placebo plus SoC treatment in hospitalized adults with confirmed moderate to severe 
COVID-19, the disease caused by SARS-CoV-2 infection.  
This study will be executed during a worldwide outbreak of COVID-19 that has resulted in 
capacity issues at many medical facilities. Additionally, the highly contagious nature of 
COVID-19 (compounded by a shortage of personal protective equipment) has caused concerns 
about the safety of healthcare providers caring for these seriously sick patients. Consequently, 
this study is designed to minimize any additional burden on clinical sites, including minimizing 
the number of assessments and interventions that the study will require in addition to SoC, while 
still ensuring the safety of patients. 
This study will be double-blinded and placebo-controlled to limit bias in study assessments. 
Either MP1032 or placebo will be administered as add-on therapy to SoC. Most interventions 
and assessments may be accomplished in conjunction with SoC, without requiring additional 
hospital visits or resources. 
The dose, dosing regimen, and duration of treatment planned for this study (300 mg MP1032 
BID for 28 days) were selected on the basis of: 
x The highest repeated dose was 300 mg MP1032 BID applied to both healthy volunteers 
(7 days) and psoriasis patients (3 months). MP1032 was well tolerated in all studies and 
safety analyses did not reveal any clinically important safety issues (see the current 
version of the IB for further information). 
x Acute treatment for symptoms of respiratory viral infections is typically from 14 to 
28 days.  
x A 28-day treatment period was selected because it is a standard duration of time included 
in the WHO R&D Blueprint for COVID-19 (WHO 2020d).  
All patients will be treated for 28 days (unless the study drug is discontinued for safety reasons) 
to provide a fixed duration of treatment across all patients. As it is impractical to require the 
study site to continue to hospitalize patients who no longer require hospital care, if the patient is 
discharged home before Day 28, the study team will provide the patient with the remainder of 
the assigned blinded study drug kit(s) to take home along with instructions on how to continue 
treatment at home on the day-of-discharge. Any patient who is discharged during the study 
should complete the day-of-discharge assessments before release from the hospital as noted in 
the Schedule of Assessments (Table 1). Patients who progress to the use of an invasive 
ventilation (mechanical ventilator and/or ECMO) or who can no longer swallow the study drug 
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(>2 days [ie, 2-day interruption is acceptable]) must discontinue the study drug; but whenever 
possible, the study assessments will be performed on Day 14, Day 21, Day 28, and Day 60. 
This proof-of-concept study will neither include pregnant nor breastfeeding females. In 
reproduction toxicity studies of MP1032 on fertility and early embryonic as well as on embryo-
fetal development, no pathological effects were found. Genotoxicity testing as well as the 
repeated dose toxicity studies (up to 12 months in dogs and 6 months in rats) did not indicate any 
toxicological effects. Hence, MP1032 is considered as IMP with unlikely human 
teratogenicity/fetotoxicity in early pregnancy (see the current version of the IB for more 
information). However, due to the early clinical stage of development, only women who are 
neither pregnant nor breastfeeding will be randomized in this study. Women of childbearing 
potential (WOCBP) and non-sterile male patients with female partners who are WOCBP will be 
required to use a highly effective method of contraception from the time of first dose of study 
medication until at least 30 days after the last dose of study medication.  
7.3 
End of Study  
A patient will have fulfilled the requirements for study completion if/when the patient has 
completed all study periods, including Day 60 as indicated in the Schedule of Assessments 
(Table 1).  
The end of the study will be the last patient’s last visit (ie, Day 60) as indicated in the Schedule 
of Assessments (Table 1).  
8 
SELECTION OF STUDY POPULATION 
Section 7.1 provides information regarding number of patients planned to be randomized. 
8.1 
Inclusion Criteria 
Individuals must meet all of the following criteria to be included in the study: 
1. The patient must be willing and able to give informed consent to participate in the study 
and to adhere to the procedures stated in the protocol or, for adults incapable of 
consenting due to their medical condition (eg, too weak or debilitated, severe shortness of 
breath) or due to literacy issues, the patient’s legally authorized representative (LAR) 
must be willing and able to give informed consent on behalf of the patient to participate 
in the study as permitted by local regulatory authorities, institutional review 
boards (IRBs)/independent ethics committees (IECs), or local laws. 
2. The patient is male or female adult aged 18 years (as per local laws) at the time of 
giving informed consent. 
3. The patient is admitted to a hospital and has a positive SARS-CoV-2 test by standard 
RT-PCR assay or equivalent test. Please note: If the patient has a previous confirmation 
of SARS-CoV-2 (within 7 days of Day 1), the SARS-CoV-2 test at screening is not 
required.  
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4. The patient has the presence of any symptom(s) suggestive of moderate or severe 
systemic illness with COVID-19 on Day 1, such as presence of fever (38.0°C 
[100.4°F] by any route), loss of smell or taste, cough, sore throat, malaise, headache, 
muscle pain, gastrointestinal symptoms, shortness of breath upon exertion and/or at rest, 
or respiratory distress. 
5. The patient has the presence of moderate to severe clinical signs indicative of moderate 
or severe illness with COVID-19 on Day 1:  
a. Moderate:  
i. Clinical signs suggestive of moderate illness with COVID-19, such as 
respiratory rate 20 breaths per minute, SpO2 >93% (on room air at sea 
level, if possible), heart rate 90 beats per minute  
ii. No clinical signs indicative of severe or critical COVID-19 
b. Severe:  
i. Clinical signs suggestive of severe systemic illness with COVID-19, such 
as respiratory rate 30 breaths per minute, heart rate 125 beats per 
minute, SpO2 93% (on room air at sea level, if possible), 
PaO2/FiO2 <300, or diagnosed with ARDS (according to the Berlin 
definition; see Table 3) 
ii. No criteria met for critical COVID-19 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition 
(eg, emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19 
(unless the patient meets the definition for critical COVID-19). For questions related to 
COVID-19 severity, the investigator should contact the medical monitor. 
6. The patient does not require hemodialysis (chronic) or any renal replacement therapies at 
screening or Day 1. 
7. The patient is able to swallow the study drug (hard gelatin capsules).  
8. The patient agrees to minimize strong sun exposure (sunbathing) and strong ultraviolet 
exposure during the course of the study. Additionally, during the study, patients must 
agree to use sunscreen when spending an extended period outdoors. 
9. Men whose sexual partners are WOCBP must agree to comply with 1 of the following 
contraception requirements from the time of first dose of study medication (Day 1) until 
at least 30 days after the last dose of study medication: 
a. Vasectomy with documentation of azoospermia.  
b. Sexual abstinence (defined as refraining from heterosexual intercourse from the 
time of first dose of study medication until at least 30 days after the last dose of 
study medication) 
c. Male condom plus partner use of 1 of the contraceptive options below: 
contraceptive subdermal implant; intrauterine device or intrauterine system; oral 
contraceptive, either combined or progestogen alone; injectable progestogen; 
contraceptive vaginal ring; percutaneous contraceptive patches.  
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The above is an all-inclusive list of those methods that meet the following definition of 
highly effective: having a failure rate of <1% per year when used consistently and 
correctly and, when applicable, in accordance with the product label. For non-product 
methods (eg, male sterility), the investigator will determine what is consistent and correct 
use. The investigator is responsible for ensuring that patients understand how to properly 
use these methods of contraception.  
10. WOCBP must agree to comply with 1 of the following contraception requirements from 
the time of first dose of study medication (Day 1) until at least 30 days after the last dose 
of study medication: 
a. Sexual abstinence (defined as refraining from heterosexual intercourse from the 
time of first dose of study medication until at least 30 days after the last dose of 
study medication) 
b. Use of 1 of the contraceptive options below plus use of a condom by male 
partner: contraceptive subdermal implant; intrauterine device or intrauterine 
system; oral contraceptive, either combined or progestogen alone; injectable 
progestogen; contraceptive vaginal ring; percutaneous contraceptive patches.  
c. Vasectomy of male partner with documentation of azoospermia.  
The above is an all-inclusive list of those methods that meet the following definition of 
highly effective: having a failure rate of <1% per year when used consistently and 
correctly and, when applicable, in accordance with the product label. The investigator is 
responsible for ensuring that patients understand how to properly use these methods of 
contraception. Women of non-reproductive potential are defined as:  
a. Premenopausal females with 1 of the following: documented tubal ligation; 
documented hysteroscopic tubal occlusion procedure with follow-up confirmation 
of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy.  
b. Postmenopausal defined as 12 months of spontaneous amenorrhea [in 
questionable cases a blood sample with simultaneous follicle stimulating hormone 
and estradiol levels consistent with menopause (refer to laboratory reference 
ranges for confirmatory levels)]. Women on hormone replacement therapy (HRT) 
and whose menopausal status is in doubt will be required to use 1 of the highly 
effective contraception methods listed above if they wish to continue their HRT 
during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before randomization.  
8.2 
Exclusion Criteria 
Individuals meeting any of the following criteria are ineligible to participate in this study:  
1. The patient, in the opinion of the investigator, is not likely to survive for 48 hours 
beyond Day 1.  
2. The patient has a diagnosis of asymptomatic COVID-19, mild COVID-19, or critical 
COVID-19 on Day 1.  
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a. Asymptomatic COVID-19 is defined as a patient with a positive SARS-CoV-2 
test by standard RT-PCR assay or equivalent test but not experiencing symptoms.  
b. Mild COVID-19 is defined as a patient with a positive SARS-CoV-2 test by 
standard RT-PCR assay or equivalent test and experiencing symptoms of mild 
illness but no clinical signs indicative of moderate, severe, or critical COVID-19.  
c. Critical COVID-19 is defined as a patient with a positive SARS-CoV-2 test by 
standard RT-PCR assay or equivalent test and experiencing at least 1 of the 
following: shock defined by systolic blood pressure <90 mm Hg or diastolic 
blood pressure <60 mm Hg, or requiring vasopressors; respiratory failure 
requiring endotracheal intubation and invasive mechanical ventilation, oxygen 
delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via 
reinforced nasal cannula at flow rates >20 L/min with fraction of delivered 
oxygen 0.5), non-invasive positive pressure ventilation, ECMO, or clinical 
diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, 
but preceding therapies not able to be administered in setting of resource 
limitation), and/or multi-organ dysfunction/failure. 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition 
(eg, emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19 
(unless the patient meets the definition for critical COVID-19). For questions related to 
COVID-19 severity, the investigator should contact the medical monitor. 
3. The patient has a Child Pugh score  C. 
4. The patient has a documented medical history of infection with hepatitis A, B, or C at 
screening or Day 1. 
5. The patient has a documented medical history of infection with human 
immunodeficiency virus and has a detectable viral load and CD4 count <500 cells/L.  
6. The patient has a documented active infection with tuberculosis at screening or Day 1. 
7. The patient has clinically significant electrocardiogram (ECG) abnormalities at screening. 
8. A female patient who is pregnant, planning to become pregnant during the study, 
breastfeeding, or has a positive pregnancy test at screening (by serum) or before dosing 
on Day 1 (by urine) as determined by human chorionic gonadotrophin (hCG) tests. 
9. The patient is planning to donate or bank ova or sperm from Day 1 until 30 days after the 
last dose of study drug. 
10. The patient has a known history of drug or alcohol abuse within 6 months of study start 
that would interfere with the patient’s participation in the study. 
11. The patient has a history of sensitivity to any of the study medications, components 
thereof (eg, mannitol or gelatin), or a history of drug or other allergy that, in the opinion 
of the investigator or medical monitor, would contraindicate their participation. 
12. The patient has participated in and/or plans to participate in another clinical study using 
an investigational product within the following period before the first dosing day in the 
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current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the 
investigational product (whichever is longer). 
13. The patient will be transferred to another hospital that is not a study site within 72 hours. 
Please note: If the investigator has admitting privileges to the transfer hospital, the patient 
may be considered for randomization. 
14. The patient is employed by MetrioPharm, the contract research organization or clinical 
site involved in the clinical study. 
15. The investigator makes a decision that study involvement is not in patient’s best interest, 
or the patient has any condition or critical illness, in the opinion of the investigator, that 
will not allow the protocol to be followed safely. 
8.3 
Rescreening 
Individuals who give informed consent to participate in the study but who do not subsequently 
meet all the requirements as outlined in the inclusion and exclusion criteria and therefore are not 
randomized (screen failures) may be rescreened. Such individuals may be allowed to rescreen 
only 1 time. 
8.4 
Study Withdrawal, Removal, and Replacement of Patients 
Patients who terminate the study before Day 28 will be asked to complete the day-of-discharge 
study procedures. Patients who terminate the study after Day 28 will be asked to complete the 
Day 60 study procedures. Please note: It is expected that patients who discontinue the study drug 
early remain in the study, whenever possible, until the completion of the Day 60 study 
procedures. If it is not possible to follow-up with the patient until Day 60, then follow-up should 
occur until at least Day 28.  
Once a patient is withdrawn from the study, the patient may not return to the study. 
A patient may voluntarily withdraw or be withdrawn from the study at any time for the following 
reasons:  
x patient withdrawal of consent (at any time, a patient's participation in the study may be 
terminated at his/her request)  
x lost to follow-up: the patient stopped coming for visits, and study personnel were unable 
to contact the patient.  
Please note: In cases in which the patient is deemed lost to follow-up, the investigator or 
designee must make every effort to regain contact with the patient (eg, telephone calls, letter to 
the patient’s last known mailing address, or local equivalent methods). In cases where the 
patient’s LAR provides informed consent on behalf of the patient, the study site should attempt 
to contact the LAR. Additionally, the study site should attempt to regain contact with the patient 
using the alternative contact information provided by the patient/LAR at the time of informed 
consent. These contact attempts must be documented in the patient’s medical records. 
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The reason and date for patient withdrawal from the study must be recorded on the electronic 
case report form (eCRF). 
Additionally, the sponsor or DMC may stop the study at any time for safety, regulatory, legal, or 
other reasons aligned with good clinical practice (GCP). This study may be terminated at the 
discretion of the sponsor or any regulatory agency. An investigator may elect to terminate or stop 
the study at his or her study site for any reason, including safety or low recruitment. 
9 
TREATMENTS 
9.1 
Details of Study Drugs 
Both MP1032 hard gelatin capsules 50 mg and matching placebo capsules will be supplied as 
14-day blinded study drug kits. Each kit will also include reserve supply for 1 additional day. 
Thus, each kit will include 180 capsules in total. IMP will be packaged and labelled according to 
all applicable local legal requirements. Study drug must be stored in a controlled environment at 
the study site’s pharmacy where storage temperature is monitored, and access is limited to 
authorized personnel only. In the pharmacy, both MP1032 capsules and matching placebo 
capsules must be stored in the primary and/or secondary packaging at room temperature (15°C to 
25°C [59°F to 77°F]) and protected from light. If the patient is discharged home before Day 28, 
the study team will provide the patient with the remainder of the assigned blinded study drug 
kit(s) to take home along with instructions on the day-of-discharge. 
Further details of the blinded study drug kits will be described in a Pharmacy Manual. 
9.2 
Dosage Schedule 
All randomized patients will receive study drug from Day 1 to Day 28 according to their 
assigned treatment and according to the randomization scheme.  
Please note: Patients who remain hospitalized after 28 days of consecutive treatment with study 
drug are not eligible for additional treatments with study drug. Patients will receive 6 capsules in 
the morning and 6 capsules in the evening (ie, approximately every 12 hours, approximately at 
the same time every day, and at least 8 hours apart) according to their randomized treatment arm 
assignment as described below:  
x Arm A: MP1032 (300 mg [6 × MP1032 hard gelatin capsules 50 mg] BID) for oral 
administration 
x Arm B: 6 × placebo capsules (ie, matching MP1032 hard gelatin capsules 50 mg) BID for 
oral administration  
In Arm A, the planned total daily dose of MP1032 is 600 mg. In Arm B, the planned total daily 
dose of MP1032 is 0 mg. 
Study drug will be administered to each patient with water (ad libitum) for oral administration. 
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For all patients (except on Day 1 and Day 7 for patients in the PK subset): Patients should not eat 
within the 30 minutes before planned study drug administration and within the 30 minutes after 
study drug dosing, when feasible. However, if a patient has eaten within the 30 minutes before 
their planned study drug administration, study drug dosing may proceed. The study site should 
record the date and time of dosing (recorded as the time when the first capsule is administered).
For patients in the PK subset on Day 1 and Day 7 only: Patients should not eat within the 4 hours 
before planned study drug administration and within the 120 minutes after study drug dosing, 
when feasible. Thus, study drug should be administered in fasted state ( 4 hours), when 
feasible. However, if a patient has eaten within the 4 hours before their planned administration, 
study drug dosing may proceed. The patient’s fed or fasted state, as well as food intake (yes/no) 
within the 120 minutes after study drug dosing should be recorded. The PK samples should be 
collected as planned regardless of the patients’ fasted/fed state. The study site should record the 
date and time of dosing (recorded as the time when the first capsule is administered).
Any missed dose study drug may be administered as soon as possible and the next scheduled 
dose may be administered according to the planned schedule as long as the doses are at least 6 to 
8 hours apart. If study drug administration is interrupted for >2 days, the investigator should 
notify the medical monitor to determine if the study drug administration can be resumed.
Patients will be asked to abstain from the following products that may potentially affect their 
safety and/or the PK profile of the study drug: 
x
soft or hard drugs (including cannabis) from screening and throughout the study 
x
smoking or using electronic cigarettes while admitted to the hospital
x
consumption of alcohol-based products will be prohibited from screening until the final 
dose of study drug
9.3
Measures to Minimize Bias: Randomization and Blinding
Randomization 
The randomization of patients to treatment groups will be performed centrally by an IWRS using 
a randomization scheme that will be produced by an unblinded, independent statistician. During 
the randomization process, IWRS will assign a randomization number. Each patient will be 
assigned one kit number at randomization and a second kit number at the Day 14 visit. The study 
drug kits will contain the respective blinded treatment available at the study site. Further 
information on IWRS process will be provided in the IWRS Manual.
Approximately 120 patients will be randomly assigned (2:1) as follows: 
x
Arm A (300 mg MP1032 BID plus SoC): approximately 80 patients
x
Arm B (placebo BID plus SoC): approximately 40 patients
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The stratification factor for randomization will include baseline COVID-19 severity (moderate 
versus severe) and age-class (aged 65 years versus >65 years). COVID-19 severity will be 
determined using the following criteria:
x
Moderate COVID-19: 
o
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
o
Symptoms of moderate illness with COVID-19, which could include any 
symptom of mild illness or shortness of breath with exertion
o
Clinical signs suggestive of moderate illness with COVID-19, such as respiratory 
rate 20 breaths per minute, SpO2 >93% (on room air at sea level, if possible), 
heart rate 90 beats per minute 
o
No clinical signs indicative of severe or critical COVID-19
x
Severe COVID-19: 
o
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
o
Symptoms suggestive of severe systemic illness with COVID-19, which could 
include any symptom of moderate illness or shortness of breath at rest, or 
respiratory distress
o
Clinical signs indicative of severe systemic illness with COVID-19, such as 
respiratory rate 30 breaths per minute, heart rate 125 beats per minute, SpO2
93% (on room air at sea level, if possible), PaO2/FiO2 <300, or diagnosed with 
ARDS (according to the Berlin definition; see Table 3)
o
No criteria met for critical COVID-19
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will 
be measured when the patient is on room air at sea level (ie, no supplemental oxygen, if possible) 
and at rest for at least 5 minutes. If possible, the site should collect the information from each 
patient at the same time each day (±1 hour). 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition (eg, 
emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19 (unless the 
patient meets the definition for critical COVID-19). For questions related to COVID-19 severity, 
the investigator should contact the medical monitor.
Blinding
The study is double-blinded. Study drug will be identical in appearance and labeled in a blinded 
manner. All patients (and their LARs), investigators, and all study staff involved in the conduct 
of the study (including sponsor personnel or sponsor designees), including data management and 
biostatistics, will be blinded to treatment assignment. 
Exception: An unblinded, independent statistician will be assigned to produce the randomization 
schedule and unblinded tables, figures, and listings for the DMC. The unblinded statistician will 
not otherwise participate in study procedures.
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In the event that emergency unblinding is required for a given patient because of AEs or 
concerns for the patient’s safety or well-being, the investigator may break the randomization 
code for the patient via the IWRS, by which system the unblinding will be captured. The 
investigator is responsible for notifying the medical monitor and/or sponsor of such an event as 
soon as possible. The unblinding and its cause will also be documented in the eCRF. 
If an investigator becomes unblinded to a given patient’s study drug, that patient will be 
discontinued from the study drug unless there are ethical reasons for that patient not to be 
discontinued; approval from the sponsor’s medical monitor must be obtained in such instances. 
9.4 
Treatment Modifications and Discontinuations 
Dose reductions and adjustments are not permitted; any dose reductions and adjustments that 
occur will be recorded and considered protocol deviations. 
Delays and omissions of study drug administration because of medical or non-medical reasons 
are allowed. All delays and omissions of study drug that occur during the study will be recorded 
and considered protocol deviations. 
All patients will be treated for 28 days unless the study drug is discontinued for safety reasons, or 
the patient withdraws consent. If a patient is discontinued from the study drug for any reason, the 
study site must immediately notify the medical monitor.  
A patient may voluntarily discontinue the study drug or be discontinued from the study drug at 
any time for reasons including, but not limited to, the following: 
x progressive disease (related to COVID-19). Please note: Patients who progress to the use 
of an invasive ventilation (mechanical ventilator and/or ECMO) or who can no longer 
swallow the study drug (>2 days [ie, 2-day interruption is acceptable]) must discontinue 
the study drug; but whenever possible, the study assessments will be performed on 
Day 14, Day 21, Day 28, and Day 60. 
x unacceptable AE and/or SAE 
x patient withdrawal of consent (at any time, a patient's participation in the study may be 
terminated at his/her request)  
x on the basis of the investigator’s clinical judgment  
x general or specific changes in the patient's condition that render him/her ineligible for 
further treatment according to the inclusion/exclusion criteria 
x patient fails to adhere to the protocol requirements (eg, drug noncompliance)  
x lost to follow-up: the patient stopped coming for visits, and study personnel were unable 
to contact the patient.  
Please note: In cases in which the patient is deemed lost to follow-up, the investigator or 
designee must make every effort to regain contact with the patient (eg, telephone calls, 
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letter to the patient’s last known mailing address, or local equivalent methods). In cases 
where the patient’s LAR provides informed consent on behalf of the patient, the study 
site should attempt to contact the LAR. Additionally, the study site should attempt to 
regain contact with the patient using the alternative contact information provided by the 
patient/LAR at the time of informed consent. These contact attempts must be documented 
in the patient’s medical records. 
x pregnancy, as indicated in Section 12.6.5. 
The reason and date for the patient’s discontinuation from study drug must be recorded on the 
eCRF. 
Please note: It is expected that patients who discontinue study drug early remain in the study, 
whenever possible, until the completion of the Day 60 study procedures. If it is not possible to 
follow-up with the patient until Day 60, then follow-up should occur until at least Day 28. 
9.5 
Treatment Accountability and Compliance 
The pharmacist or other designated individual will maintain records of study drug delivered to 
the study site, the inventory at the study site, the distribution to and use by each patient, and the 
return of materials to the sponsor for storage or disposal. These records should include dates, 
quantities, batch/serial numbers, expiration dates, in-clinic temperature log, and unique code 
numbers assigned to the product and patients. 
During hospitalization, the administration of the study drug will be performed by the investigator 
(or qualified blinded designee) to ensure compliance. If the patient is discharged home before 
Day 28, the study team will provide the patient with the remainder of the assigned blinded study 
drug kit(s) to take home along with instructions to continue treatment at home; for these patients, 
treatment compliance will be conducted via a diary. If the patient does not feel comfortable to 
complete the diary, the site will alternatively provide the patient with the option to be called, 
twice a day, to confirm that the study drug is taken as instructed. Patients are to be reminded of 
the importance of compliance with their assigned regimen, with an emphasis on taking their 
study drug on schedule and maintaining the prescribed interval between doses. 
Investigators will maintain records that adequately document that the patients were provided 
with the correct study drug kit(s) and reconcile the products received from the drug dispensing 
center. Investigational product will not be returned to the sponsor until accountability has been 
fully monitored. 
Noncompliance is defined as taking <80% or >120% of study drug. Discontinuation for 
noncompliance is at the investigator’s discretion and is to be noted on the eCRF. 
9.6 
Prior and Concomitant Medications 
Restricted prior medications are provided in Section 8.2.  
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All medications and other treatments taken by the patient during the study, including those 
treatments initiated before the start of the study, must be recorded on the eCRF. 
Medications taken by or administered to the patient for the period before screening will be 
recorded in the eCRF. After the screening visit, medications are generally permitted; however, 
the following therapies are expressly prohibited during the screening and treatment periods and 
up through the end of the follow-up period (ie, up through Day 28):  
x an investigational product from another clinical study  
Any medication or therapy that is taken by or administered to the patient during the course of the 
study must be recorded in the eCRF. The entry must include the dose, regimen, route, indication, 
and dates of use. 
10 
STUDY PROCEDURES 
Table 1 outlines the timing of procedures and assessments to be performed throughout the study. 
Section 12.5 specifies clinical laboratory assessment samples to be obtained. See Section 11, 
Section 12, Section 13, and Section 14 for additional details regarding efficacy, safety, PK, other 
assessments, respectively.  
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Table 1: 
Schedule of Assessments 
Study Period 
Screening 
Period 
 
Treatment Period 
Follow-up Period  
- 
Visit Name 
Screeninga 
Day 1a 
Days 2 to 
13 
Day 14b 
Day 21b 
Day 28 
(End of 
Treatment 
Visit)b 
Day 60 
(Follow-up Visit)b / 
Early Study 
Termination after 
Day 28 
 
Day of Discharge / 
Early Study 
Termination before 
Day 28 
Study Day (window) 
Day -7 to  
Day -1 
Day 1 (NA) Days 2 to 
13 (NA) 
Day 14 
(±2 days) 
Day 21 
(±2 days) 
Day 28 
(±3 days) 
Day 60 (±3 days)  
Day of Discharge 
Informed consentc 
X 
- 
- 
- 
 
- 
- 
 
- 
COVID-19 testingd 
X 
X 
- 
Xe 
 
Xe 
Xe 
 
- 
Demographicsf 
X 
- 
- 
- 
 
- 
- 
 
- 
Medical/surgical historyg  
X 
X (updates 
only) 
- 
- 
 
- 
- 
 
- 
Inclusion/exclusion criteria 
X 
X 
- 
- 
 
- 
- 
 
- 
Complete physical examinationh 
X 
- 
- 
- 
 
- 
- 
 
- 
Limited physical examinationh 
- 
X 
X (only 
Day 8 
[±3 days])s 
Xe 
 
Xe 
- 
 
X 
Vital signsi 
X 
X 
Xj 
Xe 
 
Xe 
Xe 
 
X 
Height 
X 
- 
- 
- 
 
- 
- 
 
- 
Weight and BMI 
X 
X 
- 
Xe 
 
Xe 
Xe 
 
X 
Clinical laboratory assessments (hematology, 
blood biochemistry, coagulation, and urinalysis) 
X 
X 
X (only 
Day 8 
[±3 days])s 
X (Days 14, 21, and 28)e, u 
- 
 
X 
ECGk 
X 
- 
- 
- 
 
- 
- 
 
- 
Pregnancy test (WOCBP only)l 
X 
X 
- 
X 
 
- 
- 
 
X (only if discharged 
before Day 14 or at 
Early Study 
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Study Period 
Screening 
Period 
 
Treatment Period 
Follow-up Period  
- 
Visit Name 
Screeninga 
Day 1a 
Days 2 to 
13 
Day 14b 
Day 21b 
Day 28 
(End of 
Treatment 
Visit)b 
Day 60 
(Follow-up Visit)b / 
Early Study 
Termination after 
Day 28 
 
Day of Discharge / 
Early Study 
Termination before 
Day 28 
Study Day (window) 
Day -7 to  
Day -1 
Day 1 (NA) Days 2 to 
13 (NA) 
Day 14 
(±2 days) 
Day 21 
(±2 days) 
Day 28 
(±3 days) 
Day 60 (±3 days)  
Day of Discharge 
Termination before Day 
14) 
Randomization via IWRS 
- 
X 
- 
- 
 
- 
- 
 
- 
Retrieve the 14-day blinded study drug kit via the 
study drug kit number assigned by IWRS 
 
X 
 
Xv 
 
 
 
 
X (only if discharged 
before Day 14; NA for 
Early Study 
Termination) 
Blood sample collection for biomarkers  
- 
Xo 
X (only 
Day 7)o 
X (Days 14, 21, and 28)o 
Xe,o  
 
- 
Administer blinded study drug BID 
- 
 
Xt 
- 
 
- 
Provide remainder of the assigned blinded study 
drug kit(s) to the patient along with instructionsm 
- 
- 
- 
- 
 
- 
- 
 
X (only if discharged 
during the treatment 
period; NA for Early 
Study Termination) 
Provide patient with the diary and train patient on 
use of the diarym 
- 
- 
- 
- 
 
- 
- 
 
X (only if discharged 
during the treatment 
period; NA for Early 
Study Termination) 
COVID-19 symptoms 
X 
X 
- 
X 
 
X 
X 
 
X 
COVID-19 severityp 
X 
X 
- 
- 
 
- 
- 
 
- 
Clinical status related to COVID-19 on the NIAID 
8-point ordinal scaleq 
X 
X 
X 
X 
 
X 
X 
 
X 
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Study Period 
Screening 
Period 
 
Treatment Period 
Follow-up Period  
- 
Visit Name 
Screeninga 
Day 1a 
Days 2 to 
13 
Day 14b 
Day 21b 
Day 28 
(End of 
Treatment 
Visit)b 
Day 60 
(Follow-up Visit)b / 
Early Study 
Termination after 
Day 28 
 
Day of Discharge / 
Early Study 
Termination before 
Day 28 
Study Day (window) 
Day -7 to  
Day -1 
Day 1 (NA) Days 2 to 
13 (NA) 
Day 14 
(±2 days) 
Day 21 
(±2 days) 
Day 28 
(±3 days) 
Day 60 (±3 days)  
Day of Discharge 
EQ-5D-5L questionnairer 
- 
- 
- 
- 
 
- 
X 
 
X (only if discharged/ 
early terminated before 
Day 60) 
Blood sample collection (plasma) for PK (from the 
PK subset of approximately 30 patients who give 
optional consent)n 
- 
X 
X (only 
Day 7)j 
 
 
- 
- 
 
- 
AEs 
X 
X 
Prior and concomitant medications 
X 
X 
Abbreviations: AE = adverse event; BID = twice daily; BMI = body mass index; COVID-19 = coronavirus 2019; ECG = electrocardiogram; eCRF = electronic case report form; 
EQ-5D-5L = EuroQol-5D-5L; IEC = independent ethics committee; ICU = intensive care unit; IRB = institutional review board; IWRS = interactive web-response system; 
LAR = legally authorized representative; NA = not applicable; NIAID = National Institute of Allergy and Infectious Diseases; PK = pharmacokinetic; RT-PCR = reverse 
transcription-polymerase chain reaction; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus type 2; SoC = standard of care; 
SpO2 = saturation of oxygen; WOCBP = women of childbearing potential 
 
a. 
Those patients who are fully eligible (all screening assessments are available) can have Day 1 performed on the same day as screening. If screening and Day 1 are 
performed on the same day, visit procedures required for both visits do not need to be repeated.  
b. Patients will be assessed while hospitalized. If patients are discharged from the hospital, they can have the study visits at Day 14, Day 21, Day 28, and Day 60 as an 
outpatient visit. Patients discharged early will continue to receive study drug through Day 28. For discharged patients, Day 14 and Day 28 visits are preferred to be 
conducted in person at the study site. If restrictions limit the ability of the patient to return to the study site, these visits may be conducted by home healthcare visit or by 
telephone/virtual call (the patient’s caregiver may assist during the telephone/virtual call). For discharged patients, it is sufficient to conduct the Day 60 Follow-up Visit as 
a telephone/virtual call (the patient’s caregiver may assist during the telephone/virtual call) or an outpatient or home healthcare visit is also allowed. Please note: In cases 
in which the patient is deemed lost to follow-up, the investigator or designee must make every effort to regain contact with the patient (eg, telephone calls, letter to the 
patient’s last known mailing address, or local equivalent methods). In cases where the patient’s LAR provides informed consent on behalf of the patient, the study site 
should attempt to contact the LAR. Additionally, the study site should attempt to regain contact with the patient using the alternative contact information provided by the 
patient/LAR at the time of informed consent. These contact attempts must be documented in the patient’s medical records. 
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c. 
The patient must give informed consent to participate in the study or, for adults incapable of consenting due to their medical condition (eg, too weak or debilitated, severe 
shortness of breath) or due to literacy issues, the patient’s LAR must be willing give informed consent on behalf of the patient to participate in the study as permitted by 
local regulatory authorities, IRBs/IECs, or local laws. 
d. At the screening visit, the local laboratory may perform COVID-19 testing by standard RT-PCR assay or equivalent test. At screening, a positive test must be available in 
order for the patient to be randomized on Day 1. If the patient has a previous confirmation of SARS-CoV-2 (within 7 days of Day 1), the SARS-CoV-2 test at screening is 
not required. On Day 1, Day 14, Day 28, and Day 60, samples will be sent to the central laboratory for COVID-19 testing by standard RT-PCR assay. The result of the 
COVID-19 tests (positive/negative) must be documented in the eCRF. Further details will be described in the laboratory manual. Please note: If COVID-19 tests are 
performed at unscheduled time points (eg, according to SoC), findings (ie, positive/negative result) must be recorded in the eCRF. 
e. 
Not all assessments will be able to be performed if the Day 14, Day 28, and/or 60 visits are conducted via a telephone/virtual call (the patient’s caregiver may assist during 
the telephone/virtual call). If the assessment can be conducted via a telephone/virtual call, the study site should record the details; otherwise, the missed assessment will 
not be considered a protocol deviation. If the visit is conducted by a home healthcare nurse, these assessments should be conducted, if possible; if the assessment can be 
conducted via home healthcare nurse, the study site should record the details; otherwise, the missed assessment will not be considered a protocol deviation. These 
assessments must be conducted if the visit is conducted at the study site. All efforts should be made to collect clinical laboratory assessments on Day 14 (± 2 days) and 
Day 28 (± 3 days). Please note: In cases in which the patient is deemed lost to follow-up, the investigator or designee must make every effort to regain contact with the 
patient (eg, telephone calls, letter to the patient’s last known mailing address, or local equivalent methods). In cases where the patient’s LAR provides informed consent 
on behalf of the patient, the study site should attempt to contact the LAR. Additionally, the study site should attempt to regain contact with the patient using the alternative 
contact information provided by the patient/LAR at the time of informed consent. These contact attempts must be documented in the patient’s medical records. 
f. 
Demographics will include sex, age, and race and/or ethnicity. 
g. Medical/surgical medical history includes all active and chronic diseases (eg, asthma and COPD), and any diseases diagnosed in the past 1 year (before screening) that the 
investigator considers clinically significant. Additional pre-existing conditions present at the time when informed consent is given and up to the time of first dosing 
(Day 1) are to be regarded as concomitant. Medical history will include documentation of social behaviors, including use of tobacco, nicotine (including use of electronic 
cigarettes), and soft or hard drugs (including cannabis), as well as alcohol consumption, if applicable. Smoking history also must be documented as part of medical history 
and includes never, light (<100 cigarettes/lifetime), active smoker, and former smoker (quit date). History of number packs/day, number of smoking years, and quitting 
time for former and active smokers must also be documented. Additionally, the investigators will document at screening the patient’s Charlson score via the Charlson 
Comorbidity Index (see Section 12.1 for further details) (Appendix 1). 
h. A complete physical examination will be performed at screening. Physical examinations will be performed by a physician, nurse, or other appropriately trained staff. The 
complete physical examination includes head, eyes, ears, nose, and throat; heart; lungs; abdomen; skin; cervical and axillary lymph nodes; and neurological and 
musculoskeletal systems. A limited physical examination to verify continued patient eligibility and to follow-up regarding any change in medical history will be 
performed at the visits indicated above. Symptom-driven, limited physical examinations may be performed as clinically indicated during the study (according to SoC). 
i. 
Vital signs include systolic and diastolic blood pressure, heart rate, respiration rate, SpO2, and body temperature. All vital signs will be measured after the patient has been 
resting for at least 5 minutes. Blood pressure measurements are to be taken in the same arm for the duration of the study. Moreover, additional vital signs may be 
performed as needed in case of any cardiac AE.  
j. 
For patients who remain hospitalized only.  
k. A 12-lead, resting ECG will be obtained locally at screening. At screening, the investigator must examine the ECG traces for clinically significant abnormalities that could 
exclude the patient from the study. ECGs should always be obtained in supine position after adequate rest (5 minutes).  
l. 
For WOCBP, a serum sample for pregnancy testing must be collected at screening and a urine sample for pregnancy testing must be collected before the first dose on 
Day 1. Pregnancy tests must be negative for the patient to be randomized and treated. A urine pregnancy test will be repeated on Day 14 (± 7 days). If the patient is 
discharged before Day 14, urine pregnancy test at day of discharge should be done, and urine pregnancy test at Day 14 is not required. If the patient is discharged after 
Day 14, urine pregnancy test should be done at Day 14, and urine pregnancy test at day of discharge is not required (whichever comes first). Patients with a positive 
pregnancy test will be discontinued from study drug. 
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m. Only for patients discharged before Day 28. If the patient does not feel comfortable to complete the diary, the site will alternatively provide the patient with the option to 
be called, twice a day, to confirm that the study drug is taken as instructed. 
n. Plasma PK samples will be collected via sparse sampling from approximately 30 patients (who give optional consent) in a 2:1 ratio to assess the PK of MP1032 on Day 1 
(single dose) and Day 7 (steady state). A total of 16 samples will be collected relative to the first dose on Day 1 and the first dose on Day 7. Samples on Day 1 and Day 7 
will be collected predose (within 10 minutes before the first daily dose) and postdose at 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 8 hours (before 
next dose), and 24 hours before the next morning dose (if applicable), if possible. Patients who provide consent for the PK sampling, but are no longer hospitalized on 
Day 7, will not have Day 7 PK samples collected.  
o. Blood samples to be obtained on Day 1 (before the first study drug administration) and Days 7, 14, 21, 28, and 60 (when possible). Blood samples for biomarkers must be 
collected on Days 7, 14, 21, 28, and 60 if a patient is still hospitalized. If a patient is discharged, the study site should arrange an outpatient visit (ie, at the study site) to 
accommodate the collection of blood samples for biomarkers on Days 7, 14, 21, 28, and 60.  
p. To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will be measured when the patient is on room air at sea level (ie, no 
supplemental oxygen, if possible) and at rest for at least 5 minutes. If possible, the site should collect the information from each patient at the same time each day 
(±1 hour).  
q. Record the patient’s clinical status related to COVID-19 on the NIAID 8-point ordinal scale and also record the date and time for each individual component of the NIAID 
8-point ordinal scale including: invasive or non-invasive mechanical ventilation/ECMO start/stop, high-flow/mask oxygen start/stop, supplemental oxygen start/stop 
(nasal cannula, liter flow [and its conversion to FiO2], other delivery services), hospital discharge (whether with limitations or without limitations), hospitalization type 
(eg, transfer to ICU) start/stop, and (if applicable) death, cause of death (including relatedness to COVID-19), and date/time of death. If possible, the site should collect 
the information from each patient at the same time each day (±1 hour). 
r. 
The EQ-5D-5L (Appendix 2) is only required for discharged patients and at the following visits: day of discharge, Day 60, and Early Termination visit (if applicable). The 
EQ-5D-5L is not required for patients who remain hospitalized until study end. 
s. 
The limited physical examination and clinical laboratory assessments on Day 8 (± 3 days) will be collected in all patients who remain hospitalized. If the patient is 
discharged before Day 8 (± 3 days), the site should arrange to have the physician assess the patient via a telephone/virtual call. If the physician determines during the 
telephone/virtual call that the limited physical examination and clinical laboratory assessments are clinically indicated, then the site should arrange for an outpatient visit 
to collect these assessments.  
t. 
For all patients (except on Day 1 and Day 7 for patients in the PK subset): Patients should not eat within the 30 minutes before planned study drug administration and 
within the 30 minutes after study drug dosing, when feasible. However, if a patient has eaten within the 30 minutes before their planned study drug administration, study 
drug dosing may proceed. The study site should record the date and time of dosing (recorded as the time when the first capsule is administered). For patients in the PK 
subset on Day 1 and Day 7 only: Patients should not eat within the 4 hours before planned study drug administration and within the 120 minutes after study drug dosing, 
when feasible. Thus, study drug should be administered in fasted state ( 4 hours), when feasible. However, if a patient has eaten within the 4 hours before their planned 
administration, study drug dosing may proceed. The patient’s fed or fasted state, as well as food intake (yes/no) within the 120 minutes after study drug dosing should be 
recorded. The PK samples should be collected as planned regardless of the patients’ fasted/fed state. The study site should record the date and time of dosing (recorded as 
the time when the first capsule is administered). 
u. The clinical laboratory assessments on Day 21 will be collected in all patients who remain hospitalized. If the patient is discharged before Day 21, the site should arrange 
to have the physician assess the patient via a telephone/virtual call. If the physician determines during the telephone/virtual call that the clinical laboratory assessments are 
clinically indicated, then the site should arrange for an outpatient visit to collect this assessment.  
v. The +2-day window does not apply to the retrieval of the 14-day blinded study drug kit as the second kit must be distributed at the latest on Day 14.  
 
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10.1 
Informed Consent 
Before performing any study-related procedures, the investigator (or designee) will obtain 
informed consent from the patient to participate in the study or, for adults incapable of 
consenting due to their medical condition (eg, too weak or debilitated, severe shortness of breath) 
or due to literacy issues, the patient’s LAR must be willing give informed consent on behalf of 
the patient to participate in the study as permitted by local regulatory authorities, IRBs/IECs, or 
local laws. 
Please note: The patient/LAR will be expected to provide the study site with their contact 
information so that the site can maintain contact with the patient/LAR in the event that the 
patient is discharged before the end of the study. Additionally, at the time of informed consent, 
the study site may also request for the patient/LAR to provide alternative contact information. In 
the event that rescreening occurs, the investigator (or designee) must reconsent the patient (or the 
patient’s LAR) and the patient must be assigned a new identification number. 
10.2 
Study Procedures 
Assessments and their timing are to be performed as outlined in the Schedule of Assessments 
(Table 1). Section 12.5 specifies clinical laboratory assessment samples to be obtained.  
Assessments and procedures scheduled at a visit where study drug is administered should be 
performed before administration of treatment unless otherwise indicated in the Schedule of 
Assessments (Table 1). 
Efficacy assessments are described in Section 11 and include COVID-19 symptoms, COVID-19 
severity, clinical status related to COVID-19 on the NIAID 8-point ordinal scale, HRQoL 
assessed by the EQ-5D-5L questionnaire (Appendix 2), and COVID-19 testing.  
Safety assessments are described in Section 12 and include medical/surgical history and 
demographics, vital signs, physical examinations, ECGs, clinical laboratory assessments, and 
AEs. PK assessments are described in Section 13 and include PK sampling and PK analytical 
methodology. Biomarkers are described in Section 14.1. 
The investigator may, at his/her discretion, arrange for a patient to have an unscheduled 
assessment, especially in the case of AEs that require follow-up or are considered by the 
investigator to be possibly related to the use of study drug. The unscheduled visit page in the 
eCRF must be completed.  
Procedures for early study withdrawal are described in Section 8.4. 
1 
EFFICACY ASSESSMENTS 
The Schedule of Assessments (Table 1) outlines the efficacy assessments to be performed 
throughout the study and their timing. 
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1.1 
COVID-19 Symptoms  
The assessment of the COVID-19 symptoms will be recorded at the visits specified in the 
Schedule of Assessments (Table 1). 
The patient will be assessed for the following as shown in Table 2. 
Table 2 
COVID-19 Symptoms 
Symptom 
Response Options and Scoring 
1. Stuffy or runny nose 
None = 0 
Mild = 1 
Moderate = 2 
Severe =3 
2. Sore throat 
3.  Red or irritated eyes (conjunctivitis) 
4. Shortness of breath (difficulty breathing) 
5. Cough 
6. Low energy or tiredness 
7. Muscle or body aches 
8. Headache 
9. Chills or shivering 
10. Feeling hot or feverish 
11. Nausea (feeling like you wanted to throw up) 
12. How many times did you vomit (throw up) in the 
last 24 hours? 
I did not vomit at all = 0  
1–2 times = 1  
3–4 times = 2  
5 or more times = 3  
13. How many times did you have diarrhea (loose or 
watery stools) in the last 24 hours? 
I did not have diarrhea at all = 0 
1–2 times = 1  
3–4 times = 2  
5 or more times = 3  
14. Rate your sense of smell in the last 24 hours.  
My sense of smell is THE SAME AS usual = 0  
My sense of smell is LESS THAN usual = 1  
I have NO sense of smell = 2  
15. Rate your sense of taste in the last 24 hours.  
My sense of taste is THE SAME AS usual = 0  
My sense of taste is LESS THAN usual = 1  
I have NO sense of taste = 2  
Note: Score values are included in the table for ease of reference. Score values within the response options will not 
be presented to patients to avoid confusing patients. 
1.2 
COVID-19 Severity  
The assessment of the COVID-19 severity will be recorded at the visits specified in the Schedule 
of Assessments (Table 1). As per the inclusion and exclusion criteria (see Section 8.1 and 
Section 8.2), patients who are randomized must have either moderate or severe COVID-19. The 
criteria (FDA 2020) used to determine the patient’s COVID-19 severity incorporates objective 
measures as follows:  
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Asymptomatic SARS-CoV-2 infection  
x Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test  
x No symptoms 
Mild COVID-19  
x Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test  
x Symptoms of mild illness with COVID-19 (eg, loss of smell or taste, fever, cough, sore 
throat, malaise, headache, muscle pain, gastrointestinal symptoms, and without shortness 
of breath or dyspnea) 
x No clinical signs indicative of moderate, severe, or critical COVID-19 
Moderate COVID-19  
x Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test  
x Symptoms of moderate illness with COVID-19, which could include any symptom of 
mild illness or shortness of breath with exertion  
x Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate 
20 breaths per minute, SpO2 >93% (on room air at sea level, if possible), heart rate 
90 beats per minute  
x No clinical signs indicative of severe or critical COVID-19 
Severe COVID-19  
x Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test  
x Symptoms suggestive of severe systemic illness with COVID-19, which could include 
any symptom of moderate illness or shortness of breath at rest, or respiratory distress  
x Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory 
rate 30 breaths per minute, heart rate 125 beats per minute, SpO2 93% (on room air at 
sea level, if possible), PaO2/FiO2 <300, or diagnosed with ARDS (according to the Berlin 
definition; see Table 3 for further details) 
x No criteria for critical COVID-19 
Critical COVID-19  
x Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test  
x Evidence of critical illness, defined by at least 1 of the following:  
o Respiratory failure defined based on resource utilization requiring at least 1 of the 
following:  
 Endotracheal intubation and mechanical ventilation, oxygen delivered by 
high-flow nasal cannula (heated, humidified, oxygen delivered via 
reinforced nasal cannula at flow rates >20 L/min with fraction of delivered 
oxygen 0.5), non-invasive positive pressure ventilation, ECMO, or 
clinical diagnosis of respiratory failure (ie, clinical need for 1 of the 
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preceding therapies, but preceding therapies not able to be administered in 
setting of resource limitation)  
o Shock (defined by systolic blood pressure <90 mm Hg, or diastolic blood pressure 
<60 mm Hg or requiring vasopressors)  
o Multi-organ dysfunction/failure  
A clinical diagnosis of respiratory failure (in the setting of resource limitation) in which the 
management deviates from SoC must be recorded. 
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will 
be measured when the patient is on room air at sea level (ie, no supplemental oxygen, if possible) 
and at rest for at least 5 minutes. If possible, the site should collect the information from each 
patient at the same time each day (±1 hour).  
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition (eg, 
emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19 (unless the 
patient meets the definition for critical COVID-19). For questions related to COVID-19 severity, 
the investigator should contact the medical monitor. 
Table 3: 
Acute Respiratory Distress Syndrome – Berlin Definition 
Timing 
Within 1 week of known clinical insult or new or worsening respiratory symptoms 
Chest 
imaginga 
Bilateral opacities — not fully explained by effusions, lobar/lung collapse, or nodules 
Origin of 
edema 
Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective 
assessment (eg, echocardiography) to exclude hydrostatic edema if no risk factor is present 
Oxygenationb Mild 
200 mm Hg < PaO2/FIO2 300 mm Hg with PEEP or CPAP 5 cmH2Oc 
Moderate 
100 mm Hg < PaO2/FIO2 200 mm Hg with PEEP 5 cmH2O 
Severe 
PaO2/FIO2 100 mm Hg with PEEP 5 cmH2O 
Abbreviations: ARDS = acute respiratory distress syndrome; CPAP = continuous positive airway pressure; 
FIO2 = fraction of inspired oxygen; PaO2 = partial pressure of arterial oxygen; PEEP = positive end-expiratory 
pressure. 
a 
Chest radiograph or computed tomography scan 
b 
If altitude is higher than 1,000 m, the correction factor will be calculated as follows: [PaO2/FIO2 (barometric 
pressure/760)] 
c 
This may be delivered noninvasively in the mild ARDS group 
Source: Adapted from Fanelli et al 2013 
 
1.3 
Clinical Status Related to COVID-19 on the National Institute of Allergy and 
Infectious Diseases 8-Point Ordinal Scale 
The NIAID 8-point ordinal scale is an assessment of the clinical status at the first assessment of a 
given study day. The scale is as follows: 
1. Death 
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2. Hospitalized, on invasive ventilation (mechanical ventilator and/or ECMO) 
3. Hospitalized, on non-invasive ventilation or high-flow oxygen devices 
4. Hospitalized, requiring supplemental oxygen 
5. Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care 
(COVID-19 related or otherwise) 
6. Hospitalized, not requiring supplemental oxygen and no longer requires ongoing 
medical care (used if hospitalization was extended for infection-control reasons) 
7. Not hospitalized, limitation on activities, and/or requiring home oxygen 
8. Not hospitalized, no limitations on activities 
Please note: Patients requiring oxygen before COVID-19 and returning to baseline oxygen use 
will be considered improved (ie, not requiring supplemental oxygen). Patients with a limitation 
on activities before COVID-19 and returning to baseline activity will be considered improved. 
At the visits specified in the Schedule of Assessments (Table 1), record the date and time for 
each individual component of the NIAID 8-point ordinal scale including: invasive or non-
invasive mechanical ventilation/ECMO start/stop, high-flow/mask oxygen start/stop, 
supplemental oxygen start/stop (nasal cannula, liter flow [and its conversion to FiO2], other 
delivery services), hospital discharge (whether with limitations or without limitations), 
hospitalization type (eg, transfer to ICU) start/stop, and (if applicable) death, cause of death 
(including relatedness to COVID-19), and date/time of death. If possible, the site should collect 
the information from each patient at the same time each day (±1 hour). 
A standard conversion for liter flow oxygen to FiO2 is presented in Table 4. 
Table 4 
Standard Conversion for Liter Flow Oxygen 
 
 
 
 
If there is use of a venturi mask (air-entrainment mask), the FiO2 is based on the nozzle use and 
should also be recorded. 
 
FiO2 (%) 
Room air 
21 
1 L/min 
24 
2 L/min 
27 
3 L/min 
30 
4 L/min 
33 
5 L/min 
36 
6 L/min 
39 
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1.4 
Health-related Quality of Life Assessment 
The HRQoL will be assessed via the EQ-5D-5L questionnaire (Appendix 2). The EQ-5D-5L is a 
standardized questionnaire developed by the EuroQol Group as a measure of HRQoL that 
consists of a descriptive system and a VAS. The descriptive system consists of 5 dimensions: 
mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The VAS records 
the patient’s self-rated health on a vertical VAS. This can be used as a quantitative measure of 
health outcome that reflects the patient’s own judgment. The patient is asked to indicate his/her 
current health state (ie, describe their health “today”). The scores on these 5 dimensions can be 
presented as a health profile or can be converted to a single summary index number that 
describes the patient’s current health state. The EQ-5D-5L questionnaire has been validated in a 
diverse patient population in 6 countries and is available in multiple languages. The EQ-5D-5L 
questionnaire is suitable for completion by adults (EuroQol Research Foundation 2020). 
The results of the EQ-5D-5L questionnaire will be recorded at the visits specified in the 
Schedule of Assessments (Table 1). Please note: This assessment will only be performed in 
patients who have been discharged from the hospital before Day 60.  
1.5 
COVID-19 Testing  
Samples for COVID-19 testing will be obtained at the visits specified in the Schedule of 
Assessments (Table 1). At the screening visit, the local laboratory may perform COVID-19 
testing by standard RT-PCR assay or equivalent test. At screening, a positive test must be 
available in order for the patient to be randomized on Day 1. If the patient has a previous 
confirmation of SARS-CoV-2 (within 7 days of Day 1), the SARS-CoV-2 test at screening is not 
required. The result of the COVID-19 tests (positive/negative) must be documented in the eCRF 
On Day 1, Day 14, Day 28, and Day 60, samples will be sent to the central laboratory for 
COVID-19 testing by standard RT-PCR assay. The result of the COVID-19 tests 
(positive/negative) must be documented in the eCRF. Further details will be described in the 
laboratory manual.  
Please note: If COVID-19 tests are performed at unscheduled time points (eg, according to SoC), 
findings (ie, positive/negative result) must be recorded in the eCRF. 
12 
SAFETY ASSESSMENTS 
Safety assessments (medical/surgery history, demographics, prior and concomitant medications, 
vital signs, physical examinations, ECGs, clinical laboratory assessments, and AEs) are to be 
performed at the visits specified in the Schedule of Assessments (Table 1).  
12.1 
Medical/Surgical History and Demographics 
Medical/surgical history will be recorded at screening. Investigators will document all active and 
chronic diseases (eg, asthma and COPD), and any diseases diagnosed in the past 1 year (before 
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screening) that the investigator considers clinically significant. Additional pre-existing 
conditions present at the time when informed consent is given and up to the time of first dosing 
(Day 1) are to be regarded as concomitant. Medical history will include documentation of social 
behaviors, including use of tobacco, nicotine (including use of electronic cigarettes), and soft or 
hard drugs (including cannabis), as well as alcohol consumption, if applicable. Smoking history 
also must be documented as part of medical history and includes never, light 
(<100 cigarettes/lifetime), active smoker, and former smoker (quit date). History of number 
packs/day, number of smoking years, and quitting time for former and active smokers must also 
be documented.  
Additionally, the investigators will document at screening the patient’s Charlson score via the 
Charlson Comorbidity Index (Charlson et al 1987). The Charlson Comorbidity Index may be 
used to identify patients with higher risk of COVID-19 progression (Garibaldi et al 2020) via the 
COVID-19 Inpatient Risk Calculator (online calculator available via: 
https://rsconnect.biostat.jhsph.edu/covid_predict/). The 14-item Charlson score is based on the 
patient’s comorbidities that are associated with mortality : myocardial infarction, congestive 
heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary 
disease, rheumatologic disease, peptic ulcer disease, liver disease, diabetes, hemiplegia or 
paraplegia, renal disease, malignancy, and acquired immunodeficiency syndrome/human 
immunodeficiency virus (online calculator available via: https://www.orthotoolkit.com/charlson-
comorbidity-index/). The investigator should record each individual component of the 14-item 
Charlson Comorbidity Index (Appendix 1) as well as the overall score.  
Illnesses first occurring or detected during the study and/or worsening of a concomitant illness 
during the study are to be documented as AEs on the eCRF in accordance with Section 12.6. All 
changes not present at baseline or described in the past medical history and identified as 
clinically noteworthy must be recorded as AEs. 
Additionally, demographic data will be collected for all patients and include sex, age, and race 
and/or ethnicity. 
12.2 
Vital Signs 
Vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, SpO2, and body 
temperature) will be evaluated at the visits indicated in the Schedule of Assessments (Table 1). 
All vital signs will be measured after the patient has been resting for at least 5 minutes. Blood 
pressure measurements are to be taken in the same arm for the duration of the study. Moreover, 
additional vital signs may be performed as needed in case of any cardiac AE. 
Additionally, body weight (without shoes) will be recorded at screening, Day 1, Day 14, Day 28, 
Day 60, and day of discharge (applicable); height (without shoes) will be recorded at screening 
only. Body mass index will be calculated whenever weight is recorded. 
Vital sign measurements will be repeated if clinically significant or machine/equipment errors 
occur. Out-of-range blood pressure, respiratory rate, heart rate measurements, or SpO2 will be 
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repeated at the investigator’s discretion. Any confirmed, clinically significant vital sign 
measurements must be recorded as AEs. 
12.3 
Physical Examinations 
A complete physical examination will be performed at screening. Physical examinations will be 
performed by a physician, nurse, or other appropriately trained staff. The complete physical 
examination includes head, eyes, ears, nose, and throat; heart; lungs; abdomen; skin; cervical and 
axillary lymph nodes; and neurological and musculoskeletal systems.  
A limited physical examination to verify continued patient eligibility and to follow-up regarding 
any change in medical history will be performed at the visits indicated in the Schedule of 
Assessments (Table 1). Symptom-driven, limited physical examinations may be performed as 
clinically indicated during the study (according to SoC). 
Please note: The limited physical examination on Day 8 (± 3 days) will be collected in all 
patients who remain hospitalized. If the patient is discharged before Day 8 (± 3 days), the site 
should arrange to have the physician assess the patient via a telephone/virtual call. If the 
physician determines during the telephone/virtual call that the limited physical examination is 
clinically indicated, then the site should arrange for an outpatient visit to collect this assessment. 
12.4 
Electrocardiograms 
A 12-lead, resting ECG will be obtained locally at screening as indicated in the Schedule of 
Assessments (Table 1). At screening, the investigator must examine the ECG traces for clinically 
significant abnormalities that could exclude the patient from the study. If ECGs are performed at 
unscheduled time points (eg, according to SoC), findings must be recorded in the eCRF. 
ECGs should always be obtained in supine position after adequate rest ( 5 minutes). An 
assessment of normal or abnormal will be recorded; if the ECG is considered abnormal, the 
abnormality will be documented on the eCRF. ECGs will be repeated if clinically significant 
abnormalities are observed or artifacts are present. Any ECG considered by the investigator to be 
clinically significant should be considered an AE. Moreover, additional ECGs may be obtained 
as needed in case of any cardiac AE and will be recorded on the eCRF. 
12.5 
Clinical Laboratory Assessments 
Clinical laboratory assessment samples (Table 5) will be obtained at designated visits as 
specified in the Schedule of Assessments (Table 1). 
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Table 5: 
Clinical Laboratory Assessments 
Hematology 
Blood Biochemistry 
Urinalysis (Dipstick) 
Full and differential blood count 
Hematocrit (HCT) 
Hemoglobin (Hb) 
Mean corpuscular hemoglobin (MCH) 
Mean corpuscular hemoglobin 
concentration (MCHC) 
Mean corpuscular volume (MCV) 
Platelet count (PLT Ct) 
Red blood cell count (RBC ct) 
White blood cell count (WBC ct) with 
differential 
Albumin (ALB) 
Alanine aminotransferase (ALT) 
Alkaline phosphatase (ALP) 
Aspartate aminotransferase (AST) 
Blood urea nitrogen (BUN) or urea 
Carbon dioxide (CO2) 
Creatininea (Cr) 
Creatine kinase (CK) and subtypes 
Electrolytes (sodium, potassium, 
chloride, calcium, phosphorus) 
Gamma-glutamyl transpeptidase (GGT) 
Glucose 
Lactate dehydrogenase (LDH) 
Total bilirubin (TBIL) 
Direct bilirubin (DBI) 
Total cholesterol (TC) 
Triglycerides (TG) 
Estimated glomerular filtration rateb 
(eGFR) 
Appearance 
pH 
Protein 
Glucose 
Ketone bodies 
Indicators of blood and 
white blood cells 
Specific gravity 
Urobilinogen (UROB) 
Coagulation 
Activated partial thromboplastin time 
International normalized ratio 
Partial thromboplastin time 
Pregnancy Test 
A serum pregnancy (hCG) test will be performed on all WOCBP at screening and a urine pregnancy (hCG) 
test will be performed on all WOCBP on Day 1 before randomization and dosing. A urine pregnancy test will 
be repeated on Day 14 (± 7 days). If the patient is discharged before Day 14, urine pregnancy test at day of 
discharge should be done, and urine pregnancy test at Day 14 is not required. If the patient is discharged after 
Day 14, urine pregnancy test should be done at Day 14, and urine pregnancy test at day of discharge is not 
required (whichever comes first). Patients with a positive pregnancy test will be discontinued from study 
drug. 
Please note: In questionable cases of postmenopausal status, a blood sample with simultaneous follicle 
stimulating hormone and estradiol levels may be required to determine postmenopausal status 
Abbreviations: hCG = human chorionic gonadotropin; WOCBP = women of childbearing potential. 
a Creatinine clearance will be estimated using the patient’s serum creatinine value, actual body weight, age, and the 
appropriate Cockroft-Gault formula for the patient’s sex. 
b According to Chronic Kidney Disease Epidemiology Collaboration (Levey et al 2009). 
 
Blood and urine samples will be analyzed at the site’s local laboratory facility. Urine samples 
will be analyzed by dipstick, and a microscopic analysis will be performed if the results of 
dipstick indicate abnormalities to be further investigated. All laboratory reports must be 
reviewed, signed, and dated by the investigator. A legible copy of all reports must be filed with 
both the patient’s eCRF and medical record (source document) for that visit. Any laboratory test 
result considered by the investigator to be clinically significant should be considered an AE 
(clinically significant AEs include those that require an intervention). Clinically significant 
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abnormal values occurring during the study will be followed up until repeat test results return to 
normal, stabilize, or are no longer clinically significant. If laboratory assessments are performed 
at unscheduled time points (eg, according to SoC), findings must be recorded in the eCRF.
Please note: The clinical laboratory assessments on Day 8 (± 3 days) and Day 21 (± 2 days) will 
be collected in all patients who remain hospitalized. If the patient is discharged before Day 8 
(± 3 days) or Day 21 (± 2 days), the site should arrange to have the physician assess the patient 
via a telephone/virtual call. If the physician determines during the telephone/virtual call that the 
clinical laboratory assessments are clinically indicated, then the site should arrange for an 
outpatient visit to collect this assessment. All efforts should be made to collect clinical laboratory 
assessments on Day 14 (± 2 days) and Day 28 (± 3 days).
12.6
Adverse Events
Adverse Events
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study 
or, if present at screening, worsens during the study, regardless of the suspected cause of the 
event. All medical and psychiatric conditions (except those related to the indication under study) 
present at screening will be documented on the medical history eCRF. Changes in these 
conditions and new symptoms, physical signs, syndromes, or diseases should be noted on the AE 
eCRF during the rest of the study. Clinically significant laboratory abnormalities should also be 
recorded as AEs. Surgical procedures that were planned before the patient was randomized in the 
study are not considered AEs if the conditions were known before study inclusion; the medical 
condition should be reported in the patient’s medical history.
Patients will be instructed to report AEs at each study visit. All AEs are to be followed up until 
resolution or a stable clinical endpoint is reached.
Each AE is to be documented on the eCRF with reference to date of onset, duration, frequency, 
severity, relationship to study drug, action taken with study drug, treatment of event, and 
outcome. Furthermore, each AE is to be classified as being serious or nonserious. Changes in 
AEs and resolution dates are to be documented on the eCRF.
For the purposes of this study, the period of observation for collection of AEs extends from the 
time the patient gives informed consent until the end of the follow-up period (Day 60). 
Follow-up of the AE, even after the date of study completion, is required (if possible) if the AE 
persists. The follow-up should continue until the event resolves (returns to normal or baseline 
values) or stabilizes, or until it is judged by the investigator to no longer be clinically significant.
It is understood that if a patient withdraws consent to further follow-up, then it may not be 
possible for the study site to follow the AE to resolution.
When changes in the severity of an AE occur more frequently than once a day, the maximum 
severity for the event should be noted. If the severity category changes over a number of days, 
then those changes should be recorded separately (with distinct onset dates).
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Each AE will be assigned a grade which refers to the severity of the AE based on the Common 
Terminology Criteria for Adverse Events version 5.0. The Common Terminology Criteria for 
Adverse Events v5.0 displays grades 1 through 5 with unique clinical descriptions of the severity 
for each AE based on the general guideline shown in Table 6.  
The guideline for classifying AEs by relationship to study drug are given in Table 7. 
Table 6: 
Classification of Adverse Events by Severity 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated. 
Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living. 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation 
of hospitalization indicated; disabling; limiting self-care activities of daily living. 
Grade 4: Life-threatening consequences; urgent intervention indicated. 
Grade 5: Death related to AE. 
Abbreviation: AE = adverse event. 
 
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Table 7:
Classification of Adverse Events by Relationship to Study Drug
UNRELATED: This category applies to those AEs that are clearly and incontrovertibly due to extraneous 
causes (disease, environment, etc).
UNLIKELY: This category applies to those AEs that are judged to be unrelated to the study drug but for which 
no extraneous cause may be found. An AE may be considered unlikely to be related to study drug if or when it 
meets 2 of the following criteria: (1) it does not follow a reasonable temporal sequence from administration of 
the study drug; (2) it could readily have been produced by the patient’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the patient; (3) it does not follow a known pattern of 
response to the study drug; or (4) it does not reappear or worsen when the drug is readministered.
POSSIBLY: This category applies to those AEs for which a connection with the study drug administration 
appears unlikely but cannot be ruled out with certainty. An AE may be considered possibly related if or when 
it meets 2 of the following criteria: (1) it follows a reasonable temporal sequence from administration of the 
drug; (2) it could not readily have been produced by the patient’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the patient; or (3) it follows a known pattern of response to the study 
drug.
PROBABLY: This category applies to those AEs that the investigator feels with a high degree of certainty are 
related to the study drug. An AE may be considered probably related if or when it meets 3 of the following 
criteria: (1) it follows a reasonable temporal sequence from administration of the drug; (2) it could not be 
reasonably explained by the known characteristics of the patient’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the patient; (3) it disappears or decreases on cessation or reduction 
in dose (note that there are exceptions when an AE does not disappear upon discontinuation of the drug, yet 
drug-relatedness clearly exists; for example, as in bone marrow depression, fixed drug eruptions, or tardive 
dyskinesia); or (4) it follows a known pattern of response to the study drug.
DEFINITELY: This category applies to those AEs that the investigator feels are incontrovertibly related to 
study drug. An AE may be assigned an attribution of definitely related if or when it meets all of the following 
criteria: (1) it follows a reasonable temporal sequence from administration of the drug; (2) it could not be 
reasonably explained by the known characteristics of the patient’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the patient; (3) it disappears or decreases on cessation or reduction 
in dose and recurs with reexposure to drug (if rechallenge occurs); and (4) it follows a known pattern of 
response to the study drug.
Abbreviation: AE = adverse event.
Serious Adverse Events
An SAE is any untoward medical occurrence, in the view of either the investigator or sponsor, 
that:
x
results in death
x
is life-threatening
x
results in inpatient hospitalization or prolongation of existing hospitalization
x
results in persistent or significant disability/incapacity
x
is a congenital anomaly/birth defect
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Other important medical events that may not be immediately life-threatening or result in death or 
hospitalization, based upon appropriate medical judgment, are considered SAEs if they are 
thought to jeopardize the patient and/or require medical or surgical intervention to prevent 1 of 
the outcomes defining an SAE. SAEs are critically important for the identification of significant 
safety problems; therefore, it is important to take into account both the investigator’s and the 
sponsor’s assessment. If either the sponsor or the investigator believes that an event is serious, 
the event must be considered serious and evaluated by the sponsor for expedited reporting.
Serious Adverse Event Reporting
An SAE occurring from the time the patient gives informed consent until the end of the follow-
up period (Day 60) or within 30 days of stopping the study drug (whichever is longer) must be 
reported to the Syneos Health Safety and Pharmacovigilance group and will be communicated to 
the sponsor. Any such SAE due to any cause, whether or not related to the study drug, must be 
reported within 24 hours the investigator’s awareness of the event. Notification can be made 
using the dedicated fax line or email for the Syneos Health Safety and Pharmacovigilance group:
x
Syneos Health Safety and Pharmacovigilance fax number: 
x
Syneos Health Safety and Pharmacovigilance email address: 
If the investigator contacts the Syneos Health Safety and Pharmacovigilance group by telephone, 
then a written report must follow within 24 hours and has to include a full description of the 
event and sequelae in the format detailed in the SAE reporting form.
The event must also be recorded on the standard AE eCRF. Preliminary reports of SAEs must be 
followed up by detailed descriptions later on. Clear and anonymized photocopies of hospital case 
reports, consultant reports, autopsy reports, and other documents must be provided when 
requested by Syneos Health Safety and Pharmacovigilance. SAE reports must be made whether 
or not the investigator considers the event to be related to the investigational drug.
Appropriate remedial measures should be taken to treat the SAE, and the response should be 
recorded. Clinical, laboratory, and diagnostic measures should be employed as needed to
determine the etiology of the problem. The investigator must report all additional follow-up 
evaluations to the Syneos Health Safety and Pharmacovigilance group within 24 hours of 
becoming aware of the additional information. All SAEs will be followed up until the 
investigator and sponsor agree the event is satisfactorily resolved.
Any SAE that is not resolved by the end of the study or upon discontinuation of the patient’s 
participation in the study is to be followed up, if possible, until it either resolves, stabilizes, 
returns to baseline values (if a baseline value is available), or is shown to not be attributable to 
the study drug or procedures. It is understood that if a patient withdraws consent to further 
follow-up, then it may not be possible for the study site to follow the SAE to resolution.
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Suspected Unexpected Serious Adverse Reactions
AEs that meet all of the following criteria will be classified as suspected unexpected serious 
adverse reactions (SUSARs) and reported to the appropriate regulatory authorities in accordance 
with applicable regulatory requirements for expedited reporting:
x
serious
x
unexpected (ie, the event is not consistent with the reference safety information in the
current version of the IB)
x
there is at least a reasonable possibility that there is a causal relationship between the 
event and the study drug
The investigator will assess whether an event is causally related to the study drug. Syneos Health 
will consider the investigator’s assessment and determine whether the event meets the criteria for 
being reportable as a 7-day or 15-day safety report. SUSARs that are fatal or life-threatening 
must be reported to the regulatory authorities and the IRBs/IECs (where required) within 7 days 
after Syneos Health/MetrioPharm has first knowledge of them, with a follow-up report (when 
applicable) submitted within a further 8 calendar days. Other SUSARs must be reported to the 
relevant regulatory authorities and the IRBs/IECs within 15 calendar days after
Syneos Health/MetrioPharm first has knowledge of them.
Syneos Health is responsible for reporting SUSARs and any other events required to be reported 
in an expedited manner to the regulatory authorities and for informing investigators of reportable 
events, in compliance with applicable regulatory requirements within specific timeframes. 
Investigators will notify the relevant IRBs/IECs of reportable events within the applicable 
timeframes.
Pregnancy
WOCBP must have a negative serum pregnancy test at screening and negative urine pregnancy 
test before the first dose on Day 1. A urine pregnancy test will be repeated on Day 14 (± 7 days). 
If the patient is discharged before Day 14, urine pregnancy test at day of discharge should be 
done, and urine pregnancy test at Day 14 is not required. If the patient is discharged after Day 
14, urine pregnancy test should be done at Day 14, and urine pregnancy test at day of discharge 
is not required (whichever comes first). Patients with a positive pregnancy test will be 
discontinued from study drug. After administration of study drug, any known cases of pregnancy 
in female patients will be reported until the patient completes or withdraws from the study. The 
pregnancy will be reported immediately by faxing/emailing a completed pregnancy report to 
Syneos Health Safety and Pharmacovigilance within 24 hours of knowledge of the event. The 
pregnancy will not be processed as an SAE; however, the investigator will follow up with the 
patient until completion of the pregnancy and must assess the outcome in the shortest possible 
time but not >30 days after completion of the pregnancy. (It is understood that if a patient 
withdraws consent to further follow-up, then it may not be possible for the study site to follow 
the pregnancy to completion.) The investigator should notify Syneos Health Safety and 
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Pharmacovigilance group of the pregnancy outcome by submitting a follow-up pregnancy report. 
If the outcome of the pregnancy involved spontaneous or therapeutic abortion (any congenital 
anomaly detected in an aborted fetus is to be documented), stillbirth, neonatal death, or 
congenital anomaly, the investigator will report the event by faxing/emailing a completed 
pregnancy report form to Syneos Health Safety and Pharmacovigilance group within 24 hours of 
knowledge of the event.
If the investigator becomes aware of a pregnancy occurring in the partner of a patient 
participating in the study, the pregnancy should be reported to Syneos Health Safety and 
Pharmacovigilance group within 24 hours of knowledge of the event. Information regarding the 
pregnancy must only be submitted after obtaining consent from the pregnant partner. The 
investigator will arrange counseling for the pregnant partner by a specialist to discuss the risks of 
continuing with the pregnancy and the possible effects on the fetus.
Upon discontinuation from the study drug, only those procedures that would not expose the 
patient to undue risk will be performed. The investigator should also be notified of pregnancy 
occurring during the study but confirmed after completion of the study. In the event, that a 
patient is subsequently found to be pregnant after inclusion in the study and received at least one 
dose of study drug, any pregnancy will be followed to term, and the status of mother and child 
will be reported to Syneos Health Safety and Pharmacovigilance group after delivery.
Overdose
The investigator must immediately notify Syneos Health of any occurrence of overdose with the 
study drug.
13
PHARMACOKINETICS
13.1
Pharmacokinetic Sampling
Blood samples for PK analysis of MP1032 plasma concentrations will be collected at the time
points indicated in the Schedule of Assessments (Table 1) from a PK subset of approximately 
30 patients (who give optional consent). In summary, PK samples will be collected via sparse 
sampling from these 30 patients (approximately) in a 2:1 ratio (approximately 20 patients from 
the 300 mg MP1032 BID plus SoC group and approximately 10 patients from the placebo group
plus SoC group) to assess the PK of MP1032 on Day 1 (single dose) and Day 7 (steady state). A 
total of 16 samples (approximately 4.9 mL per time point for a total of approximately 78.4 mL)
will be collected relative to the first dose on Day 1 and the first dose on Day 7. Samples on 
Day 1 and Day 7 will be collected predose (within 10 minutes before the first daily dose) and 
postdose at 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 8 hours (before next 
dose), and 24 hours before the next morning dose (if applicable), if possible. Patients who 
provide consent for the PK sampling, but are no longer hospitalized on Day 7, will not have 
Day 7 PK samples collected.
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For patients in the PK subset on Day 1 and Day 7 only: Patients should not eat within the 4 hours 
before planned study drug administration and within the 120 minutes after study drug dosing, 
when feasible. Thus, study drug should be administered in fasted state ( 4 hours), when 
feasible. However, if a patient has eaten within the 4 hours before their planned administration, 
study drug dosing may proceed. The patient’s fed or fasted state, as well as food intake (yes/no) 
within the 120 minutes after study drug dosing should be recorded. The PK samples should be 
collected as planned regardless of the patients’ fasted/fed state. The study site should record the 
date and time of dosing (recorded as the time when the first capsule is administered). 
Intravenous cannulas may be used for blood collection to avoid multiple skin punctures, when 
appropriate. Otherwise, blood samples will be collected by direct venipuncture. The actual date 
and time of each blood sample collection will be recorded. Sample collections completed outside 
the predefined time windows (windows to be specified in the laboratory manual) will not be 
considered as protocol deviations because actual postdose sampling times will be used for PK 
and statistical analyses. 
PK samples will be analyzed by a central laboratory facility (Prolytic GmbH). Details of PK 
blood sample collection, processing (including separation of plasma), storage, and shipping 
procedures will be provided in a separate laboratory manual. 
13.2 
Pharmacokinetic Analytical Methodology 
The concentration of study drug will be determined from the plasma samples using a validated 
analytical method. Details of the method validation and sample analysis will be included with the 
final clinical study report (CSR). 
14 
OTHER ASSESSMENTS 
14.1 
Biomarkers 
Blood samples will be obtained at the visits specified in the Schedule of Assessments (Table 1) 
on Day 1 (before the first study drug administration) and Days 7, 14, 21, 28, and 60 (when 
possible) to measure biomarkers levels. Blood samples for biomarkers must be collected on Days 
7, 14, 21, 28, and 60 if a patient is still hospitalized. If a patient is discharged, the study site 
should arrange an outpatient visit (ie, at the study site) to accommodate the collection of blood 
samples for biomarkers on Days 7, 14, 21, 28, and 60. 
Biomarkers will potentially include, but will not be limited, to cytokines (eg, C-reactive protein, 
IL-1E, IL-6, TNF-Į, and IFN-J), and other coagulation/inflammatory biomarkers (eg, D-dimer 
and ferritin). Samples may be collected at the same time that samples are collected for the 
clinical laboratory assessments. Blood samples will be analyzed by a central laboratory facility. 
Details of sample collection, processing, storage, shipping procedures, and analysis will be 
provided in a separate laboratory manual. 
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Please note: Patients will be requested to provide consent for the sponsor to store and use 
leftover blood samples for future exploratory biomarker research. Patient participation in the 
storage and use of leftover blood samples is optional. If the patient consents, the sponsor will 
store and use the leftover blood samples for a period of 3 years after the last patient has 
completed his/her last visit in this study. 
15 
STATISTICAL ANALYSIS 
The statistical analysis plan (SAP) will provide further details regarding the definition of analysis 
variables and analysis methodology to address all study objectives. The SAP will be finalized 
before any statistical output (eg, DSMB output) is produced. The SAP will serve as a companion 
document to the protocol. The SAP will further describe the statistical analyses. All data will be 
included with the final CSR.  
The statistical evaluation will be performed using SAS® software version 9.4 or higher 
(
 
).  
Summary statistics will be presented by treatment group. Continuous and ordinal variables will 
be summarized by the number of patients (N), mean, standard deviation, median, minimum, and 
maximum for actual values and change from baseline. Additionally, for ordinal data, the number 
and percentage of patients in each category will be presented. Binary and categorical variables 
will be summarized for each treatment group by presenting the number and percentage of 
patients in the categories.  
Statistical tests for comparison between treatments will be performed using a two-sided alpha 
level of 10%. No adjustment for multiple testing will be applied in this descriptive proof-of-
concept study. 
15.1 
Determination of Sample Size 
The primary efficacy endpoint “proportion of patients with disease progression on Day 14” is 
assumed to be 10% in the 300 mg MP1032 BID plus SoC treatment group (Arm A) and 30% in 
the placebo plus SoC treatment group (Arm B). Using the Chi-square test with type I error 
alpha=10% two-sided for this proof-of-concept study and 2:1 randomization ratio, with 
114 randomized patients (76 in Arm A and 38 in Arm B) a statistical power of 83% can be 
achieved. Considering about 5% early study terminations, the necessary sample size to 
randomize results is 120 patients in total (80 in Arm A and 40 in Arm B). If during the conduct 
of the study the early study termination rate is higher than the estimated 5%, then an increase in 
the randomized number of patients may be necessary.  
Sample size estimation was performed using nQuery 8, Version 8.6.1.0. 
A subset of randomized patients will be consented for the collection of blood samples for PK 
measurements. The PK subset consists of approximately 20 patients from the 300 mg MP1032 
BID plus SoC group and approximately 10 patients from the placebo plus SoC group, up to a 
total of approximately 30 patients. 
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15.2 
Analysis Sets 
Screened Set 
The Screened Set will include all patients who give informed consent and are screened. For this 
group, patient disposition, and reasons for premature study termination or screening failure will 
be described.  
Randomized Set 
The Randomized Set will include all patients randomized. Unless specified otherwise, this set 
will be used for all subject listings with exception of the listing presenting screening failures and 
the respective reason(s) for screen failure. 
Intention-To-Treat Set 
The Intention-to-Treat (ITT) set, correspond with randomized set, will include all randomized 
patients irrespective of any deviation from the protocol or premature discontinuation from study 
drug/withdrawal from study. The treatment group assignment will be designated according to 
initial randomization. The ITT will serve as the basis for the analysis of efficacy and summary of 
demographics and baseline characteristics. 
Per Protocol Set 
The Per Protocol Set (PPS) will include all patients from ITT who received at least 1 dose of 
study drug and who do not have any major protocol deviations impacting the efficacy 
assessments. The PPS will be used for supportive analyses of efficacy. 
Safety Set 
The Safety Set (SS) will include all randomized patients who receive at least 1 dose of study 
drug. The treatment group assignment in the SS will be defined by the treatment actually 
received. The SS will be used for the analysis of safety. 
PK Analysis Set 
The PK Analysis Set (PKS) will include all the patients who have been administered active study 
drug and have at least 1 postdose evaluable plasma concentration after Day 1 dose. 
15.3 
Efficacy Analysis 
The estimands for the primary efficacy endpoint, and for the 4 key secondary endpoints 
comparing the 2 treatment groups, will be tested with consideration of a two-sided type-1 error 
alpha of 10% for each test on the ITT. Additionally, 95% confidence intervals will be provided. 
Also, the treatment comparison with regards to the other secondary efficacy endpoints will be 
performed using a two-sided alpha level of 10%.  
 
The main estimand for the primary efficacy endpoint is defined as follows: 
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x Treatment: 300 mg MP1032 BID plus SoC in Arm A and placebo BID plus SoC in Arm 
B. If a patient terminates the study drug, but still remains in the study and is followed up, 
then the patient will continue to receive either SoC alone or SoC+ additional treatment. 
These treatments are defined with regards to intercurrent events as ‘other treatments’. 
x Population: Of all patients defined by the study inclusion/exclusion criteria, the analysis 
population will include patients who were randomized to study drug (ITT population). 
x Variable: A binary variable indicating disease progression (death or respiratory failure) at 
Day 14. Respiratory failure is defined as patients who have a score of 2, 3, or 4 on the 
NIAID 8-point ordinal scale. 
x Intercurrent events: All events that lead to study drug discontinuation and/or switch to 
other treatment before Day 14 will be handled using the treatment-policy strategy (ie, the 
NIAID score at Day 14 will be used for definition of the failure in such patients).  
x Population-level summary: Common risk difference resulting from the Mantel-
Haenszel (MH) test considering the 4 strata out of the combinations of the 
2 randomization stratification factors disease severity (moderate versus severe) and age-
class (aged 65 years versus >65 years) at baseline. 
Missing data on Day 14 resulting from study termination before Day 14 are not expected. 
However, in case they happen, such monotone missings will be imputed by multiple imputation 
using information from similar patients of the same treatment group. Missing postbaseline data 
for patients randomized but not treated will be imputed by the respective baseline value (baseline 
observation carried forward [BOCF]). The comparison between the treatment groups will be 
performed on the ITT after imputation of missing values using MH test for common risk 
difference considering the 4 strata resulting from the 2 randomization stratification factors 
disease severity (moderate versus severe) and age-class (aged 65 years versus >65 years). The 
95% confidence intervals will be provided for the risk difference. 
Similar MH analyses and presentation of 95% confidence intervals will be applied to the main 
estimand of the first key secondary efficacy endpoint, which is defined as a binary variable 
indicating disease progression (death or respiratory failure) at Day 28, and the main estimand of 
the second key secondary efficacy endpoint that is defined as a binary variable indicating disease 
resolution (alive and have a score of 6, 7 or 8 on NIAID) at Day 28. Intercurrent events that lead 
to study drug discontinuation and/or switch to other treatment before Day 28 will be handled 
using the treatment-policy strategy for these 2 estimands (ie, the NIAID score at Day 28 will be 
used for definition of the failure or response, respectively) in such patients. Missing data on Day 
28 will be imputed by multiple imputation using information from similar patients of the same 
treatment group. Missing postbaseline data for patients randomized but not treated will be 
imputed by BOCF. 
A similar MH approach and presentation of 95% confidence intervals as described above will be 
applied also to the main estimand of the third key secondary efficacy endpoint, which is the all-
cause mortality at Day 28. Intercurrent events that lead to study drug discontinuation and/or 
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switch to other treatment before Day 28 will be handled using the treatment-policy strategy (ie, 
the life status at Day 28 will be considered). No missing data of life status on Day 28 is expected.  
The main estimand of the fourth key secondary efficacy endpoint, change of clinical status 
related to COVID-19 on Day 28 compared with baseline according to the NIAID 8-point ordinal 
scale, will be compared using the risk difference from the analysis of covariance model with 
treatment and the 2 binary stratification factors (eg, severity and age-class) as independent 
factors and the baseline value of NIAID as independent covariate. Intercurrent events that lead to 
study drug discontinuation and/or switch to other treatment before Day 28 will be handled using 
the treatment-policy strategy for this estimand (ie, the NIAID score at Day 28 will be used). 
Missing data on Day 28 will be imputed by multiple imputation using information from similar 
patients of the same treatment group. Missing post-baseline data for patients randomized but not 
treated will be imputed by BOCF. The 95% confidence intervals will be provided for the risk 
difference. 
The population for all above described estimands of the key secondary endpoints is the ITT. 
Sensitivity analyses for the main estimands of the primary and key efficacy endpoints will be 
performed by assuming missing data at Day 14 or Day 28 as failure or non-resolution for the 
binary endpoints, and by multiple imputation using information from similar patients of the 
placebo group for the NIAID 8-point ordinal scale. 
All above analyses for the main estimands of the primary efficacy and key secondary efficacy 
endpoints will be repeated on PPS as supportive analysis. Additionally, for the primary efficacy 
and binary key secondary efficacy endpoints, logistic regression model with treatment and the 
2 stratification factors as covariables will be performed on the ITT. Further estimands for the 
primary and key secondary efficacy endpoints will be provided in the SAP. 
The proportion of patients with disease resolution at Day 14 and the all-cause mortality rate at 
Day 14 and Day 60 will be analyzed using similar MH methods as described above for Day 28. 
Cumulative proportion of patients with disease resolution will be plotted by time. 
A similar analysis of covariance approach as described above for Day 28 will be applied for the 
analysis of the change of clinical status related to COVID-19 on Day 14 compared with baseline 
on the NIAID 8-point ordinal scale. The endpoint considering the proportion of patients 
requiring invasive ventilation (mechanical ventilator and/or ECMO) or who are not alive, the 
proportion of patients in each NIAID category, and the proportion of patients alive and testing 
negative for COVID-19 on Day 14, Day 28, and Day 60, respectively, will be compared between 
the treatment groups using MH test. Overall survival, time to (first) improvement of at least 
1 category on the NIAID scale and total hospitalization duration (from baseline to discharge; 
with death censored on last day of the observed period í at Day 28 or Day 60, respectively í 
depending on the analyses) will be summarized using the Kaplan-Meier method and will be 
compared between treatment groups using log-rank tests. Additionally, Cox proportional hazards 
model will be applied with treatment and the 2 stratification factors as covariables. 
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The odds ratio between MP1032 and SoC and placebo and SoC for the number of patients with 
clinical status improvement from baseline on the NIAID 8-point ordinal scale (ie, an 
improvement of at least 1 category) at Day 14 and Day 28 will be analyzed using a logistic 
regression with consideration of the 2 stratification factors. 
The time to recovery of all at baseline present COVID-19 symptoms (stuffy or runny nose, sore 
throat, red or irritated eyes, shortness of breath, cough, low energy or tiredness, muscle or body 
aches, headache, chills or shivering, feeling hot or feverish, nausea, and number of times of 
vomit, times of diarrhea, sense of smell, sense of taste in the last 24 hours) will be presented by 
Kaplan-Meier estimates and figure. The change from baseline will be presented in shift tables for 
each single symptom, with the number and percentage of subjects in each category at post-
baseline assessment time-point compared to baseline for each treatment group.  
Total number of days in ICU, duration of invasive mechanical ventilation, and duration of 
ECMO will be descriptively summarized by treatment group using mean days with 
90% confidence intervals and additionally by median days and quartiles. To consider death 
sufficiently unfavorable in these measures, in case of death, the duration of the respective 
measure will be considered with the longest duration possible (eg, if a summary of the first 28 
days is presented, then death before Day 28 will be considered as duration 28 days, and if the 
summary also includes follow-up period until Day 60, then death before Day 60 will be 
considered as duration of 60 days). Both summaries (up to Day 28 and up to Day 60) will be 
provided.   
For HRQoL assessments at discharge and Day 60, the EQ index value and the EQ VAS, both 
based on the EQ-5D-5L questionnaire (Appendix 2), will be calculated and summarized by visit 
and treatment group. Additionally, change at Day 60 from discharge will be summarized by 
treatment group. 
All efficacy endpoints will be summarized using descriptive statistics by treatment group and by 
visit, as appropriate: Binary and categorical endpoints will be summarized by treatment group by 
presenting the number and percentage of patients in the categories. Continuous and ordinal 
endpoints will be described by mean, standard deviation, median, minimum, and maximum for 
actual values and change from baseline. Additionally, for ordinal data, the number and 
percentage of patients in each category will be presented. 
15.4 
Safety Analysis 
All safety parameters will be summarized descriptively by treatment group for the entire study 
period. 
Study drug duration and SoC therapies will be described for each treatment group. 
All reported AEs will be coded into preferred term (PT) and grouped by SOC using the most 
recent Medical Dictionary for Regulatory Activities version. An overall summary will be 
provided with the number and percentage of patients reporting TEAEs, serious TEAEs, 
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treatment-related TEAEs, TEAEs leading to withdrawal, and TEAEs leading to death. For 
patients with any serious TEAE and for patients with any related serious TEAE exposure-
adjusted events rates will be calculated and compared between treatment groups using the risk 
ratio [(300 mg MP1032 BID plus SoC) / (placebo plus SoC)] with respective 95% confidence 
intervals. This comparison will also be performed for the rate of rehospitalization which is 
considered a serious AE. The number and percentage of patients with TEAEs, serious TEAEs, 
TEAEs leading to withdrawal, and treatment-related TEAEs will be summarized by SOC and PT 
for each treatment group, and total. In these tables, the incidence of TEAEs by SOC and PT will 
also be included. TEAEs will also be summarized by maximum severity and relationship to 
study drug. Events with missing onset dates will be considered as TEAEs. If a patient 
experienced >1 occurrence of the same AE, the occurrence with the greatest severity and the 
closest association with the study drug will be used in the corresponding summary tables. In case 
that for one AE several AE episodes with changing severity is reported, an aggregation of all 
respective episodes to one AE will be performed before summarization. The worst severity and 
the worst causality will be assigned to the aggregated AE and used for the respective AE 
summaries. All reported AE episodes will be listed by patient, along with information regarding 
onset, duration, severity and relationship to study drug, action taken with study drug, treatment 
of event, and outcome. Additionally, the aggregated AEs with the resulting worst severity and 
worst relationship will be included in the AE listings. 
Vital signs including SpO2 (%) will be summarized using descriptive statistics, including mean 
values and mean change from baseline values. Clinical laboratory data of local laboratories will 
be presented with the number and percentage of patients with values below, within, or above the 
normal range at each time point. Additionally, a shift table of the number and percentage of 
patients with normal and abnormal, and clinically significant abnormal values at each scheduled 
postbaseline visit compared with the normal/abnormal/clinically significant abnormal 
categorization at baseline will be provided by treatment group. Summarizing of clinical 
laboratory data of local laboratories using descriptive statistics, including mean values and mean 
change from baseline values will be only possible after normalization of the values using a 
reference laboratory. Details for normalization will be provided in the SAP. 
Summary tables will be provided for concomitant medications. 
15.5 
Pharmacokinetic Analysis 
The PK parameters (such as Cmax, Tmax, AUC0-t, and others) of MP1032 on Day 1 (single dose) 
and Day 7 (steady state; if available), using up to 8 hours postdose, will be derived applying non-
compartmental analysis. PK parameters will be summarized along with plasma concentrations at 
various time points. Individual and mean plasma concentration versus time will be presented on 
linear, and semi-log scales. Further details of the PK analysis will be described in the SAP. Any 
possible correlation between plasma exposure and biomarkers (eg, change from baseline in 
cytokines, or other coagulation/inflammatory biomarkers) or efficacy measures can be explored 
by appropriate regression analysis methods during the final data analysis.  
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15.6
Biomarker Analysis
The change from baseline biomarker levels will be summarized descriptively by treatment group 
and visit. The change in biomarker levels will also be evaluated with any change of COVID-19
clinical status. 
15.7
Interim Analysis 
Not applicable. 
15.8
Data Monitoring Committee
An independent DMC will be established by the sponsor or designee to review accumulating 
study data at regular intervals (as per the DMC charter) throughout the study to ensure the safety 
of patients and review overall study conduct. Additional data may be reviewed that are related to 
efficacy, but the DMC will only be reviewing data for risk-benefit purposes. Members will 
include experts in drug safety and/or medical specialist and biostatistics, who are not 
participating in this study and do not have affiliation with the investigators or the sponsor. The 
DMC can recommend in writing to the sponsor whether to continue, modify, or stop the clinical 
study on the basis of safety considerations. The pre-specified study stopping rules for the trial are 
defined as follows: 
x
death (not including disease progression) in any patient in whom the cause of death is 
judged to be related to the study drug by investigator
x
the occurrence in any patient of a SAE whose causal relationship (ie, without a plausible 
alternative explanation) to the study drug is judged to be related by investigator
x
two occurrences of a clinically significant Grade 3 or higher laboratory abnormality 
assessed to be related to the study drug by investigator.
The DMC’s specific duties will be fully described in a DMC charter.
16
STUDY MANAGEMENT
16.1
Approval and Consent
Regulatory Guidelines
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and all relevant regulations as set forth in Parts 50, 56, 312, Subpart D, of Title 21 of 
the United States Code of Federal Regulations (CFR), in compliance with International Council 
for Harmonisation and GCP guidelines and according to the appropriate regulatory requirements 
in the countries where the study will be conducted.
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Institutional Review Board/Independent Ethics Committee
Conduct of the study must be approved by an appropriately constituted IRB/IEC. Approval is 
required for the study protocol, protocol amendments (if applicable), IB, ICFs, recruitment 
material and patient information sheets, and other patient-facing material.
Informed Consent
For each patient (or the patient’s LAR), informed consent will be obtained before any 
protocol-related activities. As part of this procedure, the principal investigator (PI) or designee 
must explain the nature of the study, its purpose, procedures, expected duration, alternative 
therapy available, and the benefits and risks involved in study participation. The patient (or the 
patient’s LAR) should be informed that he/she may withdraw from the study at any time, and the 
patient will receive all information that is required by local regulations and guidelines for 
International Council for Harmonisation. The PI will provide the sponsor or its representative 
with a copy of the IRB/IEC-approved ICF before the start of the study.
16.2
Data Handling
Data reported on the eCRF that are derived from source documents should be consistent with the 
source documents, or the discrepancies must be explained (see also Section 16.3).
Clinical data will be entered by site personnel on eCRFs for transmission to the sponsor. Data on 
eCRFs transmitted via the web-based data system must correspond to and be supported by source 
documentation maintained at the study site. All study forms and records transmitted to the 
sponsor must only include coded identifiers such that directly identifying personal information is 
not transmitted. The primary method of data transmittal is via the secure, internet-based 
electronic data capture (EDC) system maintained by Syneos Health. Access to the EDC system 
is available to only authorized users via the study’s internet website, where a user unique
assigned username and password are required for access.
Any changes made to data after collection will be made through the use of data clarification 
forms or the EDC system. When all missing and/or incorrect data have been resolved, eCRFs 
will be considered complete.
16.3
Source Documents
Source documents are considered to be all information in original records and certified copies of 
original records of clinical findings, observations, data, or other activities in a clinical study 
necessary for the reconstruction and evaluation of the study. The investigator will provide direct 
access to source documents and/or source data in the facilitation of study-related monitoring, 
audits, review by IRB/IECs, and regulatory inspections.
The investigator/institution should maintain adequate and accurate source documents and study
records that include all pertinent observations on each of the site’s patients. Source data should 
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be attributable, legible, contemporaneous, original, accurate, and complete. Changes to source 
data should be traceable, not obscure the original entry, and be explained if necessary. 
16.4 
Record Retention 
Study records and source documents must be preserved for at least 30 years after the completion 
or discontinuation of/withdrawal from the study, at least 2 years after the drug being studied has 
received its last approval for sale, or at least 2 years after the drug development has stopped, and 
in accordance with the applicable local privacy laws, whichever is the longer period. 
The investigator agrees to comply with all applicable federal, state, and local laws and 
regulations relating to the privacy of patient health information, including, but not limited to, the 
Standards for Individually Identifiable Health Information, 45 CFR, Parts 160 and 164 (the 
Health Insurance Portability Accountability Act of 1996 Privacy Regulation). The investigator 
shall ensure that study patients authorize the use and disclosure of protected health information 
in accordance with Health Insurance Portability Accountability Act Privacy Regulation and in a 
form satisfactory to the sponsor. 
16.5 
Monitoring 
The study will be monitored to ensure that it is conducted and documented properly according to 
the protocol, GCP, and all applicable regulatory requirements. 
Monitoring visits, on-site and remote (telephone), or a combination of these and contacts will be 
made at appropriate times during the study. The PI will assure he/she and adequate site personnel 
must be available throughout the study to collaborate with clinical monitors. Clinical monitors 
must have direct access to source documentation to check the completeness, clarity, and 
consistency of the data recorded in the eCRFs for each patient. 
The investigator will make available to the clinical monitor all source documents and medical 
records necessary to review protocol adherence and eCRFs. In addition, the investigator will 
work closely with the clinical monitor and, as needed, provide them appropriate evidence that the 
study is being conducted in accordance with the protocol, applicable regulations, and GCP 
guidelines. 
16.6 
Quality Control and Quality Assurance 
The sponsor or its designee will perform the quality assurance and quality control activities of 
this study; however, responsibility for the accuracy, completeness, security, and reliability of the 
study data presented to the sponsor lies with the investigator generating the data. 
The sponsor may arrange audits as part of the implementation of quality assurance to ensure that 
the study is being conducted in compliance with the protocol, standard operating procedures, 
GCP, and all applicable regulatory requirements. Audits will be independent of and separate 
from the routine monitoring and quality control functions. Quality assurance procedures will be 
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performed at study sites and during data management to assure that safety and efficacy data are 
adequate and well documented.
16.7
Protocol Amendment and Protocol Deviation
Protocol Amendment
Amendments to the protocol that entail corrections of typographical errors, clarifications of 
confusing wording, changes in study personnel, and minor modifications that have no effect on 
the safety of patients or the conduct of the study will be classed as administrative amendments 
and will be submitted to the IRB/IEC for information only. The sponsor will ensure that 
acknowledgment is received and filed. Amendments that are classed as substantial amendments 
must be submitted to the appropriate regulatory authorities and the IRB/IECs for approval and 
will not be implemented at sites until such approvals are received other than in the case of an 
urgent safety measure.
Protocol Deviations
Should a protocol deviation occur, the sponsor must be informed as soon as possible. Protocol 
deviations and/or violations and the reasons they occurred will be included in the CSR. 
Reporting of protocol deviations to the IRB/IEC and in accordance with applicable regulatory 
authority mandates is the investigator’s responsibility.
16.8
Ethical Considerations
This study will be conducted in accordance with this protocol, the accepted version of the 
Declaration of Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, 
Subpart D, of Title 21 of the CFR; EU 536/2014, Annex 1, D, 17 (a); and in compliance with 
GCP guidelines.
IRB/IECs will review and approve this protocol and the ICF. All patients (or the patient’s LAR)
are required to give informed consent before participation in the study.
16.9
Financing and Insurance
Before the study commences, the sponsor (or its designee) and the investigator (or the institution, 
as applicable) will agree on costs necessary to perform the study. This agreement will be 
documented in a financial agreement that will be signed by the investigator (or the institution 
signatory) and the sponsor (or its designee).
The investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice. The sponsor will provide no-exclusion insurance coverage for the clinical 
study as required by national regulations.
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16.10 
Publication Policy/Disclosure of Data 
Both the use of data and the publication policy are detailed within the clinical study agreement. 
Intellectual property rights (and related matters) generated by the investigator and others 
performing the clinical study will be subject to the terms of a clinical study agreement that will 
be agreed between the institution and the sponsor or their designee. With respect to such rights, 
the sponsor or its designee will solely own all rights and interests in any materials, data, and 
intellectual property rights developed by investigators and others performing the clinical study 
described in this protocol, subject to the terms of any such agreement. In order to facilitate such 
ownership, investigators will be required to assign all such inventions either to their institution or 
directly to the sponsor or its designee, as will be set forth in the clinical study agreement. 
 
 
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17 
REFERENCES 
Beigel JH, Tomashek KM, Dodd LE, et al. ACTT-1 Study Group Members. Remdesivir for the 
treatment of Covid-19 - final report. N Engl J Med. Published online October 8, 2020. 
doi:10.1056/NEJMoa2007764.  
Cennimo DJ. Coronavirus Disease 2019 (COVID-19). Updated January 09, 2021. Accessed 
January 13, 2021. https://emedicine.medscape.com/article/2500114-overview.  
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic 
comorbidity in longitudinal studies: development and validation. J Chronic Dis. 
1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8.  
Curtin N, Bányai K, Thaventhiran J, et al. Repositioning PARP inhibitors for SARSဨCoVဨ2 
infection (COVIDဨ19); a new multiဨpronged therapy for acute respiratory distress syndrome? 
Br J Pharmacol. 2020;177(16): 3635-3645. doi:10.1111/bph.15137. 
EuroQol Research Foundation. EQ-5D Instruments. Accessed October 9, 2020. 
https://euroqol.org/eq-5d-instruments/. 
Fanelli V, Vlachou A, Ghannadian S, et al. Acute respiratory distress syndrome: new definition, 
current and future therapeutic options. J Thorac Dis. 2013;5(3):326-334. 
doi:10.3978/j.issn.2072-1439.2013.04.05.  
Food and Drug Administration (FDA). COVID-19: Developing drugs and biological products for 
treatment or prevention, guidance for industry, May 2020. Accessed November 11, 2020. 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/covid-19-
developing-drugs-and-biological-products-treatment-or-prevention. 
Garibaldi BT, Fiksel J, Muschelli J, et al. Patient trajectories among persons hospitalized for 
COVID-19: a cohort study. Ann Intern Med. Published online September 22, 2020. 
doi:10.7326/M20-3905. 
Gloire G, Legrand-Poels S, Piette J. NF-kappaB activation by reactive oxygen species: fifteen 
years later. Biochem Pharmacol. 2006;72(11):1493-1505. doi:10.1016/j.bcp.2006.04.011.  
Grunewald ME, Fehr AR, Athmer J, Perlman S. The coronavirus nucleocapsid protein is ADP-
ribosylated. Virology. 2018;517:62-68. doi:10.1016/j.virol.2017.11.020.  
Hillienhof A. COVID-19: What immune reactions are triggered. German Medical Journal 
(Deutsches Ärzteblatt). 2020;117(39):A-1822.  
Ke Y, Wang C, Zhang J, et al. The role of PARPs in inflammation-and metabolic-related 
diseases: molecular mechanisms and beyond. Cells. 2019;8(9):1047. doi:10.3390/cells8091047.  
Khomich OA, Kochetkov SN, Bartosch B, Ivanov AV. Redox biology of respiratory viral 
infections. Viruses. 2018;10(8):392. doi:10.3390/v10080392.  
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Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. 
Ann Intern Med. 2009;150(9):604-612. 
Levin AT, Hanage WP, Owusu-Boatey N, et al. Assessing the age specifity of infection fatality 
rates for COVID-19: systematic review, meta-analysis, and public policy implications. Eur J 
Epidemiol. 2020;35(12):1123-1138. doi: 10.1007/s10654-020-00698-1. 
Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease 
(COVID-19) outbreak. J Autoimmun. 2020;109:102433. Published online February 26, 2020. 
doi:10.1016/j.jaut.2020.102433. 
Schumann S, Kaiser A, Nicoletti F, et al. Immune-modulating drug MP1032 with SARS-CoV-2 
antiviral activity in vitro: a potential multi-target approach for prevention and early intervention 
treatment of COVID-19. Int J Mol Sci. 2020;21(22):8803. doi:10.3390/ijms21228803. 
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. 
Lancet. 2020;395(10234):1417-1418. Published online April 21, 2020. doi:10.1016/S0140-
6736(20)30937-5.  
WHO Rapid Evidence Appraisal for COVID-19 Therapies (WHO-REACT) Working Group, 
Sterne JAC, Murthy S, Diaz JV, et al. Association between administration of systemic 
corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. 
JAMA. Published online September 2, 2020. 324(13):1-13. doi:10.1001/jama.2020.17023.  
World Health Organization (WHO). 2020a. January 12, 2020. Accessed January 14, 2021. 
https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/. 
World Health Organization (WHO). 2020b. Estimating mortality from COVID-19. Scientific 
brief, August 4, 2020. Accessed October 27, 2020. 
https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci-Brief-Mortality-2020.1  
World Health Organization (WHO). 2020c. Therapeutics and COVID-19. Living Guideline. 
December 17, 2020. Accessed December 17, 2020. 
https://www.who.int/publications/i/item/therapeutics-and-covid-19-living-guideline. WHO 
reference number: WHO/2019-nCoV/therapeutics/2020.1. 
World Health Organization (WHO). 2020d. WHO R&D Blueprint. Novel coronavirus: 
COVID-19 therapeutic trial synopsis. February 18, 2020. Accessed October 19, 2020. 
https://www.who.int/publications-detail/covid-19-therapeutic-trial-synopsis.  
 
 
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18 
APPENDICES 
APPENDIX 1 describes the Charlson Comorbidity Index (CCI) applicable for this study. 
APPENDIX 2 describes the EuroQol-5D-5L (EQ-5D-5L) questionnaire applicable for this study. 
 
 
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APPENDIX 1. 
CHARLSON COMORBIDITY INDEX 
https://orthotoolkit.com/charlson-comorbidity-index/ 
 
 
 
 
 
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APPENDIX 2. 
EUROQOL-5D-5L (EQ-5D-5L) QUESTIONNAIRE 
 
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1
CLINICAL STUDY PROTOCOL 
Protocol Title: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF MP1032 PLUS
STANDARD OF CARE VS STANDARD OF CARE IN THE TREATMENT OF 
HOSPITALIZED PATIENTS WITH MODERATE TO SEVERE COVID-19
Protocol Number: MP1032-CT05
Short Title: MP1032 Treatment in Patients with Moderate to Severe COVID-19
Investigational New Drug Number:
153604
Name of Investigational Product:
MP1032 hard gelatin capsules 50 mg 
Phase of Development:
IIa
Indication:
Treatment of symptomatic patients with moderate to severe 
coronavirus disease 2019 (COVID-19) disease 
EudraCT Number:
2021-000344-21
Sponsor’s EU Representative:
MetrioPharm Deutschland GmbH
Am Borsigturm 100
13507 Berlin
Germany
Sponsor:
MetrioPharm AG
Bleicherweg 10
8002 Zürich
Switzerland
Protocol Version: 
Final 2.0 - Bulgaria
Protocol Date:
31-Jan-2022
-CONFIDENTIAL-
This document and its contents are the property of and confidential to MetrioPharm AG. Any unauthorized 
copying or use of this document is prohibited.
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PROTOCOL APPROVAL SIGNATURES
Protocol Title:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF 
MP1032 PLUS STANDARD OF CARE VS STANDARD OF CARE IN 
THE TREATMENT OF HOSPITALIZED PATIENTS WITH 
MODERATE TO SEVERE COVID-19
Protocol Number:
MP1032-CT05
This study will be conducted in compliance with the clinical study protocol (and 
amendments), International Council for Harmonisation guidelines for current Good 
Clinical Practice (GCP), and applicable regulatory requirements.
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INVESTIGATOR SIGNATURE PAGE
Protocol Title:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF MP1032 
PLUS STANDARD OF CARE VS STANDARD OF CARE IN THE 
TREATMENT OF HOSPITALIZED PATIENTS WITH MODERATE TO 
SEVERE COVID-19
Protocol Number:
MP1032-CT05
Confidentiality and Current Good Clinical Practice (GCP)/E6(R2)/Compliance Statement
x
I, the undersigned, have reviewed this protocol (and any amendments), including appendices, and I 
will conduct the study as described in compliance with this protocol (and any amendments), GCP, 
and relevant International Council for Harmonisation guidelines.
x
I am thoroughly familiar with the appropriate use of the study drug, as described in this protocol and 
any other information provided MetrioPharm AG including, but not limited to, the current 
investigator’s brochure.
x
Once the protocol has been approved by the institutional review board (IRB)/independent ethics 
committee (IEC), I will not modify this protocol without obtaining prior approval of 
MetrioPharm AG and of the IRB/IEC. I will submit the protocol amendments and/or any informed 
consent form (ICF) modifications to MetrioPharm AG and the IRB/IEC, and approval will be 
obtained before any amendments are implemented.
x
I ensure that all persons or parties assisting me with the study are adequately qualified and informed 
about the MetrioPharm AG study drug and of their delegated study-related duties and functions as 
described in the protocol.
x
I ensure that source documents and study records that include all pertinent observations on each of the 
site’s patients will be attributable, legible, contemporaneous, original, accurate, and complete. 
x
I understand that all information obtained during the conduct of the study with regard to the patients’
state of health will be regarded as confidential. No patients’ names will be disclosed. All patients
will be identified by assigned numbers on all case report forms, laboratory samples, or source 
documents forwarded to the sponsor. Clinical information may be reviewed by the sponsor or its 
agents or regulatory agencies. Agreement must be obtained from the patient before disclosure of 
patient information to a third party.
x
Information developed in this clinical study may be disclosed by MetrioPharm AG to other clinical 
investigators, regulatory agencies, or other health authority or government agencies as required.
Printed Name 
Investigator Signature
Title 
Date (DD-Mmm-YYYY)
Institution
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2
SYNOPSIS 
Title of Study:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF MP1032 
PLUS STANDARD OF CARE VS STANDARD OF CARE IN THE 
TREATMENT OF HOSPITALIZED PATIENTS WITH MODERATE TO 
SEVERE COVID-19
Protocol Number:
MP1032-CT05
Investigators/Study Sites:
Approximately 40 sites worldwide will participate in this study.
Phase of Development:
Phase IIa
Study Objectives:
The primary objective of this study is:
x
To measure the effect of MP1032 plus standard of care (SoC) versus
placebo plus SoC on Day 14 on disease progression in patients with 
moderate to severe coronavirus disease 2019 (COVID-19) 
The secondary objectives of this study are:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
Day 28 on disease progression in patients with moderate to severe 
COVID-19
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
disease resolution on Day 14 and Day 28
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
the mortality rate and other specific COVID-19 related characteristics
x
To assess the safety of MP1032 (eg, adverse events [AEs] and laboratory 
abnormalities)
x
To assess the pharmacokinetics (PK) of MP1032 on Day 1 (single dose) 
and Day 7 (steady state) in a PK subset of patients
The exploratory objectives of this study are:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
some additional COVID-19 related characteristics
x
To evaluate the health-related quality of life (HRQoL) of patients treated 
MP1032 plus SoC compared with placebo plus SoC
x
To evaluate biomarker levels
Study Endpoints:
The primary efficacy endpoint of this study is:
x
Proportion of patients with disease progression on Day 14. Disease 
progression is defined as the proportion of patients who are not alive or who 
have respiratory failure. Respiratory failure is defined as patients who have a 
score of 2, 3, or 4 on the National Institute of Allergy and Infectious Diseases 
(NIAID) 8-point ordinal scale (see below). 
The key secondary efficacy endpoints of this study are:
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x
Proportion of patients with disease progression on Day 28. Disease 
progression is defined as the proportion of patients who are not alive or who 
have respiratory failure. Respiratory failure is defined as patients who have a 
score of 2, 3, or 4 on the NIAID 8-point ordinal scale (see below).
x
Proportion of patients with disease resolution on Day 28. Disease resolution 
is defined as patients who are alive and have a score of 6, 7, or 8 on the 
NIAID 8-point ordinal scale. 
x
All-cause mortality rate at Day 28
x
Change of clinical status related to COVID-19 on Day 28 compared with 
baseline according to the following NIAID 8-point ordinal scale:
1.
Death
2.
Hospitalized, on invasive ventilation (mechanical ventilator and/or 
extracorporeal membrane oxygenation [ECMO])
3.
Hospitalized, on non-invasive ventilation or high-flow oxygen devices
4.
Hospitalized, requiring supplemental oxygen
5.
Hospitalized, not requiring supplemental oxygen, but requiring ongoing 
medical care (COVID-19 related or otherwise)
6.
Hospitalized, not requiring supplemental oxygen and no longer requires 
ongoing medical care (used if hospitalization was extended for 
infection-control reasons)
7.
Not hospitalized, limitation on activities, and/or requiring home oxygen
8.
Not hospitalized, no limitations on activities
Please note: Patients requiring oxygen before COVID-19 and returning to 
baseline oxygen use will be considered improved (ie, not requiring supplemental 
oxygen). Patients with a limitation on activities before COVID-19 and returning 
to baseline activity will be considered improved. In case of death before Day 14 
or Day 28, the patient will be considered with the NIAID score for death (score of 
1) on the date of death in the analysis.
The other secondary endpoints of this study are:
x
Proportion of patients with disease resolution on Day 14. Disease resolution 
is defined as patients who are alive and have a score of 6, 7, or 8 on the 
NIAID 8-point ordinal scale. 
x
All-cause mortality rate at Day 14 and Day 60
x
Change of clinical status related to COVID-19 on Day 14 compared with 
baseline according to the NIAID 8-point ordinal scale as listed above.
x
Proportion of patients requiring invasive ventilation (mechanical ventilator 
and/or ECMO), or who are not alive on Day 14 or Day 28 
x
Proportion of patients in each category of the NIAID 8-point ordinal scale
x
Time to (first) improvement of at least 1 category on the NIAID 8-point 
ordinal scale (until Day 28). Patients who did not improve at least 1 category 
on the NIAID scale or die before Day 28 will be censored at Day 28.
x
The odds ratio between MP1032 and SoC and placebo and SoC for the 
number of patients with clinical status improvement from baseline on the 
NIAID 8-point ordinal scale (ie, an improvement of at least 1 category) at 
Day 14 and Day 28 
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x
Total duration of hospitalization on Day 28 and Day 60 (from baseline to 
discharge; with death censored on the last day of the observed period – at
Day 28 or Day 60, respectively)
x
Proportion of patients alive and testing negative for COVID-19 on Day 14, 
Day 28, and Day 60
x
Safety and tolerability assessed by:
o
Cumulative incidence of treatment-emergent AEs (summarized by 
seriousness, severity, relationship to the study medication, outcome, 
and duration) 
o
Vital sign parameters 
o
Clinical laboratory parameters
o
Physical examination findings
x
MP1032 plasma concentrations and PK parameters (if possible) including 
maximum observed plasma concentration, area under the concentration-time 
curve, elimination parameters, apparent body clearance, apparent volume of 
distribution, trough concentration, average observed plasma concentration at 
steady state, and other relevant PK parameters assessed via MP1032 plasma 
exposure on Day 1 and Day 7 in a PK subset of patients
Exploratory endpoints of this study are:
x
Change in saturation of oxygen (SpO2)/fraction of inspired oxygen (FiO2)
ratio (for patients alive) on Day 14 or Day 28 compared with baseline
x
Total number of days in the intensive care unit (ICU)
x
Duration of invasive mechanical ventilation 
x
Duration of ECMO
x
Time to recovery from COVID-19 symptoms (stuffy or runny nose, sore 
throat, red or irritated eyes, shortness of breath, cough, low energy or 
tiredness, muscle or body aches, headache, chills or shivering, feeling hot or 
feverish, nausea, and number of times of vomit, times of diarrhea, sense of 
smell, sense of taste in the last 24 hours) at Day 14, Day 28, and Day 60
x
Change from discharge in the EuroQol (EQ) index value and EQ visual 
analog scale (VAS) based on the EuroQol-5D-5L (EQ-5D-5L) questionnaire 
at Day 60
x
Change from baseline in biomarker levels potentially including, but not 
limited to, cytokines (eg, C-reactive protein, interleukin [IL]-1E, IL-6, tumor 
necrosis factor-Į, and interferon-J), and other coagulation/inflammatory 
biomarkers (eg, D-dimer and ferritin)
Study Design:
This is a Phase IIa, randomized, double-blind, placebo-controlled, multicenter,
proof-of-concept study designed to assess the efficacy and safety of 300 mg
MP1032 twice daily (BID) plus SoC versus placebo plus SoC in hospitalized 
adults with moderate to severe COVID-19.
Approximately 140 patients will be screened to randomize approximately 
120 patients in 2:1 ratio as follows: 
x
Arm A (300 mg MP1032 BID plus SoC): approximately 80 patients
x
Arm B (placebo BID plus SoC): approximately 40 patients
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The stratification factor for randomization will include baseline COVID-19
severity (moderate versus severe) and age-class (aged 65 years versus 
>65 years). COVID-19 severity will be determined using the following criteria:
x
Moderate COVID-19:
o
Positive severe acute respiratory syndrome coronavirus type 2
(SARS-CoV-2) testing by standard reverse 
transcription-polymerase chain reaction (RT-PCR) assay or 
equivalent test 
o
Symptoms of moderate illness with COVID-19, which could 
include any symptom of mild illness or shortness of breath with 
exertion
o
Clinical signs suggestive of moderate illness with COVID-19, 
such as respiratory rate 20 breaths per minute, SpO2 >93% (on
room air at sea level, if possible), heart rate 90 beats per 
minute 
o
No clinical signs indicative of severe or critical COVID-19
x
Severe COVID-19:
o
Positive SARS-CoV-2 testing by standard RT-PCR assay or 
equivalent test 
o
Symptoms suggestive of severe systemic illness with 
COVID-19, which could include any symptom of moderate 
illness or shortness of breath at rest, or respiratory distress
o
Clinical signs suggestive of severe systemic illness with 
COVID-19, such as respiratory rate 30 breaths per minute, 
heart rate 125 beats per minute, SpO2 93% (on room air at 
sea level, if possible), partial pressure of oxygen/FiO2 <300, or 
diagnosed with acute respiratory distress syndrome (according 
to the Berlin definition)
o
No criteria met for critical COVID-19
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and 
heart rate will be measured when the patient is on room air at sea level (ie, no 
supplemental oxygen) and at rest for at least 5 minutes. If possible, the site should 
collect the information from each patient at the same time each day (±1 hour). 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic 
condition (eg, emphysema, chronic obstructive pulmonary disease [COPD], 
pulmonary arterial hypertension [PAH], idiopathic pulmonary fibrosis [IPF], etc) 
must be considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19 severity, 
the investigator should contact the medical monitor.
Each site will treat all patients with SoC for the duration of the study. The 
selected SoC will be used in accordance with the hospital’s SoC procedures and 
may include drugs under an emergency use authorization.
This study consists of 3 periods: (1) screening, (2) treatment, and (3) follow-up. 
During the screening period, each potential patient (or patient’s legally acceptable 
representative) will provide informed consent before starting any study-specific 
procedures. The randomization of patients to treatment groups will be performed 
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centrally by an interactive web-response system (IWRS) using a randomization 
scheme that will be developed by an unblinded, independent statistician. During 
the treatment period, randomized patients will be provided their assigned 
treatment and assessments according to the protocol. All patients will be treated 
for 28 days unless the study drug is discontinued for safety reasons. Patients who 
progress to the use of an invasive ventilation (mechanical ventilator and/or 
ECMO) or who can no longer swallow the study drug (>2 days [ie, 2-day 
interruption is acceptable]) must discontinue the study drug; but whenever 
possible, the study assessments will be performed on Day 8, Day 14, Day 21, 
Day 28, and Day 60. If the patient is discharged home before Day 28, the study 
team will provide the patient with the remainder of the assigned blinded study 
drug kit(s) to take home along with instructions on how to continue treatment at 
home on the day-of-discharge; for these patients, treatment compliance will be 
conducted via a diary. If the patient does not feel comfortable to complete the 
diary, the site will alternatively provide the patient with the option to be called, 
twice a day, to confirm that the study drug is taken as instructed. The treatment 
period will end with the Day 28 (End of Treatment Visit) assessments. The 
follow-up period will consist of Day 60 (Follow-up Visit) assessments.
Selection of Patients:
Inclusion Criteria:
Individuals must meet all of the following criteria to be included in the study:
1.
The patient must be willing and able to give informed consent to 
participate in the study and to adhere to the procedures stated in the 
protocol or, for adults incapable of consenting due to their medical 
condition (eg, too weak or debilitated, severe shortness of breath) or due 
to literacy issues, the patient’s legally authorized representative must be 
willing and able to give informed consent on behalf of the patient to 
participate in the study as permitted by local regulatory authorities, 
institutional review boards (IRBs)/independent ethics committees
(IECs), or local laws.
2.
The patient is male or female adult aged 18 years (as per local laws) at 
the time of giving informed consent.
3.
The patient is admitted to a hospital and has a positive SARS-CoV-2 test
by standard RT-PCR assay or equivalent test. Please note: If the patient 
has a previous confirmation of SARS-CoV-2 (within 7 days of Day 1), 
the SARS-CoV-2 test at screening is not required. 
4.
The patient has the presence of any symptom(s) suggestive of moderate 
or severe systemic illness with COVID-19 on Day 1, such as presence of
fever (38.0ιC [100.4ιF] by any route), loss of smell or taste, cough, 
sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, 
shortness of breath upon exertion and/or at rest, or respiratory distress.
5.
The patient has the presence of moderate to severe clinical signs 
indicative of moderate or severe illness with COVID-19 on Day 1: 
a)
Moderate: 
i.
Clinical signs suggestive of moderate illness with 
COVID-19, such as respiratory rate 20 breaths per 
minute, SpO2 >93% (on room air at sea level, if 
possible), heart rate 90 beats per minute 
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ii.
No clinical signs indicative of severe or critical 
COVID-19
b)
Severe: 
i.
Clinical signs suggestive of severe systemic illness 
with COVID-19, such as respiratory rate 30 breaths 
per minute, heart rate 125 beats per minute, SpO2
93% (on room air at sea level, if possible), partial 
pressure of oxygen/FiO2 <300, or diagnosed with acute 
respiratory distress syndrome (according to the Berlin 
definition)
ii.
No criteria met for critical COVID-19
Please note: Patients who are receiving oxygen therapy at baseline for a 
chronic condition (eg, emphysema, COPD, PAH, IPF, etc) must be 
considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19
severity, the investigator should contact the medical monitor.
6.
The patient does not require hemodialysis (chronic) or any renal 
replacement therapies at screening or Day 1.
7.
The patient is able to swallow the study drug (hard gelatin capsules). 
8.
The patient agrees to minimize strong sun exposure (sunbathing) and 
strong ultraviolet exposure during the course of the study. Additionally, 
during the study, patients must agree to use sunscreen when spending an 
extended period outdoors.
9.
Men whose sexual partners are women of childbearing potential 
(WOCBP) must agree to comply with 1 of the following contraception 
requirements from the time of first dose of study medication (Day 1) 
until at least 30 days after the last dose of study medication:
a)
Vasectomy with documentation of azoospermia. 
b)
Sexual abstinence (defined as refraining from heterosexual 
intercourse from the time of first dose of study medication until 
at least 30 days after the last dose of study medication)
c)
Male condom plus partner use of 1 of the contraceptive options 
below: contraceptive subdermal implant; intrauterine device or 
intrauterine system; oral contraceptive, either combined or 
progestogen alone; injectable progestogen; contraceptive 
vaginal ring; percutaneous contraceptive patches. 
The above is an all-inclusive list of those methods that meet the 
following definition of highly effective: having a failure rate of <1% per 
year when used consistently and correctly and, when applicable, in 
accordance with the product label. For non-product methods (eg, male 
sterility), the investigator will determine what is consistent and correct 
use. The investigator is responsible for ensuring that patients understand 
how to properly use these methods of contraception. 
10. WOCBP must agree to comply with 1 of the following contraception 
requirements from the time of first dose of study medication (Day 1) 
until at least 30 days after the last dose of study medication:
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a)
Sexual abstinence (defined as refraining from heterosexual 
intercourse from the time of first dose of study medication until 
at least 30 days after the last dose of study medication)
b)
Use of 1 of the contraceptive options below plus use of a 
condom by male partner: contraceptive subdermal implant; 
intrauterine device or intrauterine system; oral contraceptive, 
either combined or progestogen alone; injectable progestogen; 
contraceptive vaginal ring; percutaneous contraceptive patches. 
c)
Vasectomy of male partner with documentation of azoospermia. 
The above is an all-inclusive list of those methods that meet the 
following definition of highly effective: having a failure rate of <1% per 
year when used consistently and correctly and, when applicable, in 
accordance with the product label. The investigator is responsible for 
ensuring that patients understand how to properly use these methods of 
contraception. Women of non-reproductive potential are defined as: 
a)
Premenopausal females with 1 of the following: documented 
tubal ligation; documented hysteroscopic tubal occlusion 
procedure with follow-up confirmation of bilateral tubal 
occlusion; hysterectomy; documented bilateral oophorectomy.
b)
Postmenopausal defined as 12 months of spontaneous 
amenorrhea [in questionable cases a blood sample with 
simultaneous follicle stimulating hormone and estradiol levels 
consistent with menopause (refer to laboratory reference ranges 
for confirmatory levels)]. Women on hormone replacement 
therapy (HRT) and whose menopausal status is in doubt will be 
required to use 1 of the highly effective contraception methods 
listed above if they wish to continue their HRT during the 
study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before randomization. 
Exclusion Criteria:
Individuals meeting any of the following criteria are ineligible to participate in 
this study: 
1.
The patient, in the opinion of the investigator, is not likely to survive for 
48 hours beyond Day 1. 
2.
The patient has a diagnosis of asymptomatic COVID-19, mild 
COVID-19, or critical COVID-19 on Day 1. 
a)
Asymptomatic COVID-19 is defined as a patient with a positive 
SARS-CoV-2 test by standard RT-PCR assay or equivalent test 
but not experiencing symptoms. 
b)
Mild COVID-19 is defined as a patient with a positive SARS-
CoV-2 test by standard RT-PCR assay or equivalent test and 
experiencing symptoms of mild illness but no clinical signs 
indicative of moderate, severe, or critical COVID-19. 
c)
Critical COVID-19 is defined as a patient with a positive 
SARS-CoV-2 test by standard RT-PCR assay or equivalent test 
and experiencing at least 1 of the following: shock defined by 
systolic blood pressure <90 mm Hg or diastolic blood pressure 
<60 mm Hg, or requiring vasopressors; respiratory failure 
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requiring endotracheal intubation and invasive mechanical 
ventilation, oxygen delivered by high-flow nasal cannula 
(heated, humidified, oxygen delivered via reinforced nasal 
cannula at flow rates >20 L/min with fraction of delivered 
oxygen 0.5), non-invasive positive pressure ventilation, 
ECMO, or clinical diagnosis of respiratory failure (ie, clinical 
need for 1 of the preceding therapies, but preceding therapies 
not able to be administered in setting of resource limitation), 
and/or multi-organ dysfunction/failure.
Please note: Patients who are receiving oxygen therapy at baseline for a 
chronic condition (eg, emphysema, COPD, PAH, IPF, etc) must be 
considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19
severity, the investigator should contact the medical monitor.
3.
The patient has a Child Pugh score  C.
4.
The patient has a documented medical history of infection with hepatitis 
A, B, or C at screening or Day 1.
5.
The patient has a documented medical history of infection with human 
immunodeficiency virus and has a detectable viral load and CD4 count 
<500 cells/μL. 
6.
The patient has a documented active infection with tuberculosis at 
screening or Day 1.
7.
The patient has clinically significant electrocardiogram abnormalities at 
screening.
8.
A female patient who is pregnant, planning to become pregnant during 
the study, breastfeeding, or has a positive pregnancy test at screening (by 
serum) and before dosing on Day 1 (by urine) as determined by human 
chorionic gonadotrophin tests.
9.
The patient is planning to donate or bank ova or sperm from Day 1 until 
30 days after the last dose of study drug.
10. The patient has a known history of drug or alcohol abuse within 
6 months of study start that would interfere with the patient’s 
participation in the study.
11. The patient has a history of sensitivity to any of the study medications,
components thereof (eg, mannitol or gelatin), or a history of drug or 
other allergy that, in the opinion of the investigator or medical monitor, 
would contraindicate their participation.
12. The patient has participated in and/or plans to participate in another 
clinical study using an investigational product within the following 
period before the first dosing day in the current study: 30 days, 5 half-
lives, or twice the duration of the biological effect of the investigational 
product (whichever is longer).
13. The patient will be transferred to another hospital that is not a study site 
within 72 hours. Please note: If the investigator has admitting privileges 
to the transfer hospital, the patient may be considered for randomization.
14. The patient is employed by MetrioPharm, the contract research 
organization or clinical site involved in the clinical study.
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15. The investigator makes a decision that study involvement is not in 
patient’s best interest, or the patient has any condition or critical illness,
in the opinion of the investigator, that will not allow the protocol to be 
followed safely.
Planned Sample Size:
The primary efficacy endpoint “proportion of patients with disease progression on 
Day 14” is assumed to be 10% in the 300 mg MP1032 BID plus SoC treatment 
group (Arm A) and 30% in the placebo plus SoC treatment group (Arm B). Using 
the Chi-square test with type I error alpha=10% two-sided for this proof-of-
concept study and 2:1 randomization ratio, with 114 randomized patients (76 in 
Arm A and 38 in Arm B) a statistical power of 83% can be achieved. Considering 
about 5% early study terminations, the necessary sample size to randomize results 
is 120 patients in total (80 in Arm A and 40 in Arm B). If during the conduct of 
the study the early study termination rate is higher than the estimated 5%, then an 
increase in the randomized number of patients may be necessary. 
Sample size estimation was performed using nQuery 8, Version 8.6.1.0.
A subset of randomized patients will be consented for the collection of blood 
samples for PK measurements. The PK subset consists of approximately 
20 patients from the 300 mg MP1032 BID plus SoC group and approximately 
10 patients from the placebo plus SoC group, up to a total of approximately 
30 patients.
Study Drug, Dose, and 
Mode of Administration:
All randomized patients will receive study drug from Day 1 to Day 28 according 
to their assigned treatment and according to the randomization scheme. Patients
will receive 6 capsules in the morning and 6 capsules in the evening (ie, 
approximately every 12 hours, approximately at the same time every day, and at 
least 8 hours apart) according to their randomized treatment arm assignment as 
described below:
x
Arm A: MP1032 (300 mg [6 × MP1032 hard gelatin capsules 50 mg]
BID) for oral administration
x
Arm B: 6 × placebo capsules (ie, matching MP1032 hard gelatin 
capsules 50 mg) BID for oral administration
Standard of Care
Each site will treat all patients with SoC for the duration of the study. The 
selected SoC will be used in accordance with the hospital’s SoC procedures and 
may include drugs under an emergency use authorization.
Treatment Duration:
Patients will be treated with study drug for 28 consecutive days (unless study drug 
is discontinued for safety reasons) to provide a fixed duration of treatment across 
all patients. Patients who progress to the use of an invasive ventilation 
(mechanical ventilator and/or ECMO) or who can no longer swallow the study 
drug (>2 days [ie, 2-day interruption is acceptable]) must discontinue the study 
drug; but whenever possible, the study assessments will be performed on Day 8,
Day 14, Day 21, Day 28, and Day 60. If the patient is discharged home before 
Day 28, the study team will provide the patient with the remainder of the assigned 
blinded study drug kit(s) to take home along with instructions on how to continue 
treatment at home on the day-of-discharge; for these patients, treatment 
compliance will be conducted via a diary. If the patient does not feel comfortable 
to complete the diary, the site will alternatively provide the patient with the option 
to be called, twice a day, to confirm that the study drug is taken as instructed.
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The study duration for an individual patient will be as follows:
x
Screening period: up to 7 days 
x
Treatment period: 28 consecutive days (ie, Day 1 to Day 28)
x
Follow-up period: 32 days after Day 28 (ie, Day 60)
As such, the approximate study duration (including screening and the follow-up
period) for an individual patient is up to 67 days (±3 days).
Please note: Patients who remain hospitalized after 28 days of consecutive 
treatment with study drug are not eligible for additional treatments with study 
drug. 
Any patient who is discharged during the study should complete the day-of-
discharge assessments before release from the hospital.
Efficacy Assessments:
The following efficacy assessments will be collected:
x
COVID-19 symptoms
x
COVID-19 severity
x
Clinical status related to COVID-19 on the NIAID 8-point ordinal scale,
as well as each individual component of the NIAID 8-point ordinal scale
x
HRQoL assessed by the EQ-5D-5L questionnaire
x
COVID-19 testing 
Safety Assessments:
The following safety assessments will be collected:
x
Medical/surgical history
x
Demographics
x
Prior and concomitant medications
x
Vital signs 
x
Physical examinations
x
Electrocardiograms
x
Clinical laboratory assessments 
x
AEs 
Pharmacokinetic 
Assessments:
PK samples will be collected via sparse sampling from a subset of approximately 
30 patients (who give optional consent) in a 2:1 ratio (approximately 20 patients 
from the 300 mg MP1032 BID plus SoC group and approximately 10 patients 
from the placebo group plus SoC group) to assess the PK of MP1032 on Day 1 
(single dose) and Day 7 (steady state). A total of 16 samples will be collected 
relative to the first dose on Day 1 and the first dose on Day 7. Samples on Day 1 
and Day 7 will be collected predose (within 10 minutes before the first daily dose) 
and postdose at 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 
8 hours (before next dose), and 24 hours before the next morning dose (if 
applicable), if possible. Patients who provide consent for the PK sampling, but are 
no longer hospitalized on Day 7, will not have Day 7 PK samples collected. 
Other Assessments:
Blood samples will be obtained on Day 1 (before the first study drug 
administration) and Days 7, 14, 21, 28, and 60 to measure biomarker levels.
Biomarkers will potentially include but will not be limited to: cytokines (eg, 
C-reactive protein, IL-1E, IL-6, tumor necrosis factor-Į, and IFN-J) and other 
coagulation/inflammatory biomarkers (eg, D-dimer and ferritin).
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Statistical Methods and 
Planned Analyses:
Analysis Sets:
Intention-to-Treat Set
The   Intention-to-Treat (ITT) set, correspond with randomized set, will include 
all randomized patients irrespective of any deviation from the protocol or 
premature discontinuation from study drug/withdrawal from study. The treatment 
group assignment will be designated according to initial randomization. The ITT
will serve as the basis for the analysis of efficacy and summary of demographics 
and baseline characteristics.
Per Protocol Set
The Per Protocol Set (PPS) will include all patients from ITT who received at 
least 1 dose of study drug and who do not have any major protocol deviations 
impacting the efficacy assessments. The PPS will be used for supportive analyses 
of efficacy.
Safety Set
The Safety Set (SS) will include all randomized patients who received at least 
1 dose of study drug. The treatment group assignment in the SS will be defined by 
the treatment actually received. The SS will be used for the analysis of safety.
PK Analysis Set
The PK Analysis Set (PKS) will include all the patients who have been 
administered active study drug and have at least 1 postdose evaluable plasma 
concentration after Day 1 dose.
Analyses: 
The estimands for the primary efficacy endpoint and for the 4 key secondary 
endpoints comparing the 2 treatment groups will be tested with consideration of a 
two-sided alpha of 10% on each test-level on the ITT. Additionally, 95% 
confidence intervals will be provided. Also, the treatment comparison with 
regards to the other efficacy endpoints will be performed using a two-sided alpha 
level of 10%..
The main estimand for the primary efficacy endpoint is defined as a binary 
variable indicating disease progression (death or respiratory failure) at Day 14. 
Intercurrent events that lead to study drug discontinuation and/or switch to other 
treatment before Day 14 will be handled using the treatment-policy strategy (ie, 
the NIAID score at Day 14 will be used for definition of the failure in such 
patients). Missing data on Day 14 resulting from study termination before Day 14
are not expected. However, in case they happen, such monotone missings will be 
imputed by multiple imputation using information from similar patients of the 
same treatment group. Missing post-baseline data for patients randomized but not 
treated will be imputed by the respective baseline value (baseline observation 
carried forward, BOCF). The comparison between the treatment groups 
considering all randomized patients after having imputed missing values will be 
performed using Mantel-Haenszel (MH) test for risk difference considering the 4 
strata resulting from the 2 randomization stratification factors disease severity 
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(moderate versus severe) and age-class (aged 65 years versus >65 years) at 
baseline.
Similar MH analyses will be conducted for the main estimand of the first key 
secondary efficacy endpoint, which is defined as a binary variable indicating 
disease progression (death or respiratory failure) at Day 28, and the main 
estimand for the second key secondary efficacy endpoint, which is defined as a
binary variable indicating disease resolution (alive and have a score of 6, 7 or 8 
on NIAID) at Day 28. Intercurrent events that lead to study drug discontinuation 
and/or switch to other treatment before Day 28 will be handled using the 
treatment-policy strategy for these estimands (ie, the NIAID score at Day 28 will 
be used for definition of the failure or response, respectively) in such patients. 
Missing data on Day 28 will be imputed by multiple imputation using information 
from similar patients of the same treatment group. 
A similar MH approach as described above will be applied also to the main 
estimand of the third key secondary efficacy endpoint, which is the all-cause 
mortality at Day 28. Intercurrent events that lead to study drug discontinuation 
and/or switch to other treatment before Day 28, will be handled using the 
treatment-policy strategy (ie, the life status at Day 28 will be considered). No 
missing data of life status on Day 28 is expected. 
The main estimand of the fourth key secondary efficacy endpoint, change of 
clinical status related to COVID-19 on Day 28 compared with baseline according 
to the NIAID 8-point ordinal scale, will be compared using the risk difference 
from the analysis of covariance model with treatment and the 2 binary 
stratification factors (ie, severity and age-class) as independent factors and the 
baseline value of NIAID as independent covariate. Intercurrent events that lead to 
study drug discontinuation and/or switch to other treatment before Day 28 will be 
handled using the treatment-policy strategy for these estimands (ie, the NIAID 
score at Day 28 will be used). Missing data on Day 28 will be imputed by 
multiple imputation using information from similar patients of the same treatment 
group. 
Sensitivity analyses for the main estimands of the primary and key efficacy 
estimands will be performed by assuming missing data at Day 14 or Day 28 as 
failure or non-resolution for the binary endpoints, and by multiple imputation 
using information from similar patients of the placebo group for the NIAID 8-
point ordinal scale.
All above analyses for the main estimands of the primary efficacy and key 
secondary efficacy endpoints will be repeated on PPS as supportive analysis. 
Additionally, for the primary efficacy and binary key secondary efficacy 
endpoints logistic regression model with treatment and the 2 stratification factors 
as covariables will be performed on the ITT.
The proportion of patients with disease resolution at Day 14 and the all-cause 
mortality rate at Day 14 and Day 60 will be analyzed using similar MH methods 
as described above for Day 28. Cumulative proportion of patients with disease 
resolution will be plotted by time.
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A similar analysis of covariance approach as described above for Day 28 will be 
applied for the analysis of the change of clinical status related to COVID-19 on 
Day 14 compared with baseline on the NIAID 8 point ordinal scale. The endpoint 
considering the proportion of patients requiring invasive ventilation (mechanical 
ventilator and/or ECMO) or who are not alive, the proportion of patients in each 
NIAID category, and the proportion of patients alive and testing negative for 
COVID-19 on Day 14, Day 28, and Day 60, respectively, will be compared 
between the treatment groups using MH test. Overall survival, time to (first) 
improvement of at least 1 category on the NIAID scale and total hospitalization 
duration (from baseline to discharge; with death censored on last day of the 
observed period - at Day 28 or Day 60, respectively - depending on the analyses) 
will be summarized using the Kaplan-Meier method and will be compared 
between treatment groups using log-rank tests. Additionally, Cox proportional 
hazards model will be applied with treatment and the 2 stratification factors as
covariables.
The odds ratio between MP1032 and SoC and placebo and SoC for the number of 
patients with clinical status improvement from baseline on the NIAID 8-point 
ordinal scale (ie, an improvement of at least 1 category) at Day 14 and Day 28 
will be analyzed using a logistic regression with consideration of the 
2 stratification factors.
The time to recovery of all at baseline present COVID-19 symptoms (stuffy or 
runny nose, sore throat, red or irritated eyes, shortness of breath, cough, low 
energy or tiredness, muscle or body aches, headache, chills or shivering, feeling 
hot or feverish, nausea, and number of times of vomit, times of diarrhea, sense of 
smell, sense of taste in the last 24 hours) will be presented by Kaplan-Meier 
estimates and figure. The change from baseline will be presented in shift tables
for each single symptom, with the number and percentage of subjects in each 
category at post-baseline assessment time-point compared to baseline for each 
treatment group.
Total number of days in ICU, duration of invasive mechanical ventilation, and 
duration of ECMO will be descriptively summarized by treatment group using 
mean days with 90% confidence intervals and additionally by median days and 
quartiles. To consider death sufficiently unfavorable in these measures, in case of 
death the duration of the respective measure will be considered with the longest 
duration possible (eg, if a summary of the first 28 days is presented, then death 
before Day 28 will be considered as duration 28 days, and if the summary also 
includes follow-up period until Day 60, then death before Day 60 will be 
considered as duration of 60 days). Both summaries (up to Day 28 and up to 
Day 60) will be provided.
For HRQoL assessments at discharge and Day 60, the EQ index value and the EQ 
VAS, both based on the EQ-5D-5L questionnaire will be calculated and 
summarized by visit and treatment group. Additionally, change at Day 60 from 
discharge by treatment group.
All efficacy endpoints will be summarized using descriptive statistics by 
treatment group and by visit, as appropriate: Binary and categorical endpoints will 
be summarized by treatment group by presenting the number and percentage of 
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patients in the categories. Continuous and ordinal endpoints will be described by 
mean, standard deviation, median, minimum, and maximum for actual values and 
change from baseline. Additionally, for ordinal data, the number and percentage 
of patients in each category will be presented.
The PK parameters (such as Cmax, Tmax, AUC0-t, and others) of MP1032 on Day 1
(single dose) and Day 7 (steady state; if available), using up to 8 hours postdose,
will be derived applying non-compartmental analysis. PK parameters will be 
summarized along with plasma concentrations at various time points. Individual 
and mean plasma concentration versus time will be presented on linear, and semi-
log scales. Further details of the PK analysis will be described in the statistical 
analysis plan (SAP). Any possible correlation between plasma exposure and 
biomarkers (eg, change from baseline in cytokines, or other 
coagulation/inflammatory biomarkers) or efficacy measures can be explored by 
appropriate regression analysis methods during the final data analysis. 
The change from baseline biomarker levels will be summarized descriptively by 
treatment group and visit. The change in biomarker levels will also be evaluated 
with any change of COVID-19 clinical status.
All safety parameters will be summarized descriptively by treatment group for the 
entire study period. 
Study drug duration and SoC therapies will be described for each treatment group.
The SAP will present further estimands for the primary and key secondary 
endpoints and will describe the statistical analyses in detail.
Independent Data 
Monitoring Committee:
An independent data monitoring committee (DMC) will be established by the 
sponsor or designee to review accumulating study data at regular intervals (as per 
the DMC charter) throughout the study to ensure the safety of patients and review 
overall study conduct. Additional data may be reviewed that are related to 
efficacy, but the DMC will only be reviewing data for risk-benefit purposes. 
Members will include experts in drug safety and/or medical specialist and 
biostatistics, who are not participating in this study and do not have affiliation 
with the investigators or the sponsor. The DMC can recommend in writing to the 
sponsor whether to continue, modify, or stop the clinical study on the basis of 
safety considerations. The DMC’s specific duties will be fully described in a 
DMC charter.
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3
TABLE OF CONTENTS
1
CLINICAL STUDY PROTOCOL....................................................................................1
2
SYNOPSIS ........................................................................................................................4
3
TABLE OF CONTENTS ................................................................................................18
3.1
List of In-text Tables ..................................................................................................21
4
LIST OF ABBREVIATIONS .........................................................................................22
5
INTRODUCTION...........................................................................................................24
5.1
Background on COVID-19.........................................................................................24
5.2
Background on MP1032, Including Benefit Risk Assessment ..................................25
Nonclinical Studies ............................................................................................26
Clinical Studies ..................................................................................................27
5.3
Risk Management of MP1032....................................................................................29
5.4
Study Rationale ..........................................................................................................29
6
STUDY OBJECTIVES AND ENDPOINTS ..................................................................31
6.1
Study Objectives.........................................................................................................31
6.2
Study Endpoints..........................................................................................................31
7
INVESTIGATIONAL PLAN .........................................................................................33
7.1
Description of Overall Study Design and Plan...........................................................33
7.2
Discussion of Study Design........................................................................................36
7.3
End of Study...............................................................................................................37
8
SELECTION OF STUDY POPULATION.....................................................................37
8.1
Inclusion Criteria........................................................................................................37
8.2
Exclusion Criteria.......................................................................................................39
8.3
Rescreening ................................................................................................................41
8.4
Study Withdrawal, Removal, and Replacement of Patients.......................................41
9
TREATMENTS...............................................................................................................42
9.1
Details of Study Drugs ...............................................................................................42
9.2
Dosage Schedule ........................................................................................................42
9.3
Measures to Minimize Bias: Randomization and Blinding........................................43
Randomization ...................................................................................................43
Blinding44
9.4
Treatment Modifications and Discontinuations .........................................................45
9.5
Treatment Accountability and Compliance................................................................46
9.6
Prior and Concomitant Medications...........................................................................46
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10
STUDY PROCEDURES.................................................................................................47
10.1
Informed Consent .......................................................................................................53
10.2
Study Procedures........................................................................................................53
11
EFFICACY ASSESSMENTS.........................................................................................53
11.1
COVID-19 Symptoms................................................................................................54
11.2
COVID-19 Severity....................................................................................................54
11.3
Clinical Status Related to COVID-19 on the National Institute of Allergy and Infectious 
Diseases 8-Point Ordinal Scale ..................................................................................56
11.4
Health-related Quality of Life Assessment ................................................................58
11.5
COVID-19 Testing .....................................................................................................58
12
SAFETY ASSESSMENTS .............................................................................................58
12.1
Medical/Surgical History and Demographics ............................................................58
12.2
Vital Signs ..................................................................................................................59
12.3
Physical Examinations................................................................................................60
12.4
Electrocardiograms.....................................................................................................60
12.5
Clinical Laboratory Assessments ...............................................................................60
12.6
Adverse Events...........................................................................................................62
Adverse Events ..................................................................................................62
Serious Adverse Events .....................................................................................64
Serious Adverse Event Reporting......................................................................65
Suspected Unexpected Serious Adverse Reactions ...........................................66
Pregnancy...........................................................................................................66
Overdose ............................................................................................................67
13
PHARMACOKINETICS ................................................................................................67
13.1
Pharmacokinetic Sampling.........................................................................................67
13.2
Pharmacokinetic Analytical Methodology.................................................................68
14
OTHER ASSESSMENTS...............................................................................................68
14.1
Biomarkers .................................................................................................................68
15
STATISTICAL ANALYSIS...........................................................................................69
15.1
Determination of Sample Size....................................................................................69
15.2
Analysis Sets ..............................................................................................................70
15.3
Efficacy Analysis........................................................................................................70
15.4
Safety Analysis...........................................................................................................73
15.5
Pharmacokinetic Analysis ..........................................................................................74
15.6
Biomarker Analysis....................................................................................................75
15.7
Interim Analysis .........................................................................................................75
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15.8
Data Monitoring Committee.......................................................................................75
16
STUDY MANAGEMENT..............................................................................................75
16.1
Approval and Consent ................................................................................................75
Regulatory Guidelines........................................................................................75
Institutional Review Board/Independent Ethics Committee..............................76
Informed Consent...............................................................................................76
16.2
Data Handling.............................................................................................................76
16.3
Source Documents......................................................................................................76
16.4
Record Retention........................................................................................................77
16.5
Monitoring..................................................................................................................77
16.6
Quality Control and Quality Assurance .....................................................................77
16.7
Protocol Amendment and Protocol Deviation............................................................78
Protocol Amendment .........................................................................................78
Protocol Deviations............................................................................................78
16.8
Ethical Considerations................................................................................................78
16.9
Financing and Insurance.............................................................................................78
16.10 Publication Policy/Disclosure of Data........................................................................79
17
REFERENCES................................................................................................................80
18
APPENDICES.................................................................................................................82
APPENDIX 1.
CHARLSON COMORBIDITY INDEX......................................................83
APPENDIX 2.
EUROQOL-5D-5L (EQ-5D-5L) QUESTIONNAIRE.................................86
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3.1
List of In-text Tables 
Table 1: Schedule of Assessments ........................................................................................48 
Table 2 
COVID-19 Symptoms.............................................................................................54 
Table 3: Acute Respiratory Distress Syndrome – Berlin Definition.....................................56 
Table 4 
Standard Conversion for Liter Flow Oxygen..........................................................57 
Table 5: Clinical Laboratory Assessments............................................................................61 
Table 6: Classification of Adverse Events by Severity.........................................................63 
Table 7: Classification of Adverse Events by Relationship to Study Drug ..........................64 
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4
LIST OF ABBREVIATIONS 
Abbreviation
Definition
AE
adverse event
ARDS
acute respiratory distress syndrome
AUC0-t
area under the concentration-time curve from time zero to the last non-zero 
concentration
BID
twice daily
BOCF
baseline observation carried forward
CFR
Code of Federal Regulations
Cmax
maximum plasma concentration
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease 2019
CSR
clinical study report
DMC
data monitoring committee
ECG
electrocardiogram
ECMO
extracorporeal membrane oxygenation
eCRF
electronic case report form
EDC
electronic data capture
EQ
EuroQol
EQ-5D-5L
EuroQol-5D-5L
FiO2
fraction of inspired oxygen
GCP
good clinical practice
hCG
human chorionic gonadotropin
HRQoL
health-related quality of life
HRT
hormone replacement therapy
IB
investigator’s brochure
ICF
informed consent form
ICU
intensive care unit
IEC
independent ethics committee
IL
interleukin
IMP
investigational medicinal product
IPF
idiopathic pulmonary fibrosis
IRB
institutional review board
ITT
Intention-to-Treat
IWRS
interactive web-response system
LAR
legally authorized representative
MH
Mantel-Haenszel
NIAID
National Institute of Allergy and Infectious Diseases
PAH
pulmonary arterial hypertension
PaO2
partial pressure of oxygen
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Abbreviation
Definition
PARP1
poly-ADP-ribose-polymerase 1
PASI
Psoriasis Area and Severity Index
PI
principal investigator
PK
pharmacokinetic
PKS
PK Analysis Set
PPS
Per Protocol Set
PT
preferred term
ROS
reactive oxygen species
RT-PCR
reverse transcription-polymerase chain reaction
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus type 2
SoC
standard of care
SOC
system organ class
SpO2
saturation of oxygen
SS
Safety Set
SUSAR
suspected unexpected serious adverse reactions
TEAE
treatment-emergent adverse events
Tmax
time of observed Cmax
TNF
tumor necrosis factor
VAS
visual analog scale
WHO
World Health Organization
WOCBP
women of childbearing potential
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5
INTRODUCTION 
5.1
Background on COVID-19 
On 31 December 2019, the World Health Organization (WHO) was informed of a cluster of 
cases of pneumonia of unknown cause detected in 
. Severe 
acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) was identified as the causative 
virus by Chinese authorities on 07 January 2020 (WHO 2020a). Coronavirus disease 2019
(COVID-19) was identified as the disease caused by SARS-CoV-2 infection. In March 2020, the 
COVID-19 outbreak was declared as a pandemic by the WHO. The disease resulting from 
SARS-CoV-2 led to shutdowns and social measures in great parts of the world, particularly to 
slow down the transmission of the virus and thereby avoiding the overburden of health care 
systems. 
The pandemic is still ongoing. Estimates of actual morbidity, mortality, and lethality are highly 
variable and depend on factors such as the time of analysis, region analyzed, and surveillance 
methods. As of 04 August 2020, the WHO estimated the case fatality ratio, which estimates the 
proportion of deaths among confirmed cases, to vary from 0.1% to >25%. Whereas, the true 
severity of COVID-19 as measured by the infection fatality ratio, which estimates the proportion 
of deaths among all infected individuals, is estimated to be approximately 0.5% to 1% 
(WHO 2020b). In a more recent summary of Levin et al (2020) it could be clearly shown that the 
infection fatality ratio is highly age dependent, being in average as low as 0.004% for patients 
younger than 35 and as high as 28.3% in patients at the age of 85 and older.
Presentations of COVID-19 range from an asymptomatic course or mild symptoms to severe 
illness and mortality. Common symptoms include fever or chills, cough, shortness of breath or 
difficulty breathing, fatigue, muscle or body aches, headache, loss of taste or smell, sore throat, 
congestion or runny nose, nausea or vomiting, and diarrhea (Cennimo 2021). Less common 
symptoms are sputum production, malaise, respiratory distress, and neurologic symptoms, such 
as altered mental state. While most patients with COVID-19 seem to show mild respiratory 
symptoms only, some of them develop pneumonia, shortness of breath and hypoxia, or other 
serious conditions that require hospitalization. Generally, pneumonia seems to be the most 
common serious manifestation of COVID-19. Further, major deterioration such as an acute 
respiratory distress syndrome (ARDS) can lead to the imperative need of an intensive care unit 
(ICU) and might even require mechanical ventilation via intubation. Other complications that 
might occur during the course of the disease include sepsis, acute kidney injury, thyrotoxicosis, 
and neurologic manifestations such as myasthenia gravis. The elderly, as well as patients with 
pre-existing chronic conditions (eg, asthma, chronic obstructive pulmonary disease [COPD], 
diabetes mellitus, chronic kidney disease, immune system deficiencies, liver disease, and cardiac 
diseases, etc), seem to be more vulnerable to a severe disease course.
Although, to date, knowledge about SARS-CoV-2 and corresponding COVID-19 is still limited,
it seems to be clear that the course of the disease, and particularly severe complications, are
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based on an overshooting immune response. Details on and a deeper understanding of how the 
virus causes such a reaction will be a central part of future investigations (Hillienhof 2020).
Patients with COVID-19 show increased levels of plasma pro-inflammatory cytokines (Rothan 
and Byrareddy 2020). From a pathophysiological point of view, in severe cases the viral 
infection seems to trigger an excessive immune reaction in the host, a so-called cytokine storm,
leading to extensive tissue damage. A key player of this mechanism is interleukin (IL)-6. IL-6
inhibitors, as well as other immune modulators, must thus be considered a potential treatment 
approach. This approach seems to be particularly promising, as recent postmortem findings show 
direct viral infection of the endothelial cells and diffuse endothelial inflammation in the whole 
body (Varga et al 2020).
Recently the first vaccines to prevent COVID-19 have been approved by authorities, including
the Food and Drug Administration in the United States and the European Medicines Agency in
Europe, and numerous further vaccine projects are still under development. Nonetheless, it will 
take years until the majority of people will be vaccinated and the epidemiological situation can 
be considered as under control. Hence, there is still an urgent need for therapeutic agents to cure 
COVID-19 and/or ameliorate its symptoms. Among the antiviral treatment options, remdesivir 
has shown to be effective in reducing hospitalization time when administered early in the course 
of the disease (Beigel et al 2020); however, in the meantime the WHO has issued a conditional 
recommendation against the use of remdesivir in hospitalized patients regardless of disease 
severity (WHO 2020c) Among immune modulating drugs low-dosed dexamethasone could 
significantly lower the incidence of deaths when applied at a later time point of the disease 
course (WHO-REACT 2020) but is not recommended early in disease or in patients with mild 
symptoms only (WHO 2020c). Hence, there is still no antiviral treatment or otherwise effective 
curative agent that could really lower the burden of this pandemic. Thus, COVID-19 still 
presents an urgent unmet medical need.
5.2
Background on MP1032, Including Benefit Risk Assessment 
MP1032 is a purely synthetic, new chemical entity. MP1032 is a mono sodium salt derived from 
the aromatic system phthalazinedione, containing an additional amino group. MP1032 is 
water-soluble and hydrophilic.
The primary mechanism of action of MP1032 is assumed to be a reactive oxygen species (ROS)
scavenging action in inflamed tissues (ie, tissues that experience oxidative stress). A unique 
pharmacologic property of MP1032 is that the ROS-scavenging function of the molecule is only 
activated in tissues with pathologically high ROS concentrations (oxidative stress), which is the 
case in inflamed tissue. By re-establishing a physiologic redox balance in activated immune 
cells, MP1032 is putatively inhibiting nuclear factor-kappa B activation. Inhibition of nuclear 
factor-kappa B is expected to lead to inhibition of pro-inflammatory cytokines (eg, IL-6 and 
TNF-Į) (Gloire et al 2006). In addition, MP1032 is a specific inhibitor of poly-ADP-ribose-
polymerase 1 (PARP1). PARP1 is a nuclear enzyme involved in inflammation (Ke et al 2019).
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Further identified potential targets are the kinases human Aurora-B, human Aurora-C, 
serine/threonine-protein kinase, tyrosine kinase, and the metalloprotease TNF-Į-converting 
enzyme—however, at relatively high molarity only. Therefore, the administration of MP1032 (as 
shown nonclinically, both in vitro and in vivo), in pathological conditions only, leads to a 
reduced concentration of pro-inflammatory cytokines without completely blocking them. In 
addition to this broadly anti-inflammatory potential, MP1032 exhibits direct antiviral activity 
against SARS-CoV-2 that could be shown by a clear and dose-dependent inhibition of SARS-
CoV-2 reproduction in Vero B4 cells (African green monkey [Chlorocebus aethiops] kidney 
epithelium cells) (Schumann et al 2020).
MP1032 could attenuate prolonged virus replication by preventing oxidative stress 
(Khomich et al 2018) and/or by limiting ADP-ribosylation of the viral nucleocapsid protein via 
PARP1 inhibition (Grunewald et al 2018). PARP1 inhibitors also have been suggested for the 
treatment of COVID-19 (Curtin et al 2020).
Based on the basic chemical mechanism of MP1032 as an electron donor to ROS, the molecule 
acts similarly across a wide range of species and is thus not an agent with a high degree of 
species specificity. Further, MP1032 has no specific immune-system targets as known from 
various biologicals. MP1032 is not expressed by using mammalian systems (cells) or using raw 
materials of human or animal origin.
Nonclinical Studies
In vivo safety studies showed no evidence of neurotoxic potential or negative 
cardiohemodynamic effects; no local intolerance was observed. There was no dose-limiting or 
target organ toxicity and no substance-related findings in histopathology in rats or dogs. 
However, after 6 months of long-term treatment in rats receiving the highest dose 
(1000 mg/kg/d), liver organ weight was elevated compared with that of controls and 
histopathologically associated with hepatocellular hypertrophy. This finding was not considered 
adverse because of its adaptive character, as histopathological changes were not present at the 
end of the recovery period (ie, effect was reversible after 8 weeks).
In reproduction toxicity studies on fertility, early embryonic, and embryo-fetal development, no
pathological effects were found. On the basis of results from 4 different test systems, mutagenic 
or clastogenic effects are not considered to be a potential risk for volunteers and patients.
Transient effects on some pulmonary parameters have been observed in rats following a single 
intravenous bolus injection of the highest dose (300 mg/kg) of MP1032. No pulmonary effects 
have been observed in any of the long-term animal toxicity studies. The maximum plasma levels 
reached in humans are over 1000 times (oral) lower than for the abovementioned dose. Thus, 
pulmonary effects are not considered a potential risk for patients and volunteers.
Emesis sporadically occurred in various repeat-dose toxicology studies in dogs; the emesis was 
present in the dogs more often at the high doses of 150 mg/kg twice daily (BID) intravenous than
at 125 mg/kg BID (oral). The lowest experimental oral dose inducing emesis was 25 mg/kg BID 
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(oral) in dogs, corresponding to 1.8 g (oral; conversion based on human-equivalent dose) for a 
65-kg human. Dogs are well known to be susceptible to emesis; in addition, the maximum doses 
administered in humans are 6 to 30 times below the converted human-equivalent doses. 
Therefore, emesis is not considered a potential risk for patients and volunteers.
Transient liquid feces were sporadically observed in various repeat-dose toxicology studies in 
dogs of all dose groups treated with MP1032. However, these gastrointestinal irritations could 
not be attributed to specific animals and thus did not have an observable effect on their 
wellbeing. Further, no such observations were made in any of the other species investigated. 
Also, in the clinical studies completed so far, no cases of diarrhea have been reported as adverse 
drug reactions by the respective investigators. Gastrointestinal irritations are therefore not 
considered a potential risk for patients and volunteers.
A potential phototoxic risk cannot be excluded from the in vitro 3T3 neutral red uptake and the 
distribution quantitative whole-body autoradiography test. In the clinical studies completed so far 
with MP1032, mean maximum plasma concentrations and calculated maximum skin 
concentrations were all below the half maximal effective concentration in the 3T3 neutral red 
uptake test with safety margins between 2 to 20 times. Therefore, a phototoxic risk for patients
seems to be unlikely.
Further, a slight to moderate increase in serum creatinine level combined with a slight decrease 
of kidney weights was observed after a 90-day treatment period in male mice in a dose-range 
finding, repeated dose (oral) toxicity study at high dosed animals. However, as there were no 
associated histopathological findings in kidneys of the respective animals, this effect is also not 
considered to be adverse in nature. In the scope of extensive laboratory controls in the clinical 
studies completed so far, no respective treatment-emergent adverse events (TEAEs) have been 
reported. 
The probability of pharmacokinetic interactions of MP1032 regarding the inhibition or induction 
of Cytochrome P450 or inhibition of well-known drug transporters is rather low. However, based 
on in vitro experiments there are hints that a combination of MP1032 and dexamethasone might 
act (supra-)additive regarding the inhibition of proinflammatory cytokines (ie, IL-6). Thus, 
currently, a potential drug-drug interaction of MP1032 and dexamethasone regarding their anti-
inflammatory action cannot be excluded.
For further details of the completed nonclinical studies conducted with MP1032, readers are 
referred to the current version of the investigator’s brochure (IB).
Clinical Studies
MP1032 so far has been investigated in 3 clinical studies, including a first-in-human study 
(MP1032-CT01; EudraCT-No.: 2014-004606-15) with a single ascending dose and a multiple 
ascending dose part, as well as 2 studies in patients with moderate-to-severe psoriasis: a 6-week,
Phase IIa, pilot study (MP1032-CT02; EudraCT-No.: 2015-005159-28) and a 3-month, Phase II
study (MP1032-CT04; EudraCT-No.: 2017-003484-36).
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Among the subjects enrolled in MP1032 studies, 146 subjects were administered MP1032 orally.
Among them, 24 male subjects participated as healthy volunteers in the Phase I study, while both
male (n=89) and female (n=33) patients with psoriasis participated in the Phase II studies. The 
age of participants administered MP1032 ranged from 18 to 68 years. Pregnant and breastfeeding 
women, as well as children and adolescents have not been included in the studies.
The highest single dose of MP1032 administered was 600 mg, applied to healthy volunteers. The
highest repeated dose was 300 mg MP1032 BID, applied to both healthy volunteers (7 days) and
patients with psoriasis (3 months).
No serious adverse events (SAEs) occurred in any of the subjects administered MP1032.
No deaths occurred in the scope of the MP1032 clinical development program.
MP1032 was well tolerated in all studies, and safety analyses did not reveal any clinically 
important safety issues. In general, incidence, intensity, causality, and spreading of TEAEs over 
system organ classes (SOCs) were comparable between groups. In the recent Phase II study, the
incidence, intensity, relationship to investigational medicinal product (IMP), and causality to 
IMP for adverse events (AEs) were even lower for both MP1032 dose groups compared with
those of the placebo group and statistically significantly lower for the 300 mg MP1032 group 
compared with the placebo group.
None of the potential risks arising from preclinical data could be confirmed with clinical data. 
From the TEAEs that occurred in the MP1032 groups and were regarded as at least possibly 
related by the investigator, nasopharyngitis, pruritus, and psoriasis must be considered as 
common (1/100 to <1/10); while neutropenia, palpitations, abdominal pain upper, fatigue, 
feeling drunk, influenza-like illness, cystitis, and headache can be regarded as uncommon 
(1/1,000 to <1/100). Regarding the general spreading of AEs over SOCs and the comparison 
between groups, currently none of them can be considered a significant clinical risk.
Regarding efficacy in the treatment of moderate to severe psoriasis, the MP1032-CT02 study 
showed that after only 6 weeks of treatment, there was a clinically meaningful response in 
patients who entered the study with moderate to severe psoriasis with a Psoriasis Area and 
Severity Index (PASI) score of 10 to 20 and achieved the appropriate drug-exposure levels. 
Hence, only patients with a PASI score of 10 to 20 at baseline were randomized to the 
MP1032-CT04 study. After 12 weeks, a significant PASI reduction could be shown in the 
300 mg MP1032 BID group compared with those in the placebo group; however, this only
occurred in a prespecified subgroup of patients with PASI 15 at baseline.
Further details of the completed clinical studies conducted with MP1032 may be found in the 
current version of the IB.
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5.3
Risk Management of MP1032 
In the scope of planning and conducting future clinical studies, all potential risks associated with 
MP1032 will be considered, and measures will be taken as applicable. 
On the basis of limitations in the amount of preclinical and clinical data available so far, MP1032 
shall not be administered to patients for >3 months, and it will generally not be administered to 
children or pregnant women. 
Adverse drug reactions that have already been described in the clinical program so far, as well as 
any suspected AEs arising from risks associated with preclinical data will be evaluated 
extensively on a case-by-case base during ongoing and/or upcoming studies.
Because of potential phototoxicity, patients in upcoming studies will be advised to avoid strong 
sun exposure (sunbathing) and strong ultraviolet exposure. Furthermore, the use of sunscreen 
will be recommended when spending an extended period outdoors. It should be ensured that 
exposure to ultraviolet light (eg, from lasers in procedures) is limited while the patient is 
hospitalized.
To avoid risks associated with potential low efficacy in serious and life-threatening conditions, 
such as COVID-19, MP1032 is only recommended to be used as add-on to standard of 
care (SoC) until a respective proof-of-concept is demonstrated.
As dexamethasone is expected to be part of SoC in most institutions treating patients with
COVID-19 investigators should be aware that a (supra-)additive synergism between MP1032 
and dexamethasone regarding their anti-inflammatory activity cannot be excluded.
Further details regarding known or anticipated risks, as well as reasonably anticipated AEs for 
MP1032 may be found in the current version of the IB.
5.4
Study Rationale  
MP1032 is a small molecule that combines localized, auto-regulated ROS-scavenging and 
immune-modulating effects with potential antiviral properties against SARS-CoV-2. MP1032 
leads to a reduced concentration of pathologically increased pro-inflammatory cytokines without
completely blocking them. This downregulation to physiologic levels was shown in vivo and in
vitro for IL-1ȕ, IL-6, IL-12, IL-23, and TNF-Į in activated macrophages/neutrophils; most data
are available on the downregulation of IL-6 and TNF-Į. Once physiologic ROS levels have been
reached, concurrent with down-modulated cytokine levels, the drug activation stops. Further, 
MP1032 might suppress virus replication in patients with COVID-19 dose-dependently like it
has been shown in vitro with no effect on cell viability.
On the basis of this mechanism of action, MP1032 does not carry the risk of developing 
opportunistic infections, such as with IL-6 or TNF-Į inhibitors. On the contrary, an in vivo study 
on polymicrobial abdominal sepsis in mice showed a decrease of bacterial burden in animals 
treated with MP1032, although a direct antibacterial effect for MP1032 could not be shown.
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MP1032 has also been investigated in a small exploratory hemagglutinin type 5 neuraminidase 
type 1 virus infection model in mice, wherein animals treated with MP1032 showed a 
significantly improved clinical score on Days 6 and 7 after infection, combined with a clear trend 
of prolonged survival compared with that of the mice receiving placebo.
In summary, when administered in combination with or as add-on to standard treatments,
MP1032 may prevent and/or ameliorate any overstimulation of the immune system in the course
of a COVID-19, thereby reducing the danger of opportunistic infections and helping to reduce 
the severity of general inflammatory symptoms. At the same time, the probability of a severe 
course of the disease is reduced because of a potential direct antiviral capacity of MP1032. This 
combinative approach makes MP1032 a promising candidate for the treatment of COVID-19. In
addition, synergistic effects may be obtained when using MP1032 as an add-on to other 
medicinal products currently under investigation for treating patients with COVID-19.
There is a substantial medical need for preventive and/or therapeutic options for the COVID-19
pandemic. COVID-19 is a viral disease with a considerable mortality rate that is not yet 
completely determined and it significantly affects healthcare systems. Considering the strong 
safety profile and good tolerability of MP1032 based on both preclinical and clinical data,
combined with the signals of meaningful therapeutic effects of MP1032, it is justified that a 
proof-of-concept for MP1032 in the treatment of patients with COVID-19 is started.
As such, this proof-of-concept study is designed to investigate the efficacy and safety of MP1032
plus SoC versus placebo plus SoC treatment in hospitalized adults with confirmed moderate to 
severe COVID-19, the disease caused by SARS-CoV-2 infection. Additional exploratory 
objectives include pharmacokinetics (PK) of MP1032 in a PK subset of patients and the effect of 
MP1032 on biomarker levels.
This study will be executed during a worldwide outbreak of COVID-19, resulting in capacity 
issues at many medical facilities and concerns about the safety of healthcare providers caring for 
these seriously sick patients. Consequently, this study is designed to minimize the burden on 
clinical sites, including minimizing the number of required assessments and interventions. To 
allow close monitoring and oral administration, the intended patient population shall include 
only hospitalized patients with COVID-19 that do not require intubation at the time of screening 
and/or randomization. Only adults shall be included. Additionally, pregnant and breastfeeding 
women shall be excluded.
The study drugs will be indistinguishable to blinded study personnel to limit bias in study 
assessments. Most interventions and assessments may be accomplished in conjunction with the 
schedule dictated by SoC. An independent data monitoring committee (DMC) will be established 
by the sponsor or designee to review accumulating study data at regular intervals (as per the
DMC charter) throughout the study to ensure the safety of patients and review overall study 
conduct.
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6
STUDY OBJECTIVES AND ENDPOINTS 
6.1
Study Objectives 
The primary objective of this study is:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on Day 14 on 
disease progression in patients with moderate to severe COVID-19
The secondary objectives of this study are:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on Day 28 on 
disease progression in patients with moderate to severe COVID-19
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on disease 
resolution on Day 14 and Day 28
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on the mortality rate 
and other specific COVID-19 related characteristics
x
To assess the safety of MP1032 (eg, AEs and laboratory abnormalities)
x
To assess the PK of MP1032 on Day 1 (single dose) and Day 7 (steady state) in a PK 
subset of patients
The exploratory objectives of this study are:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on some additional 
COVID-19 related characteristics
x
To evaluate the health-related quality of life (HRQoL) of patients treated MP1032 plus
SoC compared with placebo plus SoC
x
To evaluate biomarker levels
6.2
Study Endpoints 
The primary efficacy endpoint of this study is:
x
Proportion of patients with disease progression on Day 14. Disease progression is defined 
as the proportion of patients who are not alive or who have respiratory failure. 
Respiratory failure is defined as patients who have a score of 2, 3, or 4 on the National 
Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale (see below). 
The key secondary efficacy endpoints of this study are:
x
Proportion of patients with disease progression on Day 28. Disease progression is defined 
as the proportion of patients who are not alive or who have respiratory failure. 
Respiratory failure is defined as patients who have a score of 2, 3, or 4 on the NIAID 8-
point ordinal scale (see below). 
x
Proportion of patients with disease resolution on Day 28. Disease resolution is defined as 
patients who are alive and have a score of 6, 7, or 8 on the NIAID 8-point ordinal scale. 
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x
All-cause mortality rate at Day 28
x
Change of clinical status related to COVID-19 on Day 28 compared with baseline 
according to the following NIAID 8-point ordinal scale:
1. Death
2. Hospitalized, on invasive ventilation (mechanical ventilator and/or extracorporeal 
membrane oxygenation [ECMO])
3. Hospitalized, on non-invasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 
(COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen and no longer requires ongoing 
medical care (used if hospitalization was extended for infection-control reasons)
7. Not hospitalized, limitation on activities, and/or requiring home oxygen
8. Not hospitalized, no limitations on activities
Please note: Patients requiring oxygen before COVID-19 and returning to baseline oxygen use 
will be considered improved (ie, not requiring supplemental oxygen). Patients with a limitation 
on activities before COVID-19 and returning to baseline activity will be considered improved. In 
case of death before Day 14 or Day 28, the patient will be considered with the NIAID score for 
death (score of 1) on the date of death in the analysis.
The other secondary endpoints of this study are:
x
Proportion of patients with disease resolution on Day 14. Disease resolution is defined as 
patients who are alive and have a score of 6, 7, or 8 on the NIAID 8-point ordinal scale. 
x
All-cause mortality rate at Day 14 and Day 60
x
Change of clinical status related to COVID-19 on Day 14 compared with baseline 
according to the NIAID 8-point ordinal scale as listed above
x
Proportion of patients requiring invasive ventilation (mechanical ventilator and/or 
ECMO), or who are not alive on Day 14 or Day 28 
x
Proportion of patients in each category of the NIAID 8-point ordinal scale
x
Time to (first) improvement of at least 1 category on the NIAID 8-point ordinal scale 
(until Day 28). Patients who did not improve at least 1 category on the NIAID scale or 
die before Day 28 will be censored at Day 28.
x
The odds ratio between MP1032 and SoC and placebo and SoC for the number of 
patients with clinical status improvement from baseline on the NIAID 8-point ordinal 
scale (ie, an improvement of at least 1 category) at Day 14 and Day 28 
x
Total duration of hospitalization on Day 28 and Day 60 (from baseline to discharge; with 
death censored on the last day of the observed period – at Day 28 or Day 60, 
respectively)
x
Proportion of patients alive and testing negative for COVID-19 on Day 14, Day 28, and 
Day 60
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x
Safety and tolerability assessed by:
o
Cumulative incidence of TEAEs (summarized by seriousness, severity, 
relationship to the study medication, outcome, and duration) 
o
Vital sign parameters 
o
Clinical laboratory parameters
o
Physical examination findings
x
MP1032 plasma concentrations and PK parameters (if possible) including maximum 
observed plasma concentration, area under the concentration-time curve, elimination 
parameters, apparent body clearance, apparent volume of distribution, trough 
concentration, average observed plasma concentration at steady state, and other relevant 
PK parameters assessed via MP1032 plasma exposure on Day 1 and Day 7 in a PK subset 
of patients
Exploratory endpoints of this study are:
x
Change in saturation of oxygen (SpO2)/fraction of inspired oxygen (FiO2) ratio (for 
patients alive) on Day 14 or Day 28 compared with baseline
x
Total number of days in the intensive care unit (ICU)
x
Duration of invasive mechanical ventilation 
x
Duration of ECMO
x
Time to recovery from COVID-19 symptoms (stuffy or runny nose, sore throat, red or 
irritated eyes, shortness of breath, cough, low energy or tiredness, muscle or body aches, 
headache, chills or shivering, feeling hot or feverish, nausea, and number of times of 
vomit, times of diarrhea, sense of smell, sense of taste in the last 24 hours) at Day 14, 
Day 28, and Day 60
x
Change from discharge in the EuroQol (EQ) index value and EQ visual analog scale 
(VAS) based on the EuroQol-5D-5L (EQ-5D-5L) questionnaire (Appendix 2) at Day 60
x
Change from baseline in biomarker levels potentially including, but not limited to, 
cytokines (eg, C-reactive protein, interleukin [IL]-1E, IL-6, TNF-Į, and IFN-J) and other 
coagulation/inflammatory biomarkers (eg, D-dimer and ferritin)
7
INVESTIGATIONAL PLAN 
7.1
Description of Overall Study Design and Plan 
This is a Phase IIa, randomized, double-blind, placebo-controlled, multicenter, proof-of-concept
study designed to assess the efficacy and safety of 300 mg MP1032 BID plus SoC versus
placebo plus SoC in hospitalized adults with moderate to severe COVID-19.
Approximately 40 sites worldwide will participate in this study.
Approximately 140 patients will be screened to randomize approximately 120 patients (see 
Section 15.1 for determination of sample size) in 2:1 ratio as follows: 
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x
Arm A (300 mg MP1032 BID plus SoC): approximately 80 patients
x
Arm B (placebo BID plus SoC): approximately 40 patients
The stratification factor for randomization will include baseline COVID-19 severity (moderate 
versus severe) and age-class (aged 65 years versus >65 years). COVID-19 severity will be 
determined using the following criteria:
x
Moderate COVID-19:
o
Positive SARS-CoV-2 testing by standard reverse-transcription polymerase 
chain reaction (RT-PCR) assay or equivalent test 
o
Symptoms of moderate illness with COVID-19, which could include any 
symptom of mild illness or shortness of breath with exertion
o
Clinical signs suggestive of moderate illness with COVID-19, such as 
respiratory rate 20 breaths per minute, SpO2 >93% (on room air at sea level, 
if possible), heart rate 90 beats per minute 
o
No clinical signs indicative of severe or critical COVID-19
x
Severe COVID-19:
o
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
o
Symptoms suggestive of severe systemic illness with COVID-19, which could 
include any symptom of moderate illness or shortness of breath at rest, or 
respiratory distress
o
Clinical signs indicative of severe systemic illness with COVID-19, such as 
respiratory rate 30 breaths per minute, heart rate 125 beats per minute, 
SpO2 93% (on room air at sea level, if possible), partial pressure of oxygen 
(PaO2)/FiO2 <300, or diagnosed with ARDS (according to the Berlin 
definition; see Table 3
o
No criteria met for critical COVID-19
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will 
be measured when the patient is on room air at sea level (ie, no supplemental oxygen, if possible) 
and at rest for at least 5 minutes. If possible, the site should collect the information from each 
patient at the same time each day (±1 hour). 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition (eg, 
emphysema, COPD, pulmonary arterial hypertension [PAH], idiopathic pulmonary 
fibrosis [IPF], etc) must be considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19 severity, the investigator 
should contact the medical monitor.
Each site will treat all patients with SoC for the duration of the study. The selected SoC will be 
used in accordance with the hospital’s SoC procedures and may include drugs under an 
emergency use authorization.
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This study consists of 3 periods: (1) screening, (2) treatment, and (3) follow-up. During the 
screening period, each potential patient (or patient’s legally acceptable representative) will 
provide informed consent before starting any study-specific procedures. The randomization of 
patients to treatment groups will be performed centrally by an interactive web-response 
system (IWRS) using a randomization scheme that will be developed by an unblinded, 
independent statistician. During the treatment period, randomized patients will be provided their 
assigned treatment and assessments according to the protocol. All patients will be treated for 
28 days unless the study drug is discontinued for safety reasons. If the patient is discharged home 
before Day 28, the study team will provide the patient with the remainder of the assigned blinded 
study drug kit(s) to take home along with instructions on how to continue treatment at home on 
the day-of-discharge; for these patients, treatment compliance will be conducted via a diary. If 
the patient does not feel comfortable to complete the diary, the site will alternatively provide the 
patient with the option to be called, twice a day, to confirm that the study drug is taken as 
instructed. The treatment period will end with the Day 28 (End of Treatment Visit) assessments. 
The follow-up period will consist of Day 60 (Follow-up Visit) assessments.
Please note: Patients will be assessed while hospitalized. If patients are discharged from the 
hospital, they must have study visits at Day 7, Day 8 (in case of early discharge), Day 14,
Day 21, Day 28, Day 60, and at Early Termination (as applicable) as an outpatient visit (ie, at the 
study site). Patients discharged early will continue to receive study drug through Day 28. For 
patients discharged early, it is sufficient to conduct the visits Day 2 to Day 6 and Day 9 to 
Day 13 (as applicable) as a telephone/virtual call (the patient’s caregiver may assist during the 
telephone/virtual call). All telephone/virtual call visits must be conducted by a physician.
The study duration for an individual patient will be as follows:
x
Screening period: up to 7 days
x
Treatment period: 28 consecutive days (ie, Day 1 to Day 28)
x
Follow-up period: 32 days after Day 28 (ie, Day 60)
As such, the approximate study duration (including screening and the follow-up period) for an 
individual patient is up to 67 days (±3 days).
An independent DMC will be established by the sponsor or designee to review accumulating 
study data at regular intervals (as per the DMC charter) throughout the study to ensure the safety 
of patients and review overall study conduct. The DMC can recommend in writing to the sponsor
whether to continue, modify, or stop the clinical study on the basis of safety considerations (see 
Section 15.8 for further details).
No interim analysis is planned.
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7.2
Discussion of Study Design 
This study is designed to investigate the efficacy and safety of 300 mg MP1032 BID plus SoC 
versus placebo plus SoC treatment in hospitalized adults with confirmed moderate to severe 
COVID-19, the disease caused by SARS-CoV-2 infection. 
This study will be executed during a worldwide outbreak of COVID-19 that has resulted in 
capacity issues at many medical facilities. Additionally, the highly contagious nature of 
COVID-19 (compounded by a shortage of personal protective equipment) has caused concerns 
about the safety of healthcare providers caring for these seriously sick patients. Consequently, 
this study is designed to minimize any additional burden on clinical sites, including minimizing 
the number of assessments and interventions that the study will require in addition to SoC, while 
still ensuring the safety of patients.
This study will be double-blinded and placebo-controlled to limit bias in study assessments. 
Either MP1032 or placebo will be administered as add-on therapy to SoC. Most interventions 
and assessments may be accomplished in conjunction with SoC, without requiring additional 
hospital visits or resources.
The dose, dosing regimen, and duration of treatment planned for this study (300 mg MP1032
BID for 28 days) were selected on the basis of:
x
The highest repeated dose was 300 mg MP1032 BID applied to both healthy volunteers 
(7 days) and psoriasis patients (3 months). MP1032 was well tolerated in all studies and 
safety analyses did not reveal any clinically important safety issues (see the current 
version of the IB for further information).
x
Acute treatment for symptoms of respiratory viral infections is typically from 14 to 
28 days. 
x
A 28-day treatment period was selected because it is a standard duration of time included 
in the WHO R&D Blueprint for COVID-19 (WHO 2020d).
All patients will be treated for 28 days (unless the study drug is discontinued for safety reasons)
to provide a fixed duration of treatment across all patients. As it is impractical to require the 
study site to continue to hospitalize patients who no longer require hospital care, if the patient is 
discharged home before Day 28, the study team will provide the patient with the remainder of 
the assigned blinded study drug kit(s) to take home along with instructions on how to continue 
treatment at home on the day-of-discharge. Any patient who is discharged during the study 
should complete the day-of-discharge assessments before release from the hospital as noted in 
the Schedule of Assessments (Table 1). Patients who progress to the use of an invasive 
ventilation (mechanical ventilator and/or ECMO) or who can no longer swallow the study drug
(>2 days [ie, 2-day interruption is acceptable]) must discontinue the study drug; but whenever 
possible, the study assessments will be performed on Day 8, Day 14, Day 21, Day 28, and Day 
60.
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This proof-of-concept study will neither include pregnant nor breastfeeding females. In 
reproduction toxicity studies of MP1032 on fertility and early embryonic as well as on embryo-
fetal development, no pathological effects were found. Genotoxicity testing as well as the 
repeated dose toxicity studies (up to 12 months in dogs and 6 months in rats) did not indicate any 
toxicological effects. Hence, MP1032 is considered as IMP with unlikely human 
teratogenicity/fetotoxicity in early pregnancy (see the current version of the IB for more 
information). However, due to the early clinical stage of development, only women who are 
neither pregnant nor breastfeeding will be randomized in this study. Women of childbearing 
potential (WOCBP) and non-sterile male patients with female partners who are WOCBP will be 
required to use a highly effective method of contraception from the time of first dose of study 
medication until at least 30 days after the last dose of study medication.
7.3
End of Study  
A patient will have fulfilled the requirements for study completion if/when the patient has 
completed all study periods, including Day 60 as indicated in the Schedule of Assessments 
(Table 1).
The end of the study will be the last patient’s last visit (ie, Day 60) as indicated in the Schedule 
of Assessments (Table 1).
8
SELECTION OF STUDY POPULATION 
Section 7.1 provides information regarding number of patients planned to be randomized.
8.1
Inclusion Criteria 
Individuals must meet all of the following criteria to be included in the study:
1. The patient must be willing and able to give informed consent to participate in the study 
and to adhere to the procedures stated in the protocol or, for adults incapable of 
consenting due to their medical condition (eg, too weak or debilitated, severe shortness of 
breath) or due to literacy issues, the patient’s legally authorized representative (LAR) 
must be willing and able to give informed consent on behalf of the patient to participate 
in the study as permitted by local regulatory authorities, institutional review 
boards (IRBs)/independent ethics committees (IECs), or local laws.
2. The patient is male or female adult aged 18 years (as per local laws) at the time of 
giving informed consent.
3. The patient is admitted to a hospital and has a positive SARS-CoV-2 test by standard 
RT-PCR assay or equivalent test. Please note: If the patient has a previous confirmation 
of SARS-CoV-2 (within 7 days of Day 1), the SARS-CoV-2 test at screening is not 
required. 
4. The patient has the presence of any symptom(s) suggestive of moderate or severe 
systemic illness with COVID-19 on Day 1, such as presence of fever (38.0°C 
[100.4°F] by any route), loss of smell or taste, cough, sore throat, malaise, headache, 
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muscle pain, gastrointestinal symptoms, shortness of breath upon exertion and/or at rest, 
or respiratory distress.
5. The patient has the presence of moderate to severe clinical signs indicative of moderate 
or severe illness with COVID-19 on Day 1: 
a.
Moderate: 
i. Clinical signs suggestive of moderate illness with COVID-19, such as 
respiratory rate 20 breaths per minute, SpO2 >93% (on room air at sea 
level, if possible), heart rate 90 beats per minute 
ii. No clinical signs indicative of severe or critical COVID-19
b. Severe: 
i. Clinical signs suggestive of severe systemic illness with COVID-19, such 
as respiratory rate 30 breaths per minute, heart rate 125 beats per 
minute, SpO2 93% (on room air at sea level, if possible), 
PaO2/FiO2 <300, or diagnosed with ARDS (according to the Berlin 
definition; see Table 3)
ii. No criteria met for critical COVID-19
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition 
(eg, emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19
(unless the patient meets the definition for critical COVID-19). For questions related to 
COVID-19 severity, the investigator should contact the medical monitor.
6. The patient does not require hemodialysis (chronic) or any renal replacement therapies at 
screening or Day 1.
7. The patient is able to swallow the study drug (hard gelatin capsules). 
8. The patient agrees to minimize strong sun exposure (sunbathing) and strong ultraviolet 
exposure during the course of the study. Additionally, during the study, patients must 
agree to use sunscreen when spending an extended period outdoors.
9. Men whose sexual partners are WOCBP must agree to comply with 1 of the following 
contraception requirements from the time of first dose of study medication (Day 1) until 
at least 30 days after the last dose of study medication:
a.
Vasectomy with documentation of azoospermia. 
b. Sexual abstinence (defined as refraining from heterosexual intercourse from the 
time of first dose of study medication until at least 30 days after the last dose of 
study medication)
c. Male condom plus partner use of 1 of the contraceptive options below: 
contraceptive subdermal implant; intrauterine device or intrauterine system; oral 
contraceptive, either combined or progestogen alone; injectable progestogen; 
contraceptive vaginal ring; percutaneous contraceptive patches. 
The above is an all-inclusive list of those methods that meet the following definition of 
highly effective: having a failure rate of <1% per year when used consistently and
correctly and, when applicable, in accordance with the product label. For non-product 
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methods (eg, male sterility), the investigator will determine what is consistent and correct 
use. The investigator is responsible for ensuring that patients understand how to properly 
use these methods of contraception. 
10. WOCBP must agree to comply with 1 of the following contraception requirements from 
the time of first dose of study medication (Day 1) until at least 30 days after the last dose 
of study medication:
a.
Sexual abstinence (defined as refraining from heterosexual intercourse from the 
time of first dose of study medication until at least 30 days after the last dose of 
study medication)
b. Use of 1 of the contraceptive options below plus use of a condom by male 
partner: contraceptive subdermal implant; intrauterine device or intrauterine 
system; oral contraceptive, either combined or progestogen alone; injectable 
progestogen; contraceptive vaginal ring; percutaneous contraceptive patches. 
c. Vasectomy of male partner with documentation of azoospermia. 
The above is an all-inclusive list of those methods that meet the following definition of 
highly effective: having a failure rate of <1% per year when used consistently and 
correctly and, when applicable, in accordance with the product label. The investigator is 
responsible for ensuring that patients understand how to properly use these methods of 
contraception. Women of non-reproductive potential are defined as: 
a.
Premenopausal females with 1 of the following: documented tubal ligation; 
documented hysteroscopic tubal occlusion procedure with follow-up confirmation 
of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy. 
b. Postmenopausal defined as 12 months of spontaneous amenorrhea [in 
questionable cases a blood sample with simultaneous follicle stimulating hormone 
and estradiol levels consistent with menopause (refer to laboratory reference 
ranges for confirmatory levels)]. Women on hormone replacement therapy (HRT) 
and whose menopausal status is in doubt will be required to use 1 of the highly 
effective contraception methods listed above if they wish to continue their HRT 
during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before randomization. 
8.2
Exclusion Criteria 
Individuals meeting any of the following criteria are ineligible to participate in this study: 
1. The patient, in the opinion of the investigator, is not likely to survive for 48 hours 
beyond Day 1. 
2. The patient has a diagnosis of asymptomatic COVID-19, mild COVID-19, or critical 
COVID-19 on Day 1. 
a.
Asymptomatic COVID-19 is defined as a patient with a positive SARS-CoV-2
test by standard RT-PCR assay or equivalent test but not experiencing symptoms. 
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b. Mild COVID-19 is defined as a patient with a positive SARS-CoV-2 test by 
standard RT-PCR assay or equivalent test and experiencing symptoms of mild 
illness but no clinical signs indicative of moderate, severe, or critical COVID-19.
c.
Critical COVID-19 is defined as a patient with a positive SARS-CoV-2 test by 
standard RT-PCR assay or equivalent test and experiencing at least 1 of the 
following: shock defined by systolic blood pressure <90 mm Hg or diastolic 
blood pressure <60 mm Hg, or requiring vasopressors; respiratory failure 
requiring endotracheal intubation and invasive mechanical ventilation, oxygen 
delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via 
reinforced nasal cannula at flow rates >20 L/min with fraction of delivered 
oxygen 0.5), non-invasive positive pressure ventilation, ECMO, or clinical 
diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, 
but preceding therapies not able to be administered in setting of resource 
limitation), and/or multi-organ dysfunction/failure.
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition 
(eg, emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19
(unless the patient meets the definition for critical COVID-19). For questions related to 
COVID-19 severity, the investigator should contact the medical monitor.
3. The patient has a Child Pugh score  C.
4. The patient has a documented medical history of infection with hepatitis A, B, or C at 
screening or Day 1.
5. The patient has a documented medical history of infection with human
immunodeficiency virus and has a detectable viral load and CD4 count <500 cells/μL. 
6. The patient has a documented active infection with tuberculosis at screening or Day 1.
7. The patient has clinically significant electrocardiogram (ECG) abnormalities at screening.
8. A female patient who is pregnant, planning to become pregnant during the study,
breastfeeding, or has a positive pregnancy test at screening (by serum) or before dosing 
on Day 1 (by urine) as determined by human chorionic gonadotrophin (hCG) tests.
9. The patient is planning to donate or bank ova or sperm from Day 1 until 30 days after the 
last dose of study drug.
10. The patient has a known history of drug or alcohol abuse within 6 months of study start 
that would interfere with the patient’s participation in the study.
11. The patient has a history of sensitivity to any of the study medications, components 
thereof (eg, mannitol or gelatin), or a history of drug or other allergy that, in the opinion 
of the investigator or medical monitor, would contraindicate their participation.
12. The patient has participated in and/or plans to participate in another clinical study using 
an investigational product within the following period before the first dosing day in the 
current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the 
investigational product (whichever is longer).
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13. The patient will be transferred to another hospital that is not a study site within 72 hours.
Please note: If the investigator has admitting privileges to the transfer hospital, the patient 
may be considered for randomization.
14. The patient is employed by MetrioPharm, the contract research organization or clinical 
site involved in the clinical study.
15. The investigator makes a decision that study involvement is not in patient’s best interest, 
or the patient has any condition or critical illness, in the opinion of the investigator, that 
will not allow the protocol to be followed safely.
8.3
Rescreening 
Individuals who give informed consent to participate in the study but who do not subsequently 
meet all the requirements as outlined in the inclusion and exclusion criteria and therefore are not 
randomized (screen failures) may be rescreened. Such individuals may be allowed to rescreen 
only 1 time.
8.4
Study Withdrawal, Removal, and Replacement of Patients 
Patients who terminate the study before Day 28 will be asked to complete the day-of-discharge 
study procedures. Patients who terminate the study after Day 28 will be asked to complete the 
Day 60 study procedures. Please note: It is expected that patients who discontinue the study drug 
early remain in the study, whenever possible, until the completion of the Day 60 study 
procedures. If it is not possible to follow-up with the patient until Day 60, then follow-up should 
occur until at least Day 28.
Once a patient is withdrawn from the study, the patient may not return to the study.
A patient may voluntarily withdraw or be withdrawn from the study at any time for the following 
reasons: 
x
patient withdrawal of consent (at any time, a patient's participation in the study may be 
terminated at his/her request)
x
lost to follow-up: the patient stopped coming for visits, and study personnel were unable 
to contact the patient. 
Please note: In cases in which the patient is deemed lost to follow-up, the investigator or 
designee must make every effort to regain contact with the patient (eg, telephone calls, letter to 
the patient’s last known mailing address, or local equivalent methods). In cases where the 
patient’s LAR provides informed consent on behalf of the patient, the study site should attempt 
to contact the LAR. Additionally, the study site should attempt to regain contact with the patient 
using the alternative contact information provided by the patient/LAR at the time of informed 
consent. These contact attempts must be documented in the patient’s medical records.
The reason and date for patient withdrawal from the study must be recorded on the electronic 
case report form (eCRF).
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Additionally, the sponsor or DMC may stop the study at any time for safety, regulatory, legal, or 
other reasons aligned with good clinical practice (GCP). This study may be terminated at the 
discretion of the sponsor or any regulatory agency. An investigator may elect to terminate or stop 
the study at his or her study site for any reason, including safety or low recruitment.
9
TREATMENTS 
9.1
Details of Study Drugs 
Both MP1032 hard gelatin capsules 50 mg and matching placebo capsules will be supplied as 
14-day blinded study drug kits. Each kit will also include reserve supply for 1 additional day. 
Thus, each kit will include 180 capsules in total. IMP will be packaged and labelled according to 
all applicable local legal requirements. Study drug must be stored in a controlled environment at 
the study site’s pharmacy where storage temperature is monitored, and access is limited to 
authorized personnel only. In the pharmacy, both MP1032 capsules and matching placebo 
capsules must be stored in the primary and/or secondary packaging at room temperature (15°C to
25°C [59°F to 77°F]) and protected from light. If the patient is discharged home before Day 28,
the study team will provide the patient with the remainder of the assigned blinded study drug 
kit(s) to take home along with instructions on the day-of-discharge.
Further details of the blinded study drug kits will be described in a Pharmacy Manual.
9.2
Dosage Schedule 
All randomized patients will receive study drug from Day 1 to Day 28 according to their 
assigned treatment and according to the randomization scheme. 
Please note: Patients who remain hospitalized after 28 days of consecutive treatment with study 
drug are not eligible for additional treatments with study drug. Patients will receive 6 capsules in 
the morning and 6 capsules in the evening (ie, approximately every 12 hours, approximately at 
the same time every day, and at least 8 hours apart) according to their randomized treatment arm 
assignment as described below: 
x
Arm A: MP1032 (300 mg [6 × MP1032 hard gelatin capsules 50 mg] BID) for oral 
administration
x
Arm B: 6 × placebo capsules (ie, matching MP1032 hard gelatin capsules 50 mg) BID for 
oral administration 
In Arm A, the planned total daily dose of MP1032 is 600 mg. In Arm B, the planned total daily 
dose of MP1032 is 0 mg.
Study drug will be administered to each patient with water (ad libitum) for oral administration.
For all patients (except on Day 1 and Day 7 for patients in the PK subset): Patients should not eat 
within the 30 minutes before planned study drug administration and within the 30 minutes after 
study drug dosing, when feasible. However, if a patient has eaten within the 30 minutes before 
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their planned study drug administration, study drug dosing may proceed. The study site should 
record the date and time of dosing (recorded as the time when the first capsule is administered).
For patients in the PK subset on Day 1 and Day 7 only: Patients should not eat within the 4 hours
before planned study drug administration and within the 120 minutes after study drug dosing, 
when feasible. Thus, study drug should be administered in fasted state ( 4 hours), when 
feasible. However, if a patient has eaten within the 4 hours before their planned administration, 
study drug dosing may proceed. The patient’s fed or fasted state, as well as food intake (yes/no) 
within the 120 minutes after study drug dosing should be recorded. The PK samples should be 
collected as planned regardless of the patients’ fasted/fed state. The study site should record the 
date and time of dosing (recorded as the time when the first capsule is administered).
Any missed dose study drug may be administered as soon as possible and the next scheduled 
dose may be administered according to the planned schedule as long as the doses are at least 6 to 
8 hours apart. If study drug administration is interrupted for >2 days, the investigator should 
notify the medical monitor to determine if the study drug administration can be resumed.
Patients will be asked to abstain from the following products that may potentially affect their 
safety and/or the PK profile of the study drug: 
x
soft or hard drugs (including cannabis) from screening and throughout the study 
x
smoking or using electronic cigarettes while admitted to the hospital
x
consumption of alcohol-based products will be prohibited from screening until the final
dose of study drug
9.3
Measures to Minimize Bias: Randomization and Blinding
Randomization 
The randomization of patients to treatment groups will be performed centrally by an IWRS using 
a randomization scheme that will be produced by an unblinded, independent statistician. During 
the randomization process, IWRS will assign a randomization number. Each patient will be 
assigned one kit number at randomization and a second kit number at the Day 14 visit. The study 
drug kits will contain the respective blinded treatment available at the study site. Further 
information on IWRS process will be provided in the IWRS Manual.
Approximately 120 patients will be randomly assigned (2:1) as follows: 
x
Arm A (300 mg MP1032 BID plus SoC): approximately 80 patients
x
Arm B (placebo BID plus SoC): approximately 40 patients
The stratification factor for randomization will include baseline COVID-19 severity (moderate 
versus severe) and age-class (aged 65 years versus >65 years). COVID-19 severity will be 
determined using the following criteria:
x
Moderate COVID-19:
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o
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
o
Symptoms of moderate illness with COVID-19, which could include any 
symptom of mild illness or shortness of breath with exertion
o
Clinical signs suggestive of moderate illness with COVID-19, such as respiratory 
rate 20 breaths per minute, SpO2 >93% (on room air at sea level, if possible),
heart rate 90 beats per minute 
o
No clinical signs indicative of severe or critical COVID-19
x
Severe COVID-19:
o
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
o
Symptoms suggestive of severe systemic illness with COVID-19, which could 
include any symptom of moderate illness or shortness of breath at rest, or 
respiratory distress
o
Clinical signs indicative of severe systemic illness with COVID-19, such as 
respiratory rate 30 breaths per minute, heart rate 125 beats per minute, SpO2
93% (on room air at sea level, if possible), PaO2/FiO2 <300, or diagnosed with 
ARDS (according to the Berlin definition; see Table 3)
o
No criteria met for critical COVID-19
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will 
be measured when the patient is on room air at sea level (ie, no supplemental oxygen, if possible) 
and at rest for at least 5 minutes. If possible, the site should collect the information from each 
patient at the same time each day (±1 hour). 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition (eg, 
emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19 (unless the 
patient meets the definition for critical COVID-19). For questions related to COVID-19 severity, 
the investigator should contact the medical monitor.
Blinding
The study is double-blinded. Study drug will be identical in appearance and labeled in a blinded 
manner. All patients (and their LARs), investigators, and all study staff involved in the conduct 
of the study (including sponsor personnel or sponsor designees), including data management and 
biostatistics, will be blinded to treatment assignment. 
Exception: An unblinded, independent statistician will be assigned to produce the randomization 
schedule and unblinded tables, figures, and listings for the DMC. The unblinded statistician will 
not otherwise participate in study procedures.
In the event that emergency unblinding is required for a given patient because of AEs or 
concerns for the patient’s safety or well-being, the investigator may break the randomization 
code for the patient via the IWRS, by which system the unblinding will be captured. The 
investigator is responsible for notifying the medical monitor and/or sponsor of such an event as 
soon as possible. The unblinding and its cause will also be documented in the eCRF.
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If an investigator becomes unblinded to a given patient’s study drug, that patient will be 
discontinued from the study drug unless there are ethical reasons for that patient not to be 
discontinued; approval from the sponsor’s medical monitor must be obtained in such instances.
9.4
Treatment Modifications and Discontinuations 
Dose reductions and adjustments are not permitted; any dose reductions and adjustments that 
occur will be recorded and considered protocol deviations.
Delays and omissions of study drug administration because of medical or non-medical reasons 
are allowed. All delays and omissions of study drug that occur during the study will be recorded 
and considered protocol deviations.
All patients will be treated for 28 days unless the study drug is discontinued for safety reasons or 
the patient withdraws consent. If a patient is discontinued from the study drug for any reason, the 
study site must immediately notify the medical monitor. 
A patient may voluntarily discontinue the study drug or be discontinued from the study drug at 
any time for reasons including, but not limited to, the following:
x
progressive disease (related to COVID-19). Please note: Patients who progress to the use 
of an invasive ventilation (mechanical ventilator and/or ECMO) or who can no longer 
swallow the study drug (>2 days [ie, 2-day interruption is acceptable]) must discontinue 
the study drug; but whenever possible, the study assessments will be performed on Day 8,
Day 14, Day 21, Day 28, and Day 60.
x
unacceptable AE and/or SAE
x
patient withdrawal of consent (at any time, a patient's participation in the study may be 
terminated at his/her request)
x
on the basis of the investigator’s clinical judgment 
x
general or specific changes in the patient's condition that render him/her ineligible for 
further treatment according to the inclusion/exclusion criteria
x
patient fails to adhere to the protocol requirements (eg, drug noncompliance)
x
lost to follow-up: the patient stopped coming for visits, and study personnel were unable 
to contact the patient. 
Please note: In cases in which the patient is deemed lost to follow-up, the investigator or 
designee must make every effort to regain contact with the patient (eg, telephone calls, 
letter to the patient’s last known mailing address, or local equivalent methods). In cases 
where the patient’s LAR provides informed consent on behalf of the patient, the study 
site should attempt to contact the LAR. Additionally, the study site should attempt to
regain contact with the patient using the alternative contact information provided by the 
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patient/LAR at the time of informed consent. These contact attempts must be documented 
in the patient’s medical records.
x
pregnancy, as indicated in Section 12.6.5.
The reason and date for the patient’s discontinuation from study drug must be recorded on the 
eCRF.
Please note: It is expected that patients who discontinue study drug early remain in the study, 
whenever possible, until the completion of the Day 60 study procedures. If it is not possible to 
follow-up with the patient until Day 60, then follow-up should occur until at least Day 28.
9.5
Treatment Accountability and Compliance 
The pharmacist or other designated individual will maintain records of study drug delivered to 
the study site, the inventory at the study site, the distribution to and use by each patient, and the 
return of materials to the sponsor for storage or disposal. These records should include dates, 
quantities, batch/serial numbers, expiration dates, in-clinic temperature log, and unique code 
numbers assigned to the product and patients.
During hospitalization, the administration of the study drug will be performed by the investigator 
(or qualified blinded designee) to ensure compliance. If the patient is discharged home before 
Day 28, the study team will provide the patient with the remainder of the assigned blinded study 
drug kit(s) to take home along with instructions to continue treatment at home; for these patients, 
treatment compliance will be conducted via a diary. If the patient does not feel comfortable to 
complete the diary, the site will alternatively provide the patient with the option to be called, 
twice a day, to confirm that the study drug is taken as instructed. Patients are to be reminded of 
the importance of compliance with their assigned regimen, with an emphasis on taking their 
study drug on schedule and maintaining the prescribed interval between doses.
Investigators will maintain records that adequately document that the patients were provided 
with the correct study drug kit(s) and reconcile the products received from the drug dispensing
center. Investigational product will not be returned to the sponsor until accountability has been 
fully monitored.
Noncompliance is defined as taking <80% or >120% of study drug. Discontinuation for 
noncompliance is at the investigator’s discretion and is to be noted on the eCRF.
9.6
Prior and Concomitant Medications 
Restricted prior medications are provided in Section 8.2.
All medications and other treatments taken by the patient during the study, including those 
treatments initiated before the start of the study, must be recorded on the eCRF.
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Medications taken by or administered to the patient for the period before screening will be 
recorded in the eCRF. After the screening visit, medications are generally permitted; however, 
the following therapies are expressly prohibited during the screening and treatment periods and 
up through the end of the follow-up period (ie, up through Day 28):
x
an investigational product from another clinical study 
Any medication or therapy that is taken by or administered to the patient during the course of the 
study must be recorded in the eCRF. The entry must include the dose, regimen, route, indication, 
and dates of use.
10
STUDY PROCEDURES 
Table 1 outlines the timing of procedures and assessments to be performed throughout the study. 
Section 12.5 specifies clinical laboratory assessment samples to be obtained. See Section 11,
Section 12, Section 13, and Section 14 for additional details regarding efficacy, safety, PK, other
assessments, respectively.
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Table 1:
Schedule of Assessments
Study Period
Screening 
Period
Treatment Period
Follow-up Period
-
Visit Name
Screeninga
Day 1a
Days 2 to 
13b
Day 14b
Day 21b
Day 28
(End of 
Treatment 
Visit)b
Day 60
(Follow-up Visit)b /
Early Study 
Termination after 
Day 28b
Day of Discharge / 
Early Study 
Termination before 
Day 28b
Study Day (window)
Day -7 to 
Day -1
Day 1 (NA) Days 2 to 
13 (NA)
Day 14
(±2 days)
Day 21
(±2 days)
Day 28 
(±3 days) Day 60 (±3 days)
Day of Discharge
Informed consentc
X
-
-
-
-
-
-
COVID-19 testingd
X
X
-
X
X
X
-
Demographicse
X
-
-
-
-
-
-
Medical/surgical historyf
X
X (updates 
only)
-
-
-
-
-
Inclusion/exclusion criteria
X
X
-
-
-
-
-
Complete physical examinationg
X
-
-
-
-
-
-
Limited physical examinationg
-
X
X (only 
Day 8 
[±3 days])r
X
X
-
X
Vital signsh
X
X
Xi
X
X
X
X
Height
X
-
-
-
-
-
-
Weight and BMI
X
X
-
X
X
X
X
Clinical laboratory assessments (hematology,
blood biochemistry, coagulation, and urinalysis)
X
X
X (only 
Day 8 
[±3 days])r
X (Days 14, 21, and 28)t
-
X
ECGj
X
-
-
-
-
-
-
Pregnancy test (WOCBP only)k
X
X
-
X
-
-
X (only if discharged 
before Day 14 or at 
Early Study 
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Study Period
Screening 
Period
Treatment Period
Follow-up Period
-
Visit Name
Screeninga
Day 1a
Days 2 to 
13b
Day 14b
Day 21b
Day 28
(End of 
Treatment 
Visit)b
Day 60
(Follow-up Visit)b /
Early Study 
Termination after 
Day 28b
Day of Discharge / 
Early Study 
Termination before 
Day 28b
Study Day (window)
Day -7 to 
Day -1
Day 1 (NA) Days 2 to 
13 (NA)
Day 14
(±2 days)
Day 21
(±2 days)
Day 28 
(±3 days) Day 60 (±3 days)
Day of Discharge
Termination before Day 
14)
Randomization via IWRS
-
X
-
-
-
-
-
Retrieve the 14-day blinded study drug kit via the 
study drug kit number assigned by IWRS
X
Xu
X (only if discharged 
before Day 14; NA for 
Early Study 
Termination )
Blood sample collection for biomarkers 
-
Xn
X (only 
Day 7)n
X (Days 14, 21, and 28)n
Xn
-
Administer blinded study drug BID
-
Xs
-
-
Provide remainder of the assigned blinded study 
drug kit(s) to the patient along with instructionsl
-
-
-
-
-
-
X (only if discharged 
during the treatment 
period; NA for Early 
Study Termination)
Provide patient with the diary and train patient on 
use of the diaryl
-
-
-
-
-
-
X (only if discharged 
during the treatment 
period; NA for Early 
Study Termination)
COVID-19 symptoms
X
X
-
X
X
X
X
COVID-19 severityo
X
X
-
-
-
-
-
Clinical status related to COVID-19 on the NIAID 
8-point ordinal scalep
X
X
X
X
X
X
X
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Study Period
Screening 
Period
Treatment Period
Follow-up Period
-
Visit Name
Screeninga
Day 1a
Days 2 to 
13b
Day 14b
Day 21b
Day 28
(End of 
Treatment 
Visit)b
Day 60
(Follow-up Visit)b /
Early Study 
Termination after 
Day 28b
Day of Discharge / 
Early Study 
Termination before 
Day 28b
Study Day (window)
Day -7 to 
Day -1
Day 1 (NA) Days 2 to 
13 (NA)
Day 14
(±2 days)
Day 21
(±2 days)
Day 28 
(±3 days) Day 60 (±3 days)
Day of Discharge
EQ-5D-5L questionnaireq
-
-
-
-
-
X
X (only if discharged/ 
early terminated before 
Day 60)
Blood sample collection (plasma) for PK (from the 
PK subset of approximately 30 patients who give 
optional consent)m
-
X
X (only 
Day 7)i
-
-
-
AEs
X
X
Prior and concomitant medications
X
X
Abbreviations: AE = adverse event; BID = twice daily; BMI = body mass index; COVID-19 = coronavirus 2019; ECG = electrocardiogram; eCRF = electronic case report form; 
EQ-5D-5L = EuroQol-5D-5L; IEC = independent ethics committee; ICU = intensive care unit; IRB = institutional review board; IWRS = interactive web-response system;
LAR = legally authorized representative; NA = not applicable; NIAID = National Institute of Allergy and Infectious Diseases; PK = pharmacokinetic; RT-PCR = reverse 
transcription-polymerase chain reaction; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus type 2; SoC = standard of care;
SpO2 = saturation of oxygen; WOCBP = women of childbearing potential.
a.
Those patients who are fully eligible (all screening assessments are available) can have Day 1 performed on the same day as screening. If screening and Day 1 are 
performed on the same day, visit procedures required for both visits do not need to be repeated. 
b.
Patients will be assessed while hospitalized. If patients are discharged from the hospital, they must have study visits at Day7, Day 8 (in case of early discharge), Day 14, 
Day 21, Day 28, Day 60, and at Early Termination (as applicable) as an outpatient visit (ie, at the study site). Patients discharged early will continue to receive study drug 
through Day 28. For patients discharged early, it is sufficient to conduct the visits Day 2 to Day 6 and Day 9 to Day 13 (as applicable) as a telephone/virtual call (the 
patient’s caregiver may assist during the telephone/virtual call). All telephone/virtual call visits must be conducted by a physician. Please note: In cases in which the 
patient is deemed lost to follow-up, the investigator or designee must make every effort to regain contact with the patient (eg, telephone calls, letter to the patient’s last 
known mailing address, or local equivalent methods). In cases where the patient’s LAR provides informed consent on behalf of the patient, the study site should attempt to 
contact the LAR. Additionally, the study site should attempt to regain contact with the patient using the alternative contact information provided by the patient/LAR at the 
time of informed consent. These contact attempts must be documented in the patient’s medical records.
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c.
The patient must give informed consent to participate in the study or, for adults incapable of consenting due to their medical condition (eg, too weak or debilitated, severe 
shortness of breath) or due to literacy issues, the patient’s LAR must be willing give informed consent on behalf of the patient to participate in the study as permitted by 
local regulatory authorities, IRBs/IECs, or local laws.
d.
At the screening visit, the local laboratory may perform COVID-19 testing by standard RT-PCR assay or equivalent test. At screening, a positive test must be available in 
order for the patient to be randomized on Day 1. If the patient has a previous confirmation of SARS-CoV-2 (within 7 days of Day 1), the SARS-CoV-2 test at screening is 
not required. On Day 1, Day 14, Day 28, and Day 60, samples will be sent to the central laboratory for COVID-19 testing by standard RT-PCR assay. The result of the 
COVID-19 tests (positive/negative) must be documented in the eCRF. Further details will be described in the laboratory manual. Please note: If COVID-19 tests are 
performed at unscheduled time points (eg, according to SoC), findings (ie, positive/negative result) must be recorded in the eCRF.
e.
Demographics will include sex, age, and race and/or ethnicity.
f.
Medical/surgical medical history includes all active and chronic diseases (eg, asthma and COPD), and any diseases diagnosed in the past 1 year (before screening) that the 
investigator considers clinically significant. Additional pre-existing conditions present at the time when informed consent is given and up to the time of first dosing 
(Day 1) are to be regarded as concomitant. Medical history will include documentation of social behaviors, including use of tobacco, nicotine (including use of electronic 
cigarettes), and soft or hard drugs (including cannabis), as well as alcohol consumption, if applicable. Smoking history also must be documented as part of medical history 
and includes never, light (<100 cigarettes/lifetime), active smoker, and former smoker (quit date). History of number packs/day, number of smoking years, and quitting 
time for former and active smokers must also be documented. Additionally, the investigators will document at screening the patient’s Charlson score via the Charlson 
Comorbidity Index (see Section 12.1 for further details) (Appendix 1).
g.
A complete physical examination will be performed at screening. Physical examinations will be performed by a physician. The complete physical examination includes 
head, eyes, ears, nose, and throat; heart; lungs; abdomen; skin; cervical and axillary lymph nodes; and neurological and musculoskeletal systems. A limited physical 
examination to verify continued patient eligibility and to follow-up regarding any change in medical history will be performed at the visits indicated above. Symptom-
driven, limited physical examinations may be performed as clinically indicated during the study (according to SoC).
h.
Vital signs include systolic and diastolic blood pressure, heart rate, respiration rate, SpO2, and body temperature. All vital signs will be measured after the patient has been 
resting for at least 5 minutes. Blood pressure measurements are to be taken in the same arm for the duration of the study. Moreover, additional vital signs may be 
performed as needed in case of any cardiac AE. 
i.
For patients who remain hospitalized only. 
j.
A 12-lead, resting ECG will be obtained locally at screening. At screening, the investigator must examine the ECG traces for clinically significant abnormalities that could 
exclude the patient from the study. ECGs should always be obtained in supine position after adequate rest (5 minutes). 
k.
For WOCBP, a serum sample for pregnancy testing must be collected at screening and a urine sample for pregnancy testing must be collected before the first dose on 
Day 1. Pregnancy tests must be negative for the patient to be randomized and treated. A urine pregnancy test will be repeated on Day 14 (± 7 days). If the patient is 
discharged before Day 14, urine pregnancy test at day of discharge should be done, and urine pregnancy test at Day 14 is not required. If the patient is discharged after 
Day 14, urine pregnancy test should be done at Day 14, and urine pregnancy test at day of discharge is not required (whichever comes first). Patients with a positive 
pregnancy test will be discontinued from study drug.
l.
Only for patients discharged before Day 28. If the patient does not feel comfortable to complete the diary, the site will alternatively provide the patient with the option to 
be called, twice a day, to confirm that the study drug is taken as instructed.
m. Plasma PK samples will be collected via sparse sampling from approximately 30 patients (who give optional consent) in a 2:1 ratio to assess the PK of MP1032 on Day 1 
(single dose) and Day 7 (steady state). A total of 16 samples will be collected relative to the first dose on Day 1 and the first dose on Day 7. Samples on Day 1 and Day 7 
will be collected predose (within 10 minutes before the first daily dose) and postdose at 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 8 hours (before 
next dose), and 24 hours before the next morning dose (if applicable), if possible. Patients who provide consent for the PK sampling, but are no longer hospitalized on 
Day 7, will not have Day 7 PK samples collected. 
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n.
Blood samples to be obtained on Day 1 (before the first study drug administration) and Days 7, 14, 21, 28, and 60. Blood samples for biomarkers must be collected on 
Days 7, 14, 21, 28, and 60 if a patient is still hospitalized. If a patient is discharged, the study site should arrange an outpatient visit (ie, at the study site) to accommodate 
the collection of blood samples for biomarkers on Days 7, 14, 21, 28, and 60. 
o.
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will be measured when the patient is on room air at sea level (ie, no 
supplemental oxygen, if possible) and at rest for at least 5 minutes. If possible, the site should collect the information from each patient at the same time each day 
(±1 hour). 
p.
Record the patient’s clinical status related to COVID-19 on the NIAID 8-point ordinal scale and also record the date and time for each individual component of the NIAID 
8-point ordinal scale including: invasive or non-invasive mechanical ventilation/ECMO start/stop, high-flow/mask oxygen start/stop, supplemental oxygen start/stop 
(nasal cannula, liter flow [and its conversion to FiO2], other delivery services), hospital discharge (whether with limitations or without limitations), hospitalization type 
(eg, transfer to ICU) start/stop, and (if applicable) death, cause of death (including relatedness to COVID-19), and date/time of death. If possible, the site should collect 
the information from each patient at the same time each day (±1 hour).
q.
The EQ-5D-5L (Appendix 2) is only required for discharged patients and at the following visits: day of discharge, Day 60, and Early Termination visit (if applicable). The 
EQ-5D-5L is not required for patients who remain hospitalized until study end.
r.
The limited physical examination and clinical laboratory assessments on Day 8 (± 3 days) will be collected in all patients who remain hospitalized. If the patient is 
discharged before Day 8 (± 3 days), these assessments should only be done if the physician determines during the outpatient visit (ie, at the study site) that the limited 
physical examination and clinical laboratory assessments are clinically indicated.
s.
For all patients (except on Day 1 and Day 7 for patients in the PK subset): Patients should not eat within the 30 minutes before planned study drug administration and 
within the 30 minutes after study drug dosing, when feasible. However, if a patient has eaten within the 30 minutes before their planned study drug administration, study 
drug dosing may proceed. The study site should record the date and time of dosing (recorded as the time when the first capsule is administered). For patients in the PK 
subset on Day 1 and Day 7 only: Patients should not eat within the 4 hours before planned study drug administration and within the 120 minutes after study drug dosing, 
when feasible. Thus, study drug should be administered in fasted state ( 4 hours), when feasible. However, if a patient has eaten within the 4 hours before their planned 
administration, study drug dosing may proceed. The patient’s fed or fasted state, as well as food intake (yes/no) within the 120 minutes after study drug dosing should be 
recorded. The PK samples should be collected as planned regardless of the patients’ fasted/fed state. The study site should record the date and time of dosing (recorded as 
the time when the first capsule is administered).
t.
The clinical laboratory assessments on Day 8 (± 3 days) and Day 21(± 2 days) will be collected in all patients who remain hospitalized. If the patient is discharged before 
Day 8 (± 3 days) or Day 21 (± 2 days), the physician should assess the patient at the outpatient visit (ie, at the study site). If the physician determines during the outpatient
visit (ie, at the study site) that the clinical laboratory assessments are clinically indicated, then the site should arrange to collect this assessment.
u.
The +2-day window does not apply to the retrieval of the 14-day blinded study drug kit as the second kit must be distributed at the latest on Day 14. 
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10.1
Informed Consent 
Before performing any study-related procedures, the investigator (or designee) will obtain 
informed consent from the patient to participate in the study or, for adults incapable of 
consenting due to their medical condition (eg, too weak or debilitated, severe shortness of breath) 
or due to literacy issues, the patient’s LAR must be willing give informed consent on behalf of 
the patient to participate in the study as permitted by local regulatory authorities, IRBs/IECs, or 
local laws.
Please note: The patient/LAR will be expected to provide the study site with their contact 
information so that the site can maintain contact with the patient/LAR in the event that the 
patient is discharged before the end of the study. Additionally, at the time of informed consent, 
the study site may also request for the patient/LAR to provide alternative contact information. In 
the event that rescreening occurs, the investigator (or designee) must reconsent the patient (or the 
patient’s LAR) and the patient must be assigned a new identification number.
10.2
Study Procedures 
Assessments and their timing are to be performed as outlined in the Schedule of Assessments 
(Table 1). Section 12.5 specifies clinical laboratory assessment samples to be obtained. 
Assessments and procedures scheduled at a visit where study drug is administered should be 
performed before administration of treatment unless otherwise indicated in the Schedule of 
Assessments (Table 1).
Efficacy assessments are described in Section 11 and include COVID-19 symptoms, COVID-19
severity, clinical status related to COVID-19 on the NIAID 8-point ordinal scale, HRQoL
assessed by the EQ-5D-5L questionnaire (Appendix 2), and COVID-19 testing.
Safety assessments are described in Section 12 and include medical/surgical history and 
demographics, vital signs, physical examinations, ECGs, clinical laboratory assessments, and 
AEs. PK assessments are described in Section 13 and include PK sampling and PK analytical 
methodology. Biomarkers are described in Section 14.1.
The investigator may, at his/her discretion, arrange for a patient to have an unscheduled 
assessment, especially in the case of AEs that require follow-up or are considered by the 
investigator to be possibly related to the use of study drug. The unscheduled visit page in the 
eCRF must be completed. 
Procedures for early study withdrawal are described in Section 8.4.
1
EFFICACY ASSESSMENTS 
The Schedule of Assessments (Table 1) outlines the efficacy assessments to be performed 
throughout the study and their timing.
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1.1
COVID-19 Symptoms  
The assessment of the COVID-19 symptoms will be recorded at the visits specified in the 
Schedule of Assessments (Table 1).
The patient will be assessed for the following as shown in Table 2.
Table 2
COVID-19 Symptoms
Symptom
Response Options and Scoring
1.
Stuffy or runny nose
None = 0
Mild = 1
Moderate = 2
Severe =3
2.
Sore throat
3.
Red or irritated eyes (conjunctivitis)
4.
Shortness of breath (difficulty breathing)
5.
Cough
6.
Low energy or tiredness
7.
Muscle or body aches
8.
Headache
9.
Chills or shivering
10. Feeling hot or feverish
11. Nausea (feeling like you wanted to throw up)
12. How many times did you vomit (throw up) in the 
last 24 hours?
I did not vomit at all = 0 
1–2 times = 1 
3–4 times = 2 
5 or more times = 3 
13. How many times did you have diarrhea (loose or 
watery stools) in the last 24 hours?
I did not have diarrhea at all = 0
1–2 times = 1 
3–4 times = 2 
5 or more times = 3 
14. Rate your sense of smell in the last 24 hours.
My sense of smell is THE SAME AS usual = 0 
My sense of smell is LESS THAN usual = 1 
I have NO sense of smell = 2 
15. Rate your sense of taste in the last 24 hours.
My sense of taste is THE SAME AS usual = 0 
My sense of taste is LESS THAN usual = 1 
I have NO sense of taste = 2 
Note: Score values are included in the table for ease of reference. Score values within the response options will not 
be presented to patients to avoid confusing patients.
1.2
COVID-19 Severity  
The assessment of the COVID-19 severity will be recorded at the visits specified in the Schedule 
of Assessments (Table 1). As per the inclusion and exclusion criteria (see Section 8.1 and
Section 8.2), patients who are randomized must have either moderate or severe COVID-19. The 
criteria (FDA 2020) used to determine the patient’s COVID-19 severity incorporates objective 
measures as follows: 
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Asymptomatic SARS-CoV-2 infection 
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
No symptoms
Mild COVID-19
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
Symptoms of mild illness with COVID-19 (eg, loss of smell or taste, fever, cough, sore 
throat, malaise, headache, muscle pain, gastrointestinal symptoms, and without shortness 
of breath or dyspnea)
x
No clinical signs indicative of moderate, severe, or critical COVID-19
Moderate COVID-19
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
Symptoms of moderate illness with COVID-19, which could include any symptom of 
mild illness or shortness of breath with exertion 
x
Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate 
20 breaths per minute, SpO2 >93% (on room air at sea level, if possible), heart rate 
90 beats per minute 
x
No clinical signs indicative of severe or critical COVID-19
Severe COVID-19
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
Symptoms suggestive of severe systemic illness with COVID-19, which could include 
any symptom of moderate illness or shortness of breath at rest, or respiratory distress
x
Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory 
rate 30 breaths per minute, heart rate 125 beats per minute, SpO2 93% (on room air at 
sea level, if possible), PaO2/FiO2 <300, or diagnosed with ARDS (according to the Berlin 
definition; see Table 3 for further details)
x
No criteria for critical COVID-19
Critical COVID-19
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
Evidence of critical illness, defined by at least 1 of the following: 
o
Respiratory failure defined based on resource utilization requiring at least 1 of the 
following: 

Endotracheal intubation and mechanical ventilation, oxygen delivered by 
high-flow nasal cannula (heated, humidified, oxygen delivered via 
reinforced nasal cannula at flow rates >20 L/min with fraction of delivered 
oxygen 0.5), non-invasive positive pressure ventilation, ECMO, or 
clinical diagnosis of respiratory failure (ie, clinical need for 1 of the 
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preceding therapies, but preceding therapies not able to be administered in 
setting of resource limitation) 
o
Shock (defined by systolic blood pressure <90 mm Hg, or diastolic blood pressure 
<60 mm Hg or requiring vasopressors) 
o
Multi-organ dysfunction/failure 
A clinical diagnosis of respiratory failure (in the setting of resource limitation) in which the 
management deviates from SoC must be recorded.
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will 
be measured when the patient is on room air at sea level (ie, no supplemental oxygen, if possible)
and at rest for at least 5 minutes. If possible, the site should collect the information from each 
patient at the same time each day (±1 hour). 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition (eg, 
emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19 (unless the 
patient meets the definition for critical COVID-19). For questions related to COVID-19 severity,
the investigator should contact the medical monitor.
Table 3:
Acute Respiratory Distress Syndrome – Berlin Definition
Timing
Within 1 week of known clinical insult or new or worsening respiratory symptoms
Chest 
imaginga
Bilateral opacities — not fully explained by effusions, lobar/lung collapse, or nodules
Origin of 
edema
Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective 
assessment (eg, echocardiography) to exclude hydrostatic edema if no risk factor is present
Oxygenationb
Mild
200 mm Hg < PaO2/FIO2 300 mm Hg with PEEP or CPAP 5 cmH2Oc
Moderate
100 mm Hg < PaO2/FIO2 200 mm Hg with PEEP 5 cmH2O
Severe
PaO2/FIO2 100 mm Hg with PEEP 5 cmH2O
Abbreviations: ARDS = acute respiratory distress syndrome; CPAP = continuous positive airway pressure; 
FIO2 = fraction of inspired oxygen; PaO2 = partial pressure of arterial oxygen; PEEP = positive end-expiratory 
pressure.
a
Chest radiograph or computed tomography scan
b
If altitude is higher than 1,000 m, the correction factor will be calculated as follows: [PaO2/FIO2 (barometric 
pressure/760)]
c
This may be delivered noninvasively in the mild ARDS group
Source: Adapted from Fanelli et al 2013.
1.3
Clinical Status Related to COVID-19 on the National Institute of Allergy and 
Infectious Diseases 8-Point Ordinal Scale 
The NIAID 8-point ordinal scale is an assessment of the clinical status at the first assessment of a 
given study day. The scale is as follows:
1. Death
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2. Hospitalized, on invasive ventilation (mechanical ventilator and/or ECMO)
3. Hospitalized, on non-invasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care 
(COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen and no longer requires ongoing 
medical care (used if hospitalization was extended for infection-control reasons)
7. Not hospitalized, limitation on activities, and/or requiring home oxygen
8. Not hospitalized, no limitations on activities
Please note: Patients requiring oxygen before COVID-19 and returning to baseline oxygen use 
will be considered improved (ie, not requiring supplemental oxygen). Patients with a limitation 
on activities before COVID-19 and returning to baseline activity will be considered improved.
At the visits specified in the Schedule of Assessments (Table 1), record the date and time for 
each individual component of the NIAID 8-point ordinal scale including: invasive or non-
invasive mechanical ventilation/ECMO start/stop, high-flow/mask oxygen start/stop, 
supplemental oxygen start/stop (nasal cannula, liter flow [and its conversion to FiO2], other 
delivery services), hospital discharge (whether with limitations or without limitations), 
hospitalization type (eg, transfer to ICU) start/stop, and (if applicable) death, cause of death 
(including relatedness to COVID-19), and date/time of death. If possible, the site should collect 
the information from each patient at the same time each day (±1 hour).
A standard conversion for liter flow oxygen to FiO2 is presented in Table 4.
Table 4
Standard Conversion for Liter Flow Oxygen
If there is use of a venturi mask (air-entrainment mask), the FiO2 is based on the nozzle use and 
should also be recorded.
FiO2 (%)
Room air
21
1 L/min
24
2 L/min
27
3 L/min
30
4 L/min
33
5 L/min
36
6 L/min
39
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1.4
Health-related Quality of Life Assessment 
The HRQoL will be assessed via the EQ-5D-5L questionnaire (Appendix 2). The EQ-5D-5L is a 
standardized questionnaire developed by the EuroQol Group as a measure of HRQoL that 
consists of a descriptive system and a VAS. The descriptive system consists of 5 dimensions: 
mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The VAS records 
the patient’s self-rated health on a vertical VAS. This can be used as a quantitative measure of 
health outcome that reflects the patient’s own judgment. The patient is asked to indicate his/her 
current health state (ie, describe their health “today”). The scores on these 5 dimensions can be 
presented as a health profile or can be converted to a single summary index number that
describes the patient’s current health state. The EQ-5D-5L questionnaire has been validated in a 
diverse patient population in 6 countries and is available in multiple languages. The EQ-5D-5L
questionnaire is suitable for completion by adults (EuroQol Research Foundation 2020).
The results of the EQ-5D-5L questionnaire will be recorded at the visits specified in the 
Schedule of Assessments (Table 1). Please note: This assessment will only be performed in 
patients who have been discharged from the hospital before Day 60. 
1.5
COVID-19 Testing  
Samples for COVID-19 testing will be obtained at the visits specified in the Schedule of 
Assessments (Table 1). At the screening visit, the local laboratory may perform COVID-19
testing by standard RT-PCR assay or equivalent test. At screening, a positive test must be 
available in order for the patient to be randomized on Day 1. If the patient has a previous 
confirmation of SARS-CoV-2 (within 7 days of Day 1), the SARS-CoV-2 test at screening is not
required. The result of the COVID-19 tests (positive/negative) must be documented in the eCRF
On Day 1, Day 14, Day 28, and Day 60, samples will be sent to the central laboratory for 
COVID-19 testing by standard RT-PCR assay. The result of the COVID-19 tests 
(positive/negative) must be documented in the eCRF. Further details will be described in the 
laboratory manual. 
Please note: If COVID-19 tests are performed at unscheduled time points (eg, according to SoC), 
findings (ie, positive/negative result) must be recorded in the eCRF.
12
SAFETY ASSESSMENTS 
Safety assessments (medical/surgery history, demographics, prior and concomitant medications, 
vital signs, physical examinations, ECGs, clinical laboratory assessments, and AEs) are to be 
performed at the visits specified in the Schedule of Assessments (Table 1).
12.1
Medical/Surgical History and Demographics 
Medical/surgical history will be recorded at screening. Investigators will document all active and 
chronic diseases (eg, asthma and COPD), and any diseases diagnosed in the past 1 year (before 
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screening) that the investigator considers clinically significant. Additional pre-existing 
conditions present at the time when informed consent is given and up to the time of first dosing 
(Day 1) are to be regarded as concomitant. Medical history will include documentation of social 
behaviors, including use of tobacco, nicotine (including use of electronic cigarettes), and soft or 
hard drugs (including cannabis), as well as alcohol consumption, if applicable. Smoking history 
also must be documented as part of medical history and includes never, light 
(<100 cigarettes/lifetime), active smoker, and former smoker (quit date). History of number 
packs/day, number of smoking years, and quitting time for former and active smokers must also 
be documented.
Additionally, the investigators will document at screening the patient’s Charlson score via the 
Charlson Comorbidity Index (Charlson et al 1987) (Appendix 1). The Charlson Comorbidity 
Index may be used to identify patients with higher risk of COVID-19 progression (Garibaldi et al
2020) via the COVID-19 Inpatient Risk Calculator (online calculator available via: 
https://rsconnect.biostat.jhsph.edu/covid_predict/). The 14-item Charlson score is based on the
patient’s comorbidities that are associated with mortality: myocardial infarction, congestive heart 
failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary 
disease, rheumatologic disease, peptic ulcer disease, liver disease, diabetes, hemiplegia or 
paraplegia, renal disease, malignancy, and acquired immunodeficiency syndrome/human
immunodeficiency virus (online calculator available via: https://www.orthotoolkit.com/charlson-
comorbidity-index/). The investigator should record each individual component of the 14-item 
Charlson Comorbidity Index (Appendix 1) as well as the overall score. 
Illnesses first occurring or detected during the study and/or worsening of a concomitant illness 
during the study are to be documented as AEs on the eCRF in accordance with Section 12.6.1.
All changes not present at baseline or described in the past medical history and identified as 
clinically noteworthy must be recorded as AEs.
Additionally, demographic data will be collected for all patients and include sex, age, and race
and/or ethnicity.
12.2
Vital Signs 
Vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, SpO2, and body 
temperature) will be evaluated at the visits indicated in the Schedule of Assessments (Table 1).
All vital signs will be measured after the patient has been resting for at least 5 minutes. Blood 
pressure measurements are to be taken in the same arm for the duration of the study. Moreover, 
additional vital signs may be performed as needed in case of any cardiac AE.
Additionally, body weight (without shoes) will be recorded at screening, Day 1, Day 14, Day 28, 
Day 60, and day of discharge (applicable); height (without shoes) will be recorded at screening 
only. Body mass index will be calculated whenever weight is recorded.
Vital sign measurements will be repeated if clinically significant or machine/equipment errors 
occur. Out-of-range blood pressure, respiratory rate, heart rate measurements, or SpO2 will be 
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repeated at the investigator’s discretion. Any confirmed, clinically significant vital sign 
measurements must be recorded as AEs.
12.3
Physical Examinations 
A complete physical examination will be performed at screening. Physical examinations will be 
performed by a physician. The complete physical examination includes head, eyes, ears, nose,
and throat; heart; lungs; abdomen; skin; cervical and axillary lymph nodes; and neurological and 
musculoskeletal systems. 
A limited physical examination to verify continued patient eligibility and to follow-up regarding 
any change in medical history will be performed at the visits indicated in the Schedule of 
Assessments (Table 1). Symptom-driven, limited physical examinations may be performed as 
clinically indicated during the study (according to SoC).
Please note: The limited physical examination on Day 8 (± 3 days) will be collected in all 
patients who remain hospitalized. If the patient is discharged before Day 8 (± 3 days), these
assessments should only be done if the physician determines during the outpatient visit (ie, at the 
study site) that the limited physical examination is clinically indicated.
12.4
Electrocardiograms 
A 12-lead, resting ECG will be obtained locally at screening as indicated in the Schedule of 
Assessments (Table 1). At screening, the investigator must examine the ECG traces for clinically 
significant abnormalities that could exclude the patient from the study. If ECGs are performed at 
unscheduled time points (eg, according to SoC), findings must be recorded in the eCRF.
ECGs should always be obtained in supine position after adequate rest ( 5 minutes). An
assessment of normal or abnormal will be recorded; if the ECG is considered abnormal, the 
abnormality will be documented on the eCRF. ECGs will be repeated if clinically significant 
abnormalities are observed or artifacts are present. Any ECG considered by the investigator to be 
clinically significant should be considered an AE. Moreover, additional ECGs may be obtained 
as needed in case of any cardiac AE and will be recorded on the eCRF.
12.5
Clinical Laboratory Assessments 
Clinical laboratory assessment samples (Table 5) will be obtained at designated visits as 
specified in the Schedule of Assessments (Table 1).
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Table 5:
Clinical Laboratory Assessments
Hematology 
Blood Biochemistry 
Urinalysis (Dipstick) 
Full and differential blood count
Hematocrit (HCT)
Hemoglobin (Hb)
Mean corpuscular hemoglobin (MCH)
Mean corpuscular hemoglobin 
concentration (MCHC)
Mean corpuscular volume (MCV)
Platelet count (PLT Ct)
Red blood cell count (RBC ct)
White blood cell count (WBC ct) with 
differential
Albumin (ALB)
Alanine aminotransferase (ALT)
Alkaline phosphatase (ALP)
Aspartate aminotransferase (AST)
Blood urea nitrogen (BUN) or urea
Carbon dioxide (CO2)
Creatininea (Cr)
Creatine kinase (CK) and subtypes
Electrolytes (sodium, potassium, 
chloride, calcium, phosphorus)
Gamma-glutamyl transpeptidase (GGT)
Glucose
Lactate dehydrogenase (LDH)
Total bilirubin (TBIL)
Direct bilirubin (DBI)
Total cholesterol (TC)
Triglycerides (TG)
Estimated glomerular filtration rateb
(eGFR)
Appearance
pH
Protein
Glucose
Ketone bodies
Indicators of blood and 
white blood cells
Specific gravity
Urobilinogen (UROB)
Coagulation
Activated partial thromboplastin time
International normalized ratio
Partial thromboplastin time
Pregnancy Test
A serum pregnancy (hCG) test will be performed on all WOCBP at screening and a urine pregnancy (hCG)
test will be performed on all WOCBP on Day 1 before randomization and dosing. A urine pregnancy test will 
be repeated on Day 14 (± 7 days). If the patient is discharged before Day 14, urine pregnancy test at day of
discharge should be done, and urine pregnancy test at Day 14 is not required. If the patient is discharged after 
Day 14, urine pregnancy test should be done at Day 14, and urine pregnancy test at day of discharge is not
required (whichever comes first). Patients with a positive pregnancy test will be discontinued from study 
drug.
Please note: In questionable cases of postmenopausal status, a blood sample with simultaneous follicle 
stimulating hormone and estradiol levels may be required to determine postmenopausal status.
Abbreviations: hCG = human chorionic gonadotropin; WOCBP = women of childbearing potential.
a Creatinine clearance will be estimated using the patient’s serum creatinine value, actual body weight, age, and the 
appropriate Cockroft-Gault formula for the patient’s sex.
b According to Chronic Kidney Disease Epidemiology Collaboration (Levey et al 2009).
Blood and urine samples will be analyzed at the site’s local laboratory facility. Urine samples 
will be analyzed by dipstick, and a microscopic analysis will be performed if the results of 
dipstick indicate abnormalities to be further investigated. All laboratory reports must be 
reviewed, signed, and dated by the investigator. A legible copy of all reports must be filed with 
both the patient’s eCRF and medical record (source document) for that visit. Any laboratory test 
result considered by the investigator to be clinically significant should be considered an AE 
(clinically significant AEs include those that require an intervention). Clinically significant 
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abnormal values occurring during the study will be followed up until repeat test results return to 
normal, stabilize, or are no longer clinically significant. If laboratory assessments are performed 
at unscheduled time points (eg, according to SoC), findings must be recorded in the eCRF.
Please note: The clinical laboratory assessments on Day 8 (± 3 days) and Day 21 (± 2 days) will 
be collected in all patients who remain hospitalized. If the patient is discharged before Day 8
(± 3 days) or Day 21 (± 2 days), the physician should assess the patient at the outpatient visit (ie, 
at the study site). If the physician determines during the outpatient visit (ie, at the study site) that 
the clinical laboratory assessments are clinically indicated, then the site should arrange to collect 
this assessment.
12.6
Adverse Events
Adverse Events
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study
or, if present at screening, worsens during the study, regardless of the suspected cause of the 
event. All medical and psychiatric conditions (except those related to the indication under study) 
present at screening will be documented on the medical history eCRF. Changes in these 
conditions and new symptoms, physical signs, syndromes, or diseases should be noted on the AE 
eCRF during the rest of the study. Clinically significant laboratory abnormalities should also be 
recorded as AEs. Surgical procedures that were planned before the patient was randomized in the 
study are not considered AEs if the conditions were known before study inclusion; the medical 
condition should be reported in the patient’s medical history.
Patients will be instructed to report AEs at each study visit. All AEs are to be followed up until 
resolution or a stable clinical endpoint is reached.
Each AE is to be documented on the eCRF with reference to date of onset, duration, frequency, 
severity, relationship to study drug, action taken with study drug, treatment of event, and 
outcome. Furthermore, each AE is to be classified as being serious or nonserious. Changes in 
AEs and resolution dates are to be documented on the eCRF.
For the purposes of this study, the period of observation for collection of AEs extends from the 
time the patient gives informed consent until the end of the follow-up period (Day 60).
Follow-up of the AE, even after the date of study completion, is required (if possible) if the AE 
persists. The follow-up should continue until the event resolves (returns to normal or baseline 
values) or stabilizes, or until it is judged by the investigator to no longer be clinically significant.
It is understood that if a patient withdraws consent to further follow-up, then it may not be 
possible for the study site to follow the AE to resolution.
When changes in the severity of an AE occur more frequently than once a day, the maximum 
severity for the event should be noted. If the severity category changes over a number of days, 
then those changes should be recorded separately (with distinct onset dates).
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Each AE will be assigned a grade which refers to the severity of the AE based on the Common 
Terminology Criteria for Adverse Events version 5.0. The Common Terminology Criteria for 
Adverse Events v5.0 displays grades 1 through 5 with unique clinical descriptions of the severity 
for each AE based on the general guideline shown in Table 6.
The guideline for classifying AEs by relationship to study drug are given in Table 7.
Table 6:
Classification of Adverse Events by Severity
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated.
Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living.
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation 
of hospitalization indicated; disabling; limiting self-care activities of daily living.
Grade 4: Life-threatening consequences; urgent intervention indicated.
Grade 5: Death related to AE.
Abbreviation: AE = adverse event.
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Table 7:
Classification of Adverse Events by Relationship to Study Drug
UNRELATED: This category applies to those AEs that are clearly and incontrovertibly due to extraneous 
causes (disease, environment, etc).
UNLIKELY: This category applies to those AEs that are judged to be unrelated to the study drug but for which 
no extraneous cause may be found. An AE may be considered unlikely to be related to study drug if or when it 
meets 2 of the following criteria: (1) it does not follow a reasonable temporal sequence from administration of 
the study drug; (2) it could readily have been produced by the patient’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the patient; (3) it does not follow a known pattern of 
response to the study drug; or (4) it does not reappear or worsen when the drug is readministered.
POSSIBLY: This category applies to those AEs for which a connection with the study drug administration 
appears unlikely but cannot be ruled out with certainty. An AE may be considered possibly related if or when 
it meets 2 of the following criteria: (1) it follows a reasonable temporal sequence from administration of the 
drug; (2) it could not readily have been produced by the patient’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the patient; or (3) it follows a known pattern of response to the study 
drug.
PROBABLY: This category applies to those AEs that the investigator feels with a high degree of certainty are 
related to the study drug. An AE may be considered probably related if or when it meets 3 of the following 
criteria: (1) it follows a reasonable temporal sequence from administration of the drug; (2) it could not be 
reasonably explained by the known characteristics of the patient’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the patient; (3) it disappears or decreases on cessation or reduction 
in dose (note that there are exceptions when an AE does not disappear upon discontinuation of the drug, yet 
drug-relatedness clearly exists; for example, as in bone marrow depression, fixed drug eruptions, or tardive 
dyskinesia); or (4) it follows a known pattern of response to the study drug.
DEFINITELY: This category applies to those AEs that the investigator feels are incontrovertibly related to 
study drug. An AE may be assigned an attribution of definitely related if or when it meets all of the following 
criteria: (1) it follows a reasonable temporal sequence from administration of the drug; (2) it could not be 
reasonably explained by the known characteristics of the patient’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the patient; (3) it disappears or decreases on cessation or reduction 
in dose and recurs with reexposure to drug (if rechallenge occurs); and (4) it follows a known pattern of 
response to the study drug.
Abbreviation: AE = adverse event.
Serious Adverse Events
An SAE is any untoward medical occurrence, in the view of either the investigator or sponsor,
that:
x
results in death
x
is life-threatening
x
results in inpatient hospitalization or prolongation of existing hospitalization
x
results in persistent or significant disability/incapacity
x
is a congenital anomaly/birth defect
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Other important medical events that may not be immediately life-threatening or result in death or 
hospitalization, based upon appropriate medical judgment, are considered SAEs if they are 
thought to jeopardize the patient and/or require medical or surgical intervention to prevent 1 of
the outcomes defining an SAE. SAEs are critically important for the identification of significant 
safety problems; therefore, it is important to take into account both the investigator’s and the 
sponsor’s assessment. If either the sponsor or the investigator believes that an event is serious, 
the event must be considered serious and evaluated by the sponsor for expedited reporting.
Serious Adverse Event Reporting
An SAE occurring from the time the patient gives informed consent until the end of the follow-
up period (Day 60) or within 30 days of stopping the study drug (whichever is longer) must be 
reported to the Syneos Health Safety and Pharmacovigilance group and will be communicated to 
the sponsor. Any such SAE due to any cause, whether or not related to the study drug, must be 
reported within 24 hours the investigator’s awareness of the event. Notification can be made 
using the dedicated fax line or email for the Syneos Health Safety and Pharmacovigilance group:
x
Syneos Health Safety and Pharmacovigilance fax number: 
x
Syneos Health Safety and Pharmacovigilance email address: 
If the investigator contacts the Syneos Health Safety and Pharmacovigilance group by telephone, 
then a written report must follow within 24 hours and has to include a full description of the 
event and sequelae in the format detailed in the SAE reporting form.
The event must also be recorded on the standard AE eCRF. Preliminary reports of SAEs must be 
followed up by detailed descriptions later on. Clear and anonymized photocopies of hospital case 
reports, consultant reports, autopsy reports, and other documents must be provided when 
requested by Syneos Health Safety and Pharmacovigilance. SAE reports must be made whether 
or not the investigator considers the event to be related to the investigational drug.
Appropriate remedial measures should be taken to treat the SAE, and the response should be 
recorded. Clinical, laboratory, and diagnostic measures should be employed as needed to
determine the etiology of the problem. The investigator must report all additional follow-up
evaluations to the Syneos Health Safety and Pharmacovigilance group within 24 hours of
becoming aware of the additional information. All SAEs will be followed up until the 
investigator and sponsor agree the event is satisfactorily resolved.
Any SAE that is not resolved by the end of the study or upon discontinuation of the patient’s 
participation in the study is to be followed up, if possible, until it either resolves, stabilizes, 
returns to baseline values (if a baseline value is available), or is shown to not be attributable to 
the study drug or procedures. It is understood that if a patient withdraws consent to further 
follow-up, then it may not be possible for the study site to follow the SAE to resolution.
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Suspected Unexpected Serious Adverse Reactions
AEs that meet all of the following criteria will be classified as suspected unexpected serious 
adverse reactions (SUSARs) and reported to the appropriate regulatory authorities in accordance 
with applicable regulatory requirements for expedited reporting:
x
serious
x
unexpected (ie, the event is not consistent with the reference safety information in the
current version of the IB)
x
there is at least a reasonable possibility that there is a causal relationship between the 
event and the study drug
The investigator will assess whether an event is causally related to the study drug. Syneos Health 
will consider the investigator’s assessment and determine whether the event meets the criteria for 
being reportable as a 7-day or 15-day safety report. SUSARs that are fatal or life-threatening 
must be reported to the regulatory authorities and the IRBs/IECs (where required) within 7 days 
after Syneos Health/MetrioPharm has first knowledge of them, with a follow-up report (when 
applicable) submitted within a further 8 calendar days. Other SUSARs must be reported to the 
relevant regulatory authorities and the IRBs/IECs within 15 calendar days after 
Syneos Health/MetrioPharm first has knowledge of them.
Syneos Health is responsible for reporting SUSARs and any other events required to be reported 
in an expedited manner to the regulatory authorities and for informing investigators of reportable 
events, in compliance with applicable regulatory requirements within specific timeframes.
Investigators will notify the relevant IRBs/IECs of reportable events within the applicable 
timeframes.
Pregnancy
WOCBP must have a negative serum pregnancy test at screening and negative urine pregnancy 
test before the first dose on Day 1. A urine pregnancy test will be repeated on Day 14 (± 7 days).
If the patient is discharged before Day 14, urine pregnancy test at day of discharge should be
done, and urine pregnancy test at Day 14 is not required. If the patient is discharged after 
Day 14, urine pregnancy test should be done at Day 14, and urine pregnancy test at day of
discharge is not required (whichever comes first). Patients with a positive pregnancy test will be 
discontinued from study drug. After administration of study drug, any known cases of pregnancy 
in female patients will be reported until the patient completes or withdraws from the study. The 
pregnancy will be reported immediately by faxing/emailing a completed pregnancy report to 
Syneos Health Safety and Pharmacovigilance within 24 hours of knowledge of the event. The 
pregnancy will not be processed as an SAE; however, the investigator will follow up with the 
patient until completion of the pregnancy and must assess the outcome in the shortest possible 
time but not >30 days after completion of the pregnancy. (It is understood that if a patient 
withdraws consent to further follow-up, then it may not be possible for the study site to follow 
the pregnancy to completion.) The investigator should notify Syneos Health Safety and 
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Pharmacovigilance group of the pregnancy outcome by submitting a follow-up pregnancy report. 
If the outcome of the pregnancy involved spontaneous or therapeutic abortion (any congenital 
anomaly detected in an aborted fetus is to be documented), stillbirth, neonatal death, or 
congenital anomaly, the investigator will report the event by faxing/emailing a completed 
pregnancy report form to Syneos Health Safety and Pharmacovigilance group within 24 hours of 
knowledge of the event.
If the investigator becomes aware of a pregnancy occurring in the partner of a patient 
participating in the study, the pregnancy should be reported to Syneos Health Safety and 
Pharmacovigilance group within 24 hours of knowledge of the event. Information regarding the 
pregnancy must only be submitted after obtaining consent from the pregnant partner. The 
investigator will arrange counseling for the pregnant partner by a specialist to discuss the risks of 
continuing with the pregnancy and the possible effects on the fetus.
Upon discontinuation from the study drug, only those procedures that would not expose the 
patient to undue risk will be performed. The investigator should also be notified of pregnancy 
occurring during the study but confirmed after completion of the study. In the event, that a 
patient is subsequently found to be pregnant after inclusion in the study and received at least one 
dose of study drug, any pregnancy will be followed to term, and the status of mother and child 
will be reported to Syneos Health Safety and Pharmacovigilance group after delivery.
Overdose
The investigator must immediately notify Syneos Health of any occurrence of overdose with the 
study drug.
13
PHARMACOKINETICS
13.1
Pharmacokinetic Sampling
Blood samples for PK analysis of MP1032 plasma concentrations will be collected at the time
points indicated in the Schedule of Assessments (Table 1) from a PK subset of approximately 
30 patients (who give optional consent). In summary, PK samples will be collected via sparse 
sampling from these 30 patients (approximately) in a 2:1 ratio (approximately 20 patients from 
the 300 mg MP1032 BID plus SoC group and approximately 10 patients from the placebo group
plus SoC group) to assess the PK of MP1032 on Day 1 (single dose) and Day 7 (steady state). A
total of 16 samples (approximately 4.9 mL per time point for a total of approximately 78.4 mL)
will be collected relative to the first dose on Day 1 and the first dose on Day 7. Samples on 
Day 1 and Day 7 will be collected predose (within 10 minutes before the first daily dose) and 
postdose at 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 8 hours (before next 
dose), and 24 hours before the next morning dose (if applicable), if possible. Patients who 
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provide consent for the PK sampling, but are no longer hospitalized on Day 7, will not have 
Day 7 PK samples collected.
For patients in the PK subset on Day 1 and Day 7 only: Patients should not eat within the 4 hours
before planned study drug administration and within the 120 minutes after study drug dosing, 
when feasible. Thus, study drug should be administered in fasted state ( 4 hours), when 
feasible. However, if a patient has eaten within the 4 hours before their planned administration, 
study drug dosing may proceed. The patient’s fed or fasted state, as well as food intake (yes/no) 
within the 120 minutes after study drug dosing should be recorded. The PK samples should be 
collected as planned regardless of the patients’ fasted/fed state. The study site should record the 
date and time of dosing (recorded as the time when the first capsule is administered).
Intravenous cannulas may be used for blood collection to avoid multiple skin punctures, when 
appropriate. Otherwise, blood samples will be collected by direct venipuncture. The actual date 
and time of each blood sample collection will be recorded. Sample collections completed outside 
the predefined time windows (windows to be specified in the laboratory manual) will not be 
considered as protocol deviations because actual postdose sampling times will be used for PK 
and statistical analyses.
PK samples will be analyzed by a central laboratory facility (Prolytic GmbH). Details of PK 
blood sample collection, processing (including separation of plasma), storage, and shipping 
procedures will be provided in a separate laboratory manual.
13.2
Pharmacokinetic Analytical Methodology 
The concentration of study drug will be determined from the plasma samples using a validated 
analytical method. Details of the method validation and sample analysis will be included with the 
final clinical study report (CSR).
14
OTHER ASSESSMENTS 
14.1
Biomarkers 
Blood samples will be obtained at the visits specified in the Schedule of Assessments (Table 1)
on Day 1 (before the first study drug administration) and Days 7, 14, 21, 28, and 60 to measure 
biomarkers levels. Blood samples for biomarkers must be collected on Days 7, 14, 21, 28, and 60
if a patient is still hospitalized. If a patient is discharged, the study site should arrange an 
outpatient visit (ie, at the study site) to accommodate the collection of blood samples for 
biomarkers on Days 7, 14, 21, 28, and 60.
Biomarkers will potentially include, but will not be limited to cytokines (eg, C-reactive protein,
IL-1E, IL-6, TNF-Į, and IFN-J) and other coagulation/inflammatory biomarkers (eg, D-dimer 
and ferritin). Samples may be collected at the same time that samples are collected for the
clinical laboratory assessments. Blood samples will be analyzed by a central laboratory facility.
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Details of sample collection, processing, storage, shipping procedures, and analysis will be 
provided in a separate laboratory manual.
Please note: Patients will be requested to provide consent for the sponsor to store and use 
leftover blood samples for future exploratory biomarker research. Patient participation in the 
storage and use of leftover blood samples is optional. If the patient consents, the sponsor will 
store and use the leftover blood samples for a period of 3 years after the last patient has 
completed his/her last visit in this study.
15
STATISTICAL ANALYSIS 
The statistical analysis plan (SAP) will provide further details regarding the definition of 
analysis variables and analysis methodology to address all study objectives. The SAP will be 
finalized before any statistical output (eg, DSMB output) is produced. The SAP will serve as a 
companion document to the protocol. The SAP will further describe the statistical analyses. All 
data will be included with the final CSR. 
The statistical evaluation will be performed using SAS® software version 9.4 or higher 
(
®
 
). 
Summary statistics will be presented by treatment group. Continuous and ordinal variables will 
be summarized by the number of patients (N), mean, standard deviation, median, minimum, and 
maximum for actual values and change from baseline. Additionally, for ordinal data, the number 
and percentage of patients in each category will be presented. Binary and categorical variables 
will be summarized for each treatment group by presenting the number and percentage of 
patients in the categories.
Statistical tests for comparison between treatments will be performed using a two-sided alpha 
level of 10%. No adjustment for multiple testing will be applied in this descriptive proof-of-
concept study.
15.1
Determination of Sample Size 
The primary efficacy endpoint “proportion of patients with disease progression on Day 14” is 
assumed to be 10% in the 300 mg MP1032 BID plus SoC treatment group (Arm A) and 30% in 
the placebo plus SoC treatment group (Arm B). Using the Chi-square test with type I error 
alpha=10% two-sided for this proof-of-concept study and 2:1 randomization ratio, with
114 randomized patients (76 in Arm A and 38 in Arm B) a statistical power of 83% can be 
achieved. Considering about 5% early study terminations, the necessary sample size to 
randomize results is 120 patients in total (80 in Arm A and 40 in Arm B). If during the conduct 
of the study the early study termination rate is higher than the estimated 5%, then an increase in 
the randomized number of patients may be necessary.
Sample size estimation was performed using nQuery 8, Version 8.6.1.0.
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A subset of randomized patients will be consented for the collection of blood samples for PK 
measurements. The PK subset consists of approximately 20 patients from the 300 mg MP1032 
BID plus SoC group and approximately 10 patients from the placebo plus SoC group, up to a
total of approximately 30 patients.
15.2
Analysis Sets 
Screened Set
The Screened Set will include all patients who give informed consent and are screened. For this 
group, patient disposition, and reasons for premature study termination or screening failure will
be described. 
Randomized Set
The Randomized Set will include all patients randomized. Unless specified otherwise, this set 
will be used for all subject listings with exception of the listing presenting screening failures and 
the respective reason(s) for screen failure.
Intention-To-Treat The Intention-To-Treat (ITT) set, correspond with randomized set, will 
include all randomized patients irrespective of any deviation from the protocol or premature 
discontinuation from study drug/withdrawal from study. The treatment group assignment will be 
designated according to initial randomization. The ITT will serve as the basis for the analysis of 
efficacy and summary of demographics and baseline characteristics.
Per Protocol Set
The Per Protocol Set (PPS) will include all patients from ITT who received at least 1 dose of 
study drug and who do not have any major protocol deviations impacting the efficacy 
assessments. The PPS will be used for supportive analyses of efficacy.
Safety Set
The Safety Set (SS) will include all randomized patients who receive at least 1 dose of study 
drug. The treatment group assignment in the SS will be defined by the treatment actually 
received. The SS will be used for the analysis of safety.
PK Analysis Set
The PK Analysis Set (PKS) will include all the patients who have been administered active study 
drug and have at least 1 postdose evaluable plasma concentration after Day 1 dose.
15.3
Efficacy Analysis 
The estimands for the primary efficacy endpoint and for the 4 key secondary endpoints 
comparing the 2 treatment groups will be tested with consideration of a two-sided type-1 error
alpha of 10% for each test on the ITT. Additionally, 95% confidence intervals will be provided.
Also, the treatment comparison with regards to the other secondary efficacy endpoints will be 
performed using a two-sided alpha level of 10%.
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The main estimand for the primary efficacy endpoint is defined as follows:
x
Treatment: 300 mg MP1032 BID plus SoC in Arm A and placebo BID plus SoC in Arm 
B. If a patient terminates the study drug, but still remains in the study and is followed up, 
then the patient will continue to receive either SoC alone or SoC+ additional treatment.
These treatments are defined with regards to intercurrent events as ‘other treatments’.
x
Population: Of all patients defined by the study inclusion/exclusion criteria, the analysis 
population will include patients who were randomized to study drug (ITT population).
x
Variable: A binary variable indicating disease progression (death or respiratory failure) at 
Day 14. Respiratory failure is defined as patients who have a score of 2, 3, or 4 on the 
NIAID 8-point ordinal scale.
x
Intercurrent events: All events that lead to study drug discontinuation and/or switch to 
other treatment before Day 14 will be handled using the treatment-policy strategy (ie, the
NIAID score at Day 14 will be used for definition of the failure in such patients).
x
Population-level summary: Common risk difference resulting from the Mantel-
Haenszel (MH) test considering the 4 strata out of the combinations of the 
2 randomization stratification factors disease severity (moderate versus severe) and age-
class (aged 65 years versus >65 years) at baseline.
Missing data on Day 14 resulting from study termination before Day 14 are not expected. 
However, in case they happen, such monotone missings will be imputed by multiple imputation 
using information from similar patients of the same treatment group. Missing post-baseline data 
for patients randomized but not treated will be imputed by the respective baseline value (baseline 
observation carried forward [BOCF]). The comparison between the treatment groups will be 
performed on the ITT after imputation of missing values using MH test for common risk
difference considering the 4 strata resulting from the 2 randomization stratification factors 
disease severity (moderate versus severe) and age-class (aged 65 years versus >65 years). The 
95% confidence intervals will be provided for the risk difference.
Similar MH analyses and presentation of 95% confidence intervals will be applied to the main 
estimand of the first key secondary efficacy endpoint, which is defined as a binary variable 
indicating disease progression (death or respiratory failure) at Day 28, and the main estimand of 
the second key secondary efficacy endpoint that is defined as a binary variable indicating disease 
resolution (alive and have a score of 6, 7 or 8 on NIAID) at Day 28. Intercurrent events that lead 
to study drug discontinuation and/or switch to other treatment before Day 28 will be handled 
using the treatment-policy strategy for these 2 estimands (ie, the NIAID score at Day 28 will be 
used for definition of the failure or response, respectively) in such patients. Missing data on Day 
28 will be imputed by multiple imputation using information from similar patients of the same 
treatment group. Missing post-baseline data for patients randomized but not treated will be 
imputed by BOCF.
A similar MH approach and presentation of 95% confidence intervals as described above will be 
applied also to the main estimand of the third key secondary efficacy endpoint, which is the all-
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cause mortality at Day 28. Intercurrent events that lead to study drug discontinuation and/or 
switch to other treatment before Day 28 will be handled using the treatment-policy strategy (ie,
the life status at Day 28 will be considered). No missing data of life status on Day 28 is expected. 
The main estimand of the fourth key secondary efficacy endpoint, change of clinical status 
related to COVID-19 on Day 28 compared with baseline according to the NIAID 8-point ordinal 
scale, will be compared using the risk difference from the analysis of covariance model with
treatment and the 2 binary stratification factors (eg, severity and age-class) as independent 
factors and the baseline value of NIAID as independent covariate. Intercurrent events that lead to 
study drug discontinuation and/or switch to other treatment before Day 28 will be handled using 
the treatment-policy strategy for this estimand (ie, the NIAID score at Day 28 will be used). 
Missing data on Day 28 will be imputed by multiple imputation using information from similar 
patients of the same treatment group. Missing post-baseline data for patients randomized but not 
treated will be imputed by BOCF. The 95% confidence intervals will be provided for the risk 
difference.
The population for all above described estimands of the key secondary endpoints is the ITT.
Sensitivity analyses for the main estimands of the primary and key efficacy endpoints will be 
performed by assuming missing data at Day 14 or Day 28 as failure or non-resolution for the 
binary endpoints, and by multiple imputation using information from similar patients of the 
placebo group for the NIAID 8-point ordinal scale.
All above analyses for the main estimands of the primary efficacy and key secondary efficacy 
endpoints will be repeated on PPS as supportive analysis. Additionally, for the primary efficacy 
and binary key secondary efficacy endpoints logistic regression model with treatment and the 
2 stratification factors as covariables will be performed on the ITT. Further estimands for the
primary and key secondary efficacy endpoints will be provided in the SAP.
The proportion of patients with disease resolution at Day 14 and the all-cause mortality rate at 
Day 14 and Day 60 will be analyzed using similar MH methods as described above for Day 28. 
Cumulative proportion of patients with disease resolution will be plotted by time.
A similar analysis of covariance approach as described above for Day 28 will be applied for the 
analysis of the change of clinical status related to COVID-19 on Day 14 compared with baseline 
on the NIAID 8-point ordinal scale. The endpoint considering the proportion of patients 
requiring invasive ventilation (mechanical ventilator and/or ECMO) or who are not alive, the 
proportion of patients in each NIAID category, and the proportion of patients alive and testing 
negative for COVID-19 on Day 14, Day 28, and Day 60, respectively, will be compared between 
the treatment groups using MH test. Overall survival, time to (first) improvement of at least 
1 category on the NIAID scale and total hospitalization duration (from baseline to discharge; 
with death censored on last day of the observed period í at Day 28 or Day 60, respectively í 
depending on the analyses) will be summarized using the Kaplan-Meier method and will be 
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compared between treatment groups using log-rank tests. Additionally, Cox proportional hazards 
model will be applied with treatment and the 2 stratification factors as covariables.
The odds ratio between MP1032 and SoC and placebo and SoC for the number of patients with 
clinical status improvement from baseline on the NIAID 8-point ordinal scale (ie, an 
improvement of at least 1 category) at Day 14 and Day 28 will be analyzed using a logistic 
regression with consideration of the 2 stratification factors.
The time to recovery of all at baseline present COVID-19 symptoms (stuffy or runny nose, sore 
throat, red or irritated eyes, shortness of breath, cough, low energy or tiredness, muscle or body 
aches, headache, chills or shivering, feeling hot or feverish, nausea, and number of times of 
vomit, times of diarrhea, sense of smell, sense of taste in the last 24 hours) will be presented by
Kaplan-Meier estimates and figure. The change from baseline will be presented in shift tables for 
each single symptom, with the number and percentage of subjects in each category at post-
baseline assessment time-point compared to baseline for each treatment group. 
Total number of days in ICU, duration of invasive mechanical ventilation, and duration of 
ECMO will be descriptively summarized by treatment group using mean days with 
90% confidence intervals and additionally by median days and quartiles. To consider death 
sufficiently unfavorable in these measures, in case of death the duration of the respective
measure will be considered with the longest duration possible (eg, if a summary of the first 28 
days is presented, then death before Day 28 will be considered as duration 28 days, and if the 
summary also includes follow-up period until Day 60, then death before Day 60 will be 
considered as duration of 60 days). Both summaries (up to Day 28 and up to Day 60) will be 
provided.
For HRQoL assessments at discharge and Day 60, the EQ index value and the EQ VAS, both 
based on the EQ-5D-5L questionnaire (Appendix 2), will be calculated and summarized by visit 
and treatment group. Additionally, change at Day 60 from discharge will be summarized by
treatment group.
All efficacy endpoints will be summarized using descriptive statistics by treatment group and by 
visit, as appropriate: Binary and categorical endpoints will be summarized by treatment group by 
presenting the number and percentage of patients in the categories. Continuous and ordinal 
endpoints will be described by mean, standard deviation, median, minimum, and maximum for 
actual values and change from baseline. Additionally, for ordinal data, the number and 
percentage of patients in each category will be presented.
15.4
Safety Analysis 
All safety parameters will be summarized descriptively by treatment group for the entire study
period.
Study drug duration and SoC therapies will be described for each treatment group.
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All reported AEs will be coded into preferred term (PT) and grouped by SOC using the most 
recent Medical Dictionary for Regulatory Activities version. An overall summary will be 
provided with the number and percentage of patients reporting TEAEs, serious TEAEs, 
treatment-related TEAEs, TEAEs leading to withdrawal, and TEAEs leading to death. For
patients with any serious TEAE and for patients with any related serious TEAE exposure-
adjusted events rates will be calculated and compared between treatment groups using the risk 
ratio [(300 mg MP1032 BID plus SoC) / (placebo plus SoC)] with respective 95% confidence 
intervals. This comparison will also be performed for the rate of re-hospitalization which is 
considered a serious AE. The number and percentage of patients with TEAEs, serious TEAEs, 
TEAEs leading to withdrawal, and treatment-related TEAEs will be summarized by SOC and PT 
for each treatment group, and total. In these tables, the incidence of TEAEs by SOC and PT will 
also be included. TEAEs will also be summarized by maximum severity and relationship to 
study drug. Events with missing onset dates will be considered as TEAEs. If a patient 
experienced >1 occurrence of the same AE, the occurrence with the greatest severity and the 
closest association with the study drug will be used in the corresponding summary tables. In case 
that for one AE several AE episodes with changing severity is reported, an aggregation of all 
respective episodes to one AE will be performed before summarization. The worst severity and 
the worst causality will be assigned to the aggregated AE and used for the respective AE 
summaries. All reported AE episodes will be listed by patient, along with information regarding 
onset, duration, severity and relationship to study drug, action taken with study drug, treatment 
of event, and outcome. Additionally, the aggregated AEs with the resulting worst severity and 
worst relationship will be included in the AE listings.
Vital signs including SpO2 (%) will be summarized using descriptive statistics, including mean 
values and mean change from baseline values. Clinical laboratory data of local laboratories will 
be presented with the number and percentage of patients with values below, within, or above the 
normal range at each time point. Additionally, a shift table of the number and percentage of 
patients with normal and abnormal, and clinically significant abnormal values at each scheduled 
postbaseline visit compared with the normal/abnormal/clinically significant abnormal 
categorization at baseline will be provided by treatment group. Summarizing of clinical 
laboratory data of local laboratories using descriptive statistics, including mean values and mean 
change from baseline values will be only possible after normalization of the values using a 
reference laboratory. Details for normalization will be provided in the SAP.
Summary tables will be provided for concomitant medications.
15.5
Pharmacokinetic Analysis 
The PK parameters (such as Cmax, Tmax, AUC0-t, and others) of MP1032 on Day 1 (single dose) 
and Day 7 (steady state; if available), using up to 8 hours postdose, will be derived applying non-
compartmental analysis. PK parameters will be summarized along with plasma concentrations at 
various time points. Individual and mean plasma concentration versus time will be presented on 
linear, and semi-log scales. Further details of the PK analysis will be described in the SAP. Any
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possible correlation between plasma exposure and biomarkers (eg, change from baseline in 
cytokines, or other coagulation/inflammatory biomarkers) or efficacy measures can be explored 
by appropriate regression analysis methods during the final data analysis.
15.6
Biomarker Analysis
The change from baseline biomarker levels will be summarized descriptively by treatment group 
and visit. The change in biomarker levels will also be evaluated with any change of COVID-19
clinical status.
15.7
Interim Analysis 
Not applicable. 
15.8
Data Monitoring Committee
An independent DMC will be established by the sponsor or designee to review accumulating 
study data at regular intervals (as per the DMC charter) throughout the study to ensure the safety 
of patients and review overall study conduct. Additional data may be reviewed that are related to 
efficacy, but the DMC will only be reviewing data for risk-benefit purposes. Members will 
include experts in drug safety and/or medical specialist and biostatistics, who are not 
participating in this study and do not have affiliation with the investigators or the sponsor. The 
DMC can recommend in writing to the sponsor whether to continue, modify, or stop the clinical 
study on the basis of safety considerations. The pre-specified study stopping rules for the trial are 
defined as follows: 
x
death (not including disease progression) in any patient in whom the cause of death is 
judged to be related to the study drug by investigator
x
the occurrence in any patient of a SAE whose causal relationship (ie, without a plausible 
alternative explanation) to the study drug is judged to be related by investigator
x
two occurrences of a clinically significant Grade 3 or higher laboratory abnormality 
assessed to be related to the study drug by investigator.
The DMC’s specific duties will be fully described in a DMC charter.
16
STUDY MANAGEMENT
16.1
Approval and Consent
Regulatory Guidelines
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and all relevant regulations as set forth in Parts 50, 56, 312, Subpart D, of Title 21 of 
the United States Code of Federal Regulations (CFR), in compliance with International Council 
for Harmonisation and GCP guidelines and according to the appropriate regulatory requirements 
in the countries where the study will be conducted.
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Institutional Review Board/Independent Ethics Committee
Conduct of the study must be approved by an appropriately constituted IRB/IEC. Approval is 
required for the study protocol, protocol amendments (if applicable), IB, ICFs, recruitment 
material and patient information sheets, and other patient-facing material.
Informed Consent
For each patient (or the patient’s LAR), informed consent will be obtained before any 
protocol-related activities. As part of this procedure, the principal investigator (PI) or designee 
must explain the nature of the study, its purpose, procedures, expected duration, alternative 
therapy available, and the benefits and risks involved in study participation. The patient (or the 
patient’s LAR) should be informed that he/she may withdraw from the study at any time, and the 
patient will receive all information that is required by local regulations and guidelines for 
International Council for Harmonisation. The PI will provide the sponsor or its representative 
with a copy of the IRB/IEC-approved ICF before the start of the study.
16.2
Data Handling
Data reported on the eCRF that are derived from source documents should be consistent with the 
source documents, or the discrepancies must be explained (see also Section 16.3).
Clinical data will be entered by site personnel on eCRFs for transmission to the sponsor. Data on 
eCRFs transmitted via the web-based data system must correspond to and be supported by source 
documentation maintained at the study site. All study forms and records transmitted to the 
sponsor must only include coded identifiers such that directly identifying personal information is 
not transmitted. The primary method of data transmittal is via the secure, internet-based 
electronic data capture (EDC) system maintained by Syneos Health. Access to the EDC system 
is available to only authorized users via the study’s internet website, where a user unique
assigned username and password are required for access.
Any changes made to data after collection will be made through the use of data clarification 
forms or the EDC system. When all missing and/or incorrect data have been resolved, eCRFs 
will be considered complete.
16.3
Source Documents
Source documents are considered to be all information in original records and certified copies of 
original records of clinical findings, observations, data, or other activities in a clinical study 
necessary for the reconstruction and evaluation of the study. The investigator will provide direct 
access to source documents and/or source data in the facilitation of study-related monitoring, 
audits, review by IRB/IECs, and regulatory inspections.
The investigator/institution should maintain adequate and accurate source documents and study
records that include all pertinent observations on each of the site’s patients. Source data should 
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be attributable, legible, contemporaneous, original, accurate, and complete. Changes to source 
data should be traceable, not obscure the original entry, and be explained if necessary.
16.4
Record Retention 
Study records and source documents must be preserved for at least 30 years after the completion 
or discontinuation of/withdrawal from the study, at least 2 years after the drug being studied has 
received its last approval for sale, or at least 2 years after the drug development has stopped, and 
in accordance with the applicable local privacy laws, whichever is the longer period.
The investigator agrees to comply with all applicable federal, state, and local laws and 
regulations relating to the privacy of patient health information, including, but not limited to, the 
Standards for Individually Identifiable Health Information, 45 CFR, Parts 160 and 164 (the 
Health Insurance Portability Accountability Act of 1996 Privacy Regulation). The investigator 
shall ensure that study patients authorize the use and disclosure of protected health information 
in accordance with Health Insurance Portability Accountability Act Privacy Regulation and in a 
form satisfactory to the sponsor.
16.5
Monitoring 
The study will be monitored to ensure that it is conducted and documented properly according to 
the protocol, GCP, and all applicable regulatory requirements.
Monitoring visits, on-site and remote (telephone), or a combination of these and contacts will be 
made at appropriate times during the study. The PI will assure he/she and adequate site personnel 
must be available throughout the study to collaborate with clinical monitors. Clinical monitors 
must have direct access to source documentation to check the completeness, clarity, and 
consistency of the data recorded in the eCRFs for each patient.
The investigator will make available to the clinical monitor all source documents and medical 
records necessary to review protocol adherence and eCRFs. In addition, the investigator will 
work closely with the clinical monitor and as needed, provide them appropriate evidence that the 
study is being conducted in accordance with the protocol, applicable regulations, and GCP 
guidelines.
16.6
Quality Control and Quality Assurance 
The sponsor or its designee will perform the quality assurance and quality control activities of 
this study; however, responsibility for the accuracy, completeness, security, and reliability of the 
study data presented to the sponsor lies with the investigator generating the data.
The sponsor may arrange audits as part of the implementation of quality assurance to ensure that 
the study is being conducted in compliance with the protocol, standard operating procedures, 
GCP, and all applicable regulatory requirements. Audits will be independent of and separate 
from the routine monitoring and quality control functions. Quality assurance procedures will be 
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performed at study sites and during data management to assure that safety and efficacy data are 
adequate and well documented.
16.7
Protocol Amendment and Protocol Deviation
Protocol Amendment
Amendments to the protocol that entail corrections of typographical errors, clarifications of 
confusing wording, changes in study personnel, and minor modifications that have no effect on 
the safety of patients or the conduct of the study will be classed as administrative amendments 
and will be submitted to the IRB/IEC for information only. The sponsor will ensure that 
acknowledgment is received and filed. Amendments that are classed as substantial amendments 
must be submitted to the appropriate regulatory authorities and the IRB/IECs for approval and 
will not be implemented at sites until such approvals are received other than in the case of an 
urgent safety measure.
Protocol Deviations
Should a protocol deviation occur, the sponsor must be informed as soon as possible. Protocol 
deviations and/or violations and the reasons they occurred will be included in the CSR. 
Reporting of protocol deviations to the IRB/IEC and in accordance with applicable regulatory 
authority mandates is the investigator’s responsibility.
16.8
Ethical Considerations
This study will be conducted in accordance with this protocol, the accepted version of the 
Declaration of Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, 
Subpart D, of Title 21 of the CFR; EU 536/2014, Annex 1, D, 17 (a); and in compliance with 
GCP guidelines.
IRB/IECs will review and approve this protocol and the ICF. All patients (or the patient’s LAR)
are required to give informed consent before participation in the study.
16.9
Financing and Insurance
Before the study commences, the sponsor (or its designee) and the investigator (or the institution, 
as applicable) will agree on costs necessary to perform the study. This agreement will be 
documented in a financial agreement that will be signed by the investigator (or the institution 
signatory) and the sponsor (or its designee).
The investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice. The sponsor will provide no-exclusion insurance coverage for the clinical 
study as required by national regulations.
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16.10
Publication Policy/Disclosure of Data 
Both the use of data and the publication policy are detailed within the clinical study agreement. 
Intellectual property rights (and related matters) generated by the investigator and others 
performing the clinical study will be subject to the terms of a clinical study agreement that will 
be agreed between the institution and the sponsor or their designee. With respect to such rights, 
the sponsor or its designee will solely own all rights and interests in any materials, data, and 
intellectual property rights developed by investigators and others performing the clinical study 
described in this protocol, subject to the terms of any such agreement. In order to facilitate such 
ownership, investigators will be required to assign all such inventions either to their institution or 
directly to the sponsor or its designee, as will be set forth in the clinical study agreement.
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17
REFERENCES 
Beigel JH, Tomashek KM, Dodd LE, et al. ACTT-1 Study Group Members. Remdesivir for the 
treatment of Covid-19 - final report. N Engl J Med. Published online October 8, 2020.
doi:10.1056/NEJMoa2007764. 
Cennimo DJ. Coronavirus Disease 2019 (COVID-19). Updated January 09, 2021. Accessed 
January 13, 2021. https://emedicine.medscape.com/article/2500114-overview.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic 
comorbidity in longitudinal studies: development and validation. J Chronic Dis.
1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8.
Curtin N, Bányai K, Thaventhiran J, et al. Repositioning PARP inhibitors for SARSဨCoVဨ2 
infection (COVIDဨ19); a new multiဨpronged therapy for acute respiratory distress syndrome?
Br J Pharmacol. 2020;177(16): 3635-3645. doi:10.1111/bph.15137.
EuroQol Research Foundation. EQ-5D Instruments. Accessed October 9, 2020.
https://euroqol.org/eq-5d-instruments/.
Fanelli V, Vlachou A, Ghannadian S, et al. Acute respiratory distress syndrome: new definition, 
current and future therapeutic options. J Thorac Dis. 2013;5(3):326-334.
doi:10.3978/j.issn.2072-1439.2013.04.05.
Food and Drug Administration (FDA). COVID-19: Developing drugs and biological products for 
treatment or prevention, guidance for industry, May 2020. Accessed November 11, 2020. 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/covid-19-
developing-drugs-and-biological-products-treatment-or-prevention.
Garibaldi BT, Fiksel J, Muschelli J, et al. Patient trajectories among persons hospitalized for 
COVID-19: a cohort study. Ann Intern Med. Published online September 22, 2020.
doi:10.7326/M20-3905.
Gloire G, Legrand-Poels S, Piette J. NF-kappaB activation by reactive oxygen species: fifteen 
years later. Biochem Pharmacol. 2006;72(11):1493-1505. doi:10.1016/j.bcp.2006.04.011. 
Grunewald ME, Fehr AR, Athmer J, Perlman S. The coronavirus nucleocapsid protein is ADP-
ribosylated. Virology. 2018;517:62-68. doi:10.1016/j.virol.2017.11.020. 
Hillienhof A. COVID-19: What immune reactions are triggered. German Medical Journal 
(Deutsches Ärzteblatt). 2020;117(39):A-1822.
Ke Y, Wang C, Zhang J, et al. The role of PARPs in inflammation-and metabolic-related 
diseases: molecular mechanisms and beyond. Cells. 2019;8(9):1047. doi:10.3390/cells8091047. 
Khomich OA, Kochetkov SN, Bartosch B, Ivanov AV. Redox biology of respiratory viral 
infections. Viruses. 2018;10(8):392. doi:10.3390/v10080392. 
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Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. 
Ann Intern Med. 2009;150(9):604-612.
Levin AT, Hanage WP, Owusu-Boatey N, et al. Assessing the age specifity of infection fatality 
rates for COVID-19: systematic review, meta-analysis, and public policy implications. Eur J 
Epidemiol. 2020;35(12):1123-1138. doi: 10.1007/s10654-020-00698-1.
Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease 
(COVID-19) outbreak. J Autoimmun. 2020;109:102433. Published online February 26, 2020. 
doi:10.1016/j.jaut.2020.102433.
Schumann S, Kaiser A, Nicoletti F, et al. Immune-modulating drug MP1032 with SARS-CoV-2
antiviral activity in vitro: a potential multi-target approach for prevention and early intervention 
treatment of COVID-19. Int J Mol Sci. 2020;21(22):8803. doi:10.3390/ijms21228803.
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19.
Lancet. 2020;395(10234):1417-1418. Published online April 21, 2020. doi:10.1016/S0140-
6736(20)30937-5.
WHO Rapid Evidence Appraisal for COVID-19 Therapies (WHO-REACT) Working Group, 
Sterne JAC, Murthy S, Diaz JV, et al. Association between administration of systemic 
corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. 
JAMA. Published online September 2, 2020. 324(13):1-13. doi:10.1001/jama.2020.17023.
World Health Organization (WHO). 2020a. January 12, 2020. Accessed January 14, 2021.
https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/.
World Health Organization (WHO). 2020b. Estimating mortality from COVID-19. Scientific 
brief, August 4, 2020. Accessed October 27, 2020. 
https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci-Brief-Mortality-2020.1
World Health Organization (WHO). 2020c. Therapeutics and COVID-19. Living Guideline.
December 17, 2020. Accessed December 17, 2020. 
https://www.who.int/publications/i/item/therapeutics-and-covid-19-living-guideline. WHO 
reference number: WHO/2019-nCoV/therapeutics/2020.1.
World Health Organization (WHO). 2020d. WHO R&D Blueprint. Novel coronavirus: 
COVID-19 therapeutic trial synopsis. February 18, 2020. Accessed October 19, 2020. 
https://www.who.int/publications-detail/covid-19-therapeutic-trial-synopsis. 
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18
APPENDICES 
APPENDIX 1 describes the Charlson Comorbidity Index (CCI) applicable for this study.
APPENDIX 2 describes the EuroQol-5D-5L (EQ-5D-5L) questionnaire applicable for this study.
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APPENDIX 1. 
CHARLSON COMORBIDITY INDEX 
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https://orthotoolkit.com/charlson-comorbidity-index/
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APPENDIX 2. 
EUROQOL-5D-5L (EQ-5D-5L) QUESTIONNAIRE 
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Health Questionnaire
English version for the USA
© 2009 EuroQol Research Foundation. EQ-5D™ is a trade mark of the EuroQol Research Foundation. USA (English) v1.1
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Under each heading, please check the ONE box that best describes your health 
TODAY.
MOBILITY
I have no problems walking

I have slight problems walking

I have moderate problems walking

I have severe problems walking

I am unable to walk

SELF-CARE
I have no problems washing or dressing myself

I have slight problems washing or dressing myself

I have moderate problems washing or dressing myself

I have severe problems washing or dressing myself

I am unable to wash or dress myself

USUAL ACTIVITIES (e.g. work, study, housework, family or leisure 
activities)
I have no problems doing my usual activities

I have slight problems doing my usual activities

I have moderate problems doing my usual activities

I have severe problems doing my usual activities

I am unable to do my usual activities

PAIN / DISCOMFORT
I have no pain or discomfort

I have slight pain or discomfort

I have moderate pain or discomfort

I have severe pain or discomfort

I have extreme pain or discomfort

ANXIETY / DEPRESSION
I am not anxious or depressed

I am slightly anxious or depressed

I am moderately anxious or depressed

I am severely anxious or depressed

I am extremely anxious or depressed

2
© 2009 EuroQol Research Foundation. EQ-5D™ is a trade mark of the EuroQol Research Foundation. USA (English) v1.1
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The worst health 
you can imagine
3
© 2009 EuroQol Research Foundation. EQ-5D™ is a trade mark of the EuroQol Research Foundation. USA (English) v1.1
x
We would like to know how good or bad your health is TODAY.
x
This scale is numbered from 0 to 100.
x
100 means the best health you can imagine.
0 means the worst health you can imagine.
x
Mark an X on the scale to indicate how your health is TODAY.
x
Now, please write the number you marked on the scale in the box 
below.
10
h
0
20
30
40
50
60
80
70
90
100
5
15
25
35
45
55
75
65
85
95
The best health 
you can imagine
YOUR HEALTH TODAY =
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MP1032
Protocol v2.0 - France
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1
CLINICAL STUDY PROTOCOL 
Protocol Title: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF MP1032 PLUS 
STANDARD OF CARE VS STANDARD OF CARE IN THE TREATMENT OF 
HOSPITALIZED PATIENTS WITH MODERATE TO SEVERE COVID-19
Protocol Number: MP1032-CT05
Short Title: MP1032 Treatment in Patients with Moderate to Severe COVID-19
Investigational New Drug Number:
153604
Name of Investigational Product:
MP1032 hard gelatin capsules 50 mg 
Phase of Development:
IIa
Indication:
Treatment of symptomatic patients with moderate to severe 
coronavirus disease 2019 (COVID-19) disease 
EudraCT Number:
2021-000344-21
Sponsor’s EU Representative:
MetrioPharm Deutschland GmbH
Am Borsigturm 100
13507 Berlin
Germany
Sponsor:
MetrioPharm AG
Bleicherweg 10
8002 Zürich
Switzerland
Protocol Version: 
Final 2.0 – France
Protocol Date:
31-Jan-2022
-CONFIDENTIAL-
This document and its contents are the property of and confidential to MetrioPharm AG. Any unauthorized 
copying or use of this document is prohibited.
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PROTOCOL APPROVAL SIGNATURES
Protocol Title:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF 
MP1032 PLUS STANDARD OF CARE VS STANDARD OF CARE IN 
THE TREATMENT OF HOSPITALIZED PATIENTS WITH 
MODERATE TO SEVERE COVID-19
Protocol Number:
MP1032-CT05
This study will be conducted in compliance with the clinical study protocol (and 
amendments), International Council for Harmonisation guidelines for current Good 
Clinical Practice (GCP), and applicable regulatory requirements.
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INVESTIGATOR SIGNATURE PAGE
Protocol Title:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF MP1032 
PLUS STANDARD OF CARE VS STANDARD OF CARE IN THE 
TREATMENT OF HOSPITALIZED PATIENTS WITH MODERATE TO 
SEVERE COVID-19
Protocol Number:
MP1032-CT05
Confidentiality and Current Good Clinical Practice (GCP)/E6(R2)/Compliance Statement
x
I, the undersigned, have reviewed this protocol (and any amendments), including appendices, and I 
will conduct the study as described in compliance with this protocol (and any amendments), GCP, 
and relevant International Council for Harmonisation guidelines.
x
I am thoroughly familiar with the appropriate use of the study drug, as described in this protocol and 
any other information provided MetrioPharm AG including, but not limited to, the current 
investigator’s brochure.
x
Once the protocol has been approved by the institutional review board (IRB)/independent ethics 
committee (IEC), I will not modify this protocol without obtaining prior approval of 
MetrioPharm AG and of the IRB/IEC. I will submit the protocol amendments and/or any informed 
consent form (ICF) modifications to MetrioPharm AG and the IRB/IEC, and approval will be 
obtained before any amendments are implemented.
x
I ensure that all persons or parties assisting me with the study are adequately qualified and informed 
about the MetrioPharm AG study drug and of their delegated study-related duties and functions as 
described in the protocol.
x
I ensure that source documents and study records that include all pertinent observations on each of the 
site’s patients will be attributable, legible, contemporaneous, original, accurate, and complete. 
x
I understand that all information obtained during the conduct of the study with regard to the patients’
state of health will be regarded as confidential. No patients’ names will be disclosed. All patients
will be identified by assigned numbers on all case report forms, laboratory samples, or source 
documents forwarded to the sponsor. Clinical information may be reviewed by the sponsor or its 
agents or regulatory agencies. Agreement must be obtained from the patient before disclosure of 
patient information to a third party.
x
Information developed in this clinical study may be disclosed by MetrioPharm AG to other clinical 
investigators, regulatory agencies, or other health authority or government agencies as required.
Printed Name 
Investigator Signature
Title 
Date (DD-Mmm-YYYY)
Institution
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2
SYNOPSIS 
Title of Study:
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER, PROOF-OF-CONCEPT, PHASE IIA STUDY OF MP1032 
PLUS STANDARD OF CARE VS STANDARD OF CARE IN THE 
TREATMENT OF HOSPITALIZED PATIENTS WITH MODERATE TO 
SEVERE COVID-19
Protocol Number:
MP1032-CT05
Investigators/Study Sites:
Approximately 40 sites worldwide will participate in this study.
Phase of Development:
Phase IIa
Study Objectives:
The primary objective of this study is:
x
To measure the effect of MP1032 plus standard of care (SoC) versus 
placebo plus SoC on Day 14 on disease progression in patients with 
moderate to severe coronavirus disease 2019 (COVID-19) 
The secondary objectives of this study are:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
Day 28 on disease progression in patients with moderate to severe 
COVID-19
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
disease resolution on Day 14 and Day 28 
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
the mortality rate and other specific COVID-19 related characteristics
x
To assess the safety of MP1032 (eg, adverse events [AEs] and laboratory 
abnormalities)
x
To assess the pharmacokinetics (PK) of MP1032 on Day 1 (single dose) 
and Day 7 (steady state) in a PK subset of patients
The exploratory objectives of this study are:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on 
some additional COVID-19 related characteristics
x
To evaluate the health-related quality of life (HRQoL) of patients treated 
MP1032 plus SoC compared with placebo plus SoC
x
To evaluate biomarker levels
Study Endpoints:
The primary efficacy endpoint of this study is:
x
Proportion of patients with disease progression on Day 14. Disease 
progression is defined as the proportion of patients who are not alive or who 
have respiratory failure. Respiratory failure is defined as patients who have a 
score of 2, 3, or 4 on the National Institute of Allergy and Infectious Diseases 
(NIAID) 8-point ordinal scale (see below). 
The key secondary efficacy endpoints of this study are:
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x
Proportion of patients with disease progression on Day 28. Disease 
progression is defined as the proportion of patients who are not alive or who 
have respiratory failure. Respiratory failure is defined as patients who have a 
score of 2, 3, or 4 on the NIAID 8-point ordinal scale (see below). 
x
Proportion of patients with disease resolution on Day 28. Disease resolution 
is defined as patients who are alive and have a score of 6, 7, or 8 on the 
NIAID 8-point ordinal scale. 
x
All-cause mortality rate at Day 28
x
Change of clinical status related to COVID-19 on Day 28 compared with 
baseline according to the following NIAID 8-point ordinal scale:
1.
Death
2.
Hospitalized, on invasive ventilation (mechanical ventilator and/or 
extracorporeal membrane oxygenation [ECMO])
3.
Hospitalized, on non-invasive ventilation or high-flow oxygen devices
4.
Hospitalized, requiring supplemental oxygen
5.
Hospitalized, not requiring supplemental oxygen, but requiring ongoing 
medical care (COVID-19 related or otherwise)
6.
Hospitalized, not requiring supplemental oxygen and no longer requires 
ongoing medical care (used if hospitalization was extended for 
infection-control reasons)
7.
Not hospitalized, limitation on activities, and/or requiring home oxygen
8.
Not hospitalized, no limitations on activities
Please note: Patients requiring oxygen before COVID-19 and returning to 
baseline oxygen use will be considered improved (ie, not requiring supplemental 
oxygen). Patients with a limitation on activities before COVID-19 and returning 
to baseline activity will be considered improved. In case of death before Day 14 
or Day 28, the patient will be considered with the NIAID score for death (score of 
1) on the date of death in the analysis.
The other secondary endpoints of this study are:
x
Proportion of patients with disease resolution on Day 14. Disease resolution 
is defined as patients who are alive and have a score of 6, 7, or 8 on the 
NIAID 8-point ordinal scale. 
x
All-cause mortality rate at Day 14 and Day 60
x
Change of clinical status related to COVID-19 on Day 14 compared with 
baseline according to the NIAID 8-point ordinal scale as listed above.
x
Proportion of patients requiring invasive ventilation (mechanical ventilator 
and/or ECMO), or who are not alive on Day 14 or Day 28 
x
Proportion of patients in each category of the NIAID 8-point ordinal scale
x
Time to (first) improvement of at least 1 category on the NIAID 8-point 
ordinal scale (until Day 28). Patients who did not improve at least 1 category 
on the NIAID scale or die before Day 28 will be censored at Day 28.
x
The odds ratio between MP1032 and SoC and placebo and SoC for the 
number of patients with clinical status improvement from baseline on the 
NIAID 8-point ordinal scale (ie, an improvement of at least 1 category) at 
Day 14 and Day 28 
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x
Total duration of hospitalization on Day 28 and Day 60 (from baseline to 
discharge; with death censored on the last day of the observed period – at
Day 28 or Day 60, respectively)
x
Proportion of patients alive and testing negative for COVID-19 on Day 14, 
Day 28, and Day 60
x
Safety and tolerability assessed by:
o
Cumulative incidence of treatment-emergent AEs (summarized by 
seriousness, severity, relationship to the study medication, outcome, 
and duration) 
o
Vital sign parameters 
o
Clinical laboratory parameters
o
Physical examination findings
x
MP1032 plasma concentrations and PK parameters (if possible) including 
maximum observed plasma concentration, area under the concentration-time 
curve, elimination parameters, apparent body clearance, apparent volume of 
distribution, trough concentration, average observed plasma concentration at 
steady state, and other relevant PK parameters assessed via MP1032 plasma 
exposure on Day 1 and Day 7 in a PK subset of patients
Exploratory endpoints of this study are:
x
Change in saturation of oxygen (SpO2)/fraction of inspired oxygen (FiO2)
ratio (for patients alive) on Day 14 or Day 28 compared with baseline
x
Total number of days in the intensive care unit (ICU)
x
Duration of invasive mechanical ventilation 
x
Duration of ECMO
x
Time to recovery from COVID-19 symptoms (stuffy or runny nose, sore 
throat, red or irritated eyes, shortness of breath, cough, low energy or 
tiredness, muscle or body aches, headache, chills or shivering, feeling hot or 
feverish, nausea, and number of times of vomit, times of diarrhea, sense of 
smell, sense of taste in the last 24 hours) at Day 14, Day 28, and Day 60
x
Change from discharge in the EuroQol (EQ) index value and EQ visual 
analog scale (VAS) based on the EuroQol-5D-5L (EQ-5D-5L) questionnaire 
at Day 60
x
Change from baseline in biomarker levels potentially including, but not 
limited to, cytokines (eg, C-reactive protein, interleukin [IL]-1E, IL-6, tumor 
necrosis factor-Į, and interferon-J), and other coagulation/inflammatory 
biomarkers (eg, D-dimer and ferritin)
Study Design:
This is a Phase IIa, randomized, double-blind, placebo-controlled, multicenter, 
proof-of-concept study designed to assess the efficacy and safety of 300 mg
MP1032 twice daily (BID) plus SoC versus placebo plus SoC in hospitalized 
adults with moderate to severe COVID-19.
Approximately 140 patients will be screened to randomize approximately 
120 patients in 2:1 ratio as follows: 
x
Arm A (300 mg MP1032 BID plus SoC): approximately 80 patients
x
Arm B (placebo BID plus SoC): approximately 40 patients
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The stratification factor for randomization will include baseline COVID-19
severity (moderate versus severe) and age-class (aged 65 years versus 
>65 years). COVID-19 severity will be determined using the following criteria:
x
Moderate COVID-19: 
o
Positive severe acute respiratory syndrome coronavirus type 2 
(SARS-CoV-2) testing by standard reverse 
transcription-polymerase chain reaction (RT-PCR) assay or 
equivalent test 
o
Symptoms of moderate illness with COVID-19, which could 
include any symptom of mild illness or shortness of breath with 
exertion
o
Clinical signs suggestive of moderate illness with COVID-19, 
such as respiratory rate 20 breaths per minute, SpO2 >93% (on 
room air at sea level, if possible), heart rate 90 beats per 
minute 
o
No clinical signs indicative of severe or critical COVID-19
x
Severe COVID-19: 
o
Positive SARS-CoV-2 testing by standard RT-PCR assay or 
equivalent test 
o
Symptoms suggestive of severe systemic illness with 
COVID-19, which could include any symptom of moderate 
illness or shortness of breath at rest, or respiratory distress
o
Clinical signs suggestive of severe systemic illness with 
COVID-19, such as respiratory rate 30 breaths per minute, 
heart rate 125 beats per minute, SpO2 93% (on room air at 
sea level, if possible), partial pressure of oxygen/FiO2 <300, or 
diagnosed with acute respiratory distress syndrome (according 
to the Berlin definition)
o
No criteria met for critical COVID-19
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and 
heart rate will be measured when the patient is on room air at sea level (ie, no 
supplemental oxygen) and at rest for at least 5 minutes. If possible, the site should 
collect the information from each patient at the same time each day (±1 hour). 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic 
condition (eg, emphysema, chronic obstructive pulmonary disease [COPD], 
pulmonary arterial hypertension [PAH], idiopathic pulmonary fibrosis [IPF], etc) 
must be considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19 severity, 
the investigator should contact the medical monitor.
Each site will treat all patients with SoC for the duration of the study. The 
selected SoC will be used in accordance with the hospital’s SoC procedures and 
may include drugs under an emergency use authorization.
This study consists of 3 periods: (1) screening, (2) treatment, and (3) follow-up. 
During the screening period, each potential patient (or patient’s legally acceptable 
representative) will provide informed consent before starting any study-specific 
procedures. The randomization of patients to treatment groups will be performed 
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centrally by an interactive web-response system (IWRS) using a randomization 
scheme that will be developed by an unblinded, independent statistician. During 
the treatment period, randomized patients will be provided their assigned 
treatment and assessments according to the protocol. All patients will be treated 
for 28 days unless the study drug is discontinued for safety reasons. For patients 
discharged early, study visits at Day 8, Day 14, Day 21, and Day 28 must be 
performed as an outpatient visit (ie, at the study site). Patients who progress to the 
use of an invasive ventilation (mechanical ventilator and/or ECMO) or who can 
no longer swallow the study drug (>2 days [ie, 2-day interruption is acceptable]) 
must discontinue the study drug; but whenever possible, the study assessments 
will be performed on Day 8, Day 14, Day 21, Day 28, and Day 60. If the patient is 
discharged home before Day 28, the study team will provide the patient with the 
remainder of the assigned blinded study drug kit(s) to take home along with 
instructions on how to continue treatment at home on the day-of-discharge; for 
these patients, treatment compliance will be conducted via a diary. If the patient 
does not feel comfortable to complete the diary, the site will alternatively provide 
the patient with the option to be called, twice a day, to confirm that the study drug 
is taken as instructed. The treatment period will end with the Day 28 (End of 
Treatment Visit) assessments. The follow-up period will consist of Day 60 
(Follow-up Visit) assessments.
Selection of Patients:
Inclusion Criteria:
Individuals must meet all of the following criteria to be included in the study:
1.
The patient must be willing and able to give informed consent to 
participate in the study and to adhere to the procedures stated in the 
protocol or, for adults incapable of consenting due to their medical 
condition (eg, too weak or debilitated, severe shortness of breath) or due 
to literacy issues, the patient’s legally authorized representative must be 
willing and able to give informed consent on behalf of the patient to 
participate in the study as permitted by local regulatory authorities, 
institutional review boards (IRBs)/independent ethics committees 
(IECs), or local laws.
2.
The patient is male or female adult aged 18 years (as per local laws) at 
the time of giving informed consent.
3.
The patient is admitted to a hospital and has a positive SARS-CoV-2 test 
by standard RT-PCR assay or equivalent test. Please note: If the patient 
has a previous confirmation of SARS-CoV-2 (within 7 days of Day 1), 
the SARS-CoV-2 test at screening is not required. 
4.
The patient has the presence of any symptom(s) suggestive of moderate 
or severe systemic illness with COVID-19 on Day 1, such as presence of 
fever (38.0ιC [100.4ιF] by any route), loss of smell or taste, cough, 
sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, 
shortness of breath upon exertion and/or at rest, or respiratory distress.
5.
The patient has the presence of moderate to severe clinical signs 
indicative of moderate or severe illness with COVID-19 on Day 1: 
a)
Moderate: 
i.
Clinical signs suggestive of moderate illness with 
COVID-19, such as respiratory rate 20 breaths per 
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minute, SpO2 >93% (on room air at sea level, if 
possible), heart rate 90 beats per minute 
ii.
No clinical signs indicative of severe or critical 
COVID-19
b)
Severe: 
i.
Clinical signs suggestive of severe systemic illness 
with COVID-19, such as respiratory rate 30 breaths 
per minute, heart rate 125 beats per minute, SpO2
93% (on room air at sea level, if possible), partial 
pressure of oxygen/FiO2 <300, or diagnosed with acute 
respiratory distress syndrome (according to the Berlin 
definition)
ii.
No criteria met for critical COVID-19
Please note: Patients who are receiving oxygen therapy at baseline for a 
chronic condition (eg, emphysema, COPD, PAH, IPF, etc) must be 
considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19
severity, the investigator should contact the medical monitor.
6.
The patient does not require hemodialysis (chronic) or any renal 
replacement therapies at screening or Day 1.
7.
The patient is able to swallow the study drug (hard gelatin capsules). 
8.
The patient agrees to minimize strong sun exposure (sunbathing) and 
strong ultraviolet exposure during the course of the study. Additionally, 
during the study, patients must agree to use sunscreen when spending an 
extended period outdoors.
9.
Men whose sexual partners are women of childbearing potential 
(WOCBP) must agree to comply with 1 of the following contraception 
requirements from the time of first dose of study medication (Day 1) 
until at least 30 days after the last dose of study medication:
a)
Vasectomy with documentation of azoospermia. 
b)
Sexual abstinence (defined as refraining from heterosexual 
intercourse from the time of first dose of study medication until 
at least 30 days after the last dose of study medication)
c)
Male condom plus partner use of 1 of the contraceptive options 
below: contraceptive subdermal implant; intrauterine device or 
intrauterine system; oral contraceptive, either combined or 
progestogen alone; injectable progestogen; contraceptive 
vaginal ring; percutaneous contraceptive patches. 
The above is an all-inclusive list of those methods that meet the 
following definition of highly effective: having a failure rate of <1% per 
year when used consistently and correctly and, when applicable, in 
accordance with the product label. For non-product methods (eg, male 
sterility), the investigator will determine what is consistent and correct 
use. The investigator is responsible for ensuring that patients understand 
how to properly use these methods of contraception. 
10. WOCBP must agree to comply with 1 of the following contraception 
requirements from the time of first dose of study medication (Day 1)
until at least 30 days after the last dose of study medication:
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a)
Sexual abstinence (defined as refraining from heterosexual 
intercourse from the time of first dose of study medication until 
at least 30 days after the last dose of study medication)
b)
Use of 1 of the contraceptive options below plus use of a 
condom by male partner: contraceptive subdermal implant; 
intrauterine device or intrauterine system; oral contraceptive, 
either combined or progestogen alone; injectable progestogen; 
contraceptive vaginal ring; percutaneous contraceptive patches. 
c)
Vasectomy of male partner with documentation of azoospermia. 
The above is an all-inclusive list of those methods that meet the 
following definition of highly effective: having a failure rate of <1% per 
year when used consistently and correctly and, when applicable, in 
accordance with the product label. The investigator is responsible for 
ensuring that patients understand how to properly use these methods of 
contraception. Women of non-reproductive potential are defined as: 
a)
Premenopausal females with 1 of the following: documented 
tubal ligation; documented hysteroscopic tubal occlusion 
procedure with follow-up confirmation of bilateral tubal 
occlusion; hysterectomy; documented bilateral oophorectomy.
b)
Postmenopausal defined as 12 months of spontaneous 
amenorrhea [in questionable cases a blood sample with 
simultaneous follicle stimulating hormone and estradiol levels 
consistent with menopause (refer to laboratory reference ranges 
for confirmatory levels)]. Women on hormone replacement 
therapy (HRT) and whose menopausal status is in doubt will be 
required to use 1 of the highly effective contraception methods 
listed above if they wish to continue their HRT during the 
study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before randomization. 
Exclusion Criteria:
Individuals meeting any of the following criteria are ineligible to participate in 
this study: 
1.
The patient, in the opinion of the investigator, is not likely to survive for 
48 hours beyond Day 1. 
2.
The patient has a diagnosis of asymptomatic COVID-19, mild 
COVID-19, or critical COVID-19 on Day 1. 
a)
Asymptomatic COVID-19 is defined as a patient with a positive 
SARS-CoV-2 test by standard RT-PCR assay or equivalent test 
but not experiencing symptoms. 
b)
Mild COVID-19 is defined as a patient with a positive SARS-
CoV-2 test by standard RT-PCR assay or equivalent test and 
experiencing symptoms of mild illness but no clinical signs 
indicative of moderate, severe, or critical COVID-19. 
c)
Critical COVID-19 is defined as a patient with a positive 
SARS-CoV-2 test by standard RT-PCR assay or equivalent test 
and experiencing at least 1 of the following: shock defined by 
systolic blood pressure <90 mm Hg or diastolic blood pressure
<60 mm Hg, or requiring vasopressors; respiratory failure 
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requiring endotracheal intubation and invasive mechanical 
ventilation, oxygen delivered by high-flow nasal cannula 
(heated, humidified, oxygen delivered via reinforced nasal 
cannula at flow rates >20 L/min with fraction of delivered 
oxygen 0.5), non-invasive positive pressure ventilation, 
ECMO, or clinical diagnosis of respiratory failure (ie, clinical 
need for 1 of the preceding therapies, but preceding therapies 
not able to be administered in setting of resource limitation), 
and/or multi-organ dysfunction/failure.
Please note: Patients who are receiving oxygen therapy at baseline for a 
chronic condition (eg, emphysema, COPD, PAH, IPF, etc) must be 
considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19
severity, the investigator should contact the medical monitor.
3.
The patient has a Child Pugh score  C.
4.
The patient has a documented medical history of infection with hepatitis 
A, B, or C at screening or Day 1.
5.
The patient has a documented medical history of infection with human 
immunodeficiency virus and has a detectable viral load and CD4 count 
<500 cells/μL. 
6.
The patient has a documented active infection with tuberculosis at 
screening or Day 1.
7.
The patient has clinically significant electrocardiogram abnormalities at 
screening.
8.
A female patient who is pregnant, planning to become pregnant during 
the study, breastfeeding, or has a positive pregnancy test at screening (by 
serum) and before dosing on Day 1 (by urine) as determined by human 
chorionic gonadotrophin tests.
9.
The patient is planning to donate or bank ova or sperm from Day 1 until 
30 days after the last dose of study drug.
10. The patient has a known history of drug or alcohol abuse within 
6 months of study start that would interfere with the patient’s 
participation in the study.
11. The patient has a history of sensitivity to any of the study medications, 
components thereof (eg, mannitol or gelatin), or a history of drug or 
other allergy that, in the opinion of the investigator or medical monitor, 
would contraindicate their participation.
12. The patient has participated in and/or plans to participate in another 
clinical study using an investigational product within the following 
period before the first dosing day in the current study: 30 days, 5 half-
lives, or twice the duration of the biological effect of the investigational 
product (whichever is longer).
13. The patient will be transferred to another hospital that is not a study site 
within 72 hours. Please note: If the investigator has admitting privileges 
to the transfer hospital, the patient may be considered for randomization.
14. The patient is employed by MetrioPharm, the contract research 
organization or clinical site involved in the clinical study.
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15. The investigator makes a decision that study involvement is not in 
patient’s best interest, or the patient has any condition or critical illness,
in the opinion of the investigator, that will not allow the protocol to be 
followed safely.
Planned Sample Size:
The primary efficacy endpoint “proportion of patients with disease progression on 
Day 14” is assumed to be 10% in the 300 mg MP1032 BID plus SoC treatment 
group (Arm A) and 30% in the placebo plus SoC treatment group (Arm B). Using 
the Chi-square test with type I error alpha=10% two-sided for this proof-of-
concept study and 2:1 randomization ratio, with 114 randomized patients (76 in 
Arm A and 38 in Arm B) a statistical power of 83% can be achieved. Considering 
about 5% early study terminations, the necessary sample size to randomize results 
is 120 patients in total (80 in Arm A and 40 in Arm B). If during the conduct of 
the study the early study termination rate is higher than the estimated 5%, then an 
increase in the randomized number of patients may be necessary. 
Sample size estimation was performed using nQuery 8, Version 8.6.1.0.
A subset of randomized patients will be consented for the collection of blood 
samples for PK measurements. The PK subset consists of approximately 
20 patients from the 300 mg MP1032 BID plus SoC group and approximately 
10 patients from the placebo plus SoC group, up to a total of approximately 
30 patients.
Study Drug, Dose, and 
Mode of Administration:
All randomized patients will receive study drug from Day 1 to Day 28 according 
to their assigned treatment and according to the randomization scheme. Patients 
will receive 6 capsules in the morning and 6 capsules in the evening (ie, 
approximately every 12 hours, approximately at the same time every day, and at 
least 8 hours apart) according to their randomized treatment arm assignment as 
described below: 
x
Arm A: MP1032 (300 mg [6 × MP1032 hard gelatin capsules 50 mg]
BID) for oral administration
x
Arm B: 6 × placebo capsules (ie, matching MP1032 hard gelatin 
capsules 50 mg) BID for oral administration
Standard of Care
Each site will treat all patients with SoC for the duration of the study. The 
selected SoC will be used in accordance with the hospital’s SoC procedures and 
may include drugs under an emergency use authorization.
Treatment Duration:
Patients will be treated with study drug for 28 consecutive days (unless study drug 
is discontinued for safety reasons) to provide a fixed duration of treatment across 
all patients. For patients discharged early, study visits at Day 8, Day 14, Day 21, 
and Day 28 must be performed as an outpatient visit (ie, at the study site). Patients 
who progress to the use of an invasive ventilation (mechanical ventilator and/or 
ECMO) or who can no longer swallow the study drug (>2 days [ie, 2-day 
interruption is acceptable]) must discontinue the study drug; but whenever 
possible, the study assessments will be performed on Day 8, Day 14, Day 21, Day 
28, and Day 60. If the patient is discharged home before Day 28, the study team 
will provide the patient with the remainder of the assigned blinded study drug 
kit(s) to take home along with instructions on how to continue treatment at home 
on the day-of-discharge; for these patients, treatment compliance will be 
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conducted via a diary. If the patient does not feel comfortable to complete the 
diary, the site will alternatively provide the patient with the option to be called, 
twice a day, to confirm that the study drug is taken as instructed.
The study duration for an individual patient will be as follows:
x
Screening period: up to 7 days 
x
Treatment period: 28 consecutive days (ie, Day 1 to Day 28)
x
Follow-up period: 32 days after Day 28 (ie, Day 60)
As such, the approximate study duration (including screening and the follow-up
period) for an individual patient is up to 67 days (±3 days).
Please note: Patients who remain hospitalized after 28 days of consecutive 
treatment with study drug are not eligible for additional treatments with study 
drug. 
Any patient who is discharged during the study should complete the day-of-
discharge assessments before release from the hospital.
Efficacy Assessments:
The following efficacy assessments will be collected:
x
COVID-19 symptoms
x
COVID-19 severity
x
Clinical status related to COVID-19 on the NIAID 8-point ordinal scale, 
as well as each individual component of the NIAID 8-point ordinal scale
x
HRQoL assessed by the EQ-5D-5L questionnaire
x
COVID-19 testing 
Safety Assessments:
The following safety assessments will be collected:
x
Medical/surgical history
x
Demographics
x
Prior and concomitant medications
x
Vital signs 
x
Physical examinations
x
Electrocardiograms
x
Clinical laboratory assessments 
x
AEs 
Pharmacokinetic 
Assessments:
PK samples will be collected via sparse sampling from a subset of approximately 
30 patients (who give optional consent) in a 2:1 ratio (approximately 20 patients 
from the 300 mg MP1032 BID plus SoC group and approximately 10 patients 
from the placebo group plus SoC group) to assess the PK of MP1032 on Day 1 
(single dose) and Day 7 (steady state). A total of 16 samples will be collected 
relative to the first dose on Day 1 and the first dose on Day 7. Samples on Day 1 
and Day 7 will be collected predose (within 10 minutes before the first daily dose) 
and postdose at 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 
8 hours (before next dose), and 24 hours before the next morning dose (if 
applicable), if possible. Patients who provide consent for the PK sampling, but are 
no longer hospitalized on Day 7, will not have Day 7 PK samples collected. 
Other Assessments:
Blood samples will be obtained on Day 1 (before the first study drug 
administration) and Days 7, 14, 21, 28, and 60 (when possible) to measure 
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biomarker levels. Biomarkers will potentially include but will not be limited to 
the following cytokines (eg, C-reactive protein, IL-1E, IL-6, tumor necrosis 
factor-Į, and IFN-J) and other coagulation/inflammatory biomarkers (eg, D-dimer 
and ferritin).
Statistical Methods and 
Planned Analyses:
Analysis Sets:
Intention-to-Treat Set
The Intention-to-Treat (ITT) set, correspond with randomized set, will include all
randomized patients irrespective of any deviation from the protocol or premature 
discontinuation from study drug/withdrawal from study. The treatment group 
assignment will be designated according to initial randomization. The ITT will
serve as the basis for the analysis of efficacy and summary of demographics and 
baseline characteristics.
Per Protocol Set
The Per Protocol Set (PPS) will include all patients from ITT who received at 
least 1 dose of study drug, and who do not have any major protocol deviations 
impacting the efficacy assessments. The PPS will be used for supportive analyses 
of efficacy.
Safety Set
The Safety Set (SS) will include all randomized patients who received at least 
1 dose of study drug. The treatment group assignment in the SS will be defined by
the treatment actually received. The SS will be used for the analysis of safety.
PK Analysis Set
The PK Analysis Set (PKS) will include all the patients who have been 
administered active study drug and have at least 1 postdose evaluable plasma 
concentration after Day 1 dose.
Analyses: 
The estimands for the primary efficacy endpoint and for the 4 key secondary 
endpoints comparing the 2 treatment groups will be tested with consideration of a 
two-sided alpha of 10% on each test-level on the ITT. Additionally, 95% 
confidence intervals will be provided. Also, the treatment comparison with 
regards to the other efficacy endpoints will be performed using a two-sided alpha 
level of 10%.
The main estimand for the primary efficacy endpoint is defined as a binary 
variable indicating disease progression (death or respiratory failure) at Day 14. 
Intercurrent events that lead to study drug discontinuation and/or switch to other 
treatment before Day 14 will be handled using the treatment-policy strategy (ie, 
the NIAID score at Day 14 will be used for definition of the failure in such 
patients). Missing data on Day 14 resulting from study termination before Day 14
are not expected. However, in case they happen, such monotone missings will be 
imputed by multiple imputation using information from similar patients of the 
same treatment group. Missing post-baseline data for patients randomized but not 
treated will be imputed by the respective baseline value (baseline observation 
carried forward, BOCF). The comparison between the treatment groups 
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considering all randomized patients after having imputed missing values will be 
performed using Mantel-Haenszel (MH) test for risk difference considering the 4 
strata resulting from the 2 randomization stratification factors disease severity 
(moderate versus severe) and age-class (aged 65 years versus >65 years) at 
baseline.
Similar MH analyses will be conducted for the main estimand of the first key 
secondary efficacy endpoint, which is defined as a binary variable indicating 
disease progression (death or respiratory failure) at Day 28, and the main 
estimand for the second key secondary efficacy endpoint, which is defined as a 
binary variable indicating disease resolution (alive and have a score of 6, 7 or 8 
on NIAID) at Day 28. Intercurrent events that lead to study drug discontinuation 
and/or switch to other treatment before Day 28 will be handled using the 
treatment-policy strategy for these estimands (ie, the NIAID score at Day 28 will 
be used for definition of the failure or response, respectively) in such patients. 
Missing data on Day 28 will be imputed by multiple imputation using information 
from similar patients of the same treatment group. 
A similar MH approach as described above will be applied also to the main 
estimand of the third key secondary efficacy endpoint, which is the all-cause 
mortality at Day 28. Intercurrent events that lead to study drug discontinuation 
and/or switch to other treatment before Day 28, will be handled using the 
treatment-policy strategy (ie, the life status at Day 28 will be considered). No 
missing data of life status on Day 28 is expected. 
The main estimand of the fourth key secondary efficacy endpoint, change of 
clinical status related to COVID-19 on Day 28 compared with baseline according 
to the NIAID 8-point ordinal scale, will be compared using the risk difference 
from the analysis of covariance model with treatment and the 2 binary 
stratification factors (ie, severity and age-class) as independent factors and the 
baseline value of NIAID as independent covariate. Intercurrent events that lead to 
study drug discontinuation and/or switch to other treatment before Day 28 will be 
handled using the treatment-policy strategy for these estimands (ie, the NIAID 
score at Day 28 will be used). Missing data on Day 28 will be imputed by 
multiple imputation using information from similar patients of the same treatment 
group. 
Sensitivity analyses for the main estimands of the primary and key efficacy 
estimands will be performed by assuming missing data at Day 14 or Day 28 as 
failure or non-resolution for the binary endpoints, and by multiple imputation 
using information from similar patients of the placebo group for the NIAID 8-
point ordinal scale.
All above analyses for the main estimands of the primary efficacy and key 
secondary efficacy endpoints will be repeated on PPS as supportive analysis. 
Additionally, for the primary efficacy and binary key secondary efficacy 
endpoints logistic regression model with treatment and the 2 stratification factors 
as covariables will be performed on the ITT.
The proportion of patients with disease resolution at Day 14 and the all-cause 
mortality rate at Day 14 and Day 60 will be analyzed using similar MH methods 
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as described above for Day 28. Cumulative proportion of patients with disease 
resolution will be plotted by time.
A similar analysis of covariance approach as described above for Day 28 will be 
applied for the analysis of the change of clinical status related to COVID-19 on 
Day 14 compared with baseline on the NIAID 8 point ordinal scale. The endpoint 
considering the proportion of patients requiring invasive ventilation (mechanical 
ventilator and/or ECMO) or who are not alive, the proportion of patients in each 
NIAID category, and the proportion of patients alive and testing negative for 
COVID-19 on Day 14, Day 28, and Day 60, respectively, will be compared 
between the treatment groups using MH test. Overall survival, time to (first) 
improvement of at least 1 category on the NIAID scale and total hospitalization 
duration (from baseline to discharge; with death censored on last day of the 
observed period - at Day 28 or Day 60, respectively - depending on the analyses) 
will be summarized using the Kaplan-Meier method and will be compared 
between treatment groups using log-rank tests. Additionally, Cox proportional 
hazards model will be applied with treatment and the 2 stratification factors as
covariables.
The odds ratio between MP1032 and SoC and placebo and SoC for the number of 
patients with clinical status improvement from baseline on the NIAID 8-point 
ordinal scale (ie, an improvement of at least 1 category) at Day 14 and Day 28 
will be analyzed using a logistic regression with consideration of the 
2 stratification factors.
The time to recovery of all at baseline present COVID-19 symptoms (stuffy or 
runny nose, sore throat, red or irritated eyes, shortness of breath, cough, low 
energy or tiredness, muscle or body aches, headache, chills or shivering, feeling 
hot or feverish, nausea, and number of times of vomit, times of diarrhea, sense of 
smell, sense of taste in the last 24 hours) will be presented by Kaplan-Meier 
estimates and figure. The change from baseline will be presented in shift tables
for each single symptom, with the number and percentage of subjects in each 
category at post-baseline assessment time-point compared to baseline for each 
treatment group.
Total number of days in ICU, duration of invasive mechanical ventilation, and 
duration of ECMO will be descriptively summarized by treatment group using 
mean days with 90% confidence intervals and additionally by median days and 
quartiles. To consider death sufficiently unfavorable in these measures, in case of 
death the duration of the respective measure will be considered with the longest 
duration possible (eg, if a summary of the first 28 days is presented, then death 
before Day 28 will be considered as duration 28 days, and if the summary also 
includes follow-up period until Day 60, then death before Day 60 will be 
considered as duration of 60 days). Both summaries (up to Day 28 and up to 
Day 60) will be provided.
For HRQoL assessments at discharge and Day 60, the EQ index value and the EQ 
VAS, both based on the EQ-5D-5L questionnaire will be calculated and 
summarized by visit and treatment group. Additionally, change at Day 60 from 
discharge by treatment group.
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All efficacy endpoints will be summarized using descriptive statistics by 
treatment group and by visit, as appropriate: Binary and categorical endpoints will 
be summarized by treatment group by presenting the number and percentage of 
patients in the categories. Continuous and ordinal endpoints will be described by 
mean, standard deviation, median, minimum, and maximum for actual values and 
change from baseline. Additionally, for ordinal data, the number and percentage 
of patients in each category will be presented.
The PK parameters (such as Cmax, Tmax, AUC0-t, and others) of MP1032 on Day 1
(single dose) and Day 7 (steady state; if available), using up to 8 hours postdose, 
will be derived applying non-compartmental analysis. PK parameters will be 
summarized along with plasma concentrations at various time points. Individual 
and mean plasma concentration versus time will be presented on linear, and semi-
log scales. Further details of the PK analysis will be described in the statistical 
analysis plan (SAP). Any possible correlation between plasma exposure and 
biomarkers (eg, change from baseline in cytokines, or other 
coagulation/inflammatory biomarkers) or efficacy measures can be explored by 
appropriate regression analysis methods during the final data analysis. 
The change from baseline biomarker levels will be summarized descriptively by 
treatment group and visit. The change in biomarker levels will also be evaluated 
with any change of COVID-19 clinical status.
All safety parameters will be summarized descriptively by treatment group for the 
entire study period.
Study drug duration and SoC therapies will be described for each treatment group.
The SAP will present further estimands for the primary and key secondary 
endpoints and will describe the statistical analyses in detail.
Independent Data 
Monitoring Committee:
An independent data monitoring committee (DMC) will be established by the 
sponsor or designee to review accumulating study data at regular intervals (as per 
the DMC charter) throughout the study to ensure the safety of patients and review 
overall study conduct. Additional data may be reviewed that are related to 
efficacy, but the DMC will only be reviewing data for risk-benefit purposes. 
Members will include experts in drug safety and/or medical specialist and 
biostatistics, who are not participating in this study and do not have affiliation 
with the investigators or the sponsor. The DMC can recommend in writing to the 
sponsor whether to continue, modify, or stop the clinical study on the basis of 
safety considerations. The DMC’s specific duties will be fully described in a 
DMC charter.
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3
TABLE OF CONTENTS
1
CLINICAL STUDY PROTOCOL....................................................................................1
2
SYNOPSIS ........................................................................................................................4
3
TABLE OF CONTENTS ................................................................................................18
3.1
List of In-text Tables ..................................................................................................21
4
LIST OF ABBREVIATIONS .........................................................................................22
5
INTRODUCTION...........................................................................................................24
5.1
Background on COVID-19.........................................................................................24
5.2
Background on MP1032, Including Benefit Risk Assessment ..................................25
Nonclinical Studies ............................................................................................26
Clinical Studies ..................................................................................................27
5.3
Risk Management of MP1032....................................................................................29
5.4
Study Rationale ..........................................................................................................29
6
STUDY OBJECTIVES AND ENDPOINTS ..................................................................31
6.1
Study Objectives.........................................................................................................31
6.2
Study Endpoints..........................................................................................................31
7
INVESTIGATIONAL PLAN .........................................................................................33
7.1
Description of Overall Study Design and Plan...........................................................33
7.2
Discussion of Study Design........................................................................................35
7.3
End of Study...............................................................................................................37
8
SELECTION OF STUDY POPULATION.....................................................................37
8.1
Inclusion Criteria........................................................................................................37
8.2
Exclusion Criteria.......................................................................................................39
8.3
Rescreening ................................................................................................................41
8.4
Study Withdrawal, Removal, and Replacement of Patients.......................................41
9
TREATMENTS...............................................................................................................42
9.1
Details of Study Drugs ...............................................................................................42
9.2
Dosage Schedule ........................................................................................................42
9.3
Measures to Minimize Bias: Randomization and Blinding........................................43
Randomization ...................................................................................................43
Blinding44
9.4
Treatment Modifications and Discontinuations .........................................................45
9.5
Treatment Accountability and Compliance................................................................46
9.6
Prior and Concomitant Medications...........................................................................46
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10
STUDY PROCEDURES.................................................................................................47
10.1
Informed Consent .......................................................................................................53
10.2
Study Procedures........................................................................................................53
11
EFFICACY ASSESSMENTS.........................................................................................53
11.1
COVID-19 Symptoms................................................................................................54
11.2
COVID-19 Severity....................................................................................................54
11.3
Clinical Status Related to COVID-19 on the National Institute of Allergy and Infectious 
Diseases 8-Point Ordinal Scale ..................................................................................56
11.4
Health-related Quality of Life Assessment ................................................................58
11.5
COVID-19 Testing .....................................................................................................58
12
SAFETY ASSESSMENTS .............................................................................................58
12.1
Medical/Surgical History and Demographics ............................................................58
12.2
Vital Signs ..................................................................................................................59
12.3
Physical Examinations................................................................................................60
12.4
Electrocardiograms.....................................................................................................60
12.5
Clinical Laboratory Assessments ...............................................................................60
12.6
Adverse Events...........................................................................................................62
Adverse Events ..................................................................................................62
Serious Adverse Events .....................................................................................64
Serious Adverse Event Reporting......................................................................64
Suspected Unexpected Serious Adverse Reactions ...........................................65
Pregnancy...........................................................................................................65
Overdose ............................................................................................................66
13
PHARMACOKINETICS ................................................................................................66
13.1
Pharmacokinetic Sampling.........................................................................................66
13.2
Pharmacokinetic Analytical Methodology.................................................................67
14
OTHER ASSESSMENTS...............................................................................................67
14.1
Biomarkers .................................................................................................................67
15
STATISTICAL ANALYSIS...........................................................................................68
15.1
Determination of Sample Size....................................................................................68
15.2
Analysis Sets ..............................................................................................................69
15.3
Efficacy Analysis........................................................................................................70
15.4
Safety Analysis...........................................................................................................73
15.5
Pharmacokinetic Analysis ..........................................................................................74
15.6
Biomarker Analysis....................................................................................................74
15.7
Interim Analysis .........................................................................................................74
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15.8
Data Monitoring Committee.......................................................................................74
16
STUDY MANAGEMENT..............................................................................................75
16.1
Approval and Consent ................................................................................................75
Regulatory Guidelines........................................................................................75
Institutional Review Board/Independent Ethics Committee..............................75
Informed Consent...............................................................................................75
16.2
Data Handling.............................................................................................................75
16.3
Source Documents......................................................................................................76
16.4
Record Retention........................................................................................................76
16.5
Monitoring..................................................................................................................76
16.6
Quality Control and Quality Assurance .....................................................................77
16.7
Protocol Amendment and Protocol Deviation............................................................77
Protocol Amendment .........................................................................................77
Protocol Deviations............................................................................................77
16.8
Ethical Considerations................................................................................................77
16.9
Financing and Insurance.............................................................................................78
16.10 Publication Policy/Disclosure of Data........................................................................78
17
REFERENCES................................................................................................................79
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3.1
List of In-text Tables 
Table 1: Schedule of Assessments ........................................................................................48 
Table 2 
COVID-19 Symptoms.............................................................................................54 
Table 3: Acute Respiratory Distress Syndrome – Berlin Definition.....................................56 
Table 4 
Standard Conversion for Liter Flow Oxygen..........................................................57 
Table 5: Clinical Laboratory Assessments............................................................................61 
Table 6: Classification of Adverse Events by Severity.........................................................63 
Table 7: Classification of Adverse Events by Relationship to Study Drug ..........................63 
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4
LIST OF ABBREVIATIONS 
Abbreviation
Definition
AE
adverse event
ARDS
acute respiratory distress syndrome
AUC0-t
area under the concentration-time curve from time zero to the last non-zero 
concentration
BID
twice daily
BOCF
baseline observation carried forward
CFR
Code of Federal Regulations
Cmax
maximum plasma concentration
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease 2019
CSR
clinical study report
DMC
data monitoring committee
ECG
electrocardiogram
ECMO
extracorporeal membrane oxygenation
eCRF
electronic case report form
EDC
electronic data capture
EQ
EuroQol
EQ-5D-5L
EuroQol-5D-5L
FiO2
fraction of inspired oxygen
GCP
good clinical practice
hCG
human chorionic gonadotropin
HRQoL
health-related quality of life
HRT
hormone replacement therapy
IB
investigator’s brochure
ICF
informed consent form
ICU
intensive care unit
IEC
independent ethics committee
IL
interleukin
IMP
investigational medicinal product
IPF
idiopathic pulmonary fibrosis
IRB
institutional review board
ITT
Intention-to-Treat
IWRS
interactive web-response system
LAR
legally authorized representative
MH
Mantel-Haenszel
NIAID
National Institute of Allergy and Infectious Diseases
PAH
pulmonary arterial hypertension
PaO2
partial pressure of oxygen
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Abbreviation
Definition
PARP1
poly-ADP-ribose-polymerase 1
PASI
Psoriasis Area and Severity Index
PI
principal investigator
PK
pharmacokinetic
PKS
PK Analysis Set
PPS
Per Protocol Set
PT
preferred term
ROS
reactive oxygen species
RT-PCR
reverse transcription-polymerase chain reaction
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus type 2
SoC
standard of care
SOC
system organ class
SpO2
saturation of oxygen
SS
Safety Set
SUSAR
suspected unexpected serious adverse reactions
TEAE
treatment-emergent adverse events
Tmax
time of observed Cmax
TNF
tumor necrosis factor
VAS
visual analog scale
WHO
World Health Organization
WOCBP
women of childbearing potential
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5
INTRODUCTION 
5.1
Background on COVID-19 
On 31 December 2019, the World Health Organization (WHO) was informed of a cluster of 
cases of pneumonia of unknown cause detected in 
. Severe 
acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) was identified as the causative 
virus by Chinese authorities on 07 January 2020 (WHO 2020a). Coronavirus disease 2019 
(COVID-19) was identified as the disease caused by SARS-CoV-2 infection. In March 2020, the 
COVID-19 outbreak was declared as a pandemic by the WHO. The disease resulting from 
SARS-CoV-2 led to shutdowns and social measures in great parts of the world, particularly to 
slow down the transmission of the virus and thereby avoiding the overburden of health care 
systems. 
The pandemic is still ongoing. Estimates of actual morbidity, mortality, and lethality are highly 
variable and depend on factors such as the time of analysis, region analyzed, and surveillance 
methods. As of 04 August 2020, the WHO estimated the case fatality ratio, which estimates the 
proportion of deaths among confirmed cases, to vary from 0.1% to >25%. Whereas, the true 
severity of COVID-19 as measured by the infection fatality ratio, which estimates the proportion 
of deaths among all infected individuals, is estimated to be approximately 0.5% to 1% 
(WHO 2020b). In a more recent summary of Levin et al (2020) it could be clearly shown that the 
infection fatality ratio is highly age dependent, being in average as low as 0.004% for patients 
younger than 35 and as high as 28.3% in patients at the age of 85 and older.
Presentations of COVID-19 range from an asymptomatic course or mild symptoms to severe 
illness and mortality. Common symptoms include fever or chills, cough, shortness of breath or 
difficulty breathing, fatigue, muscle or body aches, headache, loss of taste or smell, sore throat, 
congestion or runny nose, nausea or vomiting, and diarrhea (Cennimo 2021). Less common 
symptoms are sputum production, malaise, respiratory distress, and neurologic symptoms, such 
as altered mental state. While most patients with COVID-19 seem to show mild respiratory 
symptoms only, some of them develop pneumonia, shortness of breath and hypoxia, or other 
serious conditions that require hospitalization. Generally, pneumonia seems to be the most 
common serious manifestation of COVID-19. Further, major deterioration such as an acute 
respiratory distress syndrome (ARDS) can lead to the imperative need of an intensive care unit 
(ICU) and might even require mechanical ventilation via intubation. Other complications that 
might occur during the course of the disease include: sepsis, acute kidney injury, thyrotoxicosis, 
and neurologic manifestations such as myasthenia gravis. The elderly, as well as patients with 
pre-existing chronic conditions (eg, asthma, chronic obstructive pulmonary disease [COPD], 
diabetes mellitus, chronic kidney disease, immune system deficiencies, liver disease, and cardiac 
diseases, etc), seem to be more vulnerable to a severe disease course.
Although, to date, knowledge about SARS-CoV-2 and corresponding COVID-19 is still limited, 
it seems to be clear that the course of the disease, and particularly severe complications, are 
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based on an overshooting immune response. Details on and a deeper understanding of how the 
virus causes such a reaction will be a central part of future investigations (Hillienhof 2020).
Patients with COVID-19 show increased levels of plasma pro-inflammatory cytokines (Rothan 
and Byrareddy 2020). From a pathophysiological point of view, in severe cases the viral 
infection seems to trigger an excessive immune reaction in the host, a so-called cytokine storm, 
leading to extensive tissue damage. A key player of this mechanism is interleukin (IL)-6. IL-6
inhibitors, as well as other immune modulators, must thus be considered a potential treatment 
approach. This approach seems to be particularly promising, as recent postmortem findings show 
direct viral infection of the endothelial cells and diffuse endothelial inflammation in the whole 
body (Varga et al 2020).
Recently the first vaccines to prevent COVID-19 have been approved by authorities, including 
the Food and Drug Administration in the United States and the European Medicines Agency in 
Europe, and numerous further vaccine projects are still under development. Nonetheless, it will 
take years until the majority of people will be vaccinated and the epidemiological situation can 
be considered as under control. Hence, there is still an urgent need for therapeutic agents to cure 
COVID-19 and/or ameliorate its symptoms. Among the antiviral treatment options, remdesivir 
has shown to be effective in reducing hospitalization time when administered early in the course 
of the disease (Beigel et al 2020); however, in the meantime the WHO has issued a conditional 
recommendation against the use of remdesivir in hospitalized patients regardless of disease 
severity (WHO 2020c) Among immune modulating drugs low-dosed dexamethasone could 
significantly lower the incidence of deaths when applied at a later time point of the disease 
course (WHO-REACT 2020) but is not recommended early in disease or in patients with mild 
symptoms only (WHO 2020c). Hence, there is still no antiviral treatment or otherwise effective 
curative agent that could really lower the burden of this pandemic. Thus, COVID-19 still 
presents an urgent unmet medical need.
5.2
Background on MP1032, Including Benefit Risk Assessment 
MP1032 is a purely synthetic, new chemical entity. MP1032 is a mono sodium salt derived from 
the aromatic system phthalazinedione, containing an additional amino group. MP1032 is 
water-soluble and hydrophilic.
The primary mechanism of action of MP1032 is assumed to be a reactive oxygen species (ROS)
scavenging action in inflamed tissues (ie, tissues that experience oxidative stress). A unique 
pharmacologic property of MP1032 is that the ROS-scavenging function of the molecule is only 
activated in tissues with pathologically high ROS concentrations (oxidative stress), which is the 
case in inflamed tissue. By re-establishing a physiologic redox balance in activated immune 
cells, MP1032 is putatively inhibiting nuclear factor-kappa B activation. Inhibition of nuclear 
factor-kappa B is expected to lead to inhibition of pro-inflammatory cytokines (eg, IL-6 and 
TNF-Į) (Gloire et al 2006). In addition, MP1032 is a specific inhibitor of poly-ADP-ribose-
polymerase 1 (PARP1). PARP1 is a nuclear enzyme involved in inflammation (Ke et al 2019).
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Further identified potential targets are the kinases human Aurora-B, human Aurora-C, 
serine/threonine-protein kinase, tyrosine kinase, and the metalloprotease TNF-Į-converting 
enzyme—however, at relatively high molarity only. Therefore, the administration of MP1032 (as 
shown nonclinically, both in vitro and in vivo), in pathological conditions only, leads to a 
reduced concentration of pro-inflammatory cytokines without completely blocking them. In 
addition to this broadly anti-inflammatory potential, MP1032 exhibits direct antiviral activity 
against SARS-CoV-2 that could be shown by a clear and dose-dependent inhibition of SARS-
CoV-2 reproduction in Vero B4 cells (African green monkey [Chlorocebus aethiops] kidney 
epithelium cells) (Schumann et al 2020).
MP1032 could attenuate prolonged virus replication by preventing oxidative stress 
(Khomich et al 2018) and/or by limiting ADP-ribosylation of the viral nucleocapsid protein via 
PARP1 inhibition (Grunewald et al 2018). PARP1 inhibitors also have been suggested for the 
treatment of COVID-19 (Curtin et al 2020).
Based on the basic chemical mechanism of MP1032 as an electron donor to ROS, the molecule 
acts similarly across a wide range of species and is thus not an agent with a high degree of 
species specificity. Further, MP1032 has no specific immune-system targets as known from 
various biologicals. MP1032 is not expressed by using mammalian systems (cells) or using raw 
materials of human or animal origin.
Nonclinical Studies
In vivo safety studies showed no evidence of neurotoxic potential or negative 
cardiohemodynamic effects; no local intolerance was observed. There was no dose-limiting or 
target organ toxicity and no substance-related findings in histopathology in rats or dogs. 
However, after 6 months of long-term treatment in rats receiving the highest dose 
(1000 mg/kg/d), liver organ weight was elevated compared with that of controls and 
histopathologically associated with hepatocellular hypertrophy. This finding was not considered 
adverse because of its adaptive character, as histopathological changes were not present at the 
end of the recovery period (ie, effect was reversible after 8 weeks).
In reproduction toxicity studies on fertility, early embryonic, and embryo-fetal development, no 
pathological effects were found. On the basis of results from 4 different test systems, mutagenic 
or clastogenic effects are not considered to be a potential risk for volunteers and patients.
Transient effects on some pulmonary parameters have been observed in rats following a single 
intravenous bolus injection of the highest dose (300 mg/kg) of MP1032. No pulmonary effects 
have been observed in any of the long-term animal toxicity studies. The maximum plasma levels 
reached in humans are over 1000 times (oral) lower than for the abovementioned dose. Thus, 
pulmonary effects are not considered a potential risk for patients and volunteers.
Emesis sporadically occurred in various repeat-dose toxicology studies in dogs; the emesis was 
present in the dogs more often at the high doses of 150 mg/kg twice daily (BID) intravenous than 
at 125 mg/kg BID (oral). The lowest experimental oral dose inducing emesis was 25 mg/kg BID 
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(oral) in dogs, corresponding to 1.8 g (oral; conversion based on human-equivalent dose) for a 
65-kg human. Dogs are well known to be susceptible to emesis; in addition, the maximum doses 
administered in humans are 6 to 30 times below the converted human-equivalent doses. 
Therefore, emesis is not considered a potential risk for patients and volunteers.
Transient liquid feces were sporadically observed in various repeat-dose toxicology studies in 
dogs of all dose groups treated with MP1032. However, these gastrointestinal irritations could 
not be attributed to specific animals and thus did not have an observable effect on their 
wellbeing. Further, no such observations were made in any of the other species investigated. 
Also, in the clinical studies completed so far, no cases of diarrhea have been reported as adverse 
drug reactions by the respective investigators. Gastrointestinal irritations are therefore not 
considered a potential risk for patients and volunteers.
A potential phototoxic risk cannot be excluded from the in vitro 3T3 neutral red uptake and the 
distribution quantitative whole-body autoradiography test. In the clinical studies completed so far 
with MP1032, mean maximum plasma concentrations and calculated maximum skin 
concentrations were all below the half maximal effective concentration in the 3T3 neutral red 
uptake test with safety margins between 2 to 20 times. Therefore, a phototoxic risk for patients 
seems to be unlikely.
Further, a slight to moderate increase in serum creatinine level combined with a slight decrease 
of kidney weights was observed after a 90-day treatment period in male mice in a dose-range 
finding, repeated dose (oral) toxicity study at high dosed animals. However, as there were no 
associated histopathological findings in kidneys of the respective animals, this effect is also not 
considered to be adverse in nature. In the scope of extensive laboratory controls in the clinical 
studies completed so far, no respective treatment-emergent adverse events (TEAEs) have been 
reported. 
The probability of pharmacokinetic interactions of MP1032 regarding the inhibition or induction 
of Cytochrome P450 or inhibition of well-known drug transporters is rather low. However, based 
on in vitro experiments there are hints that a combination of MP1032 and dexamethasone might 
act (supra-)additive regarding the inhibition of proinflammatory cytokines (ie, IL-6). Thus, 
currently, a potential drug-drug interaction of MP1032 and dexamethasone regarding their anti-
inflammatory action cannot be excluded.
For further details of the completed nonclinical studies conducted with MP1032, readers are 
referred to the current version of the investigator’s brochure (IB).
Clinical Studies
MP1032 so far has been investigated in 3 clinical studies, including a first-in-human study 
(MP1032-CT01; EudraCT-No.: 2014-004606-15) with a single ascending dose and a multiple 
ascending dose part, as well as 2 studies in patients with moderate-to-severe psoriasis: a 6-week, 
Phase IIa, pilot study (MP1032-CT02; EudraCT-No.: 2015-005159-28) and a 3-month, Phase II 
study (MP1032-CT04; EudraCT-No.: 2017-003484-36).
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Among the subjects enrolled in MP1032 studies, 146 subjects were administered MP1032 orally. 
Among them, 24 male subjects participated as healthy volunteers in the Phase I study, while both 
male (n=89) and female (n=33) patients with psoriasis participated in the Phase II studies. The 
age of participants administered MP1032 ranged from 18 to 68 years. Pregnant and breastfeeding 
women, as well as children and adolescents have not been included in the studies.
The highest single dose of MP1032 administered was 600 mg, applied to healthy volunteers. The 
highest repeated dose was 300 mg MP1032 BID, applied to both healthy volunteers (7 days) and 
patients with psoriasis (3 months).
No serious adverse events (SAEs) occurred in any of the subjects administered MP1032.
No deaths occurred in the scope of the MP1032 clinical development program.
MP1032 was well tolerated in all studies, and safety analyses did not reveal any clinically 
important safety issues. In general, incidence, intensity, causality, and spreading of TEAEs over 
system organ classes (SOCs) were comparable between groups. In the recent Phase II study, the 
incidence, intensity, relationship to investigational medicinal product (IMP), and causality to 
IMP for adverse events (AEs) were even lower for both MP1032 dose groups compared with 
those of the placebo group and statistically significantly lower for the 300 mg MP1032 group 
compared with the placebo group.
None of the potential risks arising from preclinical data could be confirmed with clinical data. 
From the TEAEs that occurred in the MP1032 groups and were regarded as at least possibly 
related by the investigator, nasopharyngitis, pruritus, and psoriasis must be considered as 
common (1/100 to <1/10); while neutropenia, palpitations, abdominal pain upper, fatigue,
feeling drunk, influenza-like illness, cystitis, and headache can be regarded as uncommon 
(1/1,000 to <1/100). Regarding the general spreading of AEs over SOCs and the comparison 
between groups, currently none of them can be considered a significant clinical risk.
Regarding efficacy in the treatment of moderate to severe psoriasis, the MP1032-CT02 study 
showed that after only 6 weeks of treatment, there was a clinically meaningful response in 
patients who entered the study with moderate to severe psoriasis with a Psoriasis Area and 
Severity Index (PASI) score of 10 to 20 and achieved the appropriate drug-exposure levels. 
Hence, only patients with a PASI score of 10 to 20 at baseline were randomized to the 
MP1032-CT04 study. After 12 weeks, a significant PASI reduction could be shown in the 
300 mg MP1032 BID group compared with those in the placebo group; however, this only 
occurred in a prespecified subgroup of patients with PASI 15 at baseline.
Further details of the completed clinical studies conducted with MP1032 may be found in the 
current version of the IB.
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5.3
Risk Management of MP1032 
In the scope of planning and conducting future clinical studies, all potential risks associated with 
MP1032 will be considered, and measures will be taken as applicable. 
On the basis of limitations in the amount of preclinical and clinical data available so far, MP1032 
shall not be administered to patients for >3 months, and it will generally not be administered to 
children or pregnant women. 
Adverse drug reactions that have already been described in the clinical program so far, as well as 
any suspected AEs arising from risks associated with preclinical data will be evaluated 
extensively on a case-by-case base during ongoing and/or upcoming studies.
Because of potential phototoxicity, patients in upcoming studies will be advised to avoid strong 
sun exposure (sunbathing) and strong ultraviolet exposure. Furthermore, the use of sunscreen 
will be recommended when spending an extended period outdoors. It should be ensured that 
exposure to ultraviolet light (eg, from lasers in procedures) is limited while the patient is 
hospitalized.
To avoid risks associated with potential low efficacy in serious and life-threatening conditions, 
such as COVID-19, MP1032 is only recommended to be used as add-on to standard of 
care (SoC) until a respective proof-of-concept is demonstrated.
As dexamethasone is expected to be part of SoC in most institutions treating patients with 
COVID-19 investigators should be aware that a (supra-)additive synergism between MP1032 
and dexamethasone regarding their anti-inflammatory activity cannot be excluded.
Further details regarding known or anticipated risks, as well as reasonably anticipated AEs for 
MP1032 may be found in the current version of the IB.
5.4
Study Rationale  
MP1032 is a small molecule that combines localized, auto-regulated ROS-scavenging and 
immune-modulating effects with potential antiviral properties against SARS-CoV-2. MP1032 
leads to a reduced concentration of pathologically increased pro-inflammatory cytokines without 
completely blocking them. This downregulation to physiologic levels was shown in vivo and in 
vitro for IL-1ȕ, IL-6, IL-12, IL-23, and TNF-Į in activated macrophages/neutrophils; most data 
are available on the downregulation of IL-6 and TNF-Į. Once physiologic ROS levels have been 
reached, concurrent with down-modulated cytokine levels, the drug activation stops. Further, 
MP1032 might suppress virus replication in patients with COVID-19 dose-dependently like it 
has been shown in vitro with no effect on cell viability.
On the basis of this mechanism of action, MP1032 does not carry the risk of developing 
opportunistic infections, such as with IL-6 or TNF-Į inhibitors. On the contrary, an in vivo study 
on polymicrobial abdominal sepsis in mice showed a decrease of bacterial burden in animals 
treated with MP1032, although a direct antibacterial effect for MP1032 could not be shown.
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MP1032 has also been investigated in a small exploratory hemagglutinin type 5 neuraminidase
type 1 virus infection model in mice, wherein animals treated with MP1032 showed a 
significantly improved clinical score on Days 6 and 7 after infection, combined with a clear trend 
of prolonged survival compared with that of the mice receiving placebo.
In summary, when administered in combination with or as add-on to standard treatments, 
MP1032 may prevent and/or ameliorate any overstimulation of the immune system in the course 
of a COVID-19, thereby reducing the danger of opportunistic infections and helping to reduce 
the severity of general inflammatory symptoms. At the same time, the probability of a severe 
course of the disease is reduced because of a potential direct antiviral capacity of MP1032. This 
combinative approach makes MP1032 a promising candidate for the treatment of COVID-19. In 
addition, synergistic effects may be obtained when using MP1032 as an add-on to other 
medicinal products currently under investigation for treating patients with COVID-19.
There is a substantial medical need for preventive and/or therapeutic options for the COVID-19
pandemic. COVID-19 is a viral disease with a considerable mortality rate that is not yet 
completely determined and it significantly affects healthcare systems. Considering the strong 
safety profile and good tolerability of MP1032 based on both preclinical and clinical data, 
combined with the signals of meaningful therapeutic effects of MP1032, it is justified that a 
proof-of-concept for MP1032 in the treatment of patients with COVID-19 is started.
As such, this proof-of-concept study is designed to investigate the efficacy and safety of MP1032 
plus SoC versus placebo plus SoC treatment in hospitalized adults with confirmed moderate to 
severe COVID-19, the disease caused by SARS-CoV-2 infection. Additional exploratory 
objectives include pharmacokinetics (PK) of MP1032 in a PK subset of patients and the effect of 
MP1032 on biomarker levels.
This study will be executed during a worldwide outbreak of COVID-19, resulting in capacity 
issues at many medical facilities and concerns about the safety of healthcare providers caring for 
these seriously sick patients. Consequently, this study is designed to minimize the burden on 
clinical sites, including minimizing the number of required assessments and interventions. To 
allow close monitoring and oral administration, the intended patient population shall include 
only hospitalized patients with COVID-19 that do not require intubation at the time of screening 
and/or randomization. Only adults shall be included. Additionally, pregnant and breastfeeding 
women shall be excluded.
The study drugs will be indistinguishable to blinded study personnel to limit bias in study 
assessments. Most interventions and assessments may be accomplished in conjunction with the 
schedule dictated by SoC. An independent data monitoring committee (DMC) will be established 
by the sponsor or designee to review accumulating study data at regular intervals (as per the 
DMC charter) throughout the study to ensure the safety of patients and review overall study
conduct.
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6
STUDY OBJECTIVES AND ENDPOINTS 
6.1
Study Objectives 
The primary objective of this study is:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on Day 14 on 
disease progression in patients with moderate to severe COVID-19
The secondary objectives of this study are:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on Day 28 on 
disease progression in patients with moderate to severe COVID-19
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on disease 
resolution on Day 14 and Day 28
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on the mortality rate 
and other specific COVID-19 related characteristics
x
To assess the safety of MP1032 (eg, AEs and laboratory abnormalities)
x
To assess the PK of MP1032 on Day 1 (single dose) and Day 7 (steady state) in a PK 
subset of patients
The exploratory objectives of this study are:
x
To measure the effect of MP1032 plus SoC versus placebo plus SoC on some additional 
COVID-19 related characteristics
x
To evaluate the health-related quality of life (HRQoL) of patients treated MP1032 plus
SoC compared with placebo plus SoC
x
To evaluate biomarker levels
6.2
Study Endpoints 
The primary efficacy endpoint of this study is:
x
Proportion of patients with disease progression on Day 14. Disease progression is defined 
as the proportion of patients who are not alive or who have respiratory failure. 
Respiratory failure is defined as patients who have a score of 2, 3, or 4 on the National 
Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale (see below). 
The key secondary efficacy endpoints of this study are:
x
Proportion of patients with disease progression on Day 28. Disease progression is defined 
as the proportion of patients who are not alive or who have respiratory failure. 
Respiratory failure is defined as patients who have a score of 2, 3, or 4 on the NIAID 8-
point ordinal scale (see below). 
x
Proportion of patients with disease resolution on Day 28. Disease resolution is defined as 
patients who are alive and have a score of 6, 7, or 8 on the NIAID 8-point ordinal scale. 
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x
All-cause mortality rate at Day 28
x
Change of clinical status related to COVID-19 on Day 28 compared with baseline 
according to the following NIAID 8-point ordinal scale:
1. Death
2. Hospitalized, on invasive ventilation (mechanical ventilator and/or extracorporeal 
membrane oxygenation [ECMO])
3. Hospitalized, on non-invasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 
(COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen and no longer requires ongoing 
medical care (used if hospitalization was extended for infection-control reasons)
7. Not hospitalized, limitation on activities, and/or requiring home oxygen
8. Not hospitalized, no limitations on activities
Please note: Patients requiring oxygen before COVID-19 and returning to baseline oxygen use 
will be considered improved (ie, not requiring supplemental oxygen). Patients with a limitation 
on activities before COVID-19 and returning to baseline activity will be considered improved. In 
case of death before Day 14 or Day 28, the patient will be considered with the NIAID score for 
death (score of 1) on the date of death in the analysis.
The other secondary endpoints of this study are:
x
Proportion of patients with disease resolution on Day 14. Disease resolution is defined as 
patients who are alive and have a score of 6, 7, or 8 on the NIAID 8-point ordinal scale. 
x
All-cause mortality rate at Day 14 and Day 60
x
Change of clinical status related to COVID-19 on Day 14 compared with baseline 
according to the NIAID 8-point ordinal scale as listed above
x
Proportion of patients requiring invasive ventilation (mechanical ventilator and/or 
ECMO), or who are not alive on Day 14 or Day 28 
x
Proportion of patients in each category of the NIAID 8-point ordinal scale
x
Time to (first) improvement of at least 1 category on the NIAID 8-point ordinal scale 
(until Day 28). Patients who did not improve at least 1 category on the NIAID scale or 
die before Day 28 will be censored at Day 28.
x
The odds ratio between MP1032 and SoC and placebo and SoC for the number of 
patients with clinical status improvement from baseline on the NIAID 8-point ordinal 
scale (ie, an improvement of at least 1 category) at Day 14 and Day 28 
x
Total duration of hospitalization on Day 28 and Day 60 (from baseline to discharge; with 
death censored on the last day of the observed period – at Day 28 or Day 60, 
respectively)
x
Proportion of patients alive and testing negative for COVID-19 on Day 14, Day 28, and 
Day 60
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x
Safety and tolerability assessed by:
o
Cumulative incidence of TEAEs (summarized by seriousness, severity, 
relationship to the study medication, outcome, and duration) 
o
Vital sign parameters 
o
Clinical laboratory parameters
o
Physical examination findings
x
MP1032 plasma concentrations and PK parameters (if possible) including maximum 
observed plasma concentration, area under the concentration-time curve, elimination 
parameters, apparent body clearance, apparent volume of distribution, trough 
concentration, average observed plasma concentration at steady state, and other relevant 
PK parameters assessed via MP1032 plasma exposure on Day 1 and Day 7 in a PK subset
of patients
Exploratory endpoints of this study are:
x
Change in saturation of oxygen (SpO2)/fraction of inspired oxygen (FiO2) ratio (for 
patients alive) on Day 14 or Day 28 compared with baseline
x
Total number of days in the intensive care unit (ICU)
x
Duration of invasive mechanical ventilation 
x
Duration of ECMO
x
Time to recovery from COVID-19 symptoms (stuffy or runny nose, sore throat, red or 
irritated eyes, shortness of breath, cough, low energy or tiredness, muscle or body aches, 
headache, chills or shivering, feeling hot or feverish, nausea, and number of times of 
vomit, times of diarrhea, sense of smell, sense of taste in the last 24 hours) at Day 14, 
Day 28, and Day 60
x
Change from discharge in the EuroQol (EQ) index value and EQ visual analog scale 
(VAS) based on the EuroQol-5D-5L (EQ-5D-5L) questionnaire at Day 60
x
Change from baseline in biomarker levels potentially including, but not limited to, 
cytokines (eg, C-reactive protein, interleukin [IL]-1E, IL-6, TNF-Į, and IFN-J) and other 
coagulation/inflammatory biomarkers (eg, D-dimer and ferritin) 
7
INVESTIGATIONAL PLAN 
7.1
Description of Overall Study Design and Plan 
This is a Phase IIa, randomized, double-blind, placebo-controlled, multicenter, proof-of-concept 
study designed to assess the efficacy and safety of 300 mg MP1032 BID plus SoC versus 
placebo plus SoC in hospitalized adults with moderate to severe COVID-19.
Approximately 40 sites worldwide will participate in this study.
Approximately 140 patients will be screened to randomize approximately 120 patients (see 
Section 15.1 for determination of sample size) in 2:1 ratio as follows: 
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x
Arm A (300 mg MP1032 BID plus SoC): approximately 80 patients
x
Arm B (placebo BID plus SoC): approximately 40 patients
The stratification factor for randomization will include baseline COVID-19 severity (moderate 
versus severe) and age-class (aged 65 years versus >65 years). COVID-19 severity will be 
determined using the following criteria:
x
Moderate COVID-19:
o
Positive SARS-CoV-2 testing by standard reverse-transcription polymerase 
chain reaction (RT-PCR) assay or equivalent test 
o
Symptoms of moderate illness with COVID-19, which could include any 
symptom of mild illness or shortness of breath with exertion
o
Clinical signs suggestive of moderate illness with COVID-19, such as 
respiratory rate 20 breaths per minute, SpO2 >93% (on room air at sea level, 
if possible), heart rate 90 beats per minute 
o
No clinical signs indicative of severe or critical COVID-19
x
Severe COVID-19:
o
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
o
Symptoms suggestive of severe systemic illness with COVID-19, which could 
include any symptom of moderate illness or shortness of breath at rest, or 
respiratory distress
o
Clinical signs indicative of severe systemic illness with COVID-19, such as 
respiratory rate 30 breaths per minute, heart rate 125 beats per minute, 
SpO2 93% (on room air at sea level, if possible), partial pressure of oxygen 
(PaO2)/FiO2 <300, or diagnosed with ARDS (according to the Berlin 
definition; see Table 3
o
No criteria met for critical COVID-19
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will 
be measured when the patient is on room air at sea level (ie, no supplemental oxygen, if possible) 
and at rest for at least 5 minutes. If possible, the site should collect the information from each 
patient at the same time each day (±1 hour). 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition (eg, 
emphysema, COPD, pulmonary arterial hypertension [PAH], idiopathic pulmonary 
fibrosis [IPF], etc) must be considered as having severe COVID-19 (unless the patient meets the 
definition for critical COVID-19). For questions related to COVID-19 severity, the investigator 
should contact the medical monitor.
Each site will treat all patients with SoC for the duration of the study. The selected SoC will be 
used in accordance with the hospital’s SoC procedures and may include drugs under an 
emergency use authorization.
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This study consists of 3 periods: (1) screening, (2) treatment, and (3) follow-up. During the 
screening period, each potential patient (or patient’s legally acceptable representative) will 
provide informed consent before starting any study-specific procedures. The randomization of 
patients to treatment groups will be performed centrally by an interactive web-response 
system (IWRS) using a randomization scheme that will be developed by an unblinded, 
independent statistician. During the treatment period, randomized patients will be provided their
assigned treatment and assessments according to the protocol. All patients will be treated for 
28 days unless the study drug is discontinued for safety reasons. If the patient is discharged home 
before Day 28, the study team will provide the patient with the remainder of the assigned blinded 
study drug kit(s) to take home along with instructions on how to continue treatment at home on 
the day-of-discharge; for these patients, treatment compliance will be conducted via a diary. If 
the patient does not feel comfortable to complete the diary, the site will alternatively provide the 
patient with the option to be called, twice a day, to confirm that the study drug is taken as 
instructed. The treatment period will end with the Day 28 (End of Treatment Visit) assessments. 
The follow-up period will consist of Day 60 (Follow-up Visit) assessments.
Please note: Patients will be assessed while hospitalized. For patients discharged early, study 
visits at Day 8, Day 14, Day 21, and Day 28 must be performed as an outpatient visit (ie, at the 
study site). Patients discharged early will continue to receive study drug through Day 28.
The study duration for an individual patient will be as follows:
x
Screening period: up to 7 days
x
Treatment period: 28 consecutive days (ie, Day 1 to Day 28)
x
Follow-up period: 32 days after Day 28 (ie, Day 60)
As such, the approximate study duration (including screening and the follow-up period) for an 
individual patient is up to 67 days (±3 days).
An independent DMC will be established by the sponsor or designee to review accumulating 
study data at regular intervals (as per the DMC charter) throughout the study to ensure the safety 
of patients and review overall study conduct. The DMC can recommend in writing to the sponsor 
whether to continue, modify, or stop the clinical study on the basis of safety considerations (see 
Section 15.8 for further details).
No interim analysis is planned.
7.2
Discussion of Study Design 
This study is designed to investigate the efficacy and safety of 300 mg MP1032 BID plus SoC 
versus placebo plus SoC treatment in hospitalized adults with confirmed moderate to severe 
COVID-19, the disease caused by SARS-CoV-2 infection. 
This study will be executed during a worldwide outbreak of COVID-19 that has resulted in 
capacity issues at many medical facilities. Additionally, the highly contagious nature of 
COVID-19 (compounded by a shortage of personal protective equipment) has caused concerns 
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about the safety of healthcare providers caring for these seriously sick patients. Consequently, 
this study is designed to minimize any additional burden on clinical sites, including minimizing 
the number of assessments and interventions that the study will require in addition to SoC, while 
still ensuring the safety of patients.
This study will be double-blinded and placebo-controlled to limit bias in study assessments. 
Either MP1032 or placebo will be administered as add-on therapy to SoC. Most interventions 
and assessments may be accomplished in conjunction with SoC, without requiring additional 
hospital visits or resources.
The dose, dosing regimen, and duration of treatment planned for this study (300 mg MP1032 
BID for 28 days) were selected on the basis of:
x
The highest repeated dose was 300 mg MP1032 BID applied to both healthy volunteers 
(7 days) and psoriasis patients (3 months). MP1032 was well tolerated in all studies and 
safety analyses did not reveal any clinically important safety issues (see the current 
version of the IB for further information).
x
Acute treatment for symptoms of respiratory viral infections is typically from 14 to 
28 days. 
x
A 28-day treatment period was selected because it is a standard duration of time included 
in the WHO R&D Blueprint for COVID-19 (WHO 2020d).
All patients will be treated for 28 days (unless the study drug is discontinued for safety reasons)
to provide a fixed duration of treatment across all patients. As it is impractical to require the 
study site to continue to hospitalize patients who no longer require hospital care, if the patient is 
discharged home before Day 28, the study team will provide the patient with the remainder of 
the assigned blinded study drug kit(s) to take home along with instructions on how to continue 
treatment at home on the day-of-discharge. Any patient who is discharged during the study 
should complete the day-of-discharge assessments before release from the hospital as noted in 
the Schedule of Assessments (Table 1). For patients discharged early, study visits at Day 8, 
Day 14, Day 21, and Day 28 must be performed as an outpatient visit (ie, at the study site). 
Patients who progress to the use of an invasive ventilation (mechanical ventilator and/or ECMO) 
or who can no longer swallow the study drug (>2 days [ie, 2-day interruption is acceptable]) 
must discontinue the study drug; but whenever possible, the study assessments will be performed 
on Day 8, Day 14, Day 21, Day 28, and Day 60.
This proof-of-concept study will neither include pregnant nor breastfeeding females. In 
reproduction toxicity studies of MP1032 on fertility and early embryonic as well as on embryo-
fetal development, no pathological effects were found. Genotoxicity testing as well as the 
repeated dose toxicity studies (up to 12 months in dogs and 6 months in rats) did not indicate any 
toxicological effects. Hence, MP1032 is considered as IMP with unlikely human 
teratogenicity/fetotoxicity in early pregnancy (see the current version of the IB for more 
information). However, due to the early clinical stage of development, only women who are 
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neither pregnant nor breastfeeding will be randomized in this study. Women of childbearing 
potential (WOCBP) and non-sterile male patients with female partners who are WOCBP will be 
required to use a highly effective method of contraception from the time of first dose of study 
medication until at least 30 days after the last dose of study medication.
7.3
End of Study  
A patient will have fulfilled the requirements for study completion if/when the patient has 
completed all study periods, including Day 60 as indicated in the Schedule of Assessments 
(Table 1).
The end of the study will be the last patient’s last visit (ie, Day 60) as indicated in the Schedule 
of Assessments (Table 1). 
8
SELECTION OF STUDY POPULATION 
Section 7.1 provides information regarding number of patients planned to be randomized.
8.1
Inclusion Criteria 
Individuals must meet all of the following criteria to be included in the study:
1. The patient must be willing and able to give informed consent to participate in the study 
and to adhere to the procedures stated in the protocol or, for adults incapable of 
consenting due to their medical condition (eg, too weak or debilitated, severe shortness of 
breath) or due to literacy issues, the patient’s legally authorized representative (LAR) 
must be willing and able to give informed consent on behalf of the patient to participate 
in the study as permitted by local regulatory authorities, institutional review 
boards (IRBs)/independent ethics committees (IECs), or local laws.
2. The patient is male or female adult aged 18 years (as per local laws) at the time of 
giving informed consent.
3. The patient is admitted to a hospital and has a positive SARS-CoV-2 test by standard 
RT-PCR assay or equivalent test. Please note: If the patient has a previous confirmation 
of SARS-CoV-2 (within 7 days of Day 1), the SARS-CoV-2 test at screening is not 
required. 
4. The patient has the presence of any symptom(s) suggestive of moderate or severe 
systemic illness with COVID-19 on Day 1, such as presence of fever (38.0°C 
[100.4°F] by any route), loss of smell or taste, cough, sore throat, malaise, headache, 
muscle pain, gastrointestinal symptoms, shortness of breath upon exertion and/or at rest, 
or respiratory distress.
5. The patient has the presence of moderate to severe clinical signs indicative of moderate 
or severe illness with COVID-19 on Day 1: 
a.
Moderate: 
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i. Clinical signs suggestive of moderate illness with COVID-19, such as 
respiratory rate 20 breaths per minute, SpO2 >93% (on room air at sea 
level, if possible), heart rate 90 beats per minute 
ii. No clinical signs indicative of severe or critical COVID-19
b. Severe: 
i. Clinical signs suggestive of severe systemic illness with COVID-19, such 
as respiratory rate 30 breaths per minute, heart rate 125 beats per 
minute, SpO2 93% (on room air at sea level, if possible), 
PaO2/FiO2 <300, or diagnosed with ARDS (according to the Berlin 
definition; see Table 3)
ii. No criteria met for critical COVID-19
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition 
(eg, emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19
(unless the patient meets the definition for critical COVID-19). For questions related to 
COVID-19 severity, the investigator should contact the medical monitor.
6. The patient does not require hemodialysis (chronic) or any renal replacement therapies at 
screening or Day 1.
7. The patient is able to swallow the study drug (hard gelatin capsules). 
8. The patient agrees to minimize strong sun exposure (sunbathing) and strong ultraviolet 
exposure during the course of the study. Additionally, during the study, patients must 
agree to use sunscreen when spending an extended period outdoors.
9. Men whose sexual partners are WOCBP must agree to comply with 1 of the following 
contraception requirements from the time of first dose of study medication (Day 1) until 
at least 30 days after the last dose of study medication:
a.
Vasectomy with documentation of azoospermia. 
b. Sexual abstinence (defined as refraining from heterosexual intercourse from the 
time of first dose of study medication until at least 30 days after the last dose of 
study medication)
c. Male condom plus partner use of 1 of the contraceptive options below: 
contraceptive subdermal implant; intrauterine device or intrauterine system; oral 
contraceptive, either combined or progestogen alone; injectable progestogen; 
contraceptive vaginal ring; percutaneous contraceptive patches. 
The above is an all-inclusive list of those methods that meet the following definition of 
highly effective: having a failure rate of <1% per year when used consistently and 
correctly and, when applicable, in accordance with the product label. For non-product 
methods (eg, male sterility), the investigator will determine what is consistent and correct 
use. The investigator is responsible for ensuring that patients understand how to properly 
use these methods of contraception. 
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10. WOCBP must agree to comply with 1 of the following contraception requirements from 
the time of first dose of study medication (Day 1) until at least 30 days after the last dose 
of study medication:
a.
Sexual abstinence (defined as refraining from heterosexual intercourse from the 
time of first dose of study medication until at least 30 days after the last dose of 
study medication)
b. Use of 1 of the contraceptive options below plus use of a condom by male 
partner: contraceptive subdermal implant; intrauterine device or intrauterine 
system; oral contraceptive, either combined or progestogen alone; injectable 
progestogen; contraceptive vaginal ring; percutaneous contraceptive patches. 
c. Vasectomy of male partner with documentation of azoospermia. 
The above is an all-inclusive list of those methods that meet the following definition of 
highly effective: having a failure rate of <1% per year when used consistently and 
correctly and, when applicable, in accordance with the product label. The investigator is 
responsible for ensuring that patients understand how to properly use these methods of 
contraception. Women of non-reproductive potential are defined as: 
a.
Premenopausal females with 1 of the following: documented tubal ligation; 
documented hysteroscopic tubal occlusion procedure with follow-up confirmation 
of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy. 
b. Postmenopausal defined as 12 months of spontaneous amenorrhea [in 
questionable cases a blood sample with simultaneous follicle stimulating hormone 
and estradiol levels consistent with menopause (refer to laboratory reference 
ranges for confirmatory levels)]. Women on hormone replacement therapy (HRT) 
and whose menopausal status is in doubt will be required to use 1 of the highly 
effective contraception methods listed above if they wish to continue their HRT 
during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before randomization. 
8.2
Exclusion Criteria 
Individuals meeting any of the following criteria are ineligible to participate in this study: 
1. The patient, in the opinion of the investigator, is not likely to survive for 48 hours 
beyond Day 1. 
2. The patient has a diagnosis of asymptomatic COVID-19, mild COVID-19, or critical 
COVID-19 on Day 1. 
a.
Asymptomatic COVID-19 is defined as a patient with a positive SARS-CoV-2
test by standard RT-PCR assay or equivalent test but not experiencing symptoms. 
b. Mild COVID-19 is defined as a patient with a positive SARS-CoV-2 test by 
standard RT-PCR assay or equivalent test and experiencing symptoms of mild 
illness but no clinical signs indicative of moderate, severe, or critical COVID-19.
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c.
Critical COVID-19 is defined as a patient with a positive SARS-CoV-2 test by 
standard RT-PCR assay or equivalent test and experiencing at least 1 of the 
following: shock defined by systolic blood pressure <90 mm Hg or diastolic 
blood pressure <60 mm Hg, or requiring vasopressors; respiratory failure 
requiring endotracheal intubation and invasive mechanical ventilation, oxygen 
delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via 
reinforced nasal cannula at flow rates >20 L/min with fraction of delivered 
oxygen 0.5), non-invasive positive pressure ventilation, ECMO, or clinical 
diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, 
but preceding therapies not able to be administered in setting of resource 
limitation), and/or multi-organ dysfunction/failure.
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition 
(eg, emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19
(unless the patient meets the definition for critical COVID-19). For questions related to 
COVID-19 severity, the investigator should contact the medical monitor.
3. The patient has a Child Pugh score  C.
4. The patient has a documented medical history of infection with hepatitis A, B, or C at 
screening or Day 1.
5. The patient has a documented medical history of infection with human 
immunodeficiency virus and has a detectable viral load and CD4 count <500 cells/μL. 
6. The patient has a documented active infection with tuberculosis at screening or Day 1.
7. The patient has clinically significant electrocardiogram (ECG) abnormalities at screening.
8. A female patient who is pregnant, planning to become pregnant during the study, 
breastfeeding, or has a positive pregnancy test at screening (by serum) or before dosing 
on Day 1 (by urine) as determined by human chorionic gonadotrophin (hCG) tests.
9. The patient is planning to donate or bank ova or sperm from Day 1 until 30 days after the 
last dose of study drug.
10. The patient has a known history of drug or alcohol abuse within 6 months of study start 
that would interfere with the patient’s participation in the study.
11. The patient has a history of sensitivity to any of the study medications, components 
thereof (eg, mannitol or gelatin), or a history of drug or other allergy that, in the opinion 
of the investigator or medical monitor, would contraindicate their participation.
12. The patient has participated in and/or plans to participate in another clinical study using 
an investigational product within the following period before the first dosing day in the 
current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the 
investigational product (whichever is longer).
13. The patient will be transferred to another hospital that is not a study site within 72 hours.
Please note: If the investigator has admitting privileges to the transfer hospital, the patient 
may be considered for randomization.
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14. The patient is employed by MetrioPharm, the contract research organization or clinical 
site involved in the clinical study.
15. The investigator makes a decision that study involvement is not in patient’s best interest, 
or the patient has any condition or critical illness, in the opinion of the investigator, that 
will not allow the protocol to be followed safely.
8.3
Rescreening 
Individuals who give informed consent to participate in the study but who do not subsequently 
meet all the requirements as outlined in the inclusion and exclusion criteria and therefore are not 
randomized (screen failures) may be rescreened. Such individuals may be allowed to rescreen 
only 1 time.
8.4
Study Withdrawal, Removal, and Replacement of Patients 
Patients who terminate the study before Day 28 will be asked to complete the day-of-discharge 
study procedures. Patients who terminate the study after Day 28 will be asked to complete the 
Day 60 study procedures. Please note: It is expected that patients who discontinue the study drug 
early remain in the study, whenever possible, until the completion of the Day 60 study 
procedures. If it is not possible to follow-up with the patient until Day 60, then follow-up should 
occur until at least Day 28.
Once a patient is withdrawn from the study, the patient may not return to the study.
A patient may voluntarily withdraw or be withdrawn from the study at any time for the following 
reasons: 
x
patient withdrawal of consent (at any time, a patient's participation in the study may be
terminated at his/her request) 
x
lost to follow-up: the patient stopped coming for visits, and study personnel were unable 
to contact the patient. 
Please note: In cases in which the patient is deemed lost to follow-up, the investigator or 
designee must make every effort to regain contact with the patient (eg, telephone calls, letter to 
the patient’s last known mailing address, or local equivalent methods). In cases where the 
patient’s LAR provides informed consent on behalf of the patient, the study site should attempt 
to contact the LAR. Additionally, the study site should attempt to regain contact with the patient 
using the alternative contact information provided by the patient/LAR at the time of informed 
consent. These contact attempts must be documented in the patient’s medical records.
The reason and date for patient withdrawal from the study must be recorded on the electronic 
case report form (eCRF).
Additionally, the sponsor or DMC may stop the study at any time for safety, regulatory, legal, or 
other reasons aligned with good clinical practice (GCP). This study may be terminated at the 
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discretion of the sponsor or any regulatory agency. An investigator may elect to terminate or stop 
the study at his or her study site for any reason, including safety or low recruitment.
9
TREATMENTS 
9.1
Details of Study Drugs 
Both MP1032 hard gelatin capsules 50 mg and matching placebo capsules will be supplied as 
14-day blinded study drug kits. Each kit will also include reserve supply for 1 additional day. 
Thus, each kit will include 180 capsules in total. IMP will be packaged and labelled according to 
all applicable local legal requirements. Study drug must be stored in a controlled environment at 
the study site’s pharmacy where storage temperature is monitored, and access is limited to 
authorized personnel only. In the pharmacy, both MP1032 capsules and matching placebo 
capsules must be stored in the primary and/or secondary packaging at room temperature (15°C to 
25°C [59°F to 77°F]) and protected from light. If the patient is discharged home before Day 28,
the study team will provide the patient with the remainder of the assigned blinded study drug 
kit(s) to take home along with instructions on the day-of-discharge.
Further details of the blinded study drug kits will be described in a Pharmacy Manual.
9.2
Dosage Schedule 
All randomized patients will receive study drug from Day 1 to Day 28 according to their 
assigned treatment and according to the randomization scheme. 
Please note: Patients who remain hospitalized after 28 days of consecutive treatment with study
drug are not eligible for additional treatments with study drug. Patients will receive 6 capsules in 
the morning and 6 capsules in the evening (ie, approximately every 12 hours, approximately at 
the same time every day, and at least 8 hours apart) according to their randomized treatment arm 
assignment as described below: 
x
Arm A: MP1032 (300 mg [6 × MP1032 hard gelatin capsules 50 mg] BID) for oral 
administration
x
Arm B: 6 × placebo capsules (ie, matching MP1032 hard gelatin capsules 50 mg) BID for 
oral administration 
In Arm A, the planned total daily dose of MP1032 is 600 mg. In Arm B, the planned total daily 
dose of MP1032 is 0 mg.
Study drug will be administered to each patient with water (ad libitum) for oral administration.
For all patients (except on Day 1 and Day 7 for patients in the PK subset): Patients should not eat 
within the 30 minutes before planned study drug administration and within the 30 minutes after 
study drug dosing, when feasible. However, if a patient has eaten within the 30 minutes before 
their planned study drug administration, study drug dosing may proceed. The study site should 
record the date and time of dosing (recorded as the time when the first capsule is administered).
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For patients in the PK subset on Day 1 and Day 7 only: Patients should not eat within the 4 hours
before planned study drug administration and within the 120 minutes after study drug dosing, 
when feasible. Thus, study drug should be administered in fasted state ( 4 hours), when 
feasible. However, if a patient has eaten within the 4 hours before their planned administration, 
study drug dosing may proceed. The patient’s fed or fasted state, as well as food intake (yes/no) 
within the 120 minutes after study drug dosing should be recorded. The PK samples should be 
collected as planned regardless of the patients’ fasted/fed state. The study site should record the 
date and time of dosing (recorded as the time when the first capsule is administered).
Any missed dose study drug may be administered as soon as possible and the next scheduled 
dose may be administered according to the planned schedule as long as the doses are at least 6 to 
8 hours apart. If study drug administration is interrupted for >2 days, the investigator should 
notify the medical monitor to determine if the study drug administration can be resumed.
Patients will be asked to abstain from the following products that may potentially affect their 
safety and/or the PK profile of the study drug: 
x
soft or hard drugs (including cannabis) from screening and throughout the study 
x
smoking or using electronic cigarettes while admitted to the hospital
x
consumption of alcohol-based products will be prohibited from screening until the final 
dose of study drug
9.3
Measures to Minimize Bias: Randomization and Blinding
Randomization 
The randomization of patients to treatment groups will be performed centrally by an IWRS using 
a randomization scheme that will be produced by an unblinded, independent statistician. During 
the randomization process, IWRS will assign a randomization number. Each patient will be 
assigned one kit number at randomization and a second kit number at the Day 14 visit. The study 
drug kits will contain the respective blinded treatment available at the study site. Further 
information on IWRS process will be provided in the IWRS Manual.
Approximately 120 patients will be randomly assigned (2:1) as follows: 
x
Arm A (300 mg MP1032 BID plus SoC): approximately 80 patients
x
Arm B (placebo BID plus SoC): approximately 40 patients
The stratification factor for randomization will include baseline COVID-19 severity (moderate 
versus severe) and age-class (aged 65 years versus >65 years). COVID-19 severity will be 
determined using the following criteria:
x
Moderate COVID-19:
o
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
o
Symptoms of moderate illness with COVID-19, which could include any 
symptom of mild illness or shortness of breath with exertion
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o
Clinical signs suggestive of moderate illness with COVID-19, such as respiratory 
rate 20 breaths per minute, SpO2 >93% (on room air at sea level, if possible), 
heart rate 90 beats per minute 
o
No clinical signs indicative of severe or critical COVID-19
x
Severe COVID-19:
o
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
o
Symptoms suggestive of severe systemic illness with COVID-19, which could 
include any symptom of moderate illness or shortness of breath at rest, or 
respiratory distress
o
Clinical signs indicative of severe systemic illness with COVID-19, such as 
respiratory rate 30 breaths per minute, heart rate 125 beats per minute, SpO2
93% (on room air at sea level, if possible), PaO2/FiO2 <300, or diagnosed with 
ARDS (according to the Berlin definition; see Table 3)
o
No criteria met for critical COVID-19
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will 
be measured when the patient is on room air at sea level (ie, no supplemental oxygen, if possible) 
and at rest for at least 5 minutes. If possible, the site should collect the information from each 
patient at the same time each day (±1 hour). 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition (eg, 
emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19 (unless the 
patient meets the definition for critical COVID-19). For questions related to COVID-19 severity, 
the investigator should contact the medical monitor.
Blinding
The study is double-blinded. Study drug will be identical in appearance and labeled in a blinded 
manner. All patients (and their LARs), investigators, and all study staff involved in the conduct 
of the study (including sponsor personnel or sponsor designees), including data management and 
biostatistics, will be blinded to treatment assignment. 
Exception: An unblinded, independent statistician will be assigned to produce the randomization 
schedule and unblinded tables, figures, and listings for the DMC. The unblinded statistician will 
not otherwise participate in study procedures.
In the event that emergency unblinding is required for a given patient because of AEs or 
concerns for the patient’s safety or well-being, the investigator may break the randomization 
code for the patient via the IWRS, by which system the unblinding will be captured. The 
investigator is responsible for notifying the medical monitor and/or sponsor of such an event as 
soon as possible. The unblinding and its cause will also be documented in the eCRF.
If an investigator becomes unblinded to a given patient’s study drug, that patient will be 
discontinued from the study drug unless there are ethical reasons for that patient not to be 
discontinued; approval from the sponsor’s medical monitor must be obtained in such instances.
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9.4
Treatment Modifications and Discontinuations 
Dose reductions and adjustments are not permitted; any dose reductions and adjustments that 
occur will be recorded and considered protocol deviations.
Delays and omissions of study drug administration because of medical or non-medical reasons 
are allowed. All delays and omissions of study drug that occur during the study will be recorded 
and considered protocol deviations.
All patients will be treated for 28 days unless the study drug is discontinued for safety reasons or 
the patient withdraws consent. If a patient is discontinued from the study drug for any reason, the 
study site must immediately notify the medical monitor. 
A patient may voluntarily discontinue the study drug or be discontinued from the study drug at 
any time for reasons including, but not limited to, the following:
x
progressive disease (related to COVID-19). Please note: Patients who progress to the use 
of an invasive ventilation (mechanical ventilator and/or ECMO) or who can no longer 
swallow the study drug (>2 days [ie, 2-day interruption is acceptable]) must discontinue 
the study drug; but whenever possible, the study assessments will be performed on Day 8, 
Day 14, Day 21, Day 28, and Day 60.
x
unacceptable AE and/or SAE
x
patient withdrawal of consent (at any time, a patient's participation in the study may be 
terminated at his/her request) 
x
on the basis of the investigator’s clinical judgment 
x
general or specific changes in the patient's condition that render him/her ineligible for 
further treatment according to the inclusion/exclusion criteria
x
patient fails to adhere to the protocol requirements (eg, drug noncompliance) 
x
lost to follow-up: the patient stopped coming for visits, and study personnel were unable 
to contact the patient. 
Please note: In cases in which the patient is deemed lost to follow-up, the investigator or 
designee must make every effort to regain contact with the patient (eg, telephone calls, 
letter to the patient’s last known mailing address, or local equivalent methods). In cases 
where the patient’s LAR provides informed consent on behalf of the patient, the study 
site should attempt to contact the LAR. Additionally, the study site should attempt to 
regain contact with the patient using the alternative contact information provided by the 
patient/LAR at the time of informed consent. These contact attempts must be documented 
in the patient’s medical records.
x
pregnancy, as indicated in Section 12.6.5.
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The reason and date for the patient’s discontinuation from study drug must be recorded on the
eCRF.
Please note: It is expected that patients who discontinue study drug early remain in the study, 
whenever possible, until the completion of the Day 60 study procedures. If it is not possible to 
follow-up with the patient until Day 60, then follow-up should occur until at least Day 28.
9.5
Treatment Accountability and Compliance 
The pharmacist or other designated individual will maintain records of study drug delivered to 
the study site, the inventory at the study site, the distribution to and use by each patient, and the 
return of materials to the sponsor for storage or disposal. These records should include dates, 
quantities, batch/serial numbers, expiration dates, in-clinic temperature log, and unique code 
numbers assigned to the product and patients.
During hospitalization, the administration of the study drug will be performed by the investigator 
(or qualified blinded designee) to ensure compliance. If the patient is discharged home before 
Day 28, the study team will provide the patient with the remainder of the assigned blinded study 
drug kit(s) to take home along with instructions to continue treatment at home; for these patients, 
treatment compliance will be conducted via a diary. If the patient does not feel comfortable to 
complete the diary, the site will alternatively provide the patient with the option to be called, 
twice a day, to confirm that the study drug is taken as instructed. Patients are to be reminded of 
the importance of compliance with their assigned regimen, with an emphasis on taking their 
study drug on schedule and maintaining the prescribed interval between doses.
Investigators will maintain records that adequately document that the patients were provided 
with the correct study drug kit(s) and reconcile the products received from the drug dispensing 
center. Investigational product will not be returned to the sponsor until accountability has been 
fully monitored.
Noncompliance is defined as taking <80% or >120% of study drug. Discontinuation for 
noncompliance is at the investigator’s discretion and is to be noted on the eCRF.
9.6
Prior and Concomitant Medications 
Restricted prior medications are provided in Section 8.2.
All medications and other treatments taken by the patient during the study, including those 
treatments initiated before the start of the study, must be recorded on the eCRF.
Medications taken by or administered to the patient for the period before screening will be 
recorded in the eCRF. After the screening visit, medications are generally permitted; however, 
the following therapies are expressly prohibited during the screening and treatment periods and 
up through the end of the follow-up period (ie, up through Day 28):
x
an investigational product from another clinical study
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Any medication or therapy that is taken by or administered to the patient during the course of the 
study must be recorded in the eCRF. The entry must include the dose, regimen, route, indication, 
and dates of use.
10
STUDY PROCEDURES 
Table 1 outlines the timing of procedures and assessments to be performed throughout the study. 
Section 12.5 specifies clinical laboratory assessment samples to be obtained. See Section 11,
Section 12, Section 13, and Section 14 for additional details regarding efficacy, safety, PK, other 
assessments, respectively. 
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Table 1:
Schedule of Assessments
Study Period
Screening 
Period
Treatment Period
Follow-up Period
-
Visit Name
Screeninga
Day 1a
Days 2 to 
13
Day 14b
Day 21b
Day 28 
(End of 
Treatment 
Visit)b
Day 60
(Follow-up Visit)b /
Early Study 
Termination after 
Day 28
Day of Discharge / 
Early Study 
Termination before 
Day 28
Study Day (window)
Day -7 to 
Day -1
Day 1 (NA) Days 2 to 
13 (NA)
Day 14 
(±2 days)
Day 21 
(±2 days)
Day 28 
(±3 days)
Day 60 (±3 days)
Day of Discharge
Informed consentc
X
-
-
-
-
-
-
COVID-19 testingd
X
X
-
X
X
Xe
-
Demographicsf
X
-
-
-
-
-
-
Medical/surgical historyg
X
X (updates 
only)
-
-
-
-
-
Inclusion/exclusion criteria
X
X
-
-
-
-
-
Complete physical examinationh
X
-
-
-
-
-
-
Limited physical examinationh
-
X
X (only 
Day 8 
[±3 days])s
X
X
-
X
Vital signsi
X
X
Xj
X
X
Xe
X
Height
X
-
-
-
-
-
-
Weight and BMI
X
X
-
X
X
Xe
X
Clinical laboratory assessments (hematology,
blood biochemistry, coagulation, and urinalysis)
X
X
X (only 
Day 8 
[±3 days])s
X (Days 14, 21, and 28)u
-
X
ECGk
X
-
-
-
-
-
-
Pregnancy test (WOCBP only)l
X
X
-
X
-
-
X (only if discharged 
before Day 14 or at 
Early Study 
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Study Period
Screening 
Period
Treatment Period
Follow-up Period
-
Visit Name
Screeninga
Day 1a
Days 2 to 
13
Day 14b
Day 21b
Day 28 
(End of 
Treatment 
Visit)b
Day 60
(Follow-up Visit)b /
Early Study 
Termination after 
Day 28
Day of Discharge / 
Early Study 
Termination before 
Day 28
Study Day (window)
Day -7 to 
Day -1
Day 1 (NA) Days 2 to 
13 (NA)
Day 14 
(±2 days)
Day 21 
(±2 days)
Day 28 
(±3 days)
Day 60 (±3 days)
Day of Discharge
Termination before Day 
14)
Randomization via IWRS
-
X
-
-
-
-
-
Retrieve the 14-day blinded study drug kit via the 
study drug kit number assigned by IWRS
X
Xv
X (only if discharged 
before Day 14; NA for 
Early Study 
Termination)
Blood sample collection for biomarkers 
-
Xo
X (only 
Day 7)o
X (Days 14, 21, and 28)o
Xe,o
-
Administer blinded study drug BID
-
Xt
-
-
Provide remainder of the assigned blinded study 
drug kit(s) to the patient along with instructionsm
-
-
-
-
-
-
X (only if discharged 
during the treatment 
period; NA for Early 
Study Termination)
Provide patient with the diary and train patient on 
use of the diarym
-
-
-
-
-
-
X (only if discharged 
during the treatment 
period; NA for Early 
Study Termination)
COVID-19 symptoms
X
X
-
X
X
X
X
COVID-19 severityp
X
X
-
-
-
-
-
Clinical status related to COVID-19 on the NIAID 
8-point ordinal scaleq
X
X
X
X
X
X
X
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Study Period
Screening 
Period
Treatment Period
Follow-up Period
-
Visit Name
Screeninga
Day 1a
Days 2 to 
13
Day 14b
Day 21b
Day 28 
(End of 
Treatment 
Visit)b
Day 60
(Follow-up Visit)b /
Early Study 
Termination after 
Day 28
Day of Discharge / 
Early Study 
Termination before 
Day 28
Study Day (window)
Day -7 to 
Day -1
Day 1 (NA) Days 2 to 
13 (NA)
Day 14 
(±2 days)
Day 21 
(±2 days)
Day 28 
(±3 days)
Day 60 (±3 days)
Day of Discharge
EQ-5D-5L questionnairer
-
-
-
-
-
X
X (only if discharged/ 
early terminated before 
Day 60)
Blood sample collection (plasma) for PK (from the 
PK subset of approximately 30 patients who give 
optional consent)n
-
X
X (only 
Day 7)j
-
-
-
AEs
X
X
Prior and concomitant medications
X
X
Abbreviations: AE = adverse event; BID = twice daily; BMI = body mass index; COVID-19 = coronavirus 2019; ECG = electrocardiogram; eCRF = electronic case report form; 
EQ-5D-5L = EuroQol-5D-5L; IEC = independent ethics committee; ICU = intensive care unit; IRB = institutional review board; IWRS = interactive web-response system; 
LAR = legally authorized representative; NA = not applicable; NIAID = National Institute of Allergy and Infectious Diseases; PK = pharmacokinetic; RT-PCR = reverse 
transcription-polymerase chain reaction; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus type 2; SoC = standard of care; 
SpO2 = saturation of oxygen; WOCBP = women of childbearing potential
a.
Those patients who are fully eligible (all screening assessments are available) can have Day 1 performed on the same day as screening. If screening and Day 1 are 
performed on the same day, visit procedures required for both visits do not need to be repeated.
b.
Patients will be assessed while hospitalized. For patients discharged early, study visits at Day 8, Day 14, Day 21, and Day 28 must be performed as an outpatient visit (ie, 
at the study site). Patients discharged early will continue to receive study drug through Day 28. Please note: In cases in which the patient is deemed lost to follow-up, the 
investigator or designee must make every effort to regain contact with the patient (eg, telephone calls, letter to the patient’s last known mailing address, or local equivalent 
methods). In cases where the patient’s LAR provides informed consent on behalf of the patient, the study site should attempt to contact the LAR. Additionally, the study 
site should attempt to regain contact with the patient using the alternative contact information provided by the patient/LAR at the time of informed consent. These contact 
attempts must be documented in the patient’s medical records.
c.
The patient must give informed consent to participate in the study or, for adults incapable of consenting due to their medical condition (eg, too weak or debilitated, severe 
shortness of breath) or due to literacy issues, the patient’s LAR must be willing give informed consent on behalf of the patient to participate in the study as permitted by 
local regulatory authorities, IRBs/IECs, or local laws.
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d.
At the screening visit, the local laboratory may perform COVID-19 testing by standard RT-PCR assay or equivalent test. At screening, a positive test must be available in 
order for the patient to be randomized on Day 1. If the patient has a previous confirmation of SARS-CoV-2 (within 7 days of Day 1), the SARS-CoV-2 test at screening is 
not required. On Day 1, Day 14, Day 28, and Day 60, samples will be sent to the central laboratory for COVID-19 testing by standard RT-PCR assay. The result of the 
COVID-19 tests (positive/negative) must be documented in the eCRF. Further details will be described in the laboratory manual. Please note: If COVID-19 tests are 
performed at unscheduled time points (eg, according to SoC), findings (ie, positive/negative result) must be recorded in the eCRF.
e.
Not all assessments will be able to be performed if the Day 60/Early Termination visit is conducted via a telephone/virtual call (the patient’s caregiver may assist during 
the telephone/virtual call). If the assessment can be conducted via a telephone/virtual call, the study site should record the details; otherwise, the missed assessment will
not be considered a protocol deviation. All efforts should be made to collect clinical laboratory assessments on Day 14 (± 2 days) and Day 28 (± 3 days). Please note: In 
cases in which the patient is deemed lost to follow-up, the investigator or designee must make every effort to regain contact with the patient (eg, telephone calls, letter to 
the patient’s last known mailing address, or local equivalent methods). In cases where the patient’s LAR provides informed consent on behalf of the patient, the study site 
should attempt to contact the LAR. Additionally, the study site should attempt to regain contact with the patient using the alternative contact information provided by the 
patient/LAR at the time of informed consent. These contact attempts must be documented in the patient’s medical records.
f.
Demographics will include sex, age, and race and/or ethnicity.
g.
Medical/surgical medical history includes all active and chronic diseases (eg, asthma and COPD), and any diseases diagnosed in the past 1 year (before screening) that the 
investigator considers clinically significant. Additional pre-existing conditions present at the time when informed consent is given and up to the time of first dosing 
(Day 1) are to be regarded as concomitant. Medical history will include documentation of social behaviors, including use of tobacco, nicotine (including use of electronic 
cigarettes), and soft or hard drugs (including cannabis), as well as alcohol consumption, if applicable. Smoking history also must be documented as part of medical history 
and includes never, light (<100 cigarettes/lifetime), active smoker, and former smoker (quit date). History of number packs/day, number of smoking years, and quitting 
time for former and active smokers must also be documented. Additionally, the investigators will document at screening the patient’s Charlson score via the Charlson 
Comorbidity Index (see Section 12.1 for further details).
h.
A complete physical examination will be performed at screening. Physical examinations will be performed by a physician, nurse, or other appropriately trained staff. The 
complete physical examination includes: head, eyes, ears, nose, and throat; heart; lungs; abdomen; skin; cervical and axillary lymph nodes; and neurological and 
musculoskeletal systems. A limited physical examination to verify continued patient eligibility and to follow-up regarding any change in medical history will be 
performed at the visits indicated above. Symptom-driven, limited physical examinations may be performed as clinically indicated during the study (according to SoC).
i.
Vital signs include systolic and diastolic blood pressure, heart rate, respiration rate, SpO2, and body temperature. All vital signs will be measured after the patient has been 
resting for at least 5 minutes. Blood pressure measurements are to be taken in the same arm for the duration of the study. Moreover, additional vital signs may be 
performed as needed in case of any cardiac AE. 
j.
For patients who remain hospitalized only. 
k.
A 12-lead, resting ECG will be obtained locally at screening. At screening, the investigator must examine the ECG traces for clinically significant abnormalities that could 
exclude the patient from the study. ECGs should always be obtained in supine position after adequate rest (5 minutes). 
l.
For WOCBP, a serum sample for pregnancy testing must be collected at screening and a urine sample for pregnancy testing must be collected before the first dose on 
Day 1. Pregnancy tests must be negative for the patient to be randomized and treated. A urine pregnancy test will be repeated on Day 14 (± 7 days). If the patient is 
discharged before Day 14, urine pregnancy test at day of discharge should be done and urine pregnancy test at Day 14 is not required. If the patient is discharged after Day 
14, urine pregnancy test should be done at Day 14 and urine pregnancy test at day of discharge is not required (whatever comes first). Patients with a positive pregnancy 
test will be discontinued from study drug.
m. Only for patients discharged before Day 28. If the patient does not feel comfortable to complete the diary, the site will alternatively provide the patient with the option to 
be called, twice a day, to confirm that the study drug is taken as instructed.
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n.
Plasma PK samples will be collected via sparse sampling from approximately 30 patients (who give optional consent) in a 2:1 ratio to assess the PK of MP1032 on Day 1 
(single dose) and Day 7 (steady state). A total of 16 samples will be collected relative to the first dose on Day 1 and the first dose on Day 7. Samples on Day 1 and Day 7 
will be collected predose (within 10 minutes before the first daily dose) and postdose at 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 8 hours (before 
next dose), and 24 hours before the next morning dose (if applicable), if possible. Patients who provide consent for the PK sampling, but are no longer hospitalized on 
Day 7, will not have Day 7 PK samples collected. 
o.
Blood samples to be obtained on Day 1 (before the first study drug administration) and Days 7, 14, 21, 28, and 60 (when possible). Blood samples for biomarkers must be 
collected on Days 7, 14, 21, 28, and 60 if a patient is still hospitalized. If a patient is discharged, the study site should attempt to arrange an outpatient (ie, at the study site)
visit to accommodate the collection of blood samples for biomarkers on Days 7, 14, 21, 28, and 60. 
p.
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will be measured when the patient is on room air at sea level (ie, no 
supplemental oxygen, if possible) and at rest for at least 5 minutes. If possible, the site should collect the information from each patient at the same time each day 
(±1 hour).
q.
Record the patient’s clinical status related to COVID-19 on the NIAID 8-point ordinal scale and also record the date and time for each individual component of the NIAID 
8-point ordinal scale including: invasive or non-invasive mechanical ventilation/ECMO start/stop, high-flow/mask oxygen start/stop, supplemental oxygen start/stop 
(nasal cannula, liter flow [and its conversion to FiO2], other delivery services), hospital discharge (whether with limitations or without limitations), hospitalization type 
(eg, transfer to ICU) start/stop, and (if applicable) death, cause of death (including relatedness to COVID-19), and date/time of death. If possible, the site should collect 
the information from each patient at the same time each day (±1 hour).
r.
The EQ-5D-5L is only required for discharged patients and at the following visits: day of discharge, Day 60, and Early Termination visit (if applicable). The EQ-5D-5L is 
not required for patients who remain hospitalized until study end.
s.
The limited physical examination and clinical laboratory assessments on Day 8 (± 3 days) will be collected in all patients who remain hospitalized. If the patient is 
discharged before Day 8 (± 3 days), these assessments should only be done if the physician determines during the outpatient (ie, at the study site) visit that the limited 
physical examination and clinical laboratory assessments are clinically indicated.
t.
For all patients (except on Day 1 and Day 7 for patients in the PK subset): Patients should not eat within the 30 minutes before planned study drug administration and 
within the 30 minutes after study drug dosing, when feasible. However, if a patient has eaten within the 30 minutes before their planned study drug administration, study 
drug dosing may proceed. The study site should record the date and time of dosing (recorded as the time when the first capsule is administered). For patients in the PK 
subset on Day 1 and Day 7 only: Patients should not eat within the 4 hours before planned study drug administration and within the 120 minutes after study drug dosing, 
when feasible. Thus, study drug should be administered in fasted state ( 4 hours), when feasible. However, if a patient has eaten within the 4 hours before their planned 
administration, study drug dosing may proceed. The patient’s fed or fasted state, as well as food intake (yes/no) within the 120 minutes after study drug dosing should be 
recorded. The PK samples should be collected as planned regardless of the patients’ fasted/fed state. The study site should record the date and time of dosing (recorded as 
the time when the first capsule is administered).
u.
The clinical laboratory assessments on Day 8 and Day 21 will be collected in all patients who remain hospitalized. If the patient is discharged before Day 21, the 
physician should assess the patient at the outpatient (ie, at the study site) visit. If the physician determines during the outpatient (ie, at the study site) visit that the clinical 
laboratory assessments are clinically indicated, then the site should arrange to collect this assessment.
v.
The +2-day window does not apply to the retrieval of the 14-day blinded study drug kit as the second kit must be distributed at the latest on Day 14. 
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10.1
Informed Consent 
Before performing any study-related procedures, the investigator (or designee) will obtain 
informed consent from the patient to participate in the study or, for adults incapable of 
consenting due to their medical condition (eg, too weak or debilitated, severe shortness of breath) 
or due to literacy issues, the patient’s LAR must be willing give informed consent on behalf of 
the patient to participate in the study as permitted by local regulatory authorities, IRBs/IECs, or 
local laws.
Please note: The patient/LAR will be expected to provide the study site with their contact 
information so that the site can maintain contact with the patient/LAR in the event that the 
patient is discharged before the end of the study. Additionally, at the time of informed consent, 
the study site may also request for the patient/LAR to provide alternative contact information. In 
the event that rescreening occurs, the investigator (or designee) must reconsent the patient (or the 
patient’s LAR) and the patient must be assigned a new identification number.
10.2
Study Procedures 
Assessments and their timing are to be performed as outlined in the Schedule of Assessments 
(Table 1). Section 12.5 specifies clinical laboratory assessment samples to be obtained. 
Assessments and procedures scheduled at a visit where study drug is administered should be 
performed before administration of treatment unless otherwise indicated in the Schedule of 
Assessments (Table 1).
Efficacy assessments are described in Section 11 and include COVID-19 symptoms, COVID-19
severity, clinical status related to COVID-19 on the NIAID 8-point ordinal scale, HRQoL 
assessed by the EQ-5D-5L questionnaire, and COVID-19 testing. 
Safety assessments are described in Section 12 and include medical/surgical history and 
demographics, vital signs, physical examinations, ECGs, clinical laboratory assessments, and 
AEs. PK assessments are described in Section 13 and include PK sampling and PK analytical 
methodology. Biomarkers are described in Section 14.1.
The investigator may, at his/her discretion, arrange for a patient to have an unscheduled 
assessment, especially in the case of AEs that require follow-up or are considered by the 
investigator to be possibly related to the use of study drug. The unscheduled visit page in the 
eCRF must be completed. 
Procedures for early study withdrawal are described in Section 8.4.
1
EFFICACY ASSESSMENTS 
The Schedule of Assessments (Table 1) outlines the efficacy assessments to be performed 
throughout the study and their timing.
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1.1
COVID-19 Symptoms  
The assessment of the COVID-19 symptoms will be recorded at the visits specified in the 
Schedule of Assessments (Table 1).
The patient will be assessed for the following as shown in Table 2.
Table 2
COVID-19 Symptoms
Symptom
Response Options and Scoring
1.
Stuffy or runny nose
None = 0
Mild = 1
Moderate = 2
Severe =3
2.
Sore throat
3.
Red or irritated eyes (conjunctivitis)
4.
Shortness of breath (difficulty breathing)
5.
Cough
6.
Low energy or tiredness
7.
Muscle or body aches
8.
Headache
9.
Chills or shivering
10. Feeling hot or feverish
11. Nausea (feeling like you wanted to throw up)
12. How many times did you vomit (throw up) in the 
last 24 hours?
I did not vomit at all = 0 
1–2 times = 1 
3–4 times = 2 
5 or more times = 3 
13. How many times did you have diarrhea (loose or 
watery stools) in the last 24 hours?
I did not have diarrhea at all = 0
1–2 times = 1 
3–4 times = 2 
5 or more times = 3 
14. Rate your sense of smell in the last 24 hours. 
My sense of smell is THE SAME AS usual = 0 
My sense of smell is LESS THAN usual = 1 
I have NO sense of smell = 2 
15. Rate your sense of taste in the last 24 hours. 
My sense of taste is THE SAME AS usual = 0 
My sense of taste is LESS THAN usual = 1 
I have NO sense of taste = 2 
Note: Score values are included in the table for ease of reference. Score values within the response options will not 
be presented to patients to avoid confusing patients.
1.2
COVID-19 Severity  
The assessment of the COVID-19 severity will be recorded at the visits specified in the Schedule 
of Assessments (Table 1). As per the inclusion and exclusion criteria (see Section 8.1 and 
Section 8.2), patients who are randomized must have either moderate or severe COVID-19. The 
criteria (FDA 2020) used to determine the patient’s COVID-19 severity incorporates objective 
measures as follows: 
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Asymptomatic SARS-CoV-2 infection 
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
No symptoms
Mild COVID-19
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
Symptoms of mild illness with COVID-19 (eg, loss of smell or taste, fever, cough, sore 
throat, malaise, headache, muscle pain, gastrointestinal symptoms, and without shortness 
of breath or dyspnea)
x
No clinical signs indicative of moderate, severe, or critical COVID-19
Moderate COVID-19
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
Symptoms of moderate illness with COVID-19, which could include any symptom of
mild illness or shortness of breath with exertion 
x
Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate 
20 breaths per minute, SpO2 >93% (on room air at sea level, if possible), heart rate 
90 beats per minute 
x
No clinical signs indicative of severe or critical COVID-19
Severe COVID-19
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
Symptoms suggestive of severe systemic illness with COVID-19, which could include 
any symptom of moderate illness or shortness of breath at rest, or respiratory distress 
x
Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory 
rate 30 breaths per minute, heart rate 125 beats per minute, SpO2 93% (on room air at 
sea level, if possible), PaO2/FiO2 <300, or diagnosed with ARDS (according to the Berlin 
definition; see Table 3 for further details)
x
No criteria for critical COVID-19
Critical COVID-19
x
Positive SARS-CoV-2 testing by standard RT-PCR assay or equivalent test 
x
Evidence of critical illness, defined by at least 1 of the following: 
o
Respiratory failure defined based on resource utilization requiring at least 1 of the 
following: 

Endotracheal intubation and mechanical ventilation, oxygen delivered by 
high-flow nasal cannula (heated, humidified, oxygen delivered via 
reinforced nasal cannula at flow rates >20 L/min with fraction of delivered 
oxygen 0.5), non-invasive positive pressure ventilation, ECMO, or 
clinical diagnosis of respiratory failure (ie, clinical need for 1 of the 
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preceding therapies, but preceding therapies not able to be administered in 
setting of resource limitation) 
o
Shock (defined by systolic blood pressure <90 mm Hg, or diastolic blood pressure 
<60 mm Hg or requiring vasopressors) 
o
Multi-organ dysfunction/failure 
A clinical diagnosis of respiratory failure (in the setting of resource limitation) in which the 
management deviates from SoC must be recorded.
To standardize the assessment of COVID-19 severity, respiratory rate, SpO2, and heart rate will 
be measured when the patient is on room air at sea level (ie, no supplemental oxygen, if possible) 
and at rest for at least 5 minutes. If possible, the site should collect the information from each 
patient at the same time each day (±1 hour). 
Please note: Patients who are receiving oxygen therapy at baseline for a chronic condition (eg, 
emphysema, COPD, PAH, IPF, etc) must be considered as having severe COVID-19 (unless the 
patient meets the definition for critical COVID-19). For questions related to COVID-19 severity, 
the investigator should contact the medical monitor.
Table 3:
Acute Respiratory Distress Syndrome – Berlin Definition
Timing
Within 1 week of known clinical insult or new or worsening respiratory symptoms
Chest 
imaginga
Bilateral opacities — not fully explained by effusions, lobar/lung collapse, or nodules
Origin of 
edema
Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective 
assessment (eg, echocardiography) to exclude hydrostatic edema if no risk factor is present
Oxygenationb
Mild
200 mm Hg < PaO2/FIO2 300 mm Hg with PEEP or CPAP 5 cmH2Oc
Moderate
100 mm Hg < PaO2/FIO2 200 mm Hg with PEEP 5 cmH2O
Severe
PaO2/FIO2 100 mm Hg with PEEP 5 cmH2O
Abbreviations: ARDS = acute respiratory distress syndrome; CPAP = continuous positive airway pressure; 
FIO2 = fraction of inspired oxygen; PaO2 = partial pressure of arterial oxygen; PEEP = positive end-expiratory 
pressure.
a
Chest radiograph or computed tomography scan
b
If altitude is higher than 1,000 m, the correction factor will be calculated as follows: [PaO2/FIO2 (barometric 
pressure/760)]
c
This may be delivered noninvasively in the mild ARDS group
Source: Adapted from Fanelli et al 2013
1.3
Clinical Status Related to COVID-19 on the National Institute of Allergy and 
Infectious Diseases 8-Point Ordinal Scale 
The NIAID 8-point ordinal scale is an assessment of the clinical status at the first assessment of a 
given study day. The scale is as follows:
1. Death
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2. Hospitalized, on invasive ventilation (mechanical ventilator and/or ECMO)
3. Hospitalized, on non-invasive ventilation or high-flow oxygen devices
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care 
(COVID-19 related or otherwise)
6. Hospitalized, not requiring supplemental oxygen and no longer requires ongoing 
medical care (used if hospitalization was extended for infection-control reasons)
7. Not hospitalized, limitation on activities, and/or requiring home oxygen
8. Not hospitalized, no limitations on activities
Please note: Patients requiring oxygen before COVID-19 and returning to baseline oxygen use 
will be considered improved (ie, not requiring supplemental oxygen). Patients with a limitation 
on activities before COVID-19 and returning to baseline activity will be considered improved.
At the visits specified in the Schedule of Assessments (Table 1), record the date and time for 
each individual component of the NIAID 8-point ordinal scale including: invasive or non-
invasive mechanical ventilation/ECMO start/stop, high-flow/mask oxygen start/stop, 
supplemental oxygen start/stop (nasal cannula, liter flow [and its conversion to FiO2], other 
delivery services), hospital discharge (whether with limitations or without limitations), 
hospitalization type (eg, transfer to ICU) start/stop, and (if applicable) death, cause of death 
(including relatedness to COVID-19), and date/time of death. If possible, the site should collect 
the information from each patient at the same time each day (±1 hour).
A standard conversion for liter flow oxygen to FiO2 is presented in Table 4.
Table 4
Standard Conversion for Liter Flow Oxygen
If there is use of a venturi mask (air-entrainment mask), the FiO2 is based on the nozzle use and 
should also be recorded.
FiO2 (%)
Room air
21
1 L/min
24
2 L/min
27
3 L/min
30
4 L/min
33
5 L/min
36
6 L/min
39
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1.4
Health-related Quality of Life Assessment 
The HRQoL will be assessed via the EQ-5D-5L questionnaire. The EQ-5D-5L is a standardized 
questionnaire developed by the EuroQol Group as a measure of HRQoL that consists of a 
descriptive system and a VAS. The descriptive system consists of 5 dimensions: mobility, self-
care, usual activities, pain/discomfort, and anxiety/depression. The VAS records the patient’s 
self-rated health on a vertical VAS. This can be used as a quantitative measure of health outcome 
that reflects the patient’s own judgment. The patient is asked to indicate his/her current health 
state (ie, describe their health “today”). The scores on these 5 dimensions can be presented as a 
health profile or can be converted to a single summary index number that describes the patient’s 
current health state. The EQ-5D-5L questionnaire has been validated in a diverse patient 
population in 6 countries and is available in multiple languages. The EQ-5D-5L questionnaire is 
suitable for completion by adults (EuroQol Research Foundation 2020).
The results of the EQ-5D-5L questionnaire will be recorded at the visits specified in the 
Schedule of Assessments (Table 1). Please note: This assessment will only be performed in 
patients who have been discharged from the hospital before Day 60. 
1.5
COVID-19 Testing  
Samples for COVID-19 testing will be obtained at the visits specified in the Schedule of 
Assessments (Table 1). At the screening visit, the local laboratory may perform COVID-19
testing by standard RT-PCR assay or equivalent test. At screening, a positive test must be 
available in order for the patient to be randomized on Day 1. If the patient has a previous 
confirmation of SARS-CoV-2 (within 7 days of Day 1), the SARS-CoV-2 test at screening is not 
required. The result of the COVID-19 tests (positive/negative) must be documented in the eCRF
On Day 1, Day 14, Day 28, and Day 60, samples will be sent to the central laboratory for 
COVID-19 testing by standard RT-PCR assay. The result of the COVID-19 tests 
(positive/negative) must be documented in the eCRF. Further details will be described in the 
laboratory manual. 
Please note: If COVID-19 tests are performed at unscheduled time points (eg, according to SoC), 
findings (ie, positive/negative result) must be recorded in the eCRF.
12
SAFETY ASSESSMENTS 
Safety assessments (medical/surgery history, demographics, prior and concomitant medications, 
vital signs, physical examinations, ECGs, clinical laboratory assessments, and AEs) are to be 
performed at the visits specified in the Schedule of Assessments (Table 1).
12.1
Medical/Surgical History and Demographics 
Medical/surgical history will be recorded at screening. Investigators will document all active and 
chronic diseases (eg, asthma and COPD), and any diseases diagnosed in the past 1 year (before 
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screening) that the investigator considers clinically significant. Additional pre-existing 
conditions present at the time when informed consent is given and up to the time of first dosing 
(Day 1) are to be regarded as concomitant. Medical history will include documentation of social 
behaviors, including use of tobacco, nicotine (including use of electronic cigarettes), and soft or 
hard drugs (including cannabis), as well as alcohol consumption, if applicable. Smoking history 
also must be documented as part of medical history and includes: never, light 
(<100 cigarettes/lifetime), active smoker, and former smoker (quit date). History of number 
packs/day, number of smoking years, and quitting time for former and active smokers must also 
be documented. 
Additionally, the investigators will document at screening the patient’s Charlson score via the 
Charlson Comorbidity Index (Charlson et al 1987). The Charlson Comorbidity Index may be 
used to identify patients with higher risk of COVID-19 progression (Garibaldi et al 2020) via the 
COVID-19 Inpatient Risk Calculator (online calculator available via: 
https://rsconnect.biostat.jhsph.edu/covid_predict/). The 14-item Charlson score is based on the
patient’s comorbidities that are associated with mortality: myocardial infarction, congestive heart 
failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary 
disease, rheumatologic disease, peptic ulcer disease, liver disease, diabetes, hemiplegia or 
paraplegia, renal disease, malignancy, and acquired immunodeficiency syndrome/human 
immunodeficiency virus (online calculator available via: https://www.orthotoolkit.com/charlson-
comorbidity-index/). The investigator should record each individual component of the 14-item 
Charlson Comorbidity Index as well as the overall score. 
Illnesses first occurring or detected during the study and/or worsening of a concomitant illness 
during the study are to be documented as AEs on the eCRF in accordance with Section 12.6.1.
All changes not present at baseline or described in the past medical history and identified as 
clinically noteworthy must be recorded as AEs.
Additionally, demographic data will be collected for all patients and include sex, age, and race 
and/or ethnicity.
12.2
Vital Signs 
Vital signs (systolic and diastolic blood pressure, heart rate, respiration rate, SpO2, and body 
temperature) will be evaluated at the visits indicated in the Schedule of Assessments (Table 1).
All vital signs will be measured after the patient has been resting for at least 5 minutes. Blood 
pressure measurements are to be taken in the same arm for the duration of the study. Moreover, 
additional vital signs may be performed as needed in case of any cardiac AE.
Additionally, body weight (without shoes) will be recorded at screening, Day 1, Day 14, Day 28, 
Day 60, and day of discharge (applicable); height (without shoes) will be recorded at screening 
only. Body mass index will be calculated whenever weight is recorded.
Vital sign measurements will be repeated if clinically significant or machine/equipment errors 
occur. Out-of-range blood pressure, respiratory rate, heart rate measurements, or SpO2 will be 
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repeated at the investigator’s discretion. Any confirmed, clinically significant vital sign 
measurements must be recorded as AEs.
12.3
Physical Examinations 
A complete physical examination will be performed at screening. Physical examinations will be 
performed by a physician, nurse, or other appropriately trained staff. The complete physical 
examination includes head, eyes, ears, nose, and throat; heart; lungs; abdomen; skin; cervical and 
axillary lymph nodes; and neurological and musculoskeletal systems. 
A limited physical examination to verify continued patient eligibility and to follow-up regarding 
any change in medical history will be performed at the visits indicated in the Schedule of 
Assessments (Table 1). Symptom-driven, limited physical examinations may be performed as 
clinically indicated during the study (according to SoC).
Please note: The limited physical examination on Day 8 (± 3 days) will be collected in all 
patients who remain hospitalized. If the patient is discharged before Day 8 (± 3 days), this 
assessment should only be done if the physician determines during the outpatient (ie, at the study
site) visit that the limited physical examination is clinically indicated.
12.4
Electrocardiograms 
A 12-lead, resting ECG will be obtained locally at screening as indicated in the Schedule of 
Assessments (Table 1). At screening, the investigator must examine the ECG traces for clinically 
significant abnormalities that could exclude the patient from the study. If ECGs are performed at 
unscheduled time points (eg, according to SoC), findings must be recorded in the eCRF.
ECGs should always be obtained in supine position after adequate rest ( 5 minutes). An 
assessment of normal or abnormal will be recorded; if the ECG is considered abnormal, the 
abnormality will be documented on the eCRF. ECGs will be repeated if clinically significant 
abnormalities are observed or artifacts are present. Any ECG considered by the investigator to be 
clinically significant should be considered an AE. Moreover, additional ECGs may be obtained 
as needed in case of any cardiac AE and will be recorded on the eCRF.
12.5
Clinical Laboratory Assessments 
Clinical laboratory assessment samples (Table 5) will be obtained at designated visits as 
specified in the Schedule of Assessments (Table 1).
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Table 5:
Clinical Laboratory Assessments
Hematology 
Blood Biochemistry 
Urinalysis (Dipstick) 
Full and differential blood count
Hematocrit (HCT)
Hemoglobin (Hb)
Mean corpuscular hemoglobin (MCH)
Mean corpuscular hemoglobin 
concentration (MCHC)
Mean corpuscular volume (MCV)
Platelet count (PLT Ct)
Red blood cell count (RBC ct)
White blood cell count (WBC ct) with 
differential
Albumin (ALB)
Alanine aminotransferase (ALT)
Alkaline phosphatase (ALP)
Aspartate aminotransferase (AST)
Blood urea nitrogen (BUN) or urea
Carbon dioxide (CO2)
Creatininea (Cr)
Creatine kinase (CK) and subtypes
Electrolytes (sodium, potassium, 
chloride, calcium, phosphorus)
Gamma-glutamyl transpeptidase (GGT)
Glucose
Lactate dehydrogenase (LDH)
Total bilirubin (TBIL)
Direct bilirubin (DBI)
Total cholesterol (TC)
Triglycerides (TG)
Estimated glomerular filtration rateb
(eGFR)
Appearance
pH
Protein
Glucose
Ketone bodies
Indicators of blood and 
white blood cells
Specific gravity
Urobilinogen (UROB)
Coagulation
Activated partial thromboplastin time
International normalized ratio
Partial thromboplastin time
Pregnancy Test
A serum pregnancy (hCG) test will be performed on all WOCBP at screening and a urine pregnancy (hCG) 
test will be performed on all WOCBP on Day 1 before randomization and dosing. A urine pregnancy test will 
be repeated on Day 14 (± 7 days). If the patient is discharged before Day 14, urine pregnancy test at day of 
discharge should be done and urine pregnancy test at Day 14 is not required. If the patient is discharged after 
Day 14, urine pregnancy test should be done at Day 14 and urine pregnancy test at day of discharge is not 
required (whatever comes first). Patients with a positive pregnancy test will be discontinued from study drug.
Please note: In questionable cases of postmenopausal status, a blood sample with simultaneous follicle 
stimulating hormone and estradiol levels may be required to determine postmenopausal status
Abbreviations: hCG = human chorionic gonadotropin; WOCBP = women of childbearing potential.
a Creatinine clearance will be estimated using the patient’s serum creatinine value, actual body weight, age, and the 
appropriate Cockroft-Gault formula for the patient’s sex.
b According to Chronic Kidney Disease Epidemiology Collaboration (Levey et al 2009).
Blood and urine samples will be analyzed at the site’s local laboratory facility. Urine samples 
will be analyzed by dipstick, and a microscopic analysis will be performed if the results of 
dipstick indicate abnormalities to be further investigated. All laboratory reports must be 
reviewed, signed, and dated by the investigator. A legible copy of all reports must be filed with 
both the patient’s eCRF and medical record (source document) for that visit. Any laboratory test 
result considered by the investigator to be clinically significant should be considered an AE 
(clinically significant AEs include those that require an intervention). Clinically significant 
abnormal values occurring during the study will be followed up until repeat test results return to 
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normal, stabilize, or are no longer clinically significant. If laboratory assessments are performed 
at unscheduled time points (eg, according to SoC), findings must be recorded in the eCRF.
Please note: The clinical laboratory assessments on Day 8 (± 3 days) and Day 21 (± 2 days) will 
be collected in all patients who remain hospitalized. If the patient is discharged before Day 8 
(± 3 days) or Day 21 (± 2 days), the physician should assess the patient at the outpatient (ie, at 
the study site) visit. If the physician determines during the outpatient visit (ie, at the study site) 
that the clinical laboratory assessments are clinically indicated, then the site should arrange to 
collect this assessment.
12.6
Adverse Events
Adverse Events
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study 
or, if present at screening, worsens during the study, regardless of the suspected cause of the 
event. All medical and psychiatric conditions (except those related to the indication under study) 
present at screening will be documented on the medical history eCRF. Changes in these 
conditions and new symptoms, physical signs, syndromes, or diseases should be noted on the AE 
eCRF during the rest of the study. Clinically significant laboratory abnormalities should also be 
recorded as AEs. Surgical procedures that were planned before the patient was randomized in the 
study are not considered AEs if the conditions were known before study inclusion; the medical 
condition should be reported in the patient’s medical history.
Patients will be instructed to report AEs at each study visit. All AEs are to be followed up until 
resolution or a stable clinical endpoint is reached.
Each AE is to be documented on the eCRF with reference to date of onset, duration, frequency, 
severity, relationship to study drug, action taken with study drug, treatment of event, and 
outcome. Furthermore, each AE is to be classified as being serious or nonserious. Changes in 
AEs and resolution dates are to be documented on the eCRF.
For the purposes of this study, the period of observation for collection of AEs extends from the 
time the patient gives informed consent until the end of the follow-up period (Day 60). 
Follow-up of the AE, even after the date of study completion, is required (if possible) if the AE 
persists. The follow-up should continue until the event resolves (returns to normal or baseline 
values) or stabilizes, or until it is judged by the investigator to no longer be clinically significant. 
It is understood that if a patient withdraws consent to further follow-up, then it may not be 
possible for the study site to follow the AE to resolution.
When changes in the severity of an AE occur more frequently than once a day, the maximum 
severity for the event should be noted. If the severity category changes over a number of days, 
then those changes should be recorded separately (with distinct onset dates).
Each AE will be assigned a grade which refers to the severity of the AE based on the Common 
Terminology Criteria for Adverse Events version 5.0. The Common Terminology Criteria for 
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Adverse Events v5.0 displays grades 1 through 5 with unique clinical descriptions of the severity 
for each AE based on the general guideline shown in Table 6.
The guideline for classifying AEs by relationship to study drug are given in Table 7.
Table 6:
Classification of Adverse Events by Severity
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated.
Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living.
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation 
of hospitalization indicated; disabling; limiting self-care activities of daily living.
Grade 4: Life-threatening consequences; urgent intervention indicated.
Grade 5: Death related to AE.
Abbreviation: AE = adverse event.
Table 7:
Classification of Adverse Events by Relationship to Study Drug
UNRELATED: This category applies to those AEs that are clearly and incontrovertibly due to extraneous 
causes (disease, environment, etc).
UNLIKELY: This category applies to those AEs that are judged to be unrelated to the study drug but for which 
no extraneous cause may be found. An AE may be considered unlikely to be related to study drug if or when it 
meets 2 of the following criteria: (1) it does not follow a reasonable temporal sequence from administration of 
the study drug; (2) it could readily have been produced by the patient’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the patient; (3) it does not follow a known pattern of 
response to the study drug; or (4) it does not reappear or worsen when the drug is readministered.
POSSIBLY: This category applies to those AEs for which a connection with the study drug administration 
appears unlikely but cannot be ruled out with certainty. An AE may be considered possibly related if or when 
it meets 2 of the following criteria: (1) it follows a reasonable temporal sequence from administration of the 
drug; (2) it could not readily have been produced by the patient’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the patient; or (3) it follows a known pattern of response to the study 
drug.
PROBABLY: This category applies to those AEs that the investigator feels with a high degree of certainty are 
related to the study drug. An AE may be considered probably related if or when it meets 3 of the following 
criteria: (1) it follows a reasonable temporal sequence from administration of the drug; (2) it could not be 
reasonably explained by the known characteristics of the patient’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the patient; (3) it disappears or decreases on cessation or reduction 
in dose (note that there are exceptions when an AE does not disappear upon discontinuation of the drug, yet 
drug-relatedness clearly exists; for example, as in bone marrow depression, fixed drug eruptions, or tardive 
dyskinesia); or (4) it follows a known pattern of response to the study drug.
DEFINITELY: This category applies to those AEs that the investigator feels are incontrovertibly related to 
study drug. An AE may be assigned an attribution of definitely related if or when it meets all of the following 
criteria: (1) it follows a reasonable temporal sequence from administration of the drug; (2) it could not be 
reasonably explained by the known characteristics of the patient’s clinical state, environmental or toxic factors, 
or other modes of therapy administered to the patient; (3) it disappears or decreases on cessation or reduction 
in dose and recurs with reexposure to drug (if rechallenge occurs); and (4) it follows a known pattern of 
response to the study drug.
Abbreviation: AE = adverse event.
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Serious Adverse Events
An SAE is any untoward medical occurrence, in the view of either the investigator or sponsor, 
that:
x
results in death
x
is life-threatening
x
results in inpatient hospitalization or prolongation of existing hospitalization
x
results in persistent or significant disability/incapacity
x
is a congenital anomaly/birth defect
Other important medical events that may not be immediately life-threatening or result in death or 
hospitalization, based upon appropriate medical judgment, are considered SAEs if they are 
thought to jeopardize the patient and/or require medical or surgical intervention to prevent 1 of 
the outcomes defining an SAE. SAEs are critically important for the identification of significant 
safety problems; therefore, it is important to take into account both the investigator’s and the 
sponsor’s assessment. If either the sponsor or the investigator believes that an event is serious, 
the event must be considered serious and evaluated by the sponsor for expedited reporting.
Serious Adverse Event Reporting
An SAE occurring from the time the patient gives informed consent until the end of the follow-
up period (Day 60) or within 30 days of stopping the study drug (whichever is longer) must be 
reported to the Syneos Health Safety and Pharmacovigilance group and will be communicated to 
the sponsor. Any such SAE due to any cause, whether or not related to the study drug, must be 
reported within 24 hours the investigator’s awareness of the event. Notification can be made 
using the dedicated fax line or email for the Syneos Health Safety and Pharmacovigilance group:
x
Syneos Health Safety and Pharmacovigilance fax number: 
x
Syneos Health Safety and Pharmacovigilance email address: 
If the investigator contacts the Syneos Health Safety and Pharmacovigilance group by telephone, 
then a written report must follow within 24 hours and has to include a full description of the 
event and sequelae in the format detailed in the SAE reporting form.
The event must also be recorded on the standard AE eCRF. Preliminary reports of SAEs must be 
followed up by detailed descriptions later on. Clear and anonymized photocopies of hospital case 
reports, consultant reports, autopsy reports, and other documents must be provided when 
requested by Syneos Health Safety and Pharmacovigilance. SAE reports must be made whether 
or not the investigator considers the event to be related to the investigational drug.
Appropriate remedial measures should be taken to treat the SAE, and the response should be 
recorded. Clinical, laboratory, and diagnostic measures should be employed as needed to 
determine the etiology of the problem. The investigator must report all additional follow-up
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evaluations to the Syneos Health Safety and Pharmacovigilance group within 24 hours of 
becoming aware of the additional information. All SAEs will be followed up until the 
investigator and sponsor agree the event is satisfactorily resolved.
Any SAE that is not resolved by the end of the study or upon discontinuation of the patient’s 
participation in the study is to be followed up, if possible, until it either resolves, stabilizes, 
returns to baseline values (if a baseline value is available), or is shown to not be attributable to 
the study drug or procedures. It is understood that if a patient withdraws consent to further 
follow-up, then it may not be possible for the study site to follow the SAE to resolution.
Suspected Unexpected Serious Adverse Reactions
AEs that meet all of the following criteria will be classified as suspected unexpected serious 
adverse reactions (SUSARs) and reported to the appropriate regulatory authorities in accordance 
with applicable regulatory requirements for expedited reporting:
x
serious
x
unexpected (ie, the event is not consistent with the reference safety information in the 
current version of the IB)
x
there is at least a reasonable possibility that there is a causal relationship between the 
event and the study drug
The investigator will assess whether an event is causally related to the study drug. Syneos Health 
will consider the investigator’s assessment and determine whether the event meets the criteria for 
being reportable as a 7-day or 15-day safety report. SUSARs that are fatal or life-threatening 
must be reported to the regulatory authorities and the IRBs/IECs (where required) within 7 days 
after Syneos Health/MetrioPharm has first knowledge of them, with a follow-up report (when 
applicable) submitted within a further 8 calendar days. Other SUSARs must be reported to the 
relevant regulatory authorities and the IRBs/IECs within 15 calendar days after 
Syneos Health/MetrioPharm first has knowledge of them.
Syneos Health is responsible for reporting SUSARs and any other events required to be reported 
in an expedited manner to the regulatory authorities and for informing investigators of reportable 
events, in compliance with applicable regulatory requirements within specific timeframes. 
Investigators will notify the relevant IRBs/IECs of reportable events within the applicable 
timeframes.
Pregnancy
WOCBP must have a negative serum pregnancy test at screening and negative urine pregnancy 
test before the first dose on Day 1. A urine pregnancy test will be repeated on Day 14 (± 7 days). 
If the patient is discharged before Day 14, urine pregnancy test at day of discharge should be 
done and urine pregnancy test at Day 14 is not required. If the patient is discharged after Day 14, 
urine pregnancy test should be done at Day 14 and urine pregnancy test at day of discharge is not 
required (whatever comes first). Patients with a positive pregnancy test will be discontinued from 
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study drug. After administration of study drug, any known cases of pregnancy in female patients 
will be reported until the patient completes or withdraws from the study. The pregnancy will be 
reported immediately by faxing/emailing a completed pregnancy report to Syneos Health Safety 
and Pharmacovigilance within 24 hours of knowledge of the event. The pregnancy will not be 
processed as an SAE; however, the investigator will follow up with the patient until completion 
of the pregnancy and must assess the outcome in the shortest possible time but not >30 days after 
completion of the pregnancy. (It is understood that if a patient withdraws consent to further 
follow-up, then it may not be possible for the study site to follow the pregnancy to completion.) 
The investigator should notify Syneos Health Safety and Pharmacovigilance group of the 
pregnancy outcome by submitting a follow-up pregnancy report. If the outcome of the pregnancy 
involved spontaneous or therapeutic abortion (any congenital anomaly detected in an aborted 
fetus is to be documented), stillbirth, neonatal death, or congenital anomaly, the investigator will 
report the event by faxing/emailing a completed pregnancy report form to Syneos Health Safety 
and Pharmacovigilance group within 24 hours of knowledge of the event.
If the investigator becomes aware of a pregnancy occurring in the partner of a patient 
participating in the study, the pregnancy should be reported to Syneos Health Safety and 
Pharmacovigilance group within 24 hours of knowledge of the event. Information regarding the 
pregnancy must only be submitted after obtaining consent from the pregnant partner. The 
investigator will arrange counseling for the pregnant partner by a specialist to discuss the risks of 
continuing with the pregnancy and the possible effects on the fetus.
Upon discontinuation from the study drug, only those procedures that would not expose the 
patient to undue risk will be performed. The investigator should also be notified of pregnancy 
occurring during the study but confirmed after completion of the study. In the event, that a 
patient is subsequently found to be pregnant after inclusion in the study and received at least one 
dose of study drug, any pregnancy will be followed to term, and the status of mother and child 
will be reported to Syneos Health Safety and Pharmacovigilance group after delivery.
Overdose
The investigator must immediately notify Syneos Health of any occurrence of overdose with the 
study drug.
13
PHARMACOKINETICS
13.1
Pharmacokinetic Sampling
Blood samples for PK analysis of MP1032 plasma concentrations will be collected at the time 
points indicated in the Schedule of Assessments (Table 1) from a PK subset of approximately 
30 patients (who give optional consent). In summary, PK samples will be collected via sparse 
sampling from these 30 patients (approximately) in a 2:1 ratio (approximately 20 patients from 
the 300 mg MP1032 BID plus SoC group and approximately 10 patients from the placebo group 
plus SoC group) to assess the PK of MP1032 on Day 1 (single dose) and Day 7 (steady state). A 
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total of 16 samples (approximately 4.9 mL per time point for a total of approximately 78.4 mL)
will be collected relative to the first dose on Day 1 and the first dose on Day 7. Samples on 
Day 1 and Day 7 will be collected predose (within 10 minutes before the first daily dose) and 
postdose at 10 minutes, 20 minutes, 30 minutes, 60 minutes, 120 minutes, 8 hours (before next 
dose), and 24 hours before the next morning dose (if applicable), if possible. Patients who 
provide consent for the PK sampling, but are no longer hospitalized on Day 7, will not have 
Day 7 PK samples collected.
For patients in the PK subset on Day 1 and Day 7 only: Patients should not eat within the 4 hours
before planned study drug administration and within the 120 minutes after study drug dosing, 
when feasible. Thus, study drug should be administered in fasted state ( 4 hours), when 
feasible. However, if a patient has eaten within the 4 hours before their planned administration, 
study drug dosing may proceed. The patient’s fed or fasted state, as well as food intake (yes/no) 
within the 120 minutes after study drug dosing should be recorded. The PK samples should be 
collected as planned regardless of the patients’ fasted/fed state. The study site should record the 
date and time of dosing (recorded as the time when the first capsule is administered).
Intravenous cannulas may be used for blood collection to avoid multiple skin punctures, when 
appropriate. Otherwise, blood samples will be collected by direct venipuncture. The actual date 
and time of each blood sample collection will be recorded. Sample collections completed outside 
the predefined time windows (windows to be specified in the laboratory manual) will not be 
considered as protocol deviations because actual postdose sampling times will be used for PK 
and statistical analyses.
PK samples will be analyzed by a central laboratory facility (Prolytic GmbH). Details of PK 
blood sample collection, processing (including separation of plasma), storage, and shipping 
procedures will be provided in a separate laboratory manual.
13.2
Pharmacokinetic Analytical Methodology 
The concentration of study drug will be determined from the plasma samples using a validated 
analytical method. Details of the method validation and sample analysis will be included with the 
final clinical study report (CSR).
14
OTHER ASSESSMENTS 
14.1
Biomarkers 
Blood samples will be obtained at the visits specified in the Schedule of Assessments (Table 1)
on Day 1 (before the first study drug administration) and Days 7, 14, 21, 28, and 60 (when 
possible) to measure biomarkers levels. Blood samples for biomarkers must be collected on Days 
7, 14, 21, 28, and 60 if a patient is still hospitalized. If a patient is discharged, the study site 
should arrange an outpatient visit (ie, at the study site) to accommodate the collection of blood 
samples for biomarkers on Days 7, 14, 21, 28, and 60.
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Biomarkers will potentially include, but will not be limited, to cytokines (eg, C-reactive protein, 
IL-1E, IL-6, TNF-Į, and IFN-J) and other coagulation/inflammatory biomarkers (eg, D-dimer 
and ferritin). Samples may be collected at the same time that samples are collected for the 
clinical laboratory assessments. Blood samples will be analyzed by a central laboratory facility. 
Details of sample collection, processing, storage, shipping procedures, and analysis will be 
provided in a separate laboratory manual.
Please note: Patients will be requested to provide consent for the sponsor to store and use 
leftover blood samples for future exploratory biomarker research. Patient participation in the 
storage and use of leftover blood samples is optional. If the patient consents, the sponsor will 
store and use the leftover blood samples for a period of 3 years after the last patient has 
completed his/her last visit in this study.
15
STATISTICAL ANALYSIS 
The statistical analysis plan (SAP) will provide further details regarding the definition of analysis 
variables and analysis methodology to address all study objectives. The SAP will be finalized 
before any statistical output (eg, DSMB output) is produced. The SAP will serve as a companion 
document to the protocol. The SAP will further describe the statistical analyses. All data will be 
included with the final CSR. 
The statistical evaluation will be performed using SAS® software version 9.4 or higher 
(
®
). 
Summary statistics will be presented by treatment group. Continuous and ordinal variables will 
be summarized by the number of patients (N), mean, standard deviation, median, minimum, and 
maximum for actual values and change from baseline. Additionally, for ordinal data, the number 
and percentage of patients in each category will be presented. Binary and categorical variables 
will be summarized for each treatment group by presenting the number and percentage of 
patients in the categories.
Statistical tests for comparison between treatments will be performed using a two-sided alpha 
level of 10%. No adjustment for multiple testing will be applied in this descriptive proof-of-
concept study.
15.1
Determination of Sample Size 
The primary efficacy endpoint “proportion of patients with disease progression on Day 14” is 
assumed to be 10% in the 300 mg MP1032 BID plus SoC treatment group (Arm A) and 30% in 
the placebo plus SoC treatment group (Arm B). Using the Chi-square test with type I error 
alpha=10% two-sided for this proof-of-concept study and 2:1 randomization ratio, with 
114 randomized patients (76 in Arm A and 38 in Arm B) a statistical power of 83% can be 
achieved. Considering about 5% early study terminations, the necessary sample size to 
randomize results is 120 patients in total (80 in Arm A and 40 in Arm B). If during the conduct 
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of the study the early study termination rate is higher than the estimated 5%, then an increase in 
the randomized number of patients may be necessary.
Sample size estimation was performed using nQuery 8, Version 8.6.1.0.
A subset of randomized patients will be consented for the collection of blood samples for PK 
measurements. The PK subset consists of approximately 20 patients from the 300 mg MP1032 
BID plus SoC group and approximately 10 patients from the placebo plus SoC group, up to a 
total of approximately 30 patients.
15.2
Analysis Sets 
Screened Set
The Screened Set will include all patients who give informed consent and are screened. For this 
group, patient disposition, and reasons for premature study termination or screening failure will 
be described. 
Randomized Set
The Randomized Set will include all patients randomized. Unless specified otherwise, this set 
will be used for all subject listings with exception of the listing presenting screening failures and 
the respective reason(s) for screen failure.
Intention-To-Treat Set
The  Intention-To-Treat (ITT) set, correspond with randomized set, will include all randomized 
patients irrespective of any deviation from the protocol or premature discontinuation from study 
drug/withdrawal from study. The treatment group assignment will be designated according to 
initial randomization. The ITT will serve as the basis for the analysis of efficacy and summary of 
demographics and baseline characteristics.
Per Protocol Set
The Per Protocol Set (PPS) will include all patients from ITT who received at least 1 dose of 
study drug and who do not have any major protocol deviations impacting the efficacy 
assessments. The PPS will be used for supportive analyses of efficacy.
Safety Set
The Safety Set (SS) will include all randomized patients who receive at least 1 dose of study
drug. The treatment group assignment in the SS will be defined by the treatment actually 
received. The SS will be used for the analysis of safety.
PK Analysis Set
The PK Analysis Set (PKS) will include all the patients who have been administered active study
drug and have at least 1 postdose evaluable plasma concentration after Day 1 dose.
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15.3
Efficacy Analysis 
The estimands for the primary efficacy endpoint and for the 4 key secondary endpoints 
comparing the 2 treatment groups will be tested with consideration of a two-sided type-1 error 
alpha of 10% for each test on the ITT. Additionally, 95% confidence intervals will be provided.
Also, the treatment comparison with regards to the other secondary efficacy endpoints will be 
performed using a two-sided alpha level of 10%.
The main estimand for the primary efficacy endpoint is defined as follows:
x
Treatment: 300 mg MP1032 BID plus SoC in Arm A and placebo BID plus SoC in Arm 
B. If a patient terminates the study drug, but still remains in the study and is followed up, 
then the patient will continue to receive either SoC alone or SoC+ additional treatment. 
These treatments are defined with regards to intercurrent events as ‘other treatments’.
x
Population: Of all patients defined by the study inclusion/exclusion criteria, the analysis 
population will include patients who were randomized to study drug (ITT population).
x
Variable: A binary variable indicating disease progression (death or respiratory failure) at 
Day 14. Respiratory failure is defined as patients who have a score of 2, 3, or 4 on the 
NIAID 8-point ordinal scale.
x
Intercurrent events: All events that lead to study drug discontinuation and/or switch to 
other treatment before Day 14 will be handled using the treatment-policy strategy (ie, the 
NIAID score at Day 14 will be used for definition of the failure in such patients). 
x
Population-level summary: Common risk difference resulting from the Mantel-
Haenszel (MH) test considering the 4 strata out of the combinations of the 
2 randomization stratification factors disease severity (moderate versus severe) and age-
class (aged 65 years versus >65 years) at baseline.
Missing data on Day 14 resulting from study termination before Day 14 are not expected. 
However, in case they happen, such monotone missings will be imputed by multiple imputation 
using information from similar patients of the same treatment group. Missing post-baseline data 
for patients randomized but not treated will be imputed by the respective baseline value (baseline 
observation carried forward [BOCF]). They comparison between the treatment groups will be 
performed on the ITT after imputation of missing values using MH test for common risk 
difference considering the 4 strata resulting from the 2 randomization stratification factors 
disease severity (moderate versus severe) and age-class (aged 65 years versus >65 years). The 
95% confidence intervals will be provided for the risk difference.
Similar MH analyses and presentation of 95% confidence intervals will be applied to the main 
estimand of the first key secondary efficacy endpoint, which is defined as a binary variable 
indicating disease progression (death or respiratory failure) at Day 28, and the main estimand of 
the second key secondary efficacy endpoint that is defined as a binary variable indicating disease 
resolution (alive and have a score of 6, 7 or 8 on NIAID) at Day 28. Intercurrent events that lead 
to study drug discontinuation and/or switch to other treatment before Day 28 will be handled 
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using the treatment-policy strategy for these 2 estimands (ie, the NIAID score at Day 28 will be 
used for definition of the failure or response, respectively) in such patients. Missing data on Day 
28 will be imputed by multiple imputation using information from similar patients of the same
treatment group. Missing post-baseline data for patients randomized but not treated will be 
imputed by BOCF.
A similar MH approach and presentation of 95% confidence intervals as described above will be 
applied also to the main estimand of the third key secondary efficacy endpoint, which is the all-
cause mortality at Day 28. Intercurrent events that lead to study drug discontinuation and/or 
switch to other treatment before Day 28 will be handled using the treatment-policy strategy (ie, 
the life status at Day 28 will be considered). No missing data of life status on Day 28 is expected. 
The main estimand of the fourth key secondary efficacy endpoint, change of clinical status 
related to COVID-19 on Day 28 compared with baseline according to the NIAID 8-point ordinal 
scale, will be compared using the risk difference from the analysis of covariance model with 
treatment and the 2 binary stratification factors (eg, severity and age-class) as independent 
factors and the baseline value of NIAID as independent covariate. Intercurrent events that lead to 
study drug discontinuation and/or switch to other treatment before Day 28 will be handled using 
the treatment-policy strategy for this estimand (ie, the NIAID score at Day 28 will be used). 
Missing data on Day 28 will be imputed by multiple imputation using information from similar 
patients of the same treatment group. Missing post-baseline data for patients randomized but not 
treated will be imputed by BOCF. The 95% confidence intervals will be provided for the risk 
difference.
The population for all above described estimands of the key secondary endpoints is the ITT.
Sensitivity analyses for the main endpoints of the primary and key efficacy estimands will be 
performed by assuming missing data at Day 14 or Day 28 as failure or non-resolution for the 
binary endpoints, and by multiple imputation using information from similar patients of the 
placebo group for the NIAID 8-point ordinal scale.
All above analyses for the main estimands of the primary efficacy and key secondary efficacy 
endpoints will be repeated on PPS as supportive analysis. Additionally, for the primary efficacy 
and binary key secondary efficacy endpoints logistic regression model with treatment and the 
2 stratification factors as covariables will be performed on the ITT. Further estimands for  the
primary and key secondary efficacy endpoints will be provided in the SAP.
The proportion of patients with disease resolution at Day 14 and the all-cause mortality rate at 
Day 14 and Day 60 will be analyzed using similar MH methods as described above for Day 28. 
Cumulative proportion of patients with disease resolution will be plotted by time.
A similar analysis of covariance approach as described above for Day 28 will be applied for the 
analysis of the change of clinical status related to COVID-19 on Day 14 compared with baseline 
on the NIAID 8-point ordinal scale. The endpoint considering the proportion of patients 
requiring invasive ventilation (mechanical ventilator and/or ECMO) or who are not alive, the 
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proportion of patients in each NIAID category, and the proportion of patients alive and testing 
negative for COVID-19 on Day 14, Day 28, and Day 60, respectively, will be compared between 
the treatment groups using MH test. Overall survival, time to (first) improvement of at least 
1 category on the NIAID scale and total hospitalization duration (from baseline to discharge; 
with death censored on last day of the observed period í at Day 28 or Day 60, respectively í 
depending on the analyses) will be summarized using the Kaplan-Meier method and will be 
compared between treatment groups using log-rank tests. Additionally, Cox proportional hazards 
model will be applied with treatment and the 2 stratification factors as covariables.
The odds ratio between MP1032 and SoC and placebo and SoC for the number of patients with 
clinical status improvement from baseline on the NIAID 8-point ordinal scale (ie, an 
improvement of at least 1 category) at Day 14 and Day 28 will be analyzed using a logistic 
regression with consideration of the 2 stratification factors.
The time to recovery of all at baseline present COVID-19 symptoms (stuffy or runny nose, sore 
throat, red or irritated eyes, shortness of breath, cough, low energy or tiredness, muscle or body 
aches, headache, chills or shivering, feeling hot or feverish, nausea, and number of times of 
vomit, times of diarrhea, sense of smell, sense of taste in the last 24 hours) will be presented by 
Kaplan-Meier estimates and figure. The change from baseline will be presented in shift tables for 
each single symptom, with the number and percentage of subjects in each category at post-
baseline assessment time-point compared to baseline for each treatment group. 
Total number of days in ICU, duration of invasive mechanical ventilation, and duration of 
ECMO will be descriptively summarized by treatment group using mean days with 
90% confidence intervals and additionally by median days and quartiles. To consider death 
sufficiently unfavorable in these measures, in case of death the duration of the respective 
measure will be considered with the longest duration possible (eg, if a summary of the first 28 
days is presented, then death before Day 28 will be considered as duration 28 days, and if the 
summary also includes follow-up period until Day 60, then death before Day 60 will be 
considered as duration of 60 days). Both summaries (up to Day 28 and up to Day 60) will be 
provided.
For HRQoL assessments at discharge and Day 60, the EQ index value and the EQ VAS, both 
based on the EQ-5D-5L questionnaire will be calculated and summarized by visit and treatment 
group. Additionally, change at Day 60 from discharge will be summarized by treatment group.
All efficacy endpoints will be summarized using descriptive statistics by treatment group and by 
visit, as appropriate: Binary and categorical endpoints will be summarized by treatment group by 
presenting the number and percentage of patients in the categories. Continuous and ordinal 
endpoints will be described by mean, standard deviation, median, minimum, and maximum for 
actual values and change from baseline. Additionally, for ordinal data, the number and 
percentage of patients in each category will be presented.
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15.4
Safety Analysis 
All safety parameters will be summarized descriptively by treatment group for the entire study 
period.
Study drug duration and SoC therapies will be described for each treatment group.
All reported AEs will be coded into preferred term (PT) and grouped by SOC using the most 
recent Medical Dictionary for Regulatory Activities version. An overall summary will be 
provided with the number and percentage of patients reporting TEAEs, serious TEAEs, 
treatment-related TEAEs, TEAEs leading to withdrawal, and TEAEs leading to death. For
patients with any serious TEAE and for patients with any related serious TEAE exposure-
adjusted events rates will be calculated and compared between treatment groups using the risk 
ratio [(300 mg MP1032 BID plus SoC) / (placebo plus SoC)] with respective 95% confidence 
intervals. This comparison will also be performed for the rate of rehospitalization which is 
considered a serious AE. The number and percentage of patients with TEAEs, serious TEAEs, 
TEAEs leading to withdrawal, and treatment-related TEAEs will be summarized by SOC and PT 
for each treatment group, and total. In these tables, the incidence of TEAEs by SOC and PT will 
also be included. TEAEs will also be summarized by maximum severity and relationship to 
study drug. Events with missing onset dates will be considered as TEAEs. If a patient 
experienced >1 occurrence of the same AE, the occurrence with the greatest severity and the 
closest association with the study drug will be used in the corresponding summary tables. In case 
that for one AE several AE episodes with changing severity is reported, an aggregation of all 
respective episodes to one AE will be performed before summarization. The worst severity and 
the worst causality will be assigned to the aggregated AE and used for the respective AE 
summaries. All reported AE episodes will be listed by patient, along with information regarding 
onset, duration, severity and relationship to study drug, action taken with study drug, treatment 
of event, and outcome. Additionally, the aggregated AEs with the resulting worst severity and 
worst relationship will be included in the AE listings.
Vital signs including SpO2 (%) will be summarized using descriptive statistics, including mean 
values and mean change from baseline values. Clinical laboratory data of local laboratories will 
be presented with the number and percentage of patients with values below, within, or above the 
normal range at each time point. Additionally, a shift table of the number and percentage of 
patients with normal and abnormal, and clinically significant abnormal values at each scheduled 
postbaseline visit compared with the normal/abnormal/clinically significant abnormal 
categorization at baseline will be provided by treatment group. Summarizing of clinical 
laboratory data of local laboratories using descriptive statistics, including mean values and mean 
change from baseline values will be only possible after normalization of the values using a 
reference laboratory. Details for normalization will be provided in the SAP.
Summary tables will be provided for concomitant medications.
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15.5
Pharmacokinetic Analysis 
The PK parameters (such as Cmax, Tmax, AUC0-t, and others) of MP1032 on Day 1 (single dose) 
and Day 7 (steady state; if available), using up to 8 hours postdose, will be derived applying non-
compartmental analysis. PK parameters will be summarized along with plasma concentrations at 
various time points. Individual and mean plasma concentration versus time will be presented on 
linear, and semi-log scales. Further details of the PK analysis will be described in the SAP. Any 
possible correlation between plasma exposure and biomarkers (eg, change from baseline in 
cytokines, or other coagulation/inflammatory biomarkers) or efficacy measures can be explored 
by appropriate regression analysis methods during the final data analysis.
15.6
Biomarker Analysis 
The change from baseline biomarker levels will be summarized descriptively by treatment group 
and visit. The change in biomarker levels will also be evaluated with any change of COVID-19
clinical status. 
15.7
Interim Analysis  
Not applicable. 
15.8
Data Monitoring Committee 
An independent DMC will be established by the sponsor or designee to review accumulating 
study data at regular intervals (as per the DMC charter) throughout the study to ensure the safety 
of patients and review overall study conduct. Additional data may be reviewed that are related to 
efficacy, but the DMC will only be reviewing data for risk-benefit purposes. Members will 
include experts in drug safety and/or medical specialist and biostatistics, who are not 
participating in this study and do not have affiliation with the investigators or the sponsor. The 
DMC can recommend in writing to the sponsor whether to continue, modify, or stop the clinical 
study on the basis of safety considerations. The pre-specified study stopping rules for the trial are 
defined as follows: 
x
death (not including disease progression) in any patient in whom the cause of death is 
judged to be related to the study drug by investigator 
x
the occurrence in any patient of a SAE whose causal relationship (ie, without a plausible 
alternative explanation) to the study drug is judged to be related by investigator 
x
two occurrences of a clinically significant Grade 3 or higher laboratory abnormality 
assessed to be related to the study drug by investigator. 
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The DMC’s specific duties will be fully described in a DMC charter.
16
STUDY MANAGEMENT
16.1
Approval and Consent
Regulatory Guidelines
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and all relevant regulations as set forth in Parts 50, 56, 312, Subpart D, of Title 21 of 
the United States Code of Federal Regulations (CFR), in compliance with International Council 
for Harmonisation and GCP guidelines and according to the appropriate regulatory requirements 
in the countries where the study will be conducted.
Institutional Review Board/Independent Ethics Committee
Conduct of the study must be approved by an appropriately constituted IRB/IEC. Approval is 
required for the study protocol, protocol amendments (if applicable), IB, ICFs, recruitment 
material and patient information sheets, and other patient-facing material.
Informed Consent
For each patient (or the patient’s LAR), informed consent will be obtained before any 
protocol-related activities. As part of this procedure, the principal investigator (PI) or designee 
must explain the nature of the study, its purpose, procedures, expected duration, alternative 
therapy available, and the benefits and risks involved in study participation. The patient (or the 
patient’s LAR) should be informed that he/she may withdraw from the study at any time, and the 
patient will receive all information that is required by local regulations and guidelines for 
International Council for Harmonisation. The PI will provide the sponsor or its representative 
with a copy of the IRB/IEC-approved ICF before the start of the study.
16.2
Data Handling
Data reported on the eCRF that are derived from source documents should be consistent with the 
source documents, or the discrepancies must be explained (see also Section 16.3).
Clinical data will be entered by site personnel on eCRFs for transmission to the sponsor. Data on 
eCRFs transmitted via the web-based data system must correspond to and be supported by source 
documentation maintained at the study site. All study forms and records transmitted to the 
sponsor must only include coded identifiers such that directly identifying personal information is 
not transmitted. The primary method of data transmittal is via the secure, internet-based 
electronic data capture (EDC) system maintained by Syneos Health. Access to the EDC system 
is available to only authorized users via the study’s internet website, where a user unique 
assigned username and password are required for access.
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Any changes made to data after collection will be made through the use of data clarification 
forms or the EDC system. When all missing and/or incorrect data have been resolved, eCRFs 
will be considered complete.
16.3
Source Documents 
Source documents are considered to be all information in original records and certified copies of 
original records of clinical findings, observations, data, or other activities in a clinical study 
necessary for the reconstruction and evaluation of the study. The investigator will provide direct 
access to source documents and/or source data in the facilitation of study-related monitoring, 
audits, review by IRB/IECs, and regulatory inspections.
The investigator/institution should maintain adequate and accurate source documents and study 
records that include all pertinent observations on each of the site’s patients. Source data should 
be attributable, legible, contemporaneous, original, accurate, and complete. Changes to source 
data should be traceable, not obscure the original entry, and be explained if necessary.
16.4
Record Retention 
Study records and source documents must be preserved for at least 30 years after the completion 
or discontinuation of/withdrawal from the study, at least 2 years after the drug being studied has 
received its last approval for sale, or at least 2 years after the drug development has stopped, and 
in accordance with the applicable local privacy laws, whichever is the longer period.
The investigator agrees to comply with all applicable federal, state, and local laws and 
regulations relating to the privacy of patient health information, including, but not limited to, the 
Standards for Individually Identifiable Health Information, 45 CFR, Parts 160 and 164 (the 
Health Insurance Portability Accountability Act of 1996 Privacy Regulation). The investigator 
shall ensure that study patients authorize the use and disclosure of protected health information 
in accordance with Health Insurance Portability Accountability Act Privacy Regulation and in a 
form satisfactory to the sponsor.
16.5
Monitoring 
The study will be monitored to ensure that it is conducted and documented properly according to 
the protocol, GCP, and all applicable regulatory requirements.
Monitoring visits, on-site and remote (telephone), or a combination of these and contacts will be 
made at appropriate times during the study. The PI will assure he/she and adequate site personnel 
must be available throughout the study to collaborate with clinical monitors. Clinical monitors 
must have direct access to source documentation to check the completeness, clarity, and 
consistency of the data recorded in the eCRFs for each patient.
The investigator will make available to the clinical monitor all source documents and medical 
records necessary to review protocol adherence and eCRFs. In addition, the investigator will 
work closely with the clinical monitor and as needed, provide them appropriate evidence that the 
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study is being conducted in accordance with the protocol, applicable regulations, and GCP 
guidelines.
16.6
Quality Control and Quality Assurance
The sponsor or its designee will perform the quality assurance and quality control activities of 
this study; however, responsibility for the accuracy, completeness, security, and reliability of the 
study data presented to the sponsor lies with the investigator generating the data.
The sponsor may arrange audits as part of the implementation of quality assurance to ensure that 
the study is being conducted in compliance with the protocol, standard operating procedures, 
GCP, and all applicable regulatory requirements. Audits will be independent of and separate 
from the routine monitoring and quality control functions. Quality assurance procedures will be 
performed at study sites and during data management to assure that safety and efficacy data are 
adequate and well documented.
16.7
Protocol Amendment and Protocol Deviation
Protocol Amendment
Amendments to the protocol that entail corrections of typographical errors, clarifications of 
confusing wording, changes in study personnel, and minor modifications that have no effect on 
the safety of patients or the conduct of the study will be classed as administrative amendments 
and will be submitted to the IRB/IEC for information only. The sponsor will ensure that 
acknowledgment is received and filed. Amendments that are classed as substantial amendments 
must be submitted to the appropriate regulatory authorities and the IRB/IECs for approval and 
will not be implemented at sites until such approvals are received other than in the case of an 
urgent safety measure.
Protocol Deviations
Should a protocol deviation occur, the sponsor must be informed as soon as possible. Protocol 
deviations and/or violations and the reasons they occurred will be included in the CSR. 
Reporting of protocol deviations to the IRB/IEC and in accordance with applicable regulatory 
authority mandates is the investigator’s responsibility.
16.8
Ethical Considerations
This study will be conducted in accordance with this protocol, the accepted version of the 
Declaration of Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, 
Subpart D, of Title 21 of the CFR; EU 536/2014, Annex 1, D, 17 (a); and in compliance with 
GCP guidelines.
IRB/IECs will review and approve this protocol and the ICF. All patients (or the patient’s LAR) 
are required to give informed consent before participation in the study.
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16.9
Financing and Insurance 
Before the study commences, the sponsor (or its designee) and the investigator (or the institution, 
as applicable) will agree on costs necessary to perform the study. This agreement will be 
documented in a financial agreement that will be signed by the investigator (or the institution 
signatory) and the sponsor (or its designee).
The investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice. The sponsor will provide no-exclusion insurance coverage for the clinical 
study as required by national regulations.
16.10
Publication Policy/Disclosure of Data 
Both the use of data and the publication policy are detailed within the clinical study agreement. 
Intellectual property rights (and related matters) generated by the investigator and others 
performing the clinical study will be subject to the terms of a clinical study agreement that will 
be agreed between the institution and the sponsor or their designee. With respect to such rights, 
the sponsor or its designee will solely own all rights and interests in any materials, data, and 
intellectual property rights developed by investigators and others performing the clinical study 
described in this protocol, subject to the terms of any such agreement. In order to facilitate such 
ownership, investigators will be required to assign all such inventions either to their institution or 
directly to the sponsor or its designee, as will be set forth in the clinical study agreement.
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17
REFERENCES 
Beigel JH, Tomashek KM, Dodd LE, et al. ACTT-1 Study Group Members. Remdesivir for the 
treatment of Covid-19 - final report. N Engl J Med. Published online October 8, 2020. 
doi:10.1056/NEJMoa2007764. 
Cennimo DJ. Coronavirus Disease 2019 (COVID-19). Updated January 09, 2021. Accessed 
January 13, 2021. https://emedicine.medscape.com/article/2500114-overview. 
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic 
comorbidity in longitudinal studies: development and validation. J Chronic Dis.
1987;40(5):373-383. doi:10.1016/0021-9681(87)90171-8.
Curtin N, Bányai K, Thaventhiran J, et al. Repositioning PARP inhibitors for SARSဨCoVဨ2 
infection (COVIDဨ19); a new multiဨpronged therapy for acute respiratory distress syndrome?
Br J Pharmacol. 2020;177(16): 3635-3645. doi:10.1111/bph.15137.
EuroQol Research Foundation. EQ-5D Instruments. Accessed October 9, 2020. 
https://euroqol.org/eq-5d-instruments/.
Fanelli V, Vlachou A, Ghannadian S, et al. Acute respiratory distress syndrome: new definition, 
current and future therapeutic options. J Thorac Dis. 2013;5(3):326-334.
doi:10.3978/j.issn.2072-1439.2013.04.05.
Food and Drug Administration (FDA). COVID-19: Developing drugs and biological products for 
treatment or prevention, guidance for industry, May 2020. Accessed November 11, 2020. 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/covid-19-
developing-drugs-and-biological-products-treatment-or-prevention.
Garibaldi BT, Fiksel J, Muschelli J, et al. Patient trajectories among persons hospitalized for 
COVID-19: a cohort study. Ann Intern Med. Published online September 22, 2020. 
doi:10.7326/M20-3905.
Gloire G, Legrand-Poels S, Piette J. NF-kappaB activation by reactive oxygen species: fifteen 
years later. Biochem Pharmacol. 2006;72(11):1493-1505. doi:10.1016/j.bcp.2006.04.011. 
Grunewald ME, Fehr AR, Athmer J, Perlman S. The coronavirus nucleocapsid protein is ADP-
ribosylated. Virology. 2018;517:62-68. doi:10.1016/j.virol.2017.11.020. 
Hillienhof A. COVID-19: What immune reactions are triggered. German Medical Journal 
(Deutsches Ärzteblatt). 2020;117(39):A-1822.
Ke Y, Wang C, Zhang J, et al. The role of PARPs in inflammation-and metabolic-related 
diseases: molecular mechanisms and beyond. Cells. 2019;8(9):1047. doi:10.3390/cells8091047. 
Khomich OA, Kochetkov SN, Bartosch B, Ivanov AV. Redox biology of respiratory viral 
infections. Viruses. 2018;10(8):392. doi:10.3390/v10080392.
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Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. 
Ann Intern Med. 2009;150(9):604-612.
Levin AT, Hanage WP, Owusu-Boatey N, et al. Assessing the age specifity of infection fatality 
rates for COVID-19: systematic review, meta-analysis, and public policy implications. Eur J 
Epidemiol. 2020;35(12):1123-1138. doi: 10.1007/s10654-020-00698-1.
Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease 
(COVID-19) outbreak. J Autoimmun. 2020;109:102433. Published online February 26, 2020. 
doi:10.1016/j.jaut.2020.102433.
Schumann S, Kaiser A, Nicoletti F, et al. Immune-modulating drug MP1032 with SARS-CoV-2
antiviral activity in vitro: a potential multi-target approach for prevention and early intervention 
treatment of COVID-19. Int J Mol Sci. 2020;21(22):8803. doi:10.3390/ijms21228803.
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19.
Lancet. 2020;395(10234):1417-1418. Published online April 21, 2020. doi:10.1016/S0140-
6736(20)30937-5.
WHO Rapid Evidence Appraisal for COVID-19 Therapies (WHO-REACT) Working Group, 
Sterne JAC, Murthy S, Diaz JV, et al. Association between administration of systemic 
corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. 
JAMA. Published online September 2, 2020. 324(13):1-13. doi:10.1001/jama.2020.17023. 
World Health Organization (WHO). 2020a. January 12, 2020. Accessed January 14, 2021. 
https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en/.
World Health Organization (WHO). 2020b. Estimating mortality from COVID-19. Scientific 
brief, August 4, 2020. Accessed October 27, 2020. 
https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci-Brief-Mortality-2020.1
World Health Organization (WHO). 2020c. Therapeutics and COVID-19. Living Guideline. 
December 17, 2020. Accessed December 17, 2020. 
https://www.who.int/publications/i/item/therapeutics-and-covid-19-living-guideline. WHO 
reference number: WHO/2019-nCoV/therapeutics/2020.1.
World Health Organization (WHO). 2020d. WHO R&D Blueprint. Novel coronavirus: 
COVID-19 therapeutic trial synopsis. February 18, 2020. Accessed October 19, 2020. 
https://www.who.int/publications-detail/covid-19-therapeutic-trial-synopsis.
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M etri o P h ar m A G | Bl ei c h er w e g 1 0 | 8 0 0 2 Z üri c h | S c h w ei z
M etri o P h ar m A G
| Bl ei c h er w e g 1 0 | 8 0 0 2 Z üri c h |  S c h w ei z
 | w w w. m etri o p h ar m. c o m 
Pr ä si d e nt d e s V er w alt u n g sr at e s: 
| H a n d el sr e gi st er Z üri c h: C H E- 1 0 9. 8 5 6. 8 4 1
K o nt o v er bi n d u n g: Cr e dit S ui s s e | I B A N: C H 8 8 0 4 8 3 5 1 4 9 3 1 4 7 7 1 0 0 0 | BI C: C R E S C H Z Z 8 0 L
Pr ot o c ol Cl arifi c ati o n M e m o # 2 
Pr ot o c ol n u m b er:
M P 1 0 3 2- C T 0 5
Pr ot o c ol titl e:
A R A N D O MI Z E D, D O U B L E- B LI N D, P L A C E B O- C O N T R O L L E D, 
M U L TI C E N T E R, P R O O F- O F- C O N C E P T , P H A S E II A S T U D Y O F M P 1 0 3 2 
P L U S S T A N D A R D O F C A R E V S S T A N D A R D O F C A R E I N T H E 
T R E A T M E N T O F H O S PI T A LI Z E D P A TI E N T S WI T H M O D E R A T E T O 
S E V E R E C O VI D- 1 9
E U D R A C T n u m b er:
2 0 2 1- 0 0 0 3 4 4- 2 1
S p o n s or:
M etri o P h ar m A G
Pr ot o c ol v er si o n a n d 
d at e:
2. 0 3 1- J a n- 2 0 2 2
T h e p ur p o s e of t hi s m e m o i s t o cl arif y/ u p d at e Pr ot o c ol v er si o n 2. 0 0 9 F e b 2 0 2 1, i n or d er t o i m pr o v e cl arit y
o n t h e d efi niti o n of o v er d o s e. 
I n t h e c urr e nt pr ot o c ol v er si o n 2.0 3 1- J a n- 2 0 2 2 t h e o v er d o s e s e cti o n st a t e s o nl y t h at “ T h e i n v e sti g at or 
m u st i m m e di at el y n otif y S y n e o s H e alt h of a n y o c c urr e n c e of o v er d o s e wit h t h e st u d y dr u g”.
A s p er pr ot o c ol t h e i nt e n d e d d ail y d o s e i s 6 0 0 m g ( 2 x 3 0 0 m g) M P 1 0 3 2 ( or pl a c e b o). O v er d o s e of 
M P 1 0 3 2 i s d efi n e d a s a n y d ail y d o si n g o v er 6 0 0 m g a n d m u st b e d o c u m e nt e d a n d t h e i n v e sti g at or 
m u st i m m e di at el y n otif y S y n e o s H e alt h.  
B ot h M P 1 0 3 2 h ar d g el ati n c a p s ul e s 5 0 m g a n d m a t c hi n g pl a c e b o c a p s ul e s ar e s u p pli e d a s 1 4- d a y
bli n d e d  st u d y  dr u g  kit s.  E a c h  kit  al s o  i n cl u d e s  a  r e s er v e  s u p pl y  ( c o n si sti n g  of  1 2 c a p s ul e s)  f or  1  
a d diti o n al d a y. T h e ri s k of o v er d o si n g i n g e n er al i n t hi s tri al i s c o n si d er e d t o b e l o w a s t h e p ati e nt w o ul d 
n e e d t o i n g e st a l ar g e a m o u nt ( > 1 2 c a p s ul e s) o n 1 d a y  t o e x c e e d t h e 6 0 0 m g li mit  M P 1 0 3 2 ( or pl a c e b o). 
N e v ert h el e s s, u ni nt e nti o n al a d mi ni str ati o n of a n y d o s e  t h at d e vi at e s fr o m t h e s c h e d ul e d r e gi m e nt m u st 
b e d o c u m e nt e d. 
I n c a s e of o v er d o s e o c c urr e n c e s y m pt o m ati c tr e at m e nt s h all b e pr o vi d e d if n e c e s s ar y a n d S p o n s or 
s h o ul d b e i nf or m e d i m m e di at el y. T h er e i s n o s p e cifi c  d e s cri pti o n a v ail a bl e f or tr e ati n g s y m pt o m s of a n 
M P 1 0 3 2 o v er d o s e d u e t o t h e f a ct t h at  M P 1 0 3 2 i s v er y s af e, a n d n o t ar g et or g a n h a s b e e n i d e ntifi e d i n 
eit h er a ni m al s or h u m a n s i n t h e e v e nt of a n o v er d o s e . T h er ef or e, n o s p e cifi c t h er a p y or “ a nti d ot e” i s 
d e s cri b e d a n y w h er e a n d if si d e eff e ct s o c c ur, t h e y s h o ul d b e tr e at e d s y m pt o m ati c all y at t h e di s cr eti o n 
of t h e PI.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa g e 2 5 6 of 2 5 6
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
P P D
P P D

SAP_001.pdf: 
16.1.9 
Documentation of Statistical Methods 
The document listed below is provided in this section. 
Statistical Analysis Plan (Protocol MP1032-CT05) Version 2.0 dated 31-August-2022 
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T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
 Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 1  of 5 6  
St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s 
 
 
S p o n s or N a m e: M etri o P h ar m A G  
 
Pr ot o c ol N u m b er: M P 1 0 3 2- C T 0 5  
Pr ot o c ol Titl e: A R A N D O MI Z E D, D O U B L E- B LI N D, P L A C E B O- C O N T R O L L E D, M U L TI C E N T E R, 
P R O O F- O F- C O N C E P T, P H A S E II A S T U D Y O F M P 1 0 3 2 P L U S S T A N D A R D O F C A R E V S S T A N D A R D 
O F C A R E I N T H E T R E A T M E N T O F H O S PI T A LI Z E D P A TI E N T S WI T H M O D E R A T E T O S E V E R E 
C O VI D- 1 9 
 
Pr ot o c ol V er si o n a n d D at e:  
Fi n al 1. 0, 0 9- F e b- 2 0 2 1  
Fi n al 2. 0, 3 1- J a n- 2 0 2 2  
 
S y n e o s H e alt h Pr oj e ct C o d e: 7 0 1 9 9 3 6  
 
A ut h or s: 
, P h D, 
  
, 
 
, 
 
 
 
St ati sti c al A n al y si s Pl a n V er si o n a n d D at e:  Fi n al 2. 0, 3 1- A u g- 2 0 2 2 
 
 
 
 
N oti c e of C o nfi d e nti al a n d Pr o pri et ar y I nf or m ati o n: 
T h e i nf or m ati o n c o nt ai n e d i n t hi s d o c u m e nt i s c o nfi d e nti al b el o n gi n g t o M etri o P h ar m A G . A c c e pt a n c e of 
t hi s d o c u m e nt c o n stit ut e s a gr e e m e nt b y t h e r e ci pi e nt t h at n o i nf or m ati o n c o nt ai n e d h er ei n will b e 
p u bli s h e d or di s cl o s e d wit h o ut pri or writt e n a ut h ori z ati o n fr o m a n offi ci al of M etri o P h ar m A G . H o w e v er, 
t hi s d o c u m e nt m a y b e di s cl o s e d t o a p pr o pri at e I n stit uti o n al R e vi e w B o ar d a n d Et hi c s C o m mitt e e s or d ul y 
a ut h ori z e d r e pr e s e nt ati v e s of a n ati o n al r e g ul at or y a ut h orit y u n d er t h e c o n diti o n t h at t h e y ar e r e q u e st e d 
t o k e e p it c o nfi d e nti al. I n t h e e v e nt of a n a ct u al or s u s p e ct e d br e a c h of t hi s o bli g ati o n, S y n e o s H e alt h 
s h o ul d b e n otifi e d pr o m ptl y. 
 
 
 
 
 
 
 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI
P P D
P P D
P P D
P P D
P P D
P P D


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
 Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 2  of 5 6  
 
 
 
R e vi si o n Hi st or y 
V er si o n #  
D at e  
( D D- M m m-Y Y Y Y)  
D o c u m e nt O w n er  
R e vi si o n S u m m ar y  
1. 0  
3 1 - J a n- 2 0 2 2 
 
I niti al R el e a s e V er si o n 
2. 0  
3 1 - A u g- 2 0 2 2 
 
Cl arifi c ati o n of d efi niti o n s a n d d eri v ati o n s , a d diti o n 
of s u b gr o u p s, a d diti o n of t a bl e f or n u m b er of 
s y m pt o m s b y vi sit , a d diti o n of t a bl e f or E C G 
I nt er pr et ati o n at S cr e e ni n g 
 
 
 
 
 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
P P D
P P D
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 3 of 5 6
I c o nfir m t h at I h a v e r e vi e w e d t hi s d o c u m e nt a n d a gr e e wit h t h e c o nt e nt.
A p pr o v al s
S y n e o s H e alt h A p pr o v al
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
P P D
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D:
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 of 5 6
T a bl e of C o nt e nt s
R e vi si o n Hi st or y ............................................................................................................... ........... 2
A p pr o v al s .................................................................................................................................. 3
Gl o s s ar y of A b br e vi ati o n s................................................................................................... 8
P ur p o s e........................................................................................................................ .... 1 1
St u d y O bj e cti v e s .............................................................................................................. 1 2
St u d y D et ail s/ D e si g n ........................................................................................................ 1 3
T a bl e 1: 
S c h e d ul e of A s s e s s m e nt s..................................................................................... 1 7
E n d p oi nt s ......................................................................................................................... 2 3
A n al y si s S et s.................................................................................................................. .. 2 6
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 5 of 5 6
E sti m a n d s ........................................................................................................................ 2 7
G e n er al A s p e ct s f or St ati sti c al A n al y si s ........................................................................... 3 1
D e m o gr a p hi c, Ot h er B a s eli n e C h ar a ct eri sti c s a n d M e di c ati o n ......................................... 3 3
Effi c a c y ....................................................................................................................... ..... 3 6
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 6 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 6 of 5 6
P h ar m a c o ki n eti c s ............................................................................................................. 3 9
P h ar m a c o d y n a mi c s.......................................................................................................... 4 3
S af et y............................................................................................................................... 4 4
H e alt h E c o n o mi c s ............................................................................................................ 4 7
I nt eri m A n al y s e s or I D M C s ............................................................................................... 4 8
C h a n g e s fr o m A n al y si s Pl a n n e d i n Pr ot o c ol ..................................................................... 4 9
R ef er e n c e Li st ................................................................................................................. . 5 0
Pr o gr a m mi n g C o n si d er ati o n s ........................................................................................... 5 1
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 7 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 7 of 5 6
Q u alit y C o ntr ol ................................................................................................................ . 5 6
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 8 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D:
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 8 of 5 6
Gl o s s ar y of A b br e vi ati o n s
A b br e vi ati o n
D e s cri pti o n
A E
A d v er s e E v e nt
A D R
A d v er s e Dr u g R e a cti o n
A N C O V A
A n al y si s of C o v ari a n c e
A R D S
A c ut e R e s pir at or y Di str e s s S y n dr o m e 
A T C
A n at o mi c al T h er a p e uti c C h e mi c al
A U C
Ar e a U n d er t h e C ur v e
B D R M
Bli n d D at a R e vi e w M e eti n g
B L Q
B el o w t h e L o w er Li mit of Q u a ntifi c ati o n
B MI
B o d y M a s s i n d e x
CI
C o nfi d e n c e I nt er v al
C O VI D- 1 9
C or o n a vir u s Di s e a s e 2 0 1 9 
C O P D
C hr o ni c O b str u cti v e P ul m o n ar y Di s e a s e
C R F
C a s e R e p ort F or m
C T C A E
C o m m o n T er mi n ol o g y Crit eri a f or A d v er s e E v e nt s
C V
C o effi ci e nt of V ari ati o n
I D M C
I n d e p e n d e nt D at a M o nit ori n g C o m mitt e e 
E C G
El e ctr o c ar di o gr a m
E C M O
E xtr a c or p or e al M e m br a n e O x y g e n ati o n
E Q
E ur o Q ol
E Q- 5 D- 5L
E ur o Q ol- 5 D- 5L
e C R F
El e ctr o ni c C a s e R e p ort F or m
F D A
F o o d a n d Dr u g A d mi ni str ati o n
Fi O 2
Fr a cti o n of I n s pir e d O x y g e n
G C P
G o o d Cli ni c al Pr a cti c e
H R Q o L 
H e alt h-r el at e d Q u alit y of Lif e
I C H
I nt er n ati o n al C o nf er e n c e o n H ar m o ni z ati o n
I C U
I nt e n si v e C ar e U nit
I T T
I nt e nti o n-t o- Tr e at
I W R S
I nt er a cti v e W e b- R e s p o n s e S y st e m
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 9 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 9  of 5 6  
A b br e vi ati o n  
D e s cri pti o n  
L A R 
L e g all y A ut h ori z e d R e pr e s e nt ati v e 
L O C F 
L a st O b s er v ati o n C arri e d F or w ar d 
M A R 
Mi s si n g At R a n d o m 
M a x 
M a xi m u m 
M e d D R A 
M e di c al Di cti o n ar y f or R e g ul at or y A cti viti e s 
M H 
M a nt el- H a e n s z el 
Mi n 
Mi ni m u m 
M N A R 
Mi s si n g N ot At R a n d o m 
N/ A  
N ot A p pli c a bl e  
N A 
N ot A p pli c a bl e 
NI AI D 
N ati o n al I n stit ut e of All er g y a n d I nf e cti o u s Di s e a s e s 
P A H 
P ul m o n ar y Art eri al H y p ert e n si o n 
P a O 2  
P arti al Pr e s s ur e of O x y g e n 
P D 
P h ar m a c o d y n a mi c s 
P K 
P h ar m a c o ki n eti c s 
P K S 
P h ar m a c o ki n eti c A n al y si s S et 
P P S  
P er Pr ot o c ol S et  
P T 
Pr ef err e d T er m 
Q C 
Q u alit y C o ntr ol 
Q T c 
C orr e ct e d Q T I nt er v al 
R T- P C R 
R e v er s e-tr a n s cri pti o n P ol y m er a s e C h ai n R e a cti o n 
S A E 
S eri o u s A d v er s e E v e nt 
S A P 
St ati sti c al A n al y si s Pl a n 
S A R S- C o V- 2 
S e v er e A c ut e R e s pir at or y S y n dr o m e C or o n a vir u s T y p e 2 
S D 
St a n d ar d D e vi ati o n 
S E  
St a n d ar d Err or  
SI 
St a n d ar d I nt er n ati o n al S y st e m of U nit s 
S O C 
S y st e m Or g a n Cl a s s 
S O P 
St a n d ar d O p er ati n g Pr o c e d ur e 
S o C  
St a n d ar d of C ar e  
S p O 2   
S at ur ati o n of O x y g e n 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 0 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D:
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 1 0  of 5 6  
A b br e vi ati o n  
D e s cri pti o n  
S S 
S af et y S et 
T E A E 
Tr e at m e nt- E m er g e nt A d v er s e E v e nt 
T F L 
T a bl e, Fi g ur e a n d Li sti n g 
V A S 
Vi s u al A n al o g S c al e 
W H O 
W orl d H e alt h Or g a ni z ati o n 
W H O- D D 
W orl d H e alt h Or g a ni z ati o n Dr u g Di cti o n ar y 
WI 
W or k I n str u cti o n 
W O C B P 
W o m e n of C hil d b e ari n g P ot e nti al 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 1 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D:
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 1 1 of 5 6
P ur p o s e
T h e p ur p o s e of t hi s st ati sti c al a n al y si s pl a n ( S A P) i s t o e n s ur e t h at t h e d at a li sti n g s, s u m m ar y t a bl e s a n d 
fi g ur e s w hi c h will b e pr o d u c e d, a n d t h e st ati sti c al m et h o d ol o gi e s w hi c h will b e u s e d, ar e c o m pl et e a n d 
a p pr o pri at e t o all o w v ali d c o n cl u si o n s r e g ar di n g t h e st u d y o bj e cti v e s.
R e s p o n si biliti e s
S y n e o s H e alt h  will p erf or m t h e st ati sti c al a n al y s e s a n d i s r e s p o n si bl e f or t h e pr o d u cti o n a n d q u alit y c o ntr ol 
of all t a bl e s, fi g ur e s a n d li sti n g s ( T F L s).
Ti mi n g s of A n al y s e s
T h e a n al y si s of effi c a c y, s af et y, a n d p h ar m a c o ki n eti c s ( P K) i s pl a n n e d aft er all p ati e nt s c o m pl et e t h e fi n al 
st u d y vi sit or t er mi n at e e arl y fr o m t h e st u d y.
A n i n d e p e n d e nt D at a M o nit ori n g C o m mitt e e ( D M C)  wil l r e vi e w d e s cri pti v e s u m m ari e s of  a c c u m ul ati n g 
s af et y a n d p ati e nt di s p o siti o n t hr o u g h o ut t h e st u d y i n t h e fr e q u e n c y d e s cri b e d i n t h e  D M C  C h art er (r ef er t o 
S e cti o n 1 5).
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 2 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 1 2 of 5 6
St u d y O bj e cti v e s
Pri m ar y O bj e cti v e
T o m e a s ur e t h e eff e ct of M P 1 0 3 2 pl u s st a n d ar d of  c ar e ( S o C) v er s u s pl a c e b o pl u s S o C o n D a y 1 4 
o n di s e a s e pr o gr e s si o n i n p ati e nt s wit h m o d er at e  t o s e v er e c or o n a vir u s di s e a s e 2 0 1 9 ( C O VI D- 1 9) 
S e c o n d ar y O bj e cti v e s
T o m e a s ur e t h e eff e ct of M P 1 0 3 2 pl u s S o C v er s u s pl a c e b o pl u s S o C  o n  D a y 2 8  o n  di s e a s e  
pr o gr e s si o n i n p ati e nt s wit h m o d er at e t o s e v er e C O VI D- 1 9
T o m e a s ur e t h e eff e ct of M P 1 0 3 2 pl u s S o C v er s u s  pl a c e b o pl u s S o C o n di s e a s e r e s ol uti o n o n 
D a y 1 4 a n d D a y 2 8 
T o m e a s ur e t h e eff e ct of M P 1 0 3 2 pl u s S o C v er s u s  pl a c e b o pl u s S o C o n t h e m ort alit y r at e a n d 
ot h er s p e cifi c C O VI D- 1 9 r el at e d c h ar a ct eri sti c s
T o a s s e s s t h e s af et y of M P 1 0 3 2 ( e g, a d v er s e e v e nt s [ A E s] a n d l a b or at or y a b n or m aliti e s)
T o a s s e s s t h e P K of M P 1 0 3 2 o n D a y 1 ( si n gl e d o s e) a n d D a y 7 ( st e a d y st at e) i n a P K s u b s et of 
p ati e nt s
E x pl or at or y  O bj e cti v e s
T o m e a s ur e t h e eff e ct of M P 1 0 3 2 pl u s S o C v er s u s pl a c e b o pl u s S o C o n s o m e a d diti o n al C O VI D- 1 9 
r el at e d c h ar a ct eri sti c s
T o  e v al u at e  t h e  h e alt h-r el at e d  q u alit y  of  lif e  ( H R Q o L)  of  p ati e nt s  tr e at e d  M P 1 0 3 2 pl u s  S o C  
c o m p ar e d wit h pl a c e b o pl u s S o C
T o e v al u at e bi o m ar k er l e v el s
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 3 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 1 3 of 5 6
St u d y D et ail s/ D e si g n
Bri ef D e s cri pti o n
T hi s  i s  a  P h a s e  II a,  r a n d o mi z e d,  d o u bl e- bli n d,  pl a c e b o- c o ntr oll e d,  m ulti c e nt er,  pr o of- of- c o n c e pt  st u d y  
d e si g n e d t o a s s e s s t h e p ot e nti al effi c a c y a n d s af et y of 3 0 0 m g M P 1 0 3 2 t wi c e d ail y ( BI D) pl u s S o C v er s u s 
pl a c e b o pl u s S o C i n h o s pit ali z e d a d ult s wit h m o d er at e t o s e v er e C O VI D- 1 9.
A p pr o xi m at el y 4 0 sit e s w orl d wi d e  will p arti ci p at e i n t hi s st u d y.
A p pr o xi m at el y 1 4 0 p ati e nt s will b e s cr e e n e d t o r a n d o mi z e a p pr o xi m at el y 1 2 0 p ati e nt s i n 2: 1 r ati o a s f oll o w s: 
Ar m A ( 3 0 0 m g M P 1 0 3 2 BI D pl u s S o C): a p pr o xi m at el y 8 0 p ati e nt s
Ar m B ( pl a c e b o BI D pl u s S o C): a p pr o xi m at el y 4 0 p ati e nt s
T h e str atifi c ati o n f a ct or f or r a n d o mi z ati o n will i n cl u d e b a s eli n e C O VI D- 1 9 s e v erit y ( m o d er at e a n d s e v er e) 
a n d a g e- cl a s s ( ≤6 5 y e ar s a n d > 6 5 y e ar s). C O VI D - 1 9 s e v erit y will b e d et er mi n e d u si n g t h e f oll o wi n g crit eri a:
M o d er at e C O VI D- 1 9: 
o
P o siti v e s e v er e a c ut e r e s pir at or y s y n dr o m e c or o n a vir u s t y p e 2 ( S A R S- C o V- 2) t e sti n g 
b y  st a n d ar d  r e v er s e-tr a n s cri pti o n  p ol y m e r a s e  c h ai n  r e a cti o n  ( R T- P C R)  a s s a y  or  
e q ui v al e nt t e st 
o
S y m pt o m s of m o d er at e ill n e s s wit h C O VI D- 1 9, w hi c h c o ul d i n cl u d e a n y s y m pt o m of 
mil d ill n e s s or s h ort n e s s of br e at h wit h e x erti o n
o
Cli ni c al si g n s s u g g e sti v e of m o d er at e ill n e s s wit h C O VI D- 1 9, s u c h a s r e s pir at or y r at e 
≥2 0 br e at h s p er mi n ut e, s at ur ati o n of o x y g e n ( S p O 2 ) > 9 3 % ( o n r o o m air at s e a l e v el, if 
p o s si bl e), h e art r at e ≥9 0 b e at s p er mi n ut e 
o
N o cli ni c al si g n s i n di c ati v e of s e v er e or criti c al C O VI D- 1 9
S e v er e C O VI D- 1 9: 
o
P o siti v e S A R S- C o V- 2 t e sti n g b y st a n d ar d R T- P C R a s s a y or e q ui v al e nt t e st 
o
S y m pt o m s s u g g e sti v e of s e v er e s y st e mi c ill n e s s wit h C O VI D- 1 9, w hi c h c o ul d i n cl u d e 
a n y s y m pt o m of m o d er at e ill n e s s or s h ort n e s s of br e at h at r e st, or r e s pir at or y di str e s s
o
Cli ni c al si g n s i n di c ati v e of s e v er e s y st e mi c ill n e s s wit h C O VI D- 1 9, s u c h a s r e s pir at or y 
r at e ≥3 0 br e at h s p er mi n ut e, h e art r at e ≥1 2 5 b e at s p er mi n ut e, S p O 2 ≤9 3 % ( o n r o o m 
air at s e a l e v el, if p o s si bl e), p arti al pr e s s ur e of o x y g e n ( P a O 2 )/ fr a cti o n of i n s pir e d 
o x y g e n ( Fi O 2 ) < 3 0 0, or di a g n o s e d wit h a c ut e r e s pir at or y di str e s s s y n dr o m e ([ A R D S]
a c c or di n g t o t h e B erli n d efi niti o n; s e e T a bl e 3 i n t h e Pr ot o c ol)
o
N o crit eri a m et f or criti c al C O VI D- 1 9
T o  st a n d ar di z e  t h e  a s s e s s m e nt  of  C O VI D- 1 9  s e v erit y,  r e s pir at or y  r at e,  S p O 2 ,  a n d  h e art  r at e  will  b e  
m e a s ur e d w h e n t h e p ati e nt i s o n r o o m air at s e a l e v el (i e, n o s u p pl e m e nt al o x y g e n, if p o s si bl e) a n d at r e st 
f or at l e a st 5 mi n ut e s. If p o s si bl e, t h e sit e s h o ul d c olle ct t h e i nf or m ati o n fr o m e a c h p ati e nt at t h e s a m e ti m e 
e a c h d a y ( ± 1 h o ur). 
Pl e a s e  n ot e:  P ati e nt s  w h o  ar e  r e c ei vi n g  o x y g e n  t h er a p y  at  b a s eli n e  f or  a  c hr o ni c  c o n diti o n  ( e g,  
e m p h y s e m a,  c hr o ni c  o b str u cti v e  p ul m o n ar y  di s e a s e  ( C O P D),  p ul m o n ar y  art eri al  h y p ert e n si o n  [ P A H],  
i di o p at hi c p ul m o n ar y fi br o si s [I P F], et c.) s h o ul d b e c o n si d er e d a s h a vi n g s e v er e C O VI D- 1 9 ( u nl e s s t h e 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 4 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 1 4  of 5 6  
p ati e nt  m e et s  t h e  d efi niti o n  f or  criti c al  C O VI D- 1 9).  F or  q u e sti o n s  r el at e d  t o  C O VI D- 1 9  s e v erit y,  t h e  
i n v e sti g at or s h o ul d c o nt a ct t h e m e di c al m o nit or. 
E a c h sit e will tr e at all p ati e nt s wit h S o C f or t h e d ur ati o n of t h e st u d y. T h e s el e ct e d S o C will b e u s e d i n 
a c c or d a n c e  wit h  t h e  h o s pit al’ s  S o C  pr o c e d ur e s  a n d  m a y  i n cl u d e  dr u g s  u n d er  a n  e m er g e n c y  u s e  
a ut h ori z ati o n. 
T hi s st u d y c o n si st s of 3 p eri o d s: ( 1) s cr e e ni n g, ( 2) tr e at m e nt, a n d ( 3) f oll o w- u p. D uri n g t h e s cr e e ni n g p eri o d, 
e a c h p ot e nti al p ati e nt ( or p ati e nt’ s l e g all y a c c e pt a bl e r e pr e s e nt ati v e) will pr o vi d e i nf or m e d c o n s e nt pri or t o 
st arti n g a n y st u d y- s p e cifi c pr o c e d ur e s. T h e r a n d o mi z ati o n of p ati e nt s t o tr e at m e nt gr o u p s will b e p erf or m e d 
c e ntr all y  b y  a n  i nt er a cti v e  w e b-r e s p o n s e  s y st e m  (I W R S)  u si n g  a  r a n d o mi z ati o n  s c h e m e  t h at  will  b e  
d e v el o p e d b y a n u n bli n d e d, i n d e p e n d e nt st ati sti ci a n. D uri n g t h e tr e at m e nt p eri o d, r a n d o mi z e d p ati e nt s will 
b e pr o vi d e d t h eir a s si g n e d tr e at m e nt a n d a s s e s s m e nt s a c c or di n g t o t h e pr ot o c ol. All p ati e nt s will b e tr e at e d 
f or 2 8 d a y s, u nl e s s t h e st u d y dr u g i s di s c o nti n u e d, e g, f or s af et y r e a s o n s. If t h e p ati e nt i s di s c h ar g e d h o m e 
b ef or e D a y 2 8, t h e st u d y t e a m will pr o vi d e t h e p ati e nt wit h t h e r e m ai n d er of t h e bli n d e d st u d y dr u g kit s t o 
t a k e h o m e al o n g wit h i n str u cti o n s o n h o w t o c o nti n u e tr e at m e nt at h o m e o n t h e d a y- of- di s c h ar g e; f or t h e s e 
p ati e nt s, tr e at m e nt c o m pli a n c e will b e c o n d u ct e d vi a a di ar y. If t h e p ati e nt d o e s n ot f e el c o mf ort a bl e t o 
c o m pl et e t h e di ar y, t h e sit e will alt er n ati v el y pr o vi d e t h e p ati e nt wit h t h e o pti o n t o b e c all e d, t wi c e a d a y, t o 
c o nfir m t h at t h e st u d y dr u g i s t a k e n a s i n str u ct e d. T h e tr e at m e nt p eri o d will e n d wit h t h e D a y 2 8 ( E n d of 
Tr e at m e nt  Vi sit)  a s s e s s m e nt s.  T h e  f oll o w- u p  p eri o d  will  e n d  wit h  t h e  F oll o w- u p  Vi sit  a s s e s s m e nt s  o n  
D a y 6 0. 
Pl e a s e n ot e: P ati e nt s will b e a s s e s s e d w hil e h o s pit ali z e d. If p ati e nt s ar e di s c h ar g e d fr o m t h e h o s pit al, t h e y 
will h a v e st u d y vi sit s at D a y 1 4, D a y 2 8, a n d D a y 6 0 a s a n o ut p ati e nt vi sit. P ati e nt s di s c h ar g e d e arl y will 
c o nti n u e t o r e c ei v e st u d y dr u g t hr o u g h D a y 2 8. F or di s c h ar g e d p ati e nt s, D a y 1 4 a n d D a y 2 8 vi sit s ar e 
pr ef err e d t o b e c o n d u ct e d i n p er s o n at t h e st u d y sit e. If r e stri cti o n s li mit t h e a bilit y of t h e p ati e nt t o r et ur n t o 
t h e st u d y sit e, t h e s e vi sit s m a y b e c o n d u ct e d b y h o m e h e alt h c ar e vi sit or b y t el e p h o n e/ virt u al c all (t h e 
p ati e nt’ s c ar e gi v er m a y a s si st d uri n g t h e t el e p h o n e/ v irt u al c all). F or di s c h ar g e d p ati e nt s, it i s s uffi ci e nt t o 
c o n d u ct t h e D a y 6 0 F oll o w- u p Vi sit a s a t el e p h o n e/ virt u al c all (t h e p ati e nt’ s c ar e gi v er m a y a s si st d uri n g t h e 
t el e p h o n e/ virt u al c all) a n d a n o ut p ati e nt or h o m e h e alt h c ar e vi sit i s al s o all o w e d.  
N ot e: H o m e h e alt h c ar e vi sit s ar e o nl y all o w e d i n c o u n tri e s w h er e h o m e h e alt h c ar e vi sit s ar e e x pli citl y 
p er mitt e d b y r e g ul at or y r e q uir e m e nt s. 
T h e st u d y d ur ati o n f or a n i n di vi d u al p ati e nt will b e a s f oll o w s: 
  
S cr e e ni n g p eri o d: u p t o 7 d a y s  
  
Tr e at m e nt p eri o d: 2 8 c o n s e c uti v e d a y s (i e, D a y 1 t o D a y 2 8) 
  
F oll o w- u p p eri o d: 3 2 d a y s aft er D a y 2 8 (i e, D a y 6 0) 
A s s u c h, t h e a p pr o xi m at e st u d y d ur ati o n (i n cl u di n g s cr e e ni n g a n d t h e f oll o w- u p p eri o d) f or a n i n di vi d u al 
p ati e nt i s u p t o 6 7 d a y s ( ± 3 d a y s). 
A n i n d e p e n d e nt D M C will b e e st a bli s h e d b y t h e s p o n s or or d e si g n e e t o r e vi e w a c c u m ul ati n g st u d y d at a at 
r e g ul ar i nt er v al s ( a s p er t h e D M C c h art er) t hr o u g h o ut t he st u d y t o e n s ur e t h e s af et y of p ati e nt s a n d r e vi e w 
o v er all st u d y c o n d u ct. T h e D M C c a n r e c o m m e n d i n writi n g t o t h e s p o n s or w h et h er t o c o nti n u e, m o dif y, or 
st o p t h e cli ni c al st u d y o n t h e b a si s of s af et y c o n si d er ati o n s ( s e e S e cti o n 1 4. 8 of t h e pr ot o c ol f or f urt h er 
d et ail s). 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 5 of 5 9
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_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 1 5 of 5 6
N o i nt eri m a n al y si s i s pl a n n e d.
P ati e nt S el e cti o n
I n cl u si o n Crit eri a
T h e i n cl u si o n crit eri a ar e li st e d i n S e cti o n 8. 1 of t h e pr ot o c ol.
E x cl u si o n Crit eri a
T h e e x cl u si o n crit eri a ar e li st e d i n S e cti o n 8. 2 of t h e pr ot o c ol.
D et er mi n ati o n of S a m pl e Si z e
T h e pri m ar y effi c a c y e n d p oi nt ‘ pr o p orti o n of p ati e nt s wit h di s e a s e pr o gr e s si o n o n D a y 1 4’ i s a s s u m e d t o b e 
1 0 % i n t h e 3 0 0 m g M P 1 0 3 2 BI D pl u s S o C tr e at m e nt gr o u p ( Ar m A) a n d 3 0 % i n t h e pl a c e b o pl u s S o C 
tr e at m e nt gr o u p ( Ar m B). U si n g t h e C hi- s q u ar e t e st wit h t y p e I err or al p h a = 1 0 % t w o- si d e d f or t hi s pr o of- of-
c o n c e pt st u d y a n d 2: 1 r a n d o mi z ati o n r ati o, 1 1 4 p ati e nt s  ( 7 6 i n Ar m A a n d 3 8 i n Ar m B) ar e r e q uir e d t o 
a c hi e v e a st ati sti c al p o w er of 8 3 %. C o n si d eri n g a b o ut 5 % e arl y st u d y t er mi n ati o n s, t h e n e c e s s ar y s a m pl e 
si z e f or r a n d o mi z ati o n r e s ult s i n 1 2 0 p ati e nt s i n t ot al ( 8 0 i n Ar m A a n d 4 0 i n Arm B). If d uri n g t h e c o n d u ct 
of t h e st u d y t h e e arl y st u d y t er mi n ati o n r at e i s hi g h er t h a n t h e e sti m at e d 5 %, t h e n a n i n cr e a s e i n t h e 
r a n d o mi z e d n u m b er of p ati e nt s m a y b e n e c e s s ar y.
S a m pl e si z e e sti m ati o n i s p erf or m e d u si n g n Q u er y 8, V er si o n 8. 6. 1. 0.
A s u b s et of r a n d o mi z e d p ati e nt s will b e c o n s e nt e d f o r t h e c oll e cti o n of bl o o d s a m pl e s f or P K m e a s ur e m e nt s. 
T h e P K s u b s et c o n si st s of a p pr o xi m at el y 2 0 p ati e nt s  fr o m t h e 3 0 0 m g M P 1 0 3 2 BI D pl u s S o C gr o u p a n d 
a p pr o xi m at el y 1 0 p ati e nt s fr o m t h e pl a c e b o pl u s S o C gr o u p, u p t o a t ot al of a p pr o xi m at el y 3 0 p ati e nt s.
Tr e at m e nt A s si g n m e nt a n d Bli n di n g
T h e  r a n d o mi z ati o n  of  p ati e nt s  t o  tr e at m e nt  gr o u p s  will  b e  p erf or m e d  c e ntr all y b y a n  I nt er a cti v e  W e b-
R e s p o n s e  S y st e m  (I W R S) u si n g  a  r a n d o mi z ati o n  s c h e m e  t h at  will  b e  pr o d u c e d  b y  a n  u n bli n d e d,  
i n d e p e n d e nt st ati sti ci a n. D uri n g t h e r a n d o mi z ati o n pr o c e s s, I W R S will a s si g n a r a n d o mi z ati o n n u m b er. 
E a c h p ati e nt will b e a s si g n e d o n e kit n u m b er at r a n d o mi z ati o n a n d a s e c o n d kit n u m b er at t h e D a y 1 4 vi sit. 
T h e  st u d y  dr u g  kit s  will  c o nt ai n  t h e  r e s p e cti v e  bl i n d e d  tr e at m e nt  a v ail a bl e  at  t h e  st u d y sit e.   F urt h er  
i nf or m ati o n o n I W R S pr o c e s s will b e pr o vi d e d i n t h e I W R S M a n u al.
A p pr o xi m at el y 1 2 0 p ati e nt s will b e r a n d o ml y a s si g n e d ( 2: 1) a s f oll o w s: 
Ar m A ( 3 0 0 m g M P 1 0 3 2 BI D pl u s S o C): a p pr o xi m at el y 8 0 p ati e nt s
Ar m B ( pl a c e b o BI D pl u s S o C) : a p pr o xi m at el y 4 0 p ati e nt s
T h e r a n d o mi z ati o n will b e p erf or m e d str atifi e d c o n s i d eri n g t h e b a s eli n e C O VI D- 1 9 s e v erit y ( m o d er at e a n d 
s e v er e) a n d a g e- c l a s s (≤6 5 y e ar s a n d > 6 5 y e ar s) a n d i n bl o c k s.
A n u n bli n d e d,  i n d e p e n d e nt  st ati sti ci a n  will  b e  a s si g n e d  t o  pr o d u c e  t h e  r a n d o mi z ati o n  s c h e d ul e  a n d  
u n bli n d e d t a bl e s, fi g ur e s, a n d li sti n g s f or t h e i n d e p e n d e n t D M C. T h e u n bli n d e d st ati sti ci a n will n ot ot h er wi s e 
p arti ci p at e i n st u d y pr o c e d ur e s.
I n t h e e v e nt t h at e m er g e n c y u n bli n di n g i s r e q uir e d f or a gi v e n p ati e nt b e c a u s e of A E s or c o n c er n s f or t h e 
p ati e nt’ s s af et y or w ell - b ei n g, t h e i n v e sti g at or m a y br e a k t h e r an d o mi z ati o n c o d e f or t h e p ati e nt vi a t h e 
I W R S, b y w hi c h t h e u n bli n di n g will b e c a pt ur e d. T h e i n v e sti g at or i s r e s p o n si bl e f or n otif yi n g t h e m e di c al 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 6 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 1 6 of 5 6
m o nit or a n d/ or s p o n s or of s u c h a n e v e nt a s s o o n a s  p o s si bl e. T h e u n bli n di n g a n d it s c a u s e will al s o b e 
d o c u m e nt e d i n t h e el e ctr o ni c c a s e r e p ort f or m ( e C R F).
A d mi ni str ati o n of St u d y M e di c ati o n
All r a n d o mi z e d p ati e nt s will r e c ei v e st u d y dr u g fr o m D a y  1 t o D a y 2 8 a c c or di n g t o t h eir a s si g n e d tr e at m e nt 
a n d a c c or di n g t o t h e r a n d o mi z ati o n s c h e m e. 
Pl e a s e n ot e: P ati e nt s w h o r e m ai n h o s pit ali z e d aft er 2 8  d a y s of c o n s e c uti v e tr e at m e nt wit h st u d y dr u g ar e 
n ot eli gi bl e f or a d diti o n al tr e at m e nt s wit h st u d y dr u g . P ati e nt s will r e c ei v e 6 c a p s ul e s i n t h e m or ni n g a n d 
6 c a p s ul e s i n t h e e v e ni n g (i e, a p pr o xi m at el y e v er y 1 2 h o ur s, a p pr o xi m at el y at t h e s a m e ti m e e v er y d a y, 
a n d at l e a st 8 h o ur s a p art) a c c or di n g t o t h eir r a n d o m i z e d tr e at m e nt ar m a s si g n m ent a s d e s cri b e d b el o w: 
Ar m A: M P 1 0 3 2 ( 3 0 0 m g [ 6 × M P 1 0 3 2 h ar d g el ati n c a p s ul e s 5 0 m g] BI D) f or or al a d mi ni str ati o n
Ar m B: 6 × pl a c e b o c a p s ul e s (i e, m at c hi n g M P 1 0 3 2 h ar d g el ati n c a p s ul e s 5 0 m g) BI D f or or al 
a d mi ni str ati o n 
I n Ar m A, t h e pl a n n e d t ot al d ail y d o s e of M P 1 0 3 2 i s 6 0 0 m g. I n Ar m B, t h e pl a n n e d t ot al d ail y d o s e of 
M P 1 0 3 2 i s 0  m g.
St u d y dr u g will b e a d mi ni st er e d t o e a c h p ati e nt wit h w a t er ( a d li bit u m) f or or al a d mi ni str ati o n. F or t hi s st u d y, 
p ati e nt s s h o ul d b e, if p o s si bl e, a d mi ni st er e d st u d y dr u g i n a f a st e d st at e ( ≥4 h o ur s). H o w e v er, if a p ati e nt 
h a s e at e n pri or t o t h eir pl a n n e d a d mi ni str ati o n, t h e d o si n g m a y pr o c e e d u n d er a f e d st at e. P ati e nt s m a y e at 
a p pr o xi m at el y 3 0 mi n ut e s p o st d o s e. T h e st u d y sit e s h o u l d r e c or d t h e d at e a n d ti m e of d o si n g (r e c or d e d a s 
t h e ti m e w h e n t h e fir st c a p s ul e i s a d mi ni st er e d). F or p ati e nt s i n t h e P K s u b s et, st u d y dr u g s h o ul d b e 
a d mi ni st er e d i n f a st e d st at e o n D a y 1 a n d D a y 7, w h e n f e a si bl e. If t h e p ati e nt di d n ot r e c ei v e t h e st u d y dr u g 
i n t h e f a st e d st at e, t h e n t h e a m o u nt of f o o d c o n s u m e d wit hi n 4 h o ur s b ef or e d o si n g a n d 3 0 mi n ut e s aft er 
d o s e a d mi ni str ati o n s h o ul d b e r e c or d e d a n d t h e P K s a m pl e s s h o ul d b e c oll e ct e d a s pl a n n e d.
A n y mi s s e d d o s e of st u d y dr u g m a y b e a d mi ni st er e d a s  s o o n a s p o s si bl e a n d t h e n e xt s c h e d ul e d d o s e m a y 
b e a d mi ni st er e d a c c or di n g t o t h e pl a n n e d s c h e d ul e a s l o n g a s t h e d o s e s ar e at l e a st 6 t o 8 h o ur s a p art. If 
st u d y dr u g a d mi ni str ati o n i s i nt err u pt e d f or > 2 d a y s, t h e i n v e sti g at or s h o ul d n otif y t h e m e di c al m o nit or t o 
d et er mi n e if t h e st u d y dr u g a d mi ni str ati o n c a n b e r e s u m e d.
P ati e nt s will b e a s k e d t o a b st ai n fr o m t h e f oll o wi n g pr o d u ct s t h at m a y p ot e nti all y aff e ct t h eir s af et y a n d/ or 
t h e P K pr ofil e of t h e st u d y dr u g: 
s oft or h ar d dr u g s (i n cl u di n g c a n n a bi s) fr o m s cr e e ni n g a n d t hr o u g h o ut t h e st u d y 
s m o ki n g or u si n g el e ctr o ni c ci g ar ett e s w hil e a d mitt e d t o t h e h o s pit al
c o n s u m pti o n of al c o h ol- b a s e d pr o d u ct s will b e pr o hi bit e d fr o m s cr e e ni n g u ntil t h e fi n al d o s e of 
st u d y dr u g
St u d y Pr o c e d ur e s a n d Fl o w c h art
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 7 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 1 7  of 5 6  
T a bl e 1:  
S c h e d ul e of A s s e s s m e nt s 
St u d y P eri o d 
Scr e e ni n g 
P eri o d 
 
Tr e at m e nt P eri o d 
F oll o w- u p 
P eri o d 
 
- 
Visit N a m e 
Scr e e ni n g a D a y 1 a D a ys 2 t o 
1 3 
D a y 1 4 b  D a y 2 1 b  
D a y 2 8 
( E n d of 
Tr e at m e nt 
Visit) b  
D a y 6 0  
( F oll o w-u p 
Visit) b / 
E arl y St u d y 
T er mi n ati o n 
aft er D a y 2 8 
 
D a y of 
Disc h ar g e / 
E arl y St u d y 
T er mi n ati o n 
b ef or e D a y 
2 8 
St u d y D a y ( wi n d o w)  
D a y - 7 t o  
D a y - 1 
D a y 1 
( N A) 
D a ys 2 t o 
1 3 ( N A) 
D a y 1 4 
( ± 2 d a ys) 
D a y 2 1 
( ± 2 d a ys) 
D a y 2 8 
( ± 3 d a ys) 
D a y 6 0 
( ± 3 d a ys)  
D a y of 
Disc h ar g e 
I nf or m e d c o ns e ntc 
X 
- 
- 
- 
 
- 
- 
 
- 
C O VI D- 1 9 t esti n g d  
X 
X 
- 
X e 
 
X e 
X e 
 
- 
D e m o gr a p hics f 
X 
- 
- 
- 
 
- 
- 
 
- 
M e dic al/s ur gic al hist or y g  
X 
X 
( u p d at es 
o nl y) 
-
 -
 
  -
  -
 
 
- 
I ncl usi o n/ excl usi o n crit eri a 
X 
X 
- 
- 
 
- 
- 
 
- 
C o m pl et e p h ysic al 
ex a mi n ati o n h 
X
 -
 -
  -
 
  -
  -
 
 
- 
Li mit e d p h ysic al 
ex a mi n ati o n h 
-
 X
 
X ( o nl y 
D a y 8 
[ ± 3 d a ys])  
s 
X e 
 
Xe -
 
 
X 
Vit al si g ns i 
X 
X 
X j 
X e 
 
X e 
X e 
 
X 
H ei g ht 
X 
- 
- 
- 
 
- 
- 
 
- 
W ei g ht a n d B MI 
X 
X 
- 
X e 
 
X e 
X e 
 
X 
Cli nic al l a b or at or y 
ass ess m e nts  
( he mat ol o gy, bl o o d 
b i oc h e mistr y, 
c o a g ul ati o n, a n d 
uri n alysis) 
X
 X
 
X ( o nl y 
D a y 8 
[ ± 3 d a ys]) s 
X  ( D a ys 1 4, 2 1, a n d 2 8)e, u 
- 
 
X 
E C G k 
X 
- 
- 
- 
 
- 
- 
 
- 
Pr e g n a nc y t est ( W O C B P  
o nly) l 
X
 X
 -
  X
 
  -
  -
 
 
X ( o nl y if 
disc h ar g e d 
b ef or e D a y 
1 4 or at 
E arl y St u d y 
T er mi n ati o n 
b ef or e D a y 
1 4) 
R a n d o miz ati o n vi a I W R S 
- 
X 
- 
- 
 
- 
- 
 
- 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 8 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 1 8  of 5 6  
St u d y P eri o d 
Scr e e ni n g 
P eri o d 
 
Tr e at m e nt P eri o d 
F oll o w- u p 
P eri o d 
 
- 
Visit N a m e 
Scr e e ni n g a D a y 1 a D a ys 2 t o 
1 3 
D a y 1 4 b  D a y 2 1 b  
D a y 2 8 
( E n d of 
Tr e at m e nt 
Visit) b  
D a y 6 0  
( F oll o w-u p 
Visit) b / 
E arl y St u d y 
T er mi n ati o n 
aft er D a y 2 8 
 
D a y of 
Disc h ar g e / 
E arl y St u d y 
T er mi n ati o n 
b ef or e D a y 
2 8 
St u d y D a y ( wi n d o w)  
D a y - 7 t o  
D a y - 1 
D a y 1 
( N A) 
D a ys 2 t o 
1 3 ( N A) 
D a y 1 4 
( ± 2 d a ys) 
D a y 2 1 
( ± 2 d a ys) 
D a y 2 8 
( ± 3 d a ys) 
D a y 6 0 
( ± 3 d a ys)  
D a y of 
Disc h ar g e 
R etri e v e t h e 1 4 - d a y 
bli n d e d st u d y dr u g kit vi a 
t h e st u d y dr u g kit n u m b er 
assi g n e d b y I W R S  
 X
 
 X
v 
 
 
 
 
 
X ( o nl y if 
disc h ar g e d 
b ef or e D a y 
1 4; N A f or 
E arl y St u d y 
T er mi n ati o n 
) 
Bl o o d s a m pl e c oll ecti o n 
f or bi o m ar k ers  
-
 Xo  
X ( o nl y 
D a y 7) o  
X ( D a ys 1 4, 2 1, a n d 2 8) o  
X e, o  
 
- 
A d mi nist er bli n d e d st u dy 
dr u g BI D 
- 
 
X t -
 
 
- 
Pr o vi d e r e m ai n d er of t h e 
assi g n e d bli n d e d st u d y 
dr u g kit(s) t o t h e p ati e nt 
al o n g wit h i nstr ucti o ns m  
-
 -
 -
 -
 
  -
  -
 
 
X ( o nl y if 
disc h ar g e d 
d uri n g t h e 
tr e at m e nt 
p eri o d; N A 
f or E arl y 
St u d y 
T er mi n ati o n) 
Pr o vi d e p ati e nt wit h t h e 
di ar y a n d tr ai n p ati e nt o n 
us e of t h e di ary m  
-
 -
 -
 -
 
  -
  -
 
 
X ( o nl y if 
disc h ar g e d 
d uri n g t h e 
tr e at m e nt 
p eri o d; N A 
f or E arl y 
St u d y 
T er mi n ati o n) 
C O VI D- 1 9 s y m pt o ms 
X 
X 
- 
X 
 
X 
X 
 
X 
C O VI D- 1 9 s ev erity p 
X 
X 
- 
- 
 
- 
- 
 
- 
Cli nic al st at us r el at e d t o 
C O VI D - 1 9 o n t h e NI AI D 
8- p oi nt or di n al sc al e q 
X
 X
 X
 X
 
  X
  X
 
 
X 
E Q - 5 D- 5L q u esti o n n air er 
-
 -
 -
 -
 
  -
  X
 
 
X ( o nl y if 
disc h ar g e d/ 
e arl y 
t er mi n at e d 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 1 9 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 1 9  of 5 6  
St u d y P eri o d 
Scr e e ni n g 
P eri o d 
 
Tr e at m e nt P eri o d 
F oll o w- u p 
P eri o d 
 
- 
Visit N a m e 
Scr e e ni n g a D a y 1 a D a ys 2 t o 
1 3 
D a y 1 4 b  D a y 2 1 b  
D a y 2 8 
( E n d of 
Tr e at m e nt 
Visit) b  
D a y 6 0  
( F oll o w-u p 
Visit) b / 
E arl y St u d y 
T er mi n ati o n 
aft er D a y 2 8 
 
D a y of 
Disc h ar g e / 
E arl y St u d y 
T er mi n ati o n 
b ef or e D a y 
2 8 
St u d y D a y ( wi n d o w)  
D a y - 7 t o  
D a y - 1 
D a y 1 
( N A) 
D a ys 2 t o 
1 3 ( N A) 
D a y 1 4 
( ± 2 d a ys) 
D a y 2 1 
( ± 2 d a ys) 
D a y 2 8 
( ± 3 d a ys) 
D a y 6 0 
( ± 3 d a ys)  
D a y of 
Disc h ar g e 
b ef or e D a y 
6 0) 
Bl o o d s a m pl e c oll ecti o n 
( pl as m a) f or P K (fr o m t h e 
P K s u bs et of a p pr oxi m at ely 
3 0  p ati e nts w h o gi v e 
o pti o n al c o ns e nt) n 
-
 X
 
X ( o nl y 
D a y  7) j 
 
  -
  -
 
 
- 
A Es 
X 
X 
Pri or a n d c o nc o mit a nt 
m e dic ati o ns 
X 
X 
A b bre viati o ns: A E = a d verse e ve nt; BI D = t wice dail y; B MI = b o d y mass i n de x; C O VI D- 1 9 = c or o na vir us 2 0 1 9; 
E C G = electr ocar di o gra m; e C R F = electr o nic case re p ort f or m; E Q- 5 D- 5 L = E ur o Q ol- 5 D- 5 L; I E C = i n de pe n de nt 
et hics c o m mittee; I C U = i nte nsi ve care u nit; I R B = i nstit ut i o nal re vie w b oar d; I W R S = i nt eracti ve we b-res p o nse 
s yste m; L A R = le gall y a ut h ori ze d re prese ntati ve; N A = n ot a p plica ble; NI AI D = Nati o nal I nstit ute of Aller g y a n d 
I nfecti o us Diseases; P K = p har mac o ki netic; R T- P C R = re verse tra nscri pti o n- p ol y merase c hai n reacti o n; 
S A E = seri o us a d verse e ve nt; S A R S- C o V- 2 = se vere ac ute r e s pirat or y s y n dr o me c or o na vir us t y pe 2; S o C = sta n dar d 
of care; S p O 2 = sat urati o n of o x y ge n; W O C B P = w o me n of c hil d beari n g p ote ntial 
a. 
T h ose patie nts w h o are f ull y eli gi ble (all scree ni n g assess me nts are a vaila ble) ca n ha ve Da y 1 perf or me d o n 
t he sa me da y as scree ni n g. If s cree ni n g a n d Da y 1 are perf or me d o n t he sa me da y, visit pr oce d ures re q uire d 
f or b ot h visits d o n ot nee d t o be re peate d.  
b.  P atie nts will be assesse d w hile h os pitalize d. If patie nts ar e disc har ge d fr o m t he h os pital, t he y ca n ha ve t he 
st u d y visits at Da y 1 4, Da y 2 1, Da y 2 8, a n d Da y 6 0 as a n o ut patie nt visit. P atie nts disc har ge d earl y will 
c o nti n ue t o recei ve st u d y dr u g t hr o u g h Da y 2 8. F or disc har ge d patie nts, Da y 1 4 a n d Da y 2 8 visits are 
preferre d t o be c o n d ucte d i n pers o n at t he st u d y site. If  restri cti o ns li mit t he a bilit y of t he patie nt t o ret ur n t o 
t he st u d y site, t hese visits ma y be c o n d ucte d b y h o me healt hcare visit or b y tele p h o ne/ virt ual call (t he 
patie nt’s care gi ver ma y assist d uri n g t he tele p h o ne/ virt u al call). F or disc har ge d pa tie nts, it is s ufficie nt t o 
c o n d uct t he Da y 6 0 F oll o w- u p Visit as a tele p h o ne/ virt ual call (t he patie nt’s c are gi ver ma y assist d uri n g t he 
tele p h o ne/ virt ual call) or a n o ut patie nt or h o me healt hcare visit is als o all o we d. Please n ot e: I n cases i n 
w hic h t he patie nt is dee me d l ost t o f oll o w- u p, t he i n vest i gat or or desi g nee m ust ma ke e ver y eff ort t o re gai n 
c o ntact wit h t he patie nt (e g, tele p h o ne calls, letter t o t h e patie nt’s last k n o w n maili n g a d dress, or l ocal 
e q ui vale nt met h o ds). I n cases w here t he patie nt’s L A R pr o vi des i nf or me d c o nse nt o n be half of t he patie nt, 
t he st u d y site s h o ul d atte m pt t o c o ntact t he L A R. A d diti o nall y, t he st u d y site s h o ul d atte m pt t o re gai n 
c o ntact wit h t he patie nt usi n g t he alter nati ve c o ntact i nf or mati o n pr o vi de d  b y t he patie nt/ L A R at t he ti me of 
i nf or me d c o nse nt. T hese c o nta ct atte m pts m ust be d oc u me nt e d i n t he patie nt’s me dical rec or ds. 
c. 
T he patie nt m ust gi ve i nf or me d c o nse nt t o partici pate i n t he st u d y or, f or a d ults i nca pa ble of c o nse nti n g d ue 
t o t heir me dical c o n diti o n (e g, t o o wea k or de bilitate d, severe s h ort ness of breat h) or d ue t o literac y iss ues, 
t he patie nt’s L A R m ust be willi ng gi ve i nf or me d c o nse nt o n be half of t he patie nt t o partici pate i n t he st u d y 
as per mitte d b y l ocal re g ulat or y a ut h orities, I R Bs/I E Cs, or l ocal la ws. 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 0 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 2 0  of 5 6  
d.  At t he scree ni n g visit, t he l ocal la b orat or y ma y perf or m C O VI D- 1 9 testi n g b y sta n dar d R T- P C R assa y or 
e q ui vale nt test. At scree ni n g, a p ositi ve test m ust be a vaila ble i n or der f or t he p atie nt t o be ra n d o mize d o n 
Da y 1. If t he patie nt has a pre vi o us c o nfir mati o n of S A R S- C o V- 2 ( wit hi n 7 da ys of Da y 1), t he S A R S-
C o V- 2 test at scree ni n g is n ot re q uire d. O n Da y 1, D a y 1 4, Da y 2 8, a n d Da y 6 0, sa m ples will be se nt t o t he 
ce ntral la b orat or y f or C O VI D- 1 9 testi n g b y sta n dar d R T- P C R assa y. T he res ult of t he C O VI D- 1 9 tests 
( p ositi ve/ ne gati ve) m ust be d oc u me nte d i n t he e C R F. F urt her details will be descri be d i n t he la b orat or y 
ma n ual. Please n ote: If C O VI D- 1 9 tests are perf or me d at u nsc he d ule d ti me p oi nts (e g, acc or di n g t o S o C), 
fi n di n gs (ie, p ositi ve/ ne gati ve res ult) m ust be rec or de d i n t he e C R F. 
e. 
N ot all assess me nts will be a ble t o be perf or me d if t he Da y 1 4, Da y 2 8, a n d/ or 6 0 visits are c o n d ucte d via a 
tele p h o ne/ virt ual call (t he pati e nt’s care gi ver ma y assist d uri n g t he tele p h o ne/ virt ual call). If t he assess me nt 
ca n be c o n d ucte d via a tele p h o ne/ virt ual call, t he st u d y site s h o ul d rec or d t he details; ot her wise, t he misse d 
assess me nt will n ot be c o nsi dere d a pr ot oc ol de viati o n. If  t he visit is c o n d ucte d b y a h o me healt hcare n urse, 
t hese assess me nts s h o ul d be c o n d ucte d, if p ossi ble; if t he assess me nt ca n be c o n d ucte d via h o me healt hcare 
n urse, t he st u d y site s h o ul d re c or d t he details; ot her wis e, t he misse d assess me nt will n ot be c o nsi dere d a 
pr ot oc ol de viati o n. T hese assess me nts m ust be c o n d ucte d if t he visit is c o n d ucte d at t he st u d y site. All 
eff orts s h o ul d be ma de t o c ollect cli nical la b orat or y as sess me nts o n Da y 1 4 ( ± 2 da ys) a n d Da y 2 8 ( ± 3 
da ys). Please n ote: I n cases i n w hic h t he patie nt is de e me d l ost t o f oll o w- u p, t he i n vesti gat or or desi g nee 
m ust ma ke e ver y eff ort t o re gai n c o ntact wit h t he p atie nt (e g, tele p h o ne calls, letter t o t he patie nt’s last 
k n o w n maili n g a d dress, or l ocal e q ui vale nt met h o ds). I n cases w h ere t he patie nt’s L A R pr o vi des i nf or me d 
c o nse nt o n be half of t he patie nt, t he st u d y site s h o ul d  atte m pt t o c o ntact t he L A R. A d diti o nall y, t he st u d y 
site s h o ul d atte m pt t o re gai n c o ntact wit h t he patie nt usi n g t he alter nati ve c o ntact i nf or mati o n pr o vi de d b y 
t he patie nt/ L A R at t he ti me of i nf or me d c o nse nt. T hese c o nta ct atte m pts m ust be d oc u me nt e d i n t he 
patie nt’s me dical rec or ds.  
f. 
De m o gra p hics will i ncl u de se x, a ge, race, a n d/ or et h nicit y. 
g.  Me dical/s ur gical me dical hist or y i ncl u des all acti ve a n d c hr o nic diseases (e g, ast h ma a n d C O P D), a n d a n y 
diseases dia g n ose d i n t he past 1 year ( bef ore scree ni n g)  t hat t he i n vesti gat or c o nsi ders cli ni call y si g nifica nt. 
A d diti o nal pre-e xisti n g c o n diti o ns prese nt at t he ti me w h e n i nf or m e d c o nse nt is gi ve n a n d u p t o t he ti me of 
first d osi n g ( Da y 1) are t o be re gar de d as c o nco mita nt. Me dical hist or y will i ncl u de d oc u me ntati o n of 
s ocial be ha vi ors, i ncl u di n g us e of t o bacc o, nic oti ne (i ncl u di n g use of electr o nic ci garettes), a n d s oft or har d 
dr u gs (i ncl u di n g ca n na bis), as well as alc o h ol c o ns u m pti o n, if a p plica ble. S m o ki n g hist or y als o m ust be 
d oc u me nte d as part of me dical hist or y a n d i ncl u des: ne ver, li g ht ( < 1 0 0 ci garettes/lifeti me), acti ve s m o ker, 
a n d f or mer s m o ker ( q uit date). Hist or y of n u m ber pac k s/ da y, n u m ber of s m o ki n g years, a n d q uitti n g ti me 
f or f or mer a n d acti ve s m o kers m ust als o be d oc u me nted. A d diti o nall y, t he i n vesti gat ors will d oc u me nt at 
scree ni n g t he patie nt’s C harls o n sc ore via t he C harls o n C o m or bi dit y I n de x (see Secti o n 1 2. 1 o f pr ot oc ol f or 
f urt her details). 
h.  A c o m plete p h ysical e xa mi nati o n will be perf or me d at scree ni n g. P h ysical e xa mi nati o ns will be perf or me d 
b y a p h ysicia n, n urse, or ot her a p pr o priatel y trai ne d staff. T he c o m plete p h ysical e xa mi nati o n i ncl u des: 
hea d, e yes, ears, n ose, a n d t hr oat; heart; l u n gs; a b d o me n; s ki n; cer vical a n d a xillar y l y m p h n o des; a n d 
ne ur ol o gical a n d m usc ul os kel etal s yste ms. A li mite d p h ysic al e xa mi nati o n t o verif y c o nti n ue d patie nt 
eli gi bilit y a n d t o f oll o w- u p re gar di n g a n y c ha n ge i n me dical hist or y will be perf or me d at t he visits 
i n dicate d a b o ve. S y m pt o m- dri ve n, li mite d p h ysical e xa mi nati o ns ma y be perf or me d as cli nicall y i n dicate d 
d uri n g t he st u d y (acc or di n g t o S o C). 
i. 
Vital si g ns i ncl u de s yst olic a n d diast olic bl o o d press ure, heart rate, res pirati o n rate, S p O 2, a n d b o d y 
te m perat ure. All vital si g ns will be meas ure d after t he patie nt has bee n resti n g f or at least 5 mi n utes. Bl o o d 
press ure meas ure me nts are t o be ta ke n i n t he sa me ar m f or t he d urati o n of t he st u d y. M ore o ver, a d diti o nal 
vital si g ns ma y be perf or me d as nee de d i n case of a n y car di ac A E.  
j. 
F or patie nts w h o re mai n h os pitalize d o nl y.  
k.  A 1 2-lea d, resti n g E C G will b e o btai ne d l ocall y at scree n i n g. At scree ni n g, t he i n vesti gat or m ust e xa mi ne 
t he E C G traces f or cli nicall y si g nifica nt a b n or malities t hat c o ul d e xcl u de t he patie nt fr o m t he st u d y. E C Gs 
s h o ul d al wa ys be o btai ne d i n s u pi ne p ositio n after a de q uate r est ( ≥5  mi n utes).  
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 1 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 2 1  of 5 6  
l. 
F or W O C B P, a ser u m sa m ple f or pre g na nc y testi n g m ust be c ollecte d at scree ni n g a n d a uri ne sa m ple f or 
pre g na nc y testi n g m ust be c ollecte d bef ore t he first d ose o n Da y 1. Pre g na nc y tests m ust be ne gati ve f or t he 
patie nt t o be ra n d o mize d a n d treate d. A uri ne pre g na nc y test will be re peate d o n Da y 1 4 ( ± 7 da ys). If t he 
patie nt is disc har ge d bef ore D a y 1 4, uri ne pre g na nc y test at da y of disc har ge s ho ul d be d o ne, a n d uri ne 
pre g na nc y test at Da y 1 4 is n ot re q uire d. If t he pat ie nt is disc har ge d after Da y 1 4, uri ne pre g na nc y test 
s h o ul d be d o ne at Da y 1 4, a n d uri ne pre g na nc y test at da y of disc har ge is n ot re q uire d ( w hi c he ver c o mes 
first). P atie nts wit h a p ositi ve pre g na nc y test will be disc o nti n ue d fr o m st u d y dr u g. 
m.  O nl y f or patie nts disc har ge d bef ore Da y 2 8. If t he patie nt d o es n ot feel c o mf orta ble t o c o m plete t he diar y, 
t he site will alter nati vel y pr o vi de t he patie nt wit h t he o pti o n t o be calle d, t wice a da y, t o c o nfir m t hat t he 
st u d y dr u g is ta ke n as i nstr uct e d. 
n.  Plas ma P K sa m ples will be c ollecte d via s parse sa m pli n g fr o m a p pr o xi matel y 3 0 patie nts ( w h o gi ve 
o pti o nal c o nse nt) i n a 2: 1 rati o t o assess t he P K  of M P 1 0 3 2 o n Da y 1 (si n gle d ose) a n d Da y 7 (stea d y 
state). A t otal of 1 6 sa m ples will be c ollecte d relati ve t o t he first d ose o n Da y 1 a n d t he first d ose o n Da y 7. 
Sa m ples o n Da y 1 a n d Da y 1 7 will be c ollecte d pre d ose ( w it hi n 1 0 mi n utes bef ore t he first dail y d ose) a n d 
p ost d ose at 1 0 mi n utes, 2 0 mi n utes, 3 0 mi n utes, 6 0 mi n utes, 1 2 0 mi n utes, 8 h o urs ( bef ore ne xt d ose), a n d 
2 4 h o urs bef ore t he ne xt m or ni n g d ose (if a p plica ble), if  p ossi ble. P atie nts w h o pr o vi de c o nse nt f or t he P K 
sa m pli n g, b ut are n o l o n ger h os pitalize d o n Da y 7, will n ot ha ve Da y 7 P K sa m ples c ollecte d.  
o.  Bl o o d sa m ples t o be o btai ne d o n Da y 1 ( bef ore t he firs t st u d y dr u g a d mi nistrati o n) a n d Da ys 7, 1 4, 2 1, 2 8, 
a n d 6 0 ( w he n p ossi ble). Bl o o d sa m ples f or bi o mar kers m u st be c ollecte d o n Da ys 7, 1 4, 2 1, 2 8, a n d 6 0 if a 
patie nt is still h os pitalize d. If a patie nt is disc har ge d, t h e st u d y site s h o ul d arra n ge a n o ut p atie nt visit (ie, at 
t he st u d y site) t o acc o m m o dat e t he c ollecti o n of bl o o d sam ples f or bi o mar kers o n Da ys 7, 1 4, 2 1, 2 8, a n d 
6 0.  
p.  T o sta n dar dize t he assess me nt of C O VI D- 1 9 se verit y, res pirat or y rate, S p O 2, a n d heart rat e will be 
meas ure d w he n t he patie nt is o n r o o m air at sea le v el (ie, n o s u p ple me ntal o x y ge n, if p ossi ble) a n d at rest 
f or at least 5 mi n utes. If p ossi ble, t he site s h o ul d c ollect t he i nf or mati o n fr o m eac h patie nt at t he sa me ti me 
eac h da y ( ± 1 h o ur).  
q.  Rec or d t he patie nt’s cli nical st at us relate d t o C O VI D- 1 9 o n t he NI AI D 8- p oi nt or di nal scal e a n d als o rec or d 
t he date a n d ti me f or eac h i n di vi d ual c o m p o ne nt of t he NI AI D 8- p oi nt or di nal scale i ncl u di n g: i n vasi ve or 
n o n-i n vasi ve mec ha nical ve ntilati o n/ E C M O start/st o p , hi g h-fl o w/ mas k o x y ge n start/st o p, s u p ple me ntal 
o x y ge n start/st o p ( nasal ca n n ula, liter fl o w [a n d its c o n versi o n t o Fi O2], ot her deli ver y ser vi ces), h os pital 
disc har ge ( w het her wit h li mitati o ns or wit h o ut li mitati o ns), h os pitalizati o n t y pe (e g, tra nsfer t o I C U) 
start/st o p, a n d (if a p plica ble) deat h, ca use of deat h (i ncl u di n g relate d ness t o C O VI D- 1 9), a n d date/ti me of 
deat h. If p ossi ble, t he site s h o ul d c ollect t he i nf or mati o n fr o m eac h patie nt at t he sa me ti me eac h da y ( ± 1 
h o ur). 
r. 
T he E Q- 5 D- 5 L ( A p pe n di x 2 of pr ot oc ol) is o nl y re q uire d f or disc har ge d patie nts a n d at t he f oll o wi n g 
visits: da y of disc har ge, Da y 6 0, a n d Earl y T er mi nati o n visit (if a p plica ble). T he E Q- 5 D- 5 L is n ot re q uire d 
f or patie nts w h o re mai n h os pit alize d u ntil st u d y e n d. 
s. 
T he li mite d p h ysical e xa mi nati o n a n d cli nical la b orat or y ass ess me nts o n Da y 8 ( ± 3 da ys) will be c ollecte d 
i n all patie nts w h o re mai n h os pitalize d. If t he patie nt is disc har ge d bef ore Da y 8 ( ± 3 da ys), t he site s h o ul d 
arra n ge t o ha ve t he p h ysicia n assess t he patie nt v ia a tele p h o ne/ virt ual call. If t he p h ysicia n deter mi nes 
d uri n g t he tele p h o ne/ virt ual call t hat t he li mite d p h ysical e xa mi nati o n a n d cli nical la b orat or y assess me nts 
are cli nicall y i n dicate d, t he n t he site s h o ul d arra n ge f or a n o ut patie nt visit t o c ollect t hese assess me nts.  
t. 
F or all patie nts (e xce pt o n Da y 1 a n d Da y 7 f or patie nts i n t he P K s u bset): P atie nts s h o ul d n ot eat wit hi n t he 
3 0 mi n utes bef ore pla n ne d st u d y dr u g a d mi nistrati o n a n d wit hi n t he 3 0 mi n utes after st u d y dr u g d osi n g, 
w he n feasi ble. H o we ver, if a p atie nt has eate n wit hi n t he 3 0 mi n utes bef ore t heir pla n ne d st u d y dr u g 
a d mi nistrati o n, st u d y dr u g d osi n g ma y pr ocee d. T he st u d y site s h o ul d rec or d t he date a n d ti me of d osi n g 
(rec or de d as t he ti me w he n t he first ca ps ule is a d mi nistere d). F or patie nts i n t he P K s u bs et o n Da y 1 a n d 
Da y 7 o nl y: P atie nts s h o ul d n ot eat wit hi n t he 4 h o urs bef ore pla n ne d st u d y dr u g a d mi nistrati o n a n d wit hi n 
t he 1 2 0 mi n utes after st u d y dr u g d osi n g, w he n feasi ble. T h us, st u d y dr u g s h o ul d be a d mi nistere d i n faste d 
state (≥ 4 h o urs), w he n feasi bl e. H o we ver, if a patie nt has eate n wit hi n t he 4 h o urs bef ore t heir pla n ne d 
a d mi nistrati o n, st u d y dr u g d osi n g ma y pr ocee d. T he patie nt’s fe d or faste d state, as well as f o o d i nta ke 
( yes/ n o) wit hi n t he 1 2 0 mi n ut es after st u d y dr u g d osi n g s h o ul d be rec or d e d. T he P K sa m ples s h o ul d be 
c ollecte d as pla n ne d re gar dless of t he patie nts’ faste d/f e d state. T he st u d y site s h o ul d rec or d t he date a n d 
ti me of d osi n g (rec or de d as t he ti me w he n t he first ca ps ule is a d mi nistere d). 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 2 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 2 2  of 5 6  
u.  T he cli nical la b orat or y assess me nts o n D a y 2 1 will be c ollecte d i n all patie nts w h o re mai n h os pitalize d. If 
t he patie nt is disc har ge d bef ore Da y 2 1, t he site s h o ul d arra n ge t o ha ve t he p h ysicia n assess t he patie nt via 
a tele p h o ne/ virt ual call. If t he p h ysicia n deter mi ne s d uri n g t he tele p h o ne/ virt ual call t hat t he cli nical 
la b orat or y assess me nts are cli nicall y i n dicate d, t he n t he site s h o ul d arra n ge f or a n o ut patie nt visit t o c ollect 
t his assess me nt.  
v.  T he + 2 da y wi n d o w d oes n ot a p pl y t o t he retrie val of t he 1 4- da y bli n de d st u d y dr u g kit as t he sec o n d kit 
m ust be distri b ute d at t he latest o n Da y 1 4.  
 
  
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 3 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 2 3 of 5 6
E n d p oi nt s  
Pri m ar y Effi c a c y E n d p oi nt
T h e pri m ar y effi c a c y e n d p oi nt of t hi s st u d y i s:
Pr o p orti o n of p ati e nt s wit h di s e a s e pr o gr e s si o n o n D a y 1 4. Di s e a s e pr o gr e s si o n i s d efi n e d a s t h e 
pr o p orti o n of p ati e nt s w h o ar e n ot al i v e or w h o h a v e r e s pir at or y f ail ur e. R e s pir at or y f ail ur e i s d efi n e d 
a s p ati e nt s w h o h a v e a s c or e of 2, 3 or 4 o n t h e N ati o n al I n stit ut e of All er g y a n d I nf e cti o u s Di s e a s e s 
( NI AI D) 8- p oi nt or di n al s c al e ( s e e b el o w). 
K e y S e c o n d ar y Effi c a c y E n d p oi nt s
T h e k e y s e c o n d ar y effi c a c y e n d p oi nt s of t hi s st u d y ar e:
Pr o p orti o n of p ati e nt s wit h di s e a s e pr o gr e s si o n o n D a y 2 8. Di s e a s e pr o gr e s si o n i s d efi n e d a s t h e 
pr o p orti o n of p ati e nt s w h o ar e n ot ali v e or w h o h a v e r e s pir at or y f ail ur e. R e s pir at or y f ail ur e i s d efi n e d 
a s p ati e nt s w h o h a v e a s c or e of 2, 3 or 4 o n t h e NI AI D 8- p oi nt or di n al s c al e ( s e e b el o w). 
Pr o p orti o n of p ati e nt s wit h di s e a s e r e s ol uti o n o n D a y 2 8. Di s e a s e r e s ol uti o n i s d efi n e d a s p ati e nt s 
w h o ar e ali v e a n d h a v e a s c or e of 6, 7, or 8 o n t h e NI AI D 8- p oi nt or di n al s c al e. 
All- c a u s e m ort alit y r at e at D a y 2 8
C h a n g e of cli ni c al st at u s r el at e d t o C O VI D- 1 9 o n D a y 2 8 c o m p ar e d wit h b a s eli n e a c c or di n g t o t h e 
f oll o wi n g NI AI D 8- p oi nt or di n al s c al e:
1.  
D e at h
2.  
H o s pit ali z e d, o n i n v a si v e v e ntil ati o n ( m e c h a ni c al v e ntil at or a n d/ or E xtr a c or p or e al M e m br a n e 
O x y g e n ati o n E C M O)
3.  
H o s pit ali z e d, o n n o n-i n v a si v e v e ntil ati o n or hi g h-fl o w o x y g e n d e vi c e s
4.  
H o s pit ali z e d, r e q uiri n g s u p pl e m e nt al o x y g e n
5.  
H o s pit ali z e d, n ot r e q uiri n g s u p pl e m e nt al o x y g e n, b ut r e q uiri n g o n g oi n g m e di c al c ar e ( C O VI D-
1 9 r el at e d or ot h er wi s e)
6.  
H o s pit ali z e d, n ot r e q uiri n g s u p pl e m e nt al o x y g e n a n d n o l o n g er r e q uir e s o n g oi n g m e di c al c ar e 
( u s e d if h o s pit ali z ati o n w a s e xt e n d e d f or i nf e cti o n- c o ntr ol r e a s o n s)
7.  
N ot h o s pit ali z e d, li mit ati o n o n a cti viti e s, a n d/ or r e q uiri n g h o m e o x y g e n
8.  
N ot h o s pit ali z e d, n o li mit ati o n s o n a cti viti e s
Pl e a s e n ot e: P ati e nt s r e q uiri n g o x y g e n b ef or e C O VI D- 1 9 a n d r et ur ni n g t o b a s eli n e o x y g e n u s e will b e 
c o n si d er e d i m pr o v e d (i e, n ot r e q uiri n g s u p pl e m e nt al o x y g e n). P ati e nt s wit h a li mit ati o n o n a cti viti e s b ef or e 
C O VI D- 1 9 a n d r et ur ni n g t o b a s eli n e a cti vit y will b e c o n si d er e d i m pr o v e d. I n c a s e of d e at h b ef or e D a y 1 4 
or D a y 2 8, t h e p ati e nt will b e c o n si d er e d wit h t h e NI AI D s c or e f or d e at h ( s c or e of 1) o n t h e d at e of d e at h i n 
t h e a n al y si s.
Ot h er S e c o n d ar y Effi c a c y E n d p oi nt s
T h e ot h er s e c o n d ar y effi c a c y e n d p oi nt s of t hi s st u d y ar e:
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 4 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 2 4 of 5 6
Pr o p orti o n of p ati e nt s wit h di s e a s e r e s ol uti o n o n D a y 1 4. Di s e a s e r e s ol uti o n i s d efi n e d a s p ati e nt s 
w h o ar e ali v e a n d h a v e a s c or e of 6, 7, or 8 o n t h e NI AI D 8- p oi nt or di n al s c al e ( a s li st e d a b o v e). 
All- c a u s e m ort alit y r at e at D a y 1 4 a n d D a y 6 0
C h a n g e of cli ni c al st at u s r el at e d t o C O VI D- 1 9 o n D a y 1 4 c o m p ar e d wit h b a s eli n e a c c or di n g t o t h e 
NI AI D 8- p oi nt or di n al s c al e ( a s li st e d a b o v e)
Pr o p orti o n of p ati e nt s r e q uiri n g i n v a si v e v e ntil ati o n ( m e c h a ni c al v e ntil at or a n d/ or E C M O), or w h o 
ar e n ot ali v e o n D a y 1 4 or D a y 2 8 
Pr o p orti o n of p ati e nt s i n e a c h c at e g o r y of t h e NI AI D 8- p oi nt or di n al s c al e
Ti m e t o (fir st) i m pr o v e m e nt of at l e a st 1 c at e g or y o n t h e NI AI D 8- p oi nt or di n al s c al e ( u ntil D a y 2 8). 
P ati e nt s w h o di d n ot i m pr o v e at l e a st 1 c at e g or y o n  t h e NI AI D s c al e or d e at h s b ef or e D a y 2 8 will 
b e c e n s or e d at D a y 2 8.
T h e o d d s r ati o b et w e e n M P 1 0 3 2 a n d S o C a n d pl a c e b o a n d S o C of t h e n u m b er of p ati e nt s wit h 
cli ni c al st at u s i m pr o v e m e nt fr o m b a s eli n e o n t h e NI AI D 8- p oi nt or di n al s c al e (i e, a n i m pr o v e m e nt 
of at l e a st 1 c at e g or y) at D a y 1 4 a n d D a y 2 8 
T ot al d ur ati o n of h o s pit ali z ati o n (fr o m b a s eli n e t o di s c h ar g e; wit h d e at h c e n s or e d o n t h e l a st d a y of 
t h e o b s er v e d p eri o d – at D a y 2 8 or D a y 6 0, r e s p e cti v el y) 
Pr o p orti o n of p ati e nt s ali v e a n d t e sti n g n e g ati v e f or C O VI D- 1 9 o n D a y 1 4,  D a y 2 8 a n d D a y 6 0
E x pl or at or y Effi c a c y E n d p oi nt s
E x pl or at or y effi c a c y e n d p oi nt s of t hi s st u d y ar e:
C h a n g e i n s at ur ati o n of o x y g e n ( S p O 2 )/fr a cti o n of i n s pir e d o x y g e n ( Fi O 2 ) r ati o (f or p ati e nt s ali v e) 
o n D a y 1 4 or D a y 2 8 c o m p ar e d wit h b a s eli n e
T ot al n u m b er of d a y s i n t h e i nt e n si v e c ar e u nit (I C U)
D ur ati o n of i n v a si v e m e c h a ni c al v e ntil ati o n a n d/ or E C M O
Ti m e t o r e c o v er y fr o m C O VI D- 1 9 s y m pt o m s ( st uff y or r u n n y n o s e, s or e t hr o at, r e d or irrit at e d e y e s, 
s h ort n e s s of br e at h, c o u g h, l o w e n er g y or tir e d n e s s, m u s cl e or b o d y a c h e s, h e a d a c h e, c hill s or 
s hi v eri n g, f e eli n g h ot or f e v eri s h, n a u s e a, a n d n u m b er of ti m e s of v o mit, ti m e s of di arr h e a, s e n s e 
of s m ell, s e n s e of t a st e i n t h e l a st 2 4 h o ur s) at D a y 1 4, D a y 2 8, a n d D a y 6 0
C h a n g e fr o m di s c h ar g e i n t h e E ur o Q ol ( E Q) i n d e x v al u e a n d E Q vi s u al a n al o g s c al e ( V A S) b a s e d 
o n t h e E ur o Q ol- 5 D- 5 L ( E Q- 5 D- 5 L) q u e sti o n n air e at D a y 6 0
P h ar m a c o ki n eti c E n d p oi nt s
M P 1 0 3 2 pl a s m a  c o n c e ntr ati o n s  a n d  P K  p ar a m et e r s (if  p o s si bl e) i n cl u di n g m a xi m u m  o b s er v e d 
pl a s m a c o n c e ntr ati o n, ar e a u n d er t h e c o n c e ntr ati o n-ti m e c ur v e, eli mi n ati o n p ar a m et er s, a p p ar e nt 
b o d y cl e ar a n c e, a p p ar e nt v ol u m e of di stri b uti o n , tr o u g h c o n c e ntr ati o n, a v er a g e o b s er v e d pl a s m a 
c o n c e ntr ati o n at st e a d y st at e, a n d ot h er r el e v a nt P K p ar a m et er s a s s e s s e d vi a M P 1 0 3 2 pl a s m a 
e x p o s ur e o n D a y 1 a n d D a y 7 i n a P K s u b s et of p ati e nt s.
P h ar m a c o d y n a mi c E n d p oi nt s
C h a n g e fr o m b a s eli n e i n bi o m ar k er l e v el s p ot e nti all y i n cl u di n g, b ut n ot li mit e d t o, c yt o ki n e s ( e g, C-
r e a cti v e  pr ot ei n,  i nt erl e u ki n  [I L]- 1β ,  I L- 6,  t u m or  n e cr o si s  f a ct or-α ,  a n d  I F N-γ ),  a n d  ot h er  
c o a g ul ati o n/i nfl a m m at or y bi o m ar k er s ( e g, D- di m er a n d f erriti n)
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 5 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 2 5 of 5 6
S af et y E n d p oi nt s
S af et y a n d t ol er a bilit y a s s e s s e d b y:
o
C u m ul ati v e i n ci d e n c e of tr e at m e nt- e m er g e nt A E s ( s u m m ari z e d b y s eri o u s n e s s, s e v erit y, 
r el ati o n s hi p t o t h e st u d y m e di c ati o n, o ut c o m e, a n d d ur ati o n) 
o
Vit al si g n p ar a m et er s 
o
Cli ni c al l a b or at or y p ar a m et er s
o
P h y si c al e x a mi n ati o n fi n di n g s
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 6 of 5 9
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_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 2 6 of 5 6
A n al y si s S et s
S cr e e n e d /  R a n d o mi z e d S et
T h e S cr e e n e d S et will i n cl u d e all p a ti e nt s  w h o gi v e i nf or m e d c o n s e nt a n d ar e s cr e e n e d. U nl e s s s p e cifi e d 
ot h er wi s e, t hi s s et will b e u s e d f or s u m m ari e s of p ati e nt di s p o siti o n.
T h e R a n d o mi z e d S et will i n cl u d e all p ati e nt s r a n d o mi z e d.  U nl e s s s p e cifi e d ot h er wi s e, t hi s s et will b e u s e d 
f or all p ati e nt li sti n g s wit h e x c e pti o n of t h e li sti n g pr e se nti n g s cr e e ni n g f ail ur e s a n d t h e r e s p e cti v e r e a s o n( s) 
f or s cr e e n f ail ur e.
S af et y S et 
T h e S af et y S et ( S S) will i n cl u d e all r a n d o mi z e d p ati e nt s w h o r e c ei v e at l e a st 1 d o s e of st u d y dr u g. T h e 
tr e at m e nt gr o u p a s si g n m e nt i n t h e S S  will b e d efi n ed b y t h e tr e at m e nt a ct u all y r e c ei v e d. T h e S S  will b e 
u s e d f or t h e a n al y si s of s af et y . 
I nt e nti o n- T o- Tr e at S et
T h e I nt e nti o n- T o- Tr e at S et  (I T T) c orr e s p o n d s wit h t h e r a n d o mi z e d s et a n d  will i n cl u d e all r a n d o mi z e d 
p ati e nt s, irr e s p e cti v e of a n y d e vi ati o n fr o m t h e pr ot o c ol or pr e m at ur e di s c o nti n u ati o n fr o m st u d y dr u g or
wit h dr a w al  fr o m  st u d y.  T h e  tr e at m e nt  gr o u p  a s si g n m e nt  will  b e  d e si g n at e d  a c c or di n g  t o  i niti al  
r a n d o mi z ati o n. T h e I T T will s er v e a s t h e b a si s f or t h e a n al y si s of effi c a c y a n d s u m m ar y of d e m o gr a p hi c s 
a n d b a s eli n e c h ar a ct eri sti c s.
P er Pr ot o c ol S et 
T h e P er Pr ot o c ol S et ( P P S) will i n cl u d e all p ati e nt s fr o m I T T w h o r e c ei v e d at l e a st 1 d o s e of st u d y dr u g a n d 
w h o d o n ot h a v e a n y m aj or pr ot o c ol d e vi ati o n s aff e cti n g t h e effi c a c y a s s e s s m e nt s. P ati e nt s  will b e a n al y z e d 
a c c or di n g t o r a n d o mi z e d tr e at m e nt. T h e P P S will b e u s e d f or s u p p orti v e a n al y s e s of effi c a c y.
T h e fi n al i d e ntifi c ati o n a n d c at e g ori z ati o n of all pr ot o c ol d e vi ati o n s a n d t h e fi n al d efi niti o n of t h e a n al y si s 
p o p ul ati o n s i n cl u di n g t h e P P S  will b e p erf or m e d i n t h e Bli n d D at a R e vi e w M e eti n g ( B D R M) pri or t o d at a b a s e 
l o c k (f oll o wi n g S y n e o s H e alt h S O P 3 9 1 1).
P h ar m a c o ki n eti c A n al y si s S et
T h e P h ar m a c o ki n eti c a n al y si s s et ( P K S) will i n cl u d e a ll t h e p ati e nt s w h o h a v e b e e n a d mi ni st er e d a cti v e 
st u d y dr u g a n d h a v e at l e a st 1 p o st d o s e e v al u a bl e pl a s m a c o n c e ntr ati o n aft er D a y 1 d o s e.
Pr ot o c ol D e vi ati o n s
Pr ot o c ol d e vi ati o n s will b e i d e ntifi e d p eri o di c all y t hr o u g h o ut t h e tri al f oll o wi n g t h e ‘ Pr ot o c ol D e vi ati o n a n d 
N o n- c o m pli a n c e M a n a g e m e nt Pl a n’ ( S y n e o s H e alt h S O P a n d WI, 3 1 0 1 a n d 3 1 0 1. W 0 2). Fi n al d efi niti o n of 
pr ot o c ol d e vi ati o n s a n d c at e g ori z ati o n i nt o mi n or / m a j or will b e p erf or m e d i n t h e B D R M pri or t o d at a b a s e 
l o c k a n d u n bli n di n g. 
All  pr ot o c ol  d e vi ati o n s  r el at e d  t o  st u d y  i n cl u si o n  or  e x cl u si o n  crit eri a,  c o n d u ct  of  t h e  tri al,  p ati e nt  
m a n a g e m e nt, d o si n g, a n d s a m pli n g pr o c e d ur e s or p ati e nt a s s e s s m e nt will b e li st e d. T h e li st of pr ot o c ol 
d e vi ati o n s will b e r e vi e w e d b y t h e S p o n s or, t h e pri n ci p al i n v e sti g at or a n d t h e st u d y st ati sti ci a n, a n d fi n ali z e d 
b ef or e d at a b a s e l o c k d uri n g t h e B D R M. Al s o t h e d et er mi n ati o n w h et h er a m aj or pr ot o c ol d e vi ati o n h a s a n 
i m p a ct o n t h e a s s e s s m e nt of t h e pri m ar y effi c a c y, a n d t he d et er mi n ati o n of t h e p ati e nt s et s will b e fi n ali z e d 
i n t h e B D R M f oll o wi n g S O P 3 9 1 1.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 7 of 5 9
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_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 2 7 of 5 6
E sti m a n d s
Pri m ar y Effi c a c y E n d p oi nt
T h e m ai n e sti m a n d f or t h e pri m ar y effi c a c y e n d p oi nt i s d efi n e d a s f oll o w s:
Tr e at m e nt: 3 0 0 m g M P 1 0 3 2 BI D pl u s S o C i n Ar m A a n d pl a c e b o BI D pl u s S o C i n  Ar m B. If a p ati e nt 
t er mi n at e s t h e st u d y tr e at m e nt, b ut still r e m ai n s i n t h e st u d y a n d i s f oll o w e d u p, t h e n t h e p ati e nt 
will  c o nti n u e  t o  r e c ei v e  eit h er  S o C  al o n e  or  S o C + a d diti o n al  tr e at m e nt.  T h e s e  tr e at m e nt s  ar e  
d efi n e d  wit h r e g ar d s t o i nt er c urr e nt e v e nt s a s ‘ ot h er tr e at m e nt s’.
P o p ul ati o n: Of all p ati e nt s d efi n e d b y t h e st u d y i n cl u si o n / e x cl u si o n crit eri a, t h e a n al y si s p o p ul ati o n 
will i n cl u d e all r a n d o mi z e d  p ati e nt s (I T T p o p ul ati o n).
V ari a bl e:  A  bi n ar y  v ari a bl e  i n di c ati n g di s e a s e  pr o gr e s si o n  (r e s pir at or y  f ail ur e)  w h e n  h a vi n g  
c o m pl et e d  D a y 1 4 a s s e s s m e nt or di e d pri or t o D a y 1 4. R e s pir at or y f ail ur e i s d efi n e d a s p ati e nt s 
w h o h a v e a s c or e of 2, 3 or 4 o n t h e NI AI D 8- p oi nt or di n al s c al e.
I nt er c urr e nt e v e nt s: All e v e nt s l e a di n g t o st u d y tr e at m e nt di s c o nti n u ati o n a n d/ or s wit c h t o ot h er 
tr e at m e nt pri or t o D a y 1 4 will b e h a n dl e d u si n g t he tr e at m e nt- p oli c y str at e g y (i e, t h e o b s er v e d NI AI D 
s c or e at D a y 1 4 will b e u s e d f or d efi ni ti o n of t h e f ail ur e i n s u c h p ati e nt s). 
P o p ul ati o n-l e v el s u m m ar y: C o m m o n ri s k diff er e n c e r e s ulti n g fr o m t h e M a nt el- H a e n s z el ( M H) t e st 
c o n si d eri n g t h e 4 str at a o ut of t h e c o m bi n ati o n s of t h e 2 r a n d o mi z ati o n str atifi c ati o n f a ct or s di s e a s e 
s e v erit y ( m o d er at e v er s u s s e v er e) a n d a g e- cl a s s ( ≤6 5 y e ar s v er s u s > 6 5 y e ar s) at b a s eli n e.
Mi s si n g d at a o n D a y 1 4 r e s ulti n g fr o m st u d y t er mi n ati o n p ri or t o D a y 1 4 ar e n ot e x p e ct e d. H o w e v er, i n c a s e 
it h a p p e n s, s u c h m o n ot o n e mi s si n g s will b e i m p ut e d b y m ulti pl e i m p ut ati o n u si n g i nf or m ati o n fr o m si mil ar 
p ati e nt s of t h e s a m e tr e at m e nt gr o u p a s s u mi n g ‘ mi s si n g at r a n d o m’ ( M A R) m e c h a ni s m. Mi s si n g p o st-
b a s eli n e d at a f or p ati e nt s r a n d o mi z e d b ut n ot tr e at e d will b e i m p ut e d b y t h e r e s p e cti v e b a s eli n e v al u e 
( b a s eli n e o b s er v ati o n c arri e d f or w ar d, B O C F). I nt er m e di at e mi s si n g d at a of D a y 1 4 (i e, NI AI D a s s e s s m e nt s 
pri or D a y 1 4 a n d at D a y 2 8 ar e a v ail a bl e, b ut o nl y D a y 1 4 i s mi s si n g) will b e i m p ut e d b y L a st- o b s er v ati o n-
c arri e d-f or w ar d ( L O C F). T h e c o m p ari s o n b et w e e n t h e tr e at m e nt gr o u p s will b e p erf or m e d o n t h e I T T aft er 
i m p ut ati o n of mi s si n g v al u e s u si n g M H t e st f or c o m m o n ri s k diff er e n c e c o n si d eri n g t h e 4 str at a r e s ulti n g 
fr o m t h e 2 r a n d o mi z ati o n str atifi c ati o n f a ct or s di s e a s e s e v erit y ( m o d er at e v er s u s s e v er e) a n d a g e- cl a s s 
(≤6 5 y e ar s v er s u s > 6 5 y e ar s). 9 5 % c o nfi d e n c e i nt er v al ( CI) will b e pr o vi d e d f or t h e ri s k diff er e n c e.
A s e c o n d e sti m a n d f or t h e pri m ar y effi c a c y e n d p oi nt wi ll b e d efi n e d si mil ar t o t h e m ai n e sti m a n d b ut wit h 
t h e o nl y diff er e n c e t h at t h e i nt er c urr e nt e v e nt st u d y dr u g di s c o nti n u ati o n d u e t o A E or d u e t o l a c k of effi c a c y
will b e tr e at e d u si n g t h e c o m p o sit e str at e g y a s ‘ di s e a s e pr o gr e s si o n’, b ut t h e i n t er c urr e nt e v e nt of st u d y 
dr u g  di s c o nti n u ati o n  d u e  t o  ot h er  r e a s o n s  will  b e  still  tr e at e d  wit h  t h e  tr e at m e nt- p oli c y  str at e g y.  T h e  
i m p ut ati o n str at e g y a s d e s cri b e d f or t h e m ai n e sti m a n d will b e u s e d f or t h e s e c o n d e sti m a n d al s o. Si mil ar 
s e n siti vit y a n al y s e s a s f or t h e m ai n e sti m a n d  will b e a p pli e d f or t h e s e c o n d e sti m a n d. 
K e y S e c o n d ar y Effi c a c y E n d p oi nt 1
T h e m ai n e sti m a n d f or t h e k e y s e c o n d ar y effi c a c y e n d p oi nt 1 i s d efi n e d a s f oll o w s:
Tr e at m e nt: 3 0 0 m g M P 1 0 3 2 BI D pl u s S o C i n Ar m A a n d pl a c e b o BI D pl u s S o C i n Ar m B. If a p ati e nt 
t er mi n at e s t h e st u d y tr e at m e nt, b ut still r e m ai n s i n t h e st u d y a n d i s f oll o w e d u p, t h e n t h e p ati e nt 
will  c o nti n u e  t o  r e c ei v e  eit h er  S o C  al o n e  or  S o C + a d diti o n al  tr e at m e nt.  T h e s e  tr e at m e nt s  ar e  
d efi n e d wit h r e g ar d s t o i nt er c urr e nt e v e nt s a s ‘ ot h er tr e at m e nt s’.
P o p ul ati o n: Of all p ati e nt s d efi n e d b y t h e st u d y i n cl u si o n / e x cl u si o n crit eri a, t h e a n al y si s p o p ul ati o n 
will i n cl u d e all r a n d o mi z e d p ati e nt s (I T T p o p ul ati o n).
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 8 of 5 9
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_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 2 8 of 5 6
V ari a bl e:  A  bi n ar y  v ari a bl e  i n di c ati n g di s e a s e  pr o gr e s si o n  (r e s pir at or y  f ail ur e)  w h e n  h a vi n g  
c o m pl et e d D a y 2 8 a s s e s s m e nt or di e d pri or t o D a y 2 8. R e s pir at or y f ail ur e i s d efi n e d a s p ati e nt s 
w h o h a v e a s c or e of 2, 3 or 4 o n t h e NI AI D 8- p oi nt or di n al s c al e
I nt er c urr e nt e v e nt s: All e v e nt s l e a di n g t o st u d y tr e at m e nt di s c o nti n u ati o n a n d/ or s wit c h t o ot h er 
tr e at m e nt pri or t o D a y 2 8 will b e h a n dl e d u si n g t he tr e at m e nt- p oli c y str at e g y (i e, t h e o b s er v e d NI AI D 
s c or e at D a y 2 8  will b e u s e d f or d efi niti o n of t h e f ail ur e i n s u c h p ati e nt s). 
P o p ul ati o n-l e v el s u m m ar y:  C o m m o n ri s k  diff er e n c e  r e s ulti n g fr o m  t h e M H  t e st c o n si d eri n g t h e  
4 str at a  o ut  of  t h e  c o m bi n ati o n s  of  t h e  2  r a n d o m i z ati o n  str atifi c ati o n  f a ct or s  di s e a s e  s e v erit y  
( m o d er at e v er s u s s e v er e) a n d a g e-cl a s s ( ≤6 5 y e ar s v er s u s > 6 5 y e ar s).
Mi s si n g  d at a  o n  D a y 2 8 r e s ulti n g  fr o m  st u d y t er mi n ati o n  pri or  t o  D a y 2 8 ( m o n ot o n e  mi s si n g s)  will  b e  
i m p ut e d  b y  m ulti pl e  i m p ut ati o n  u si n g  i nf or m ati o n  fro m  si mil ar  p ati e nt s  of  t h e  s a m e  tr e at m e nt  gr o u p
a s s u mi n g ‘ M A R m e c h a ni s m . Mi s si n g p o st- b a s eli n e d at a f or p ati e nt s r a n d o mi z e d b ut n ot tr e at e d will b e 
i m p ut e d b y B O C F. T h e c o nfir m at or y c o m p ari s o n b et w e en t h e tr e at m e nt gr o u p s will b e p erf or m e d o n t h e 
I T T aft er i m p ut ati o n of mi s si n g v al u e s u si n g M H t e st f or c o m m o n ri s k diff er e n c e c o n si d eri n g t h e 4 str at a 
r e s ulti n g fr o m t h e 2 r a n d o mi z ati o n str atifi c ati o n f a ct or s di s e a s e s e v erit y ( m o d er at e v er s u s s e v er e) a n d a g e-
cl a s s ( ≤6 5 y e ar s v er s u s > 6 5 y e ar s). 9 5 % c o nfi d e n c e i nt er v al ( CI) will b e pr o vi d e d f or t h e ri s k diff er e n c e.
A s e c o n d e sti m a n d f or t h e fir st k e y s e c o n d ar y effi c a c y will b e d efi n e d si mil ar t o t h e m ai n e sti m a n d b ut wit h 
t h e o nl y diff er e n c e t h at t h e i nt er c urr e nt e v e nt st u d y dr u g di s c o nti n u ati o n d u e t o A E or d u e t o l a c k of effi c a c y 
will b e tr e at e d u si n g t h e c o m p o sit e str at e g y a s ‘ d i s e a s e pr o gr e s si o n’, b ut t h e i nt er c urr e nt e v e nt of st u d y 
dr u g  di s c o nti n u ati o n  d u e  t o  ot h er  r e a s o n s  will  b e  still  tr e at e d  wit h  t h e  tr e at m e nt- p oli c y  str at e g y.  T h e  
i m p ut ati o n str at e g y a s d e s cri b e d f or t h e m ai n e sti m a n d will b e u s e d f or t h e s e c o n d e sti m a n d al s o. Si mil ar 
s e n siti vit y a n al y s e s a s f or t h e m ai n e sti m a n d will b e a p pli e d f or t h e s e c o n d e sti m a n d. 
K e y S e c o n d ar y Effi c a c y E n d p oi nt 2
T h e m ai n e sti m a n d f or t h e k e y s e c o n d ar y effi c a c y e n d p oi nt 2 i s d efi n e d a s f oll o w s:
Tr e at m e nt: 3 0 0 m g M P 1 0 3 2 BI D pl u s S o C i n Ar m A a n d pl a c e b o BI D pl u s S o C i n  Ar m B. If a p ati e nt 
t er mi n at e s t h e st u d y tr e at m e nt, b ut still r e m ai n s i n t h e st u d y a n d i s f oll o w e d u p, t h e n t h e p ati e nt 
will  c o nti n u e  t o  r e c ei v e  eit h er  S o C  al o n e  or  S o C + a d diti o n al  tr e at m e nt.  T h e s e  tr e at m e nt s  ar e  
d efi n e d wit h r e g ar d s t o i nt er c urr e nt e v e nt s a s ‘ ot h er tr e at m e nt s’.
P o p ul ati o n: Of all p ati e nt s d efi n e d b y t h e st u d y i n cl u si o n / e x cl u si o n crit eri a, t h e a n al y si s p o p ul ati o n 
will i n cl u d e all r a n d o mi z e d  p ati e nt s (I T T p o p ul ati o n).
V ari a bl e:  A  bi n ar y  v ari a bl e  i n di c ati n g
‘di s e a s e  r e s ol uti o n ’ w h e n  h a vi n g  c o m pl et e d  D a y 2 8  
a s s e s s m e nt. Di s e a s e r e s ol uti o n i s d efi n e d a s p ati e n t s w h o ar e ali v e a n d h a v e a s c or e of 6, 7, or 8 
o n t h e NI AI D 8- p oi nt or di n al s c al e.
I nt er c urr e nt e v e nt s: All e v e nt s l e a di n g t o st u d y tr e at m e nt di s c o nti n u ati o n a n d/ or s wit c h t o ot h er 
tr e at m e nt pri or t o D a y 2 8  will b e h a n dl e d u si n g t h e tr e at m e nt- p oli c y st r at e g y (i e, t h e o b s er v e d NI AI D 
s c or e at D a y 2 8  will b e u s e d f or d efi niti o n of t h e di s e a s e r e s ol uti o n i n s u c h p ati e nt s). D e at h pri or t o 
D a y 2 8 will b e c o n si d er e d a s n o n-r e s ol uti o n of di s e a s e ( or f ail ur e) u si n g t h e c o m p o sit e str at e g y.
P o p ul ati o n-l e v el s u m m ar y:  C o m m o n ri s k  diff er e n c e  r e s ulti n g fr o m  t h e M H  t e st c o n si d eri n g t h e  
4 str at a  o ut  of  t h e  c o m bi n ati o n s  of  t h e  2  r a n d o m i z ati o n  str atifi c ati o n  f a ct or s  di s e a s e  s e v erit y  
( m o d er at e v er s u s s e v er e) a n d a g e- cl a s s (≤6 5 y e ar s v er s u s > 6 5 y e ar s).
Mi s si n g  d at a  o n  D a y 2 8  r e s ulti n g  fr o m  st u d y t er mi n ati o n  pri or  t o  D a y 2 8  ( m o n ot o n e  mi s si n g s)  will  b e  
i m p ut e d  b y  m ulti pl e  i m p ut ati o n  u si n g  i nf or m ati o n  fro m  si mil ar  p ati e nt s  of  t h e  s a m e  tr e at m e nt  gr o u p  
a s s u mi n g ‘ M A R m e c h a ni s m. Mi s si n g p o st- b a s eli n e d at a f or p ati e nt s  r a n d o mi z e d b ut n ot tr e at e d will b e 
i m p ut e d b y B O C F. T h e c o nfir m at or y c o m p ari s o n b et w e en t h e tr e at m e nt gr o u p s will b e p erf or m e d o n t h e 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 2 9 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 2 9 of 5 6
I T T aft er i m p ut ati o n of mi s si n g v al u e s u si n g M H t e st f or c o m m o n ri s k diff er e n c e c o n si d eri n g t h e 4 str at a 
r e s ulti n g fr o m t h e 2 r a n d o mi z ati o n str atifi c ati o n f a ct or s di s e a s e s e v erit y ( m o d er at e v er s u s s e v er e) a n d a g e-
cl a s s ( ≤6 5 y e ar s v er s u s > 6 5 y e ar s). 9 5 % c o nfi d e n c e i nt er v al ( CI) will b e pr o vi d e d f or t h e ri s k diff er e n c e.
A s e c o n d e sti m a n d f or t h e s e c o n d k e y s e c o n d ar y effi c a c y e n d p oi nt will b e d efi n e d si mil ar t o t h e m ai n 
e sti m a n d b ut wit h t h e o nl y diff er e n c e t h at t h e i nt er c urr e nt e v e nt st u d y dr u g di s c o nti n u ati o n d u e t o A E or 
d u e t o l a c k of effi c a c y will b e tr e at e d u si n g t h e c o m p o sit e str at e g y a s ‘ n o n -r e s ol uti o n of di s e a s e ( or f ail ur e)’, 
b ut t h e i nt er c urr e nt e v e nt of st u d y dr u g di s c o nti n u ati o n d u e t o ot h er r e a s o n s will b e still tr e at e d wit h t h e 
tr e at m e nt- p oli c y str at e g y. T h e i m p ut ati o n str at e g y a s d e s cri b e d f or t h e m ai n e sti m a n d will b e u s e d f or t h e 
s e c o n d e sti m a n d al s o. Si mil ar s e n siti vit y a n al y s e s a s f or t h e m ai n e sti m a n d will b e a p pli e d f or t h e s e c o n d 
e sti m a n d.
K e y S e c o n d ar y Effi c a c y E n d p oi nt 3
T h e m ai n e sti m a n d f or t h e k e y s e c o n d ar y effi c a c y e n d p oi nt 3 i s d efi n e d a s f oll o w s:
Tr e at m e nt: 3 0 0 m g  M P 1 0 3 2 BI D pl u s S o C i n Ar m A a n d pl a c e b o BI D pl u s S o C i n  Ar m B. If a p ati e nt 
t er mi n at e s t h e st u d y tr e at m e nt, b ut still r e m ai n s i n t h e st u d y a n d i s f oll o w e d u p, t h e n t h e p ati e nt 
will  c o nti n u e  t o  r e c ei v e  eit h er  S o C  al o n e  or  S o C + a d diti o n al  tr e at m e nt.  T h e s e  tr e at m e nt s  ar e  
d efi n e d wit h r e g ar d s t o i nt er c urr e nt e v e nt s a s ‘ ot h er tr e at m e nt s’.
P o p ul ati o n: Of all p ati e nt s d efi n e d b y t h e st u d y i n cl u si o n / e x cl u si o n crit eri a, t h e a n al y si s p o p ul ati o n 
will i n cl u d e all r a n d o mi z e d  p ati e nt s (I T T p o p ul ati o n).
V ari a bl e: A bi n ar y v ari a bl e i n di c ati n g lif e st at u s ( d e at h d u e t o a n y r e a s o n or ali v e) at D a y 2 8. 
I nt er c urr e nt e v e nt s: All e v e nt s l e a di n g t o st u d y tr e at m e nt di s c o nti n u ati o n a n d/ or s wit c h t o ot h er 
tr e at m e nt pri or t o D a y 2 8 will b e h a n dl e d u si n g t h e tre at m e nt- p oli c y str at e g y (i e, t h e lif e st at u s at 
D a y 2 8 will b e u s e d i n s u c h p ati e nt s). 
P o p ul ati o n-l e v el s u m m ar y: C o m m o n ri s k diff er e n c e of t h e all- c a u s e m ort alit y r at e r e s ulti n g fr o m t h e 
M H t e st c o n si d eri n g t h e 4 str at a o ut of t h e c o m bi n at i o n s of t h e 2 r a n d o mi z ati o n str atifi c ati o n f a ct or s 
di s e a s e s e v erit y ( m o d er at e v er s u s s e v er e) a n d a g e- cl a s s ( ≤6 5 y e ar s v er s u s > 6 5 y e ar s).
Mi s si n g d at a of t h e lif e st at u s at D a y 2 8 r e s ulti n g fr o m st u d y t er mi n ati o n pri or t o D a y 2 8 ar e n ot e x p e ct e d. 
H o w e v er, i n c a s e t h e y h a p p e n, s u c h mi s si n g s will b e i m p ut e d b y d e at h. T h e c o nfir m at or y c o m p ari s o n 
b et w e e n t h e tr e at m e nt gr o u p s will b e p erf or m e d o n t h e I T T aft er i m p ut ati o n of mi s si n g v al u e s u si n g M H 
t e st f or c o m m o n ri s k diff er e n c e c o n si d eri n g t h e 4 str at a r e s ulti n g fr o m t h e 2 r a n d o mi z ati o n str atifi c ati o n 
f a ct or s  di s e a s e  s e v erit y ( m o d er at e  v er s u s  s e v er e)  a n d  a g e-cl a s s  ( ≤6 5  y e ar s  v er s u s  > 6 5  y e ar s). 9 5 % 
c o nfi d e n c e i nt er v al ( CI) will b e pr o vi d e d f or t h e ri s k diff er e n c e.
K e y S e c o n d ar y Effi c a c y E n d p oi nt 4
T h e m ai n e sti m a n d f or t h e k e y s e c o n d ar y effi c a c y e n d p oi nt 4 i s d efi n e d a s f oll o w s:
P o p ul ati o n: Of all p ati e nt s d efi n e d b y t h e st u d y i n cl u si o n / e x cl u si o n crit eri a, t h e a n al y si s p o p ul ati o n 
will i n cl u d e all r a n d o mi z e d  p ati e nt s (I T T p o p ul ati o n).
V ari a bl e: Cli ni c al st at u s r el at e d t o C O VI D- 1 9 m e a s ur e d o n t h e NI AI D 8- p oi nt or di n al s c al e o n D a y 
2 8 c o m p ar e d t o t h e b a s eli n e a s s e s s m e nt, i e, c h a n g e fr o m b a s eli n e of NI AI D s c or e.
I nt er c urr e nt e v e nt s: All e v e nt s l e a di n g t o st u d y tr e at m e nt di s c o nti n u ati o n a n d/ or s wit c h t o ot h er 
tr e at m e nt pri or t o D a y 2 8  will b e h a n dl e d u si n g t h e tr e at m e nt- p oli c y str at e g y (i e, t h e NI AI D s c or e 
at D a y 2 8  will b e u s e d f or s u c h p ati e nt s). 
P o p ul ati o n-l e v el s u m m ar y:  Ri s k  diff er e n c e b et w e e n t h e tr e at m e nt gr o u p s of  t h e c h a n g e s fr o m  
b a s eli n e  i n  t h e  NI AI D  s c or e  a s  a s s e s s e d  i n  t h e  A N C O V A  m o d el  wit h t h e  2  r a n d o mi z ati o n  
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 0 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 3 0  of 5 6  
str atifi c ati o n f a ct or s di s e a s e s e v erit y ( m o d er at e v er s u s s e v er e) a n d a g e- cl a s s ( ≤6 5 y e ar s v er s u s 
> 6 5 y e ar s) a s i n d e p e n d e nt v ari a bl e s a d diti o n all y t o t h e tr e at m e nt v ari a bl e, a n d t h e b a s eli n e v al u e 
of t h e NI AI D s c or e a s c o v ari at e. 
Mi s si n g  d at a  o n  D a y  2 8  r e s ulti n g  fr o m  st u d y  t er mi n ati o n  pri or  t o  D a y  2 8  will  b e  i m p ut e d  b y  m ulti pl e  
i m p ut ati o n u si n g i nf or m ati o n fr o m si mil ar p ati e nt s of t h e s a m e tr e at m e nt gr o u p a s s u mi n g M A R m e c h a ni s m. 
Mi s si n g  p o st- b a s eli n e  d at a  f or  p ati e nt s  r a n d o mi z e d  b ut  n ot  tr e at e d  will  b e  i m p ut e d  b y  B O C F.  T h e  
c o nfir m at or y c o m p ari s o n b et w e e n t h e tr e at m e nt gr o u p s will b e p erf or m e d o n t h e I T T aft er i m p ut ati o n of 
mi s si n g v al u e s u si n g t h e A N C O V A m o d el c o n si d eri n g t h e 2 r a n d o mi z ati o n str atifi c ati o n f a ct or s di s e a s e 
s e v erit y ( m o d er at e v er s u s s e v er e) a n d a g e- cl a s s ( ≤6 5 y e ar s v er s u s > 6 5 y e ar s)  a s i n d e p e n d e nt v ari a bl e s 
a n d t h e b a s eli n e a s s e s s m e nt of NI AI D a s c o v ari at e. 9 5 % c o nfi d e n c e i nt er v al ( CI) will b e pr o vi d e d f or t h e 
ri s k diff er e n c e. 
 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 1 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 3 1 of 5 6
G e n er al A s p e ct s f or St ati sti c al A n al y si s
G e n er al M et h o d s
S A S ® v er si o n 9. 4 or hi g h er will b e u s e d f or all st ati sti c al a n al y s e s a n d t a b ul ati o n s.
I n g e n er al, s u m m ari e s will pr e s e nt d at a b y tr e at m e nt gr o u p a n d o v er all f or e a c h s c h e d ul e d a s s e s s m e nt 
ti m e w h er e a p pr o pri at e. Effi c a c y, P K a n d P D s u m mari e s  will b e pr e s e nt e d b y tr e at m e nt gr o u p, o nl y.
U nl e s s  st at e d  ot h er wi s e,  d e s cri pti v e  s u m m ari e s  will  b e  pr e s e nt e d  a s  f oll o w s:  C o nti n u o u s  a n d  or di n al  
v ari a bl e s will b e s u m m ari z e d b y t h e n u m b er of p ati e n t s ( N), m e a n, st a n d ar d d e vi ati o n, m e di a n, mi ni m u m, 
a n d m a xi m u m f or a ct u al v al u e s a n d c h a n g e fr o m b a s e li n e. A d diti o n all y, f or or din al d at a, t h e n u m b er a n d 
p er c e nt a g e  of  p ati e nt s  i n  e a c h  c a t e g or y  will  b e  pr e s e nt e d.  Bi n ar y a n d  c at e g ori c al  v ari a bl e s  will  b e  
s u m m ari z e d b y tr e at m e nt gr o u p b y pr e s e nti n g t h e n u m b er a n d p er c e nt a g e of p ati e nt s i n t h e c at e g ori e s. 
St ati sti c al t e st s f or c o m p ari s o n b et w e e n tr e at m e nt s f or all d efi n e d e sti m a n d s a n d e n d p oi nt s of effi c a c y will 
b e p erf or m e d u si n g a t w o- si d e d al p h a l e v el of 1 0 %. N o a d j u st m e nt f or m ulti pl e t e sti n g will b e a p pli e d i n t hi s 
d e s cri pti v e pr o of- of- c o n c e pt st u d y. A d diti o n all y, 9 5 % c o nfi d e n c e i nt er v al s will b e pr o vi d e d.
A d v er s e e v e nt s a n d m e di c al hi st or y will b e c o d e d a c c or d i n g t o t h e m o st r e c e nt v er si o n of M e di c al Di cti o n ar y 
f or R e g ul at or y A cti viti e s ( M e d D R A). Pri or a n d c o n c o mit a nt m e di c ati o n s will b e c o d e d u si n g t h e m o st r e c e nt 
W H O Dr u g Di cti o n ar y v er si o n. T h e a ct u al v er si o n of  M e d D R A a n d W H O dr u g u s e d will b e n ot e d i n t h e 
f o ot n ot e  of  t h e  r e s p e cti v e  o ut p ut.  U nl e s s  ot h er wi se  s p e cifi e d,  s u m m ari e s  will  b e  pr e s e nt e d  f or  e a c h  
tr e at m e nt a n d o v er all.
If t h er e ar e m ulti pl e a s s e s s m e nt s c oll e ct e d f or t h e s a m e s c h e d ul e d ti m e, t h e l a st a v ail a bl e a s s e s s m e nt 
b ef or e st art of st u d y tr e at m e nt will b e u s e d a s b a s eli n e v al u e a n d t h e fir st a s s e s s m e nt at t h e r e s p e cti v e 
p o st- b a s eli n e vi sit will b e u s e d f or p o st- b a s eli n e s u m m ari z ati o n, e x c e pt f or C O VI D- 1 9 t e st r e s ult s w h er e 
t h e l a st a s s e s s m e nt at t h e p o st- b a s eli n e vi sit will b e u s e d f or p o st- b a s eli n e s u m m ari z ati o n.  
All r el e v a nt p ati e nt d at a will b e i n cl u d e d i n li sti n g s. All p ati e nt s e nt er e d i nt o t h e d at a b a s e will b e i n cl u d e d i n 
p ati e nt d at a li sti n g s.
D at a c oll e ct e d at u n s c h e d ul e d vi sit s will b e i n cl u d e d i n  t h e d at a li sti n g s b ut will n ot b e i n cl u d e d i n t h e 
a n al y s e s or i n tr e at m e nt s u m m ari e s e x c e pt u n s c h e d ul e d C O VI D- 1 9 t e st r e s ult s.
K e y D efi niti o n s
B a s eli n e i s d efi n e d a s t h e l a st n o n- mi s si n g v al u e pri o r t o t h e st art d at e a n d ti m e of t h e st u d y dr u g. F or 
n o n-tr e at e d p ati e nt s, b a s eli n e i s d efi n e d a s t h e l a st n o n- mi s si n g v al u e fr o m t h e S cr e e ni n g a n d D a y 1 vi sit s.
St u d y D a y 1 i s d efi n e d a s t h e fir st d a y of st u d y dr u g a d mi ni str ati o n. St u d y d a y will b e c al c ul at e d a s d at e of 
e v e nt/ c oll e cti o n – fir st d o s e d at e of t h e st u d y + 1 f or all a s s e s sm e nt s aft er st art of st u d y dr u g, a n d a s d at e 
of e v e nt/ c oll e cti o n – fir st d o s e d at e of t h e st u d y f or all a s s e s s m e nt s pri or t o st art of st u d y dr u g. 
Mi s si n g D at a
Mi s si n g d at a will b e i m p ut e d f or t h e pri m ar y effi c a c y a n d k e y s e c o n d ar y effi c a c y v ari a bl e s a s d e s cri b e d i n 
s e cti o n s 7 a n d 1 0.
Mi s si n g or i n c o m pl et e d at e s i n s af et y d at a: I n all li sti n g s, mi s si n g or i n c o m pl et e d at e s will b e l eft a s t h e y 
h a v e b e e n r e c or d e d. H o w e v er, f or c al c ul ati o n a n d s ort i n g b a s e d o n d at e s a n d f or c o n si d er ati o n i n s u m m ar y 
t a bl e s, t h e f oll o wi n g m et h o d will b e u s e d: T h e m o st c o n ser v ati v e a p pr o a c h will b e s y st e m ati c all y c o n si d er e d 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 2 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 3 2 of 5 6
(i e, if t h e o n s et d at e of a n A E/ c o n c o mit a nt m e di c ati o n i s mi s si n g or i n c o m pl et e, it i s a s s u m e d t o h a v e 
o c c urr e d d uri n g t h e st u d y tr e at m e nt, i e , t h e A E will b e c o n si d er e d a s T E A E, e x c e pt if t h e p arti al o n s et d at e 
i n di c at e s diff er e ntl y). A mi s si n g/i n c o m pl et e d at e of m e dic al hi st or y or di s e a s e di a g n o si s will b e a s s u m e d t o 
h a v e o c c urr e d b ef or e a n y st u d y tr e at m e nt.
Mi s si n g T E A E r el ati o n s hi p will b e i m p ut e d b y ‘r el at e d’
f or s u m m ar y t a bl e s.
Vi sit Wi n d o w s
F or vi sit wi n d o w s s e e T a bl e 1: S c h e d ul e of A s s e s s m e nt s i n S e cti o n 4. 6 of t hi s S A P.
P o oli n g of C e nt er s
S u m m ari e s will b e pr o vi d e d p o ol e d f or all c e nt er s b y tr e at m e nt gr o u p if n ot i n di c at e d ot h er wi s e.
S u b gr o u p s
D e s cri pti v e s u m m ari e s of effi c a c y f or t h e pri m ar y effi c a c y e n d p oi nt a n d f or t h e k e y s e c o n d ar y effi c a c y 
e n d p oi nt s will b e r e p e at e d o n t h e s u b gr o u p s of  C O VI D- 1 9 s e v erit y ( m o d er at e a n d s e v er e), a g e-cl a s s ( ≤6 5 
y e ar s a n d > 6 5 y e ar s), v a c ci n ati o n st at u s ( v a c ci n at e d a n d n ot v a c ci n at e d), p ati e nt s t a ki n g D e x a m et h a s o n e 
a n d/ or  R e m d e si vir d uri n g  tr e at m e nt  wit h  st u d y  dr u g,  a n d  o b e sit y  ri s k  f a ct or ( B MI < 3 0. 0 k g/ m 2 a n d
B MI > = 3 0. 0 k g/ m 2 ). A d diti o n all y, b a s eli n e c h ar a ct eri stic s will b e s u m m ari z e d f or t h e s e s u b gr o u p s.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 3 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
 Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 3 3 of 5 6
D e m o gr a p hi c, Ot h er B a s eli n e C h ar a ct eri sti c s a n d M e di c ati o n
P ati e nt  Di s p o siti o n a n d Wit h dr a w al s
P ati e nt di s p o siti o n d at a will b e li st e d. S u m m ar y t a bl e s r efl e cti n g t h e n u m b er of p ati e nt s f or t h e f oll o wi n g will 
b e pr e s e nt e d: 
-
S cr e e n e d a n d r a n d o mi z e d p ati e nt s
-
I T T, P P S, S S a n d P K S
-
P ati e nt s w h o c o m pl et e d 1 4 d a y s of tr e at m e nt
-
P ati e nt s w h o e arl y t er mi n at e d a n d di d n ot c o m pl e t e 1 4- d a y s of st u d y tr e at m e nt wit h r e a s o n s f or 
e arl y tr e at m e nt t er mi n ati o n
-
P ati e nt s w h o c o m pl et e d t h e 2 8- d a y s tr e at m e nt p eri o d
-
P ati e nt s w h o e arl y t er mi n at e d t h e 2 8- d a y s st u d y tr e at m e nt p eri o d wit h r e a s o n s f or e arl y tr e at m e nt 
t er mi n ati o n
-
P ati e nt s w h o e arl y t er mi n at e d t h e st u d y tr e at m e nt b ut ar e f oll o w e d u p u ntil D a y 2 8
-
P ati e nt s w h o e arl y t er mi n at e d t h e st u d y tr e at m e nt b ut ar e f oll o w e d u p u ntil D a y 6 0
-
P ati e nt s w h o c o m pl et e d t h e st u d y i n cl u di n g t h e f oll o w- u p p eri o d ( D a y 6 0), aft er h a vi n g c o m pl et e d 
st u d y tr e at m e nt
-
P ati e nt s w h o e arl y t er mi n at e d t h e st u d y aft er h a vi n g c o m pl et e d t h e tr e at m e n t p eri o d wit h r e a s o n s 
f or e arl y st u d y t er mi n ati o n 
S cr e e n F ail ur e s u bj e ct s will b e li st e d wit h r e a s o n f or f ail ur e.
D e m o gr a p hi c a n d  B a s eli n e C h ar a ct eri sti c s
D e m o gr a p hi c c h ar a ct eri sti c s s u c h a s s e x, a g e, r a c e, et h ni cit y, h ei g ht, w ei g ht a n d B MI at s cr e e ni n g will b e 
s u m m ari z e d f or I T T a n d S S, b y tr e at m e nt a n d o v er all. N u m b er a n d p er c e nt a g e of p ati e nt s wit h a g e ≤6 5 
y e ar s a n d > 6 5 y e ar s a n d n u m b er a n d p er c e nt a g e of p ati e nt s i n t h e di s e a s e s e v erit y m o d er at e a n d s e v er e 
will  b e  pr e s e nt e d  b y  tr e at m e nt  gr o u p  a n d  o v er all  f or  t h e  I T T a n d  t h e  S S.  A d diti o n all y,  d e m o gr a p hi c  
c h ar a ct eri sti c s will b e s u m m ari z e d f or e a c h c o u ntr y b y tr e at m e nt gr o u p a n d o v er all f or t h e I T T. I n c a s e of 
i d e ntifi c ati o n of r el e v a nt h et er o g e n eit y i n t h e di stri b utio n b et w e e n c o u ntri e s, s u p p orti v e a n al y s e s of effi c a c y 
f or c o m p ari s o n b et w e e n t h e tr e at m e nt s will c o n si d er c ou ntr y ( or at l e a st r e gi o n) a s n o mi n al v ari a bl e wit hi n 
t h e r e s p e cti v e m o d el. D e m o gr a p hi c c h ar a ct eri stic s will b e li st e d f or all r a n d o mi z e d p ati e nt s.
B MI ( k g/ m 2 ) = W ei g ht ( k g)/[ H ei g ht ( m)2 ]
M e di c al a n d S ur gi c al Hi st or y
M e di c al a n d s ur gi c al hi st or y will b e c o d e d u si n g c urr e nt v er si o n of M e d D R A ®. M e di c al a n d s ur gi c al hi st or y 
will b e li st e d f or all r a n d o mi z e d p a ti e nt s. M e di c al a n d s ur gi c al hi st or y will b e s u m m ari z e d b y S y st e m Or g a n 
Cl a s s ( S O C) a n d Pr ef err e d T er m ( P T) f or e a c h tr e at m e nt gr o u p a n d o v er all.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 4 of 5 9
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_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 3 4 of 5 6
Ot h er B a s eli n e C h ar a ct eri sti c s
NI AI D at b a s eli n e will b e s u m m ari z e d b y n u m b er a n d p e r c e nt a g e of p ati e nt s i n e ac h c at e g or y b y tr e at m e nt 
gr o u p a n d o v er all f or I T T a n d S S.
M e di c ati o n
Pri or m e di c ati o n i s d efi n e d a s a n y m e di c ati o n w hi c h h a s a n e n d d at e pri or t o t h e d at e of fir st d o s e of st u d y 
dr u g a d mi ni str ati o n. 
C o n c o mit a nt m e di c ati o n i s d efi n e d a s a n y m e di c ati o n w hi c h st art s b ef or e t h e l a st d o s e of st u d y dr u g a n d 
h a s a n e n d d at e aft er t h e d at e of fir st d o s e of st u d y dr u g a d mi ni str ati o n or mi s si n g .
T h e ori gi n al v er b ati m t er m s c oll e ct e d i n t h e e C R F f o r pri or a n d c o n c o mit a nt m e di c ati o n s will b e c o d e d u si n g 
t h e W orl d H e alt h Or g a ni z ati o n Dr u g Di cti o n ar y ( W H O- D D c urr e nt v er si o n). 
Li sti n g s  will  i n cl u d e  t h e  t h er a p e uti c  (i e,  t h e  s e c o n d  l e v el  of  A n at o mi c al  T h er a p e uti c  C h e mi c al  [ A T C]  
cl a s sifi c ati o n s y st e m c o d e t h at i s c orr e s p o n di n g t o t h e fir st 3 fi g ur e s), pr ef err e d n a m e (t h e f o urt h l e v el of 
t h e A T C c o d e, t h at i s, c orr e s p o n di n g t o t h e fir st 5 fi g ur e s) a n d v er b ati m t e xt. T h e li sti n g s will b e s ort e d b y 
tr e at m e nt gr o u p, p ati e nt I D, c hr o n ol o gi c al st art d at e, st o p d at e, t h er a p e uti c cl a s s, pr ef err e d n a m e a n d 
v er b ati m n a m e a n d will c o nt ai n all r a n d o mi z e d p ati e nt s. 
A fr e q u e n c y t a bl e of t h e n u m b er a n d p er c e nt a g e of p a ti e nt s will b e pr o vi d e d f or pri or m e di c ati o n s a n d 
c o n c o mit a nt m e di c ati o n s b y t h er a p e uti c cl a s s a n d pr ef err e d n a m e f or e a c h tr e at m e nt gr o u p a n d o v er all o n 
t h e I T T.
N o n- dr u g t h er a pi e s c oll e ct e d o n t h e e C R F will b e li s t e d a n d s u m m ari z e d b y n u m b er a n d p er c e nt a g e of 
p ati e nt s.
E xt e nt of E x p o s ur e
N u m b er a n d p er c e nt a g e of p a ti e nt s w h o r e c ei v e d st u d y tr e at m e nt f or t h e fir st 1 4 d a y s, a n d w h o c o m pl et e d
all 2 8 d a y s of st u d y tr e at m e nt will b e pr e s e nt e d b y tr e at m e nt gr o u p a n d o v er all. T h e t ot al d ur ati o n of 
tr e at m e nt a n d t h e t ot al n u m b er of c a p s ul e s r e c ei v e d wit hi n t h e fir st 1 4 d a y s a n d wit hi n 2 8 d a y s will b e 
s u m m ari z e d b y tr e at m e nt gr o u p o n t h e S S a n d I T T, a s a p pr o pri at e. A li sti n g pr e s e nti n g all a b o v e d efi n e d 
v ari a bl e s of e xt e nt of e x p o s ur e will b e pr e s e nt e d f or t h e r a n d o mi z e d p ati e nt s.
Tr e at m e nt C o m pli a n c e 
D uri n g h o s pit ali z ati o n, t h e a d mi ni str ati o n of t h e st u d y dr u g will b e p erf or m e d b y t h e i n v e sti g at or ( or q u alifi e d 
bli n d e d d e si g n e e) t o e n s ur e c o m pli a n c e. If t h e p ati e n t i s di s c h ar g e d h o m e b ef or e D a y 2 8, t h e st u d y t e a m 
will pr o vi d e t h e p ati e nt wit h t h e r e m ai n d er of t h e a s si g n e d bli n d e d st u d y tr e at m e nt kit( s) t o t a k e h o m e al o n g 
wit h i n str u cti o n s t o c o nti n u e tr e at m e nt at h o m e; f or t h e s e p ati e nt s, tr e at m e nt c o m pli a n c e will b e a s s e s s e d 
vi a a di ar y. If t h e p ati e nt d o e s n ot f e el c o mf ort a bl e t o c o m pl et e t h e di ar y, t h e sit e  will alt er n ati v el y pr o vi d e 
t h e p ati e nt wit h t h e o pti o n t o b e c all e d t wi c e a d a y, t o c o nfir m t h at t h e st u d y dr u g i s t a k e n a s i n str u ct e d. 
P ati e nt s ar e t o b e r e mi n d e d of t h e i m p ort a n c e of c o m p li a n c e wit h t h eir a s si g n e d r e gi m e n, wit h a n e m p h a si s 
o n t a ki n g t h eir st u d y dr u g o n s c h e d ul e a n d m a i nt ai ni n g t h e pr e s cri b e d i nt er v al b et w e e n d o s e s.
I n v e sti g at or s  will  m ai nt ai n  r e c or d s  t h at  a d e q u at el y d o c u m e nt  t h at  t h e  p ati e nt s  w er e  pr o vi d e d  wit h  t h e  
c orr e ct st u d y tr e at m e nt kit( s) a n d r e c o n cil e t h e pr o d u ct s r e c ei v e d fr o m t h e dr u g di s p e n si n g c e nt er. 
Tr e at m e nt c o m pli a n c e i n % will b e c al c ul at e d a s
( T ot al n u m b er of c a p s ul e s t a k e n / 1 2) / tr e at m e nt d ur ati o n ( d a y s) x 1 0 0 % 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 5 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D:
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 3 5  of 5 6  
T h e tr e at m e nt c o m pli a n c e will b e c al c ul at e d f or t h e fi r st 1 4 d a y s of tr e at m e nt a n d f or t h e w h ol e 2 8 d a y s 
tr e at m e nt a n d will b e s u m m ari z e d b y tr e at m e nt gr o u p a n d o v er all o n t h e S S a n d I T T, a s a p pr o pri at e. 
N o n c o m pli a n c e i s d efi n e d a s t a ki n g < 8 0 % or > 1 2 0 % of st u d y dr u g. T h e n u m b er a n d p er c e nt a g e of p ati e nt s 
wit h n o n- c o m pli a n c e will b e pr e s e nt e d b y tr e at m e n t gr o u p a n d o v er all o n t h e S S a n d I T T, a s a p pr o pri at e. 
A li sti n g i n cl u di n g all a b o v e d efi n e d v ari a bl e s of tr e at m e nt c o m pli a n c e will b e pr e s e nt e d f or t h e r a n d o mi z e d 
p ati e nt s. 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 6 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 3 6 of 5 6
Effi c a c y
All effi c a c y e n d p oi nt s will b e s u m m ari z e d u si n g d e s cri p ti v e st ati sti c s b y tr e at m e nt gr o u p a n d b y vi sit, a s 
a p pr o pri at e: Bi n ar y a n d c at e g ori c al e n d p oi nt s will b e  s u m m ari z e d b y tr e at m e nt gr o u p b y pr e s e nti n g t h e 
n u m b er a n d p er c e nt a g e of p a ti e nt s i n e a c h c at e g or y. C o nti n u o u s a nd or di n al e n d p oi nt s will b e d e s cri b e d 
b y m e a n, st a n d ar d d e vi ati o n, m e di a n, mi ni m u m, a n d m a xi m u m f or a ct u al v al u e s a n d c h a n g e fr o m b a s eli n e. 
A d diti o n all y, f or or di n al d at a, t h e n u m b er a n d p er c e nt a g e of p ati e nt s i n e a c h c at e g or y will b e pr e s e nt e d.
St ati sti c al t e st s f or t h e c o m p ari s o n b et w e e n tr e at m e nt s  will b e p erf or m e d u si n g a t w o- si d e d al p h a of 1 0 %.
Pri m ar y Effi c a c y E sti m a n d s a n d A n al y si s
T h e m ai n e sti m a n d a n d t h e s e c o n d e sti m a n d f or t h e pr i m ar y effi c a c y e n d p oi nt t h at i s d efi n e d a s a bi n ar y 
v ari a bl e i n di c ati n g di s e a s e pr o gr e s si o n ( d e at h or r e s pir at or y f ail ur e) at D a y 1 4 will b e c o m p ar e d b et w e e n 
t h e tr e at m e nt gr o u p s b a s e d o n t h e c om m o n ri s k diff er e n c e r e s ulti n g fr o m t h e M H t e st c o n si d eri n g t h e 
4 str at a o ut of t h e c o m bi n ati o n s of t h e 2 r a n d o mi z ati o n str atifi c ati o n f a ct or s di s e a s e s e v erit y ( m o d er at e 
v er s u s s e v er e) a n d a g e- cl a s s ( ≤6 5 y e ar s v er s u s > 6 5 y e ar s).
Mi s si n g d at a o n D a y 1 4 r e s ulti n g fr o m st u d y t er mi n ati o n pri or t o D a y 1 4 ar e n ot e x p e ct e d. H o w e v er, i n c a s e 
t h e y h a p p e n, s u c h m o n ot o n e mi s si n g s will b e i m p ut e d b y m ulti pl e i m p ut ati o n u si n g i nf or m ati o n fr o m si mil ar 
p ati e nt s of t h e s a m e tr e at m e nt gr o u p a s s u mi n g t h e mi s si n g s ar e M A R. Mi s si n g p o st- b a s eli n e d at a f or 
p ati e nt s r a n d o mi z e d b ut n ot tr e at e d will b e i m p ut e d b y  B O C F. I nt er m e di at e mi s si n g d at a of D a y 1 4 (i e, 
NI AI D a s s e s s m e nt s pri or D a y 1 4 a n d at D a y 2 8 ar e a v ai l a bl e, b ut o nl y D a y 1 4 i s mi s si n g) will b e i m p ut e d 
b y L O C F. T h e c o m p ari s o n b et w e e n t h e tr e at m e nt gr o u p s will b e p erf or m e d o n t h e I T T aft er i m p ut ati o n of 
mi s si n g v al u e s u si n g t h e M H t e st. 9 5 % c o nfi d e n c e i nt er v al ( CI) will b e pr o vi d e d f or t h e ri s k diff er e n c e. A 
s e n siti vit y a n al y si s f or t h e m ai n e sti m a n d a n d t h e s e c o n d e sti m a n d will b e p erf or m e d b y i m p ut ati o n of 
mi s si n g v al u e s at D a y 1 4 wi t h ‘ pr o gr e s si o n’ a s s u mi n g t h at mi s si n g s h a p p e n n ot at r a n d o m ( M N A R). A t a bl e 
wit h n u m b er a n d t y p e/r e a s o n of mi s si n g v al u e s i n t h e pr i m ar y effi c a c y v ari a bl e will b e pr o vi d e d b y tr e at m e nt 
gr o u p o n t h e I T T.
All  a b o v e  d e s cri b e d  a n al y s e s  will  b e  r e p e at e d  o n  P P S a s  s u p p orti v e  a n al y si s. A d diti o n all y  a  l o gi sti c  
r e gr e s si o n m o d el wit h tr e at m e nt a n d t h e 2 str atifi c ati o n f a ct or s a s c o v ari a bl e s will b e a p pli e d o n t h e I T T a s 
s u p p orti v e a n al y si s.
K e y S e c o n d ar y Effi c a c y E sti m a n d s a n d A n al y s e s
K e y S e c o n d ar y Effi c a c y E n d p oi nt 1
Si mil ar M H a n al y s e s a s f or t h e m ai n e sti m a n d of t h e pr i m ar y effi c a c y e n d p oi nt will b e a p pli e d t o t h e m ai n 
e sti m a n d a n d t h e s e c o n d e sti m a n d of t h e fir st k e y s e c o n d ar y effi c a c y e n d p oi nt,  w hi c h i s d efi n e d a s a bi n ar y 
v ari a bl e i n di c ati n g di s e a s e pr o gr e s si o n ( d e at h or r e s pir at or y f ail ur e) at D a y 2 8. Pri or t o t h e a n al y si s, mi s si n g 
d at a will b e i m p ut e d a s d e s cri b e d i n S e cti o n 7. 2 of t h i s S A P. A s e n siti vit y a n al y si s f or t h e m ai n e sti m a n d 
a n d t h e s e c o n d e sti m a n d will b e p erf or m e d b y i m p ut ati o n of mi s si n g v al u e s at D a y 2 8 wit h ‘ pr o gr e s si o n’ 
a s s u mi n g M N A R. A t a bl e wit h n u m b er a n d t y p e / r e a s o n of  mi s si n g v al u e s i n t h e fir st k e y s e c o n d ar y effi c a c y 
v ari a bl e will b e pr o vi d e d b y tr e at m e nt gr o u p o n t h e I T T.
K e y S e c o n d ar y Effi c a c y E n d p oi nt 2
Si mil ar M H a n al y s e s will b e a p pli e d t o t h e m ai n e s ti m a n d a n d t h e s e c o n d e sti m a n d of t h e s e c o n d k e y 
s e c o n d ar y effi c a c y e n d p oi nt,  w hi c h i s d efi n e d a s a bi n a r y v ari a bl e i n di c ati n g di s e a s e r e s ol uti o n ( ali v e a n d 
h a v e a s c or e of 6, 7 or 8 o n NI AI D) at D a y 2 8. Pri or t o  t h e a n al y si s, mi s si n g d at a o n D a y 2 8 will b e i m p ut e d 
a s d e s cri b e d i n S e cti o n 7. 3 of  t hi s  S A P. A s e n siti v it y a n al y si s f or t h e m ai n e sti m a n d a n d t h e s e c o n d 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 7 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D:
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 3 7 of 5 6
e sti m a n d will b e p erf or m e d b y i m p ut ati o n of mi s si n g v al u e s  at D a y 2 8 wit h ‘ n o di s e a s e r e s ol uti o n’ a s s u mi n g 
M N A R. A t a bl e wit h n u m b er a n d t y p e / r e a s o n of mi s si n g v al u e s i n t h e s e c o n d k e y s e c o n d ar y effi c a c y 
v ari a bl e will b e pr o vi d e d b y tr e at m e nt gr o u p o n t h e I T T.
K e y S e c o n d ar y Effi c a c y E n d p oi nt 3
A si mil ar M H a p pr o a c h a s d e s cri b e d a b o v e will b e a p pli e d al s o t o t h e m ai n e sti m a n d of t h e t hir d k e y 
s e c o n d ar y effi c a c y e n d p oi nt,  w hi c h i s t h e all- c a u s e m ort alit y at D a y 2 8. N o mi s si n g d at a of lif e st at u s o n 
D a y 2 8 i s e x p e ct e d. H o w e v er, i n c a s e of mi s si n g  i nf or m ati o n lif e st at u s will b e i m p ut e d b y d e at h.
K e y S e c o n d ar y Effi c a c y E n d p oi nt 4
T h e m ai n e sti m a n d of t h e f o urt h k e y s e c o n d ar y effi c a c y e n d p oi nt ‘ C h a n g e of cli ni c al st at u s r el at e d t o 
C O VI D- 1 9 o n D a y 2 8 c o m p ar e d wit h b a s eli n e o n t h e NI AI D 8- p oi nt or di n al s c al e’ will b e c o m p ar e d u si n g 
t h e ri s k diff er e n c e b et w e e n t h e tr e at m e nt gr o u p s r e s ulti n g fr o m t h e a n al y si s of c o v ari a n c e ( A N C O V A) m o d el 
wit h tr e at m e nt a n d t h e 2 bi n ar y str atifi c ati o n f a ct or s s e v erit y a n d a g e- cl a s s a s i n d e p e n d e nt f a ct or s a n d t h e 
b a s eli n e v al u e of NI AI D a s i n d e p e n d e nt c o v ari at e. Pri o r t o t h e a n al y si s, mi s si n g d at a o n D a y 2 8 will b e 
i m p ut e d  a s  d e s cri b e d  i n  S e cti o n  7. 5 of  t hi s  S A P.  A  s en siti vit y a n al y si s  f or  t h e  m ai n  e sti m a n d  will  b e  
p erf or m e d b y i m p ut ati o n of mi s si n g v al u e s at D a y 2 8 i n  b ot h tr e at m e nt gr o u p s u si n g i nf or m ati o n fr o m si mil ar 
p ati e nt s of t h e pl a c e b o gr o u p a s s u mi n g M N A R. A t a bl e wit h n u m b er a n d t y p e / r e a s o n of mi s si n g v al u e s i n 
t h e f o urt h k e y s e c o n d ar y effi c a c y v ari a bl e will b e pr o vi d e d b y tr e at m e nt gr o u p o n t h e I T T.
All a b o v e d e s cri b e d a n al y s e s f or t h e k e y s e c o n d ar y e n d p oi nt s will b e r e p e at e d o n P P S a s s u p p orti v e 
a n al y s e s.  A d diti o n all y  a  l o gi sti c  r e gr e s si o n  m o d el  wit h  tr e at m e nt  a n d  t h e  2  str atifi c ati o n  f a ct or s  a s  
c o v ari a bl e s will b e a p pli e d o n t h e I T T a s s u p p orti v e a n al y si s.
Ot h er S e c o n d ar y Effi c a c y E n d p oi nt s
N o e sti m a n d s ar e d efi n e d f or ot h er s e c o n d ar y effi c a c y e n d p oi nt s. Mi s si n g lif e st at u s will b e i m p ut e d b y 
d e at h,  h o w e v er  ot h er  mi s si n g  d at a  will  n ot  b e  i m p u t e d  f or  t h e  a n al y si s  of  ot h er  s e c o n d ar y  effi c a c y  
e n d p oi nt s.  Ot h er s e c o n d ar y effi c a c y e n d p oi nt s wi ll b e s u m m ari z e d a n d a n al y z e d o n t h e I T T. 
T h e pr o p orti o n of p ati e nt s wit h di s e a s e r e s ol uti o n at D a y 1 4 a n d t h e all- c a u s e m ort alit y r at e at D a y 1 4 a n d 
D a y 6 0 will b e a n al y z e d u si n g si mil ar M H m et h o d s a s  d e s cri b e d a b o v e f or di s e a s e r e s ol uti o n at D a y 2 8. 
A d diti o n all y, t h e c u m ul ati v e pr o p orti o n of p ati e nt s wit h di s e a s e r e s ol uti o n will b e pl ott e d o v er ti m e.
A si mil ar A N C O V A a p pr o a c h a s d e s cri b e d a b o v e ( 1 0. 2. 4.)  will b e a p pli e d f or t h e a n al y si s of t h e c h a n g e of 
cli ni c al st at u s r el at e d t o C O VI D- 1 9 o n D a y 1 4 c o m p ar e d wit h b a s eli n e o n t h e NI AI D 8- p oi nt or di n al s c al e. 
T h e e n d p oi nt s c o n si d eri n g t h e pr o p orti o n of p ati e nt s r e q uiri n g i n v a si v e v e ntil ati o n ( m e c h a ni c al v e ntil at or 
a n d/ or E C M O) or w h o ar e n ot ali v e, t h e pr o p orti o n of p ati e nt s i n e a c h NI AI D c at e g or y, a n d t h e pr o p orti o n 
of p ati e nt s ali v e a n d t e sti n g n e g ati v e f or C O VI D- 1 9 o n D a y 1 4, D a y 2 8 a n d D a y 6 0, r e s p e cti v el y, will b e 
c o m p ar e d b et w e e n t h e tr e at m e nt gr o u p s  u si n g M H t e st s. O v er all s ur vi v al, ti m e t o (fir st) i m pr o v e m e nt of at 
l e a st 1 c at e g or y o n t h e NI AI D s c al e a n d t ot al h o s pit ali zati o n d ur ati o n (fr o m b a s eli n e t o di s c h ar g e; wit h d e at h 
c e n s or e d o n  l a st  d a y of  t h e o b s er v e d  p eri o d  - at D a y 2 8 or D a y 6 0, r e s p e cti v el y - d e p e n di n g  o n t h e  
a n al y s e s) will b e s u m m ari z e d u si n g K a pl a n- M ei er e sti m at e s a n d will b e c o m p ar e d b et w e e n tr e at m e nt 
gr o u p s u si n g l o gr a n k t e st s. A d diti o n all y, C o x pr o p orti o n al h a z ar d s m o d el will b e a p pli e d wit h tr e at m e nt a n d 
t h e 2 str atifi c ati o n f a ct or s a s i n d e p e n d e nt v ari a bl e s.
T h e o d d s r ati o b et w e e n M P 1 0 3 2 + S o C a n d pl a c e b o + S o C of  t h e n u m b er of p ati e nt s wit h cli ni c al st at u s 
i m pr o v e m e nt fr o m b a s eli n e o n t h e NI AI D 8- p oi nt or di n al s c al e (i e, a n i m pr o v e m e nt of at l e a st 1 c at e g or y) 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 8 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 3 8 of 5 6
at D a y 1 4 a n d D a y 2 8 will b e a n al y z e d u si n g a l o gi sti c r e gr e s si o n wit h c o n si d er ati o n of t h e 2 str atifi c ati o n 
f a ct or s.
E x pl or at or y Effi c a c y E n d p oi nt s
N o  e sti m a n d s  ar e  d efi n e d  f or  e x pl or at or y  effi c a c y  e n d p oi nt s.  E x pl or at or y  effi c a c y  e n d p oi nt s  will  b e  
s u m m ari z e d b y d e s cri pti v e st ati sti c s o n t h e I T T, o nl y . N o st ati sti c al c o m p ari s o n will b e p erf or m e d. S o m e 
e x pl or at or y effi c a c y e n d p oi nt s ar e d efi n e d i n a s u b gr o u p  of t h e r a n d o mi z e d p ati e nt s: p ot e nti al bi a s r e s ulti n g 
fr o m t hi s a s p e ct will b e c o n si d er e d i n t h e i nt er pr et ati o n of r e s p e cti v e s u m m ari e s b y tr e at m e nt. 
T h e ti m e t o r e c o v er y of all at b a s eli n e pr e s e nt  C O VI D - 1 9 s y m pt o m s ( st uff y or r u n n y n o s e, s or e t hr o at, r e d 
or irrit at e d e y e s, s h ort n e s s of br e at h, c o u g h, l o w e n er g y or tir e d n e s s, m u s cl e or b o d y a c h e s, h e a d a c h e, 
c hill s or s hi v eri n g, f e eli n g h ot or f e v eri s h, n a u s e a, a n d n u m b er of ti m e s of v o mit, ti m e s of di arr h e a, s e n s e 
of s m ell, s e n s e of t a st e i n t h e l a st 2 4 h o ur s) will b e pr e s e nt e d b y K a pl a n- M ei er e sti m at e s a n d fi g ur e. T h e 
c h a n g e  fr o m  b a s eli n e  will  b e  pr e s e nt e d  i n  s hift  t a bl e s  f or  e a c h  si n gl e  s y m pt o m  wit h  t h e  n u m b er  a n d  
p er c e nt a g e of p ati e nt s i n e a c h c at e g or y at p o st- b a s el i n e a s s e s s m e nt ti m e- p oi nt c o m p ar e d t o b a s eli n e f or 
e a c h tr e at m e nt gr o u p. N u m b er of s y m pt o m s will b e s u m m ari z e d b y vi sit a n d tr e at m e nt gr o u p.
T ot al  n u m b er  of  d a y s  i n I C U a n d d ur ati o n  of  i n v a si v e  m e c h a ni c al  v e ntil ati o n,  a n d/ or E C M O  will  b e  
d e s cri pti v el y  s u m m ari z e d  b y  tr e at m e nt  gr o u p  u si n g  m e a n  d a y s  wit h  9 0 % c o nfi d e n c e  i nt er v al s  a n d  
a d diti o n all y b y m e di a n d a y s a n d q u artil e s. T o c o n si d er  d e at h s uffi ci e ntl y u nf a v or a bl e i n t h e s e m e a s ur e s, i n 
c a s e of d e at h t h e d ur ati o n of t h e r e s p e cti v e m e a s ur e will b e c o n si d er e d wit h t h e l o n g e st d ur ati o n p o s si bl e. 
E g, if a s u m m ar y of t h e fir st 2 8 d a y s i s pr e s e nt e d, t h e n d e at h pri or t o D a y 2 8 will b e c o n si d er e d a s d ur ati o n 
2 8 d a y s, a n d if t h e s u m m ar y i n cl u d e s al s o f oll o w- u p p eri o d u ntil D a y 6 0, t h e n d e at h pri or t o D a y 6 0 will b e 
c o n si d er e d a s d ur ati o n 6 0 d a y s. B ot h s u m m ari e s ( u p t o D a y 2 8 a n d u p t o D a y 6 0) will b e pr o vi d e d. 
S at ur ati o n of o x y g e n ( S p O 2)/fr a cti o n of i n s pir e d o x y g e n  ( Fi O 2) r ati o (f or p ati e nt s ali v e) will b e s u m m ari z e d 
f or a ct u al v al u e s a n d c h a n g e fr o m b a s eli n e b y tr e at m e nt a n d vi sit.
F or H R Q o L a s s e s s m e nt s at di s c h ar g e a n d D a y 6 0, t h e E Q i n d e x v al u e a n d t h e E Q V A S, b ot h b a s e d o n 
t h e E Q- 5 D- 5 L q u e sti o n n air e will b e c al c ul at e d a n d s u m m ari z e d b y vi sit a n d tr e at m e nt gr o u p. A d diti o n all y,
t h e c h a n g e at D a y 6 0 fr o m di s c h ar g e will b e s u m mari z e d b y tr e at m e nt gr o u p. F or c o u ntri e s wit h o ut a 
p u bli s h e d i n d e x v al u e s et, t h e p u bli s h e d v al u e s et fr o m t h e g e o gr a p hi c all y cl o s e st c o u ntr y will b e u s e d.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 3 9 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 3 9 of 5 6
P h ar m a c o ki n eti c s
T h e P h ar m a c o ki n eti c A n al y si s S et will b e u s e d  f or t h e a n al y s e s s p e cifi e d i n t hi s s e cti o n.
T hi s S A P d e s cri b e s t h e m et h o d of d eri vi n g P K u si n g n o n- c o m p art m e nt al a n al y si s a p pl yi n g a p pr o pri at e 
s oft w ar e, i e, P h o e ni x ™ Wi n N o nli n ® ( V er si o n 8. 0 or hi g h er, C ert ar a C or p or ati o n), a n d all ot h er a n al y s e s a n d 
s u m m ari e s u si n g S A S ® ( V er si o n 9. 4 or hi g h er, S A S I n stit ut e I n c.),  w hi c h will b e pr e s e nt e d i n C S R. 
T h e P K a n al y s e s will b e c o n d u ct e d f or M P 1 0 3 2 i n pl a s m a a n d  will i n cl u d e a li sti n g, s u m m ar y, fi g ur e of 
c o n c e ntr ati o n s, a n d d eri v e d P K p ar a m et er s a s d e s cri b e d b el o w.
P K S a m pli n g S c h e d ul e 
T h e P K s a m pli n g s c h e d ul e of M P 1 0 3 2 i n pl a s m a o n D a y  1, a n d D a y 7 i s m e nti o n e d i n T a bl e 1 S e cti o n 4. 6.
I n  s u m m ar y,  P K  s a m pl e s  will  b e  c oll e ct e d  vi a  s p ars e  s a m pli n g  fr o m  a  P K  s u b s et  of  a p pr o xi m at el y  
3 0 p ati e nt s ( w h o gi v e o pti o n al c o n s e n t) i n a 2: 1 r ati o ( a p pr o xi m at el y 2 0 p ati e nt s fr o m t h e 3 0 0 m g M P 1 0 3 2 
BI D pl u s S o C gr o u p a n d a p pr o xi m at el y 1 0 p ati e nt s fr o m t h e pl a c e b o gr o u p pl u s S o C gr o u p) t o a s s e s s t h e 
P K of M P 1 0 3 2 o n D a y 1 ( si n gl e d o s e) a n d D a y 7 ( st e a d y st at e). A t ot al of 1 6 s a m pl e s ( a p pr o xi m at el y 
4. 9  m L p er ti m e p oi nt f or a t ot al of a p pr o xi m at el y 7 8. 4  m L ) will b e c oll e ct e d r el ati v e t o t h e fir st d o s e o n 
D a y 1 a n d t h e fir st d o s e o n D a y 7. S a m pl e s o n D a y 1 a n d D a y 7 will b e c oll e ct e d pr e d o s e ( wit hi n 1 0 mi n ut e s 
b ef or e t h e fir st d ail y d o s e) a n d p o st d o s e at 1 0  mi n ut e s, 2 0 mi n ut e s, 3 0 mi n ut e s, 6 0 mi n ut e s, 1 2 0 mi n ut e s, 
8 h o ur s ( b ef or e n e xt d o s e), a n d 2 4 h o ur s b ef or e t h e n e xt  m or ni n g d o s e (if a p pli c a bl e), if p o s si bl e. P ati e nt s 
w h o pr o vi d e c o n s e nt f or t h e P K s a m pli n g, b ut ar e n o l o n g er h o s pit ali z e d o n D a y 7, will n ot h a v e D a y 7 P K 
s a m pl e s c oll e ct e d.
Pl a s m a P K E n d p oi nt
T h e f oll o wi n g P K p ar a m et er s will b e c al c ul at e d b y st a n d ar d n o n- c o m p art m e nt al m et h o d s wit h M P 1 0 3 2
pl a s m a c o n c e ntr ati o n s, u si n g u p t o 8 h o ur s p o st- d o s e, o n D a y 1 a n d D a y 7 f or f a sti n g c o n diti o n ( or f e d, if 
f a sti n g n ot p o s si bl e):
A U C 0-i nf:
Ar e a u n d er t h e c o n c e ntr ati o n-ti m e c ur v e fr o m ti m e z er o t o i nfi nit y ( e xtr a p ol at e d), 
c al c ul at e d a s A U C 0-t + C t/ Kel , w h er e Ct i s t h e l a st o b s er v e d n o n-z er o c o n c e ntr ati o n. 
A U C 0-t:
Ar e a u n d er t h e c o n c e ntr ati o n-ti m e c ur v e fr o m ti m e z er o t o t h e l a st n o n- z er o 
c o n c e ntr ati o n. T h e c al c ul ati o n of A U C 0-t will b e d o n e u si n g t h e li n e ar tr a p e z oi d al 
m et h o d u si n g li n e ar tr a p e z oi d al li n e ar i nt er p ol ati o n.
C m a x:
C l a st:
M a xi m u m o b s er v e d c o n c e ntr ati o n.
L a st o b s er v e d c o n c e ntr ati o n.
tm a x :
Ti m e of o b s er v e d C m a x .
T ½ el :
R e si d u al ar e a:
Eli mi n ati o n h alf-lif e, c al c ul at e d a s l n ( 2)/ K el . 
R e si d u al ar e a, c al c ul at e d a s 1 0 0*( 1- A U C 0-t / A U C0-i nf ).
If R e si d u al Ar e a i s > 2 0 %, t h e n A U C0-i nf i s c o n si d er e d u nr eli a bl e; d u e t o w hi c h all 
r el at e d P K p ar a m et er s of A U C0-i nf ( Cl/ F, Vz/ F, R e si d u al ar e a, a n d A U C0-i nf ) will b e 
fl a g g e d i n i n di vi d u al li sti n g s, a n d e x cl u d e d fr o m s u m m ar y st ati sti c s if r e si d u al Ar e a 
i s > 2 0 %.
K el:
Eli mi n ati o n r at e c o n st a nt. T hi s p ar a m et er wi ll b e t h e n e g ati v e of t h e e sti m at e d sl o p e 
of t h e li n e ar r e gr e s si o n of t h e l n-tr a n sf or m e d pl a s m a c o n c e ntr ati o n v er s u s ti m e 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 0 of 5 9
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_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 0 of 5 6
pr ofil e i n t h e t er mi n al eli mi n ati o n p h a s e. B e st fit m et h o d will b e u s e d t o c al c ul at e t h e 
K el fr o m at l e a st 3 p o st Cm a x c o n c e ntr ati o n d at a p oi nt s e x cl u di n g t h e C m a x . T h e 
ti m e p oi nt w h er e l n-li n e ar Kel c al c ul ati o n b e gi n s ( K el L o w er ) a n d t h e a ct u al s a m pli n g 
ti m e of t h e l a st m e a s ur a bl e c o nc e ntr ati o n u s e d t o e sti m at e t h e K el ( Kel  U p p er ), a s w ell 
a s t h e R s q a dj u st e d f or t h e l n- li n e ar r e gr e s si o n f or t h e c al c ul ati o n of t h e eli mi n ati o n 
r at e c o n st a nt will b e r e p ort e d. Rs q a dj u st e d, t h e g o o d n e s s of fit st ati sti c f or t h e 
t er mi n al eli mi n ati o n p h a s e, a dj u st e d f or t h e n u m b er of p oi nt s u s e d i n t h e e sti m ati o n 
of K el m u st b e ≥ 0. 8. If t h e Kel c a n n ot b e m e a s ur e d ( e g: f e w er t h a n 3 n o n- z er o 
c o n c e ntr ati o n s i n t h e t er mi n al eli mi n ati o n p h a s e), t h e n K el , a n d it s r el at e d P K 
p ar a m et er s ( K el , Kel L o w er , Kel  U p p er , A U C0-i nf , R e si d u al ar e a, T½ el , Cl/ F, a n d Vz/ F) will 
n ot b e r e p ort e d f or P K pr ofil e s. If t h e R s q a dj u st e d i s < 0. 8, t h e n K el , a n d it s r el at e d 
P K p ar a m et er s ( K el , Kel L o w er , Kel  U p p er , A U C0-i nf , R e si d u al ar e a, T½ el , Cl/ F, a n d Vz/ F) 
will b e will b e i n cl u d e d a n d fl a g g e d i n t h e li sti n g s b ut will n ot b e i n cl u d e d i n t h e 
s u m m ar y st ati sti c s.
Cl/ F
A p p ar e nt t ot al b o d y cl e ar a n c e ( Cl/ F), e sti m at e d a s D o s e/ A U C 0-i nf ( D a y 1 o nl y).
V z/ F
A p p ar e nt v ol u m e of di stri b uti o n ( V z/ F), e sti m at e d a s D o s e/( Kel x A U C 0-i nf ) ( D a y 1 
o nl y).
F or D a y 2 ( or 2 4 h o ur s aft er D a y 1), D a y 7, a n d D a y 8 ( or 2 4 h o ur s aft er D a y 7):
C tr o u g h:
Pr e- d o s e c o n c e ntr ati o n ( D a y 2, 7, a n d 8).
Pr e s e nt ati o n of C o n c e ntr ati o n D at a
H a n dli n g of Mi s si n g D at a 
Mi s si n g c o n c e ntr ati o n d at a f or all p ati e nt s w h o ar e a d mi ni st er e d st u d y dr u g will b e c o n si d er e d a s n o n-
i nf or m ati v e mi s si n g a n d will n ot b e i m p ut e d. N o c o n c e ntrati o n e sti m at e s will b e pr o vi d e d f or mi s si n g s a m pl e 
v al u e s.
H a n dli n g of t h e Diff er e n c e b et w e e n t h e S c h e d ul e d ( n o mi n al ti m e) a n d t h e A ct u al S a m pli n g 
Ti m e s ( a ct u al ti m e)
F or  all  s a m pli n g  ti m e s,  t h e  a ct u al s a m pli n g  ti m e s  r e l ati v e  t o  d o si n g ar e  c al c ul at e d  a s  t h e  diff er e n c e  
b et w e e n t h e  a ct u al  cl o c k  ti m e  of  s a m pli n g  a n d  t h e  a ct u al  cl o c k  ti m e  of  d o si n g.  T h e  a ct u al p o st- d o s e  
s a m pli n g ti m e s r el ati v e t o d o si n g e x pr e s s e d i n h o ur s a n d r o u n d e d off t o t hr e e d e ci m al di git s ar e u s e d, 
e x c e pt f or pr e- d o s e s a m pl e s o c c urri n g pri or t o d o si n g, w hi c h ar e r e p ort e d a s z er o ( 0. 0 0 0), r e g ar dl e s s of 
t h e ti m e diff er e n c e. S c h e d ul e d s a m pli n g ti m e s ar e pr e s e nt e d i n c o n c e ntr ati o n t a bl e s. If t h e a ct u al ti m e of 
s a m pli n g i s mi s si n g, t h e n o mi n al ti m e i s u s e d.
Li sti n g a n d Pr e s e nt ati o n of I n di vi d u al P K D at a
T h e s a m pli n g ti m e of pr e- d o s e s a m pl e s r el ati v e t o d o si n g i s tr e at e d a s z er o f or all s a m pli n g p eri o d s 
s e p ar at el y;
All c o n c e ntr ati o n s ar e pr e s e nt e d i n ori gi n al u nit s a s r e p ort e d b y Bi o a n al yti c al l a b, e g, n g/ m L; 
All c o n c e ntr ati o n s t h at ar e b el o w t h e l o w er li mit of q u a ntifi c ati o n ( B L Q) will b e s et t o z er o; 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 1 of 5 9
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_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 1 of 5 6
Li sti n g of P K s a m pli n g ti m e s i n cl u di n g n o mi n al a n d a ct u al ti m e el a p s e d fr o m d o s e wit h t h e d e vi ati o n 
fr o m t h e n o mi n al ti m e a n d m e a s ur e d c o n c e ntr ati o n s of t h e dr u g;
N o f urt h er i m p ut ati o n will b e a p pli e d t o a n y  mi s si n g v al u e s.
I n di vi d u al  P K  c o n c e ntr ati o n  d at a  will  b e  li st e d  b y p ati e nt  I D,  ti m e  p oi nt  a n d  tr e at m e nt  (i n  r el e v a nt  
c o n c e ntr ati o n u nit s). 
T h e i n di vi d u al pl a s m a c o n c e ntr ati o n s f or M P 1 0 3 2  will  b e pr e s e nt e d gr a p hi c all y o n b ot h t h e li n e ar a n d 
s e mi-l o g arit h mi c s c al e s of D a y 1, a n d D a y 7 s e p ar at el y.
S u m m ar y of P K C o n c e ntr ati o n s
F or P K c o n c e ntr ati o n s u m m ar y, t h e f oll o wi n g r ul e s a p pl y:
P K c o n c e ntr ati o n s B L Q i n pr e- d o s e s a m pl e s a n d i n s a m pl e s t a k e n b ef or e t h e ti m e of t h e fir st 
q u a ntifi a bl e v al u e ar e s et t o z er o; 
T h e P K c o n c e ntr ati o n s B L Q aft er q u a ntifi a bl e c o n c e ntr ati o n ar e s et t o z er o; 
T h e s a m pli n g ti m e of pr e- d o s e s a m pl e s r el ati v e t o d o si n g will b e tr e at e d a s z er o;
Dr u g c o n c e ntr ati o n s will b e s u m m ari z e d b y n o mi n al ti m e p oi nt;
D e s cri pti v e st ati sti c s will b e p erf or m e d;
N o f urt h er i m p ut ati o n i s a p pli e d t o a n y mi s si n g v al u e s.
Pl a s m a M P 1 0 3 2 c o n c e ntr ati o n s will b e s u m m ari z e d d e s cri pti v el y b y st u d y d a y, ti m e p oi nt a n d tr e at m e nt 
(i n r el e v a nt c o n c e ntr ati o n u nit s) u si n g d e s cri pti v e st ati sti c s ( n, n u m b er a n d p er c e nt of p ati e nt s  wit h B L Q, 
arit h m eti c m e a n, g e o m etri c m e a n, S D, arit h m eti c a n d g e o m etri c c o effi ci e nt of v ari ati o n ( C V) %, mi ni m u m, 
m e di a n a n d m a xi m u m) pr e s e nt e d a c c or di n g t o t h e f oll o wi n g r e p orti n g pr e ci si o n.
V ari a bl e
S u m m ari z e d  wit h:
Mi ni m u m, M a xi m u m
3 si g nifi c a nt di git s or a s n e e d e d b a s e d o n a ct u al
m e a s ur e d v al u e s
Arit h m eti c M e a n, G e o m etri c M e a n, M e di a n
4 si g nifi c a nt di git s or a s n e e d e d b a s e d o n a ct u al 
m e a s ur e d v al u e s
S D
5 si g nifi c a nt di git s or a s n e e d e d b a s e d o n a ct u al 
m e a s ur e d v al u e s
C V %, a n d G e o m etri c C V %
  1 d e ci m al pl a c e or a s n e e d e d b a s e d o n a ct u al
  m e a s ur e d v al u e s
M e a n ± S D pl a s m a c o n c e ntr ati o n-ti m e pr ofil e s f or M P 1 0 3 2 of all p ati e nt o n li n e ar a n d l o g-li n e ar s c al e s
will al s o b e pr e s e nt e d.
P K P ar a m et er s D eri v ati o n
F or t h e d eri v ati o n of P K, t h e f oll o wi n g r ul e s will a p pl y:
All pl a s m a c o n c e ntr ati o n s B L Q will b e i m p ut e d wit h a v al u e of z er o;
T h e s a m pli n g ti m e of pr e- d o s e s a m pl e s r el ati v e t o d o si n g will al s o b e tr e at e d a s z er o;
A ct u al bl o o d s a m pli n g ti m e s will b e u s e d t o d eri v e P K p ar a m et er s. If t h e a ct u al bl o o d s a m pli n g i s 
n ot pr e s e nt, t h e n t h at ti m e p oi nt will n ot b e c o n si d er e d f or P K a n al y s e s. 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 2 of 5 9
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C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 2 of 5 6
If t h e pr e- d o s e s a m pl e i s n ot pr e s e nt, t h e n t h at p ati e nt will n ot b e c o n si d er e d f or P K d eri v ati o n;
N o f urt h er i m p ut ati o n will b e a p pli e d t o a n y mi s si n g v al u e s.
All P K p ar a m et er s will b e li st e d. 
P K P ar a m et er s S u m m ari z ati o n
P K p ar a m et er s a n d c o n c e ntr ati o n s d at a will b e s u m m ari z e d u si n g t h e f oll o wi n g d e s cri pti v e st ati sti c s:
V ari a bl e
S u m m ari z e d wit h:
P K c o n c e ntr ati o n at e a c h ti m e 
p oi nt
n,  arit h m eti c  m e a n,  S D,  c o effi ci e nt  of  v ari a n c e  ( C V)  %,  
mi ni m u m, m e di a n a n d m a xi m u m
A U C s, C m a x , Ctr o u g h, C L/ F, a n d 
V z/ F
n, arit h m eti c m e a n, S D, C V %, mi ni m u m, m e di a n, m a xi m u m, 
g e o m etri c m e a n a n d g e o m etri c C V % 
T ½ el , Kel
n, arit h m eti c m e a n, S D, C V %, mi ni m u m, m e di a n, m a xi m u m
tm a x ( a ct u al ti m e)
n, mi ni m u m, m e di a n, a n d m a xi m u m
N ot e: C V % = S D/ m e a n i n %; n = N o. of o b s er v ati o n s.  
F or P K t a bl e s a n d li sti n g s, t h e fi n al r e p ort a bl e r e s ult s or d at a will b e pr e s e nt e d b y r o u n di n g off t o t w o 
d e ci m al di git s, e x c e pt f or t h e f oll o wi n g sit u ati o n s (t hi s a p pli e s t o i n di vi d u al d at a a n d d e s cri pti v e st ati sti c s):
K el a n d R s q a dj u st e d d at a: r o u n d e d off t o f o ur d e ci m al di git s.
P h ar m a c o ki n eti c p ar a m et er s r el at e d t o ti m e s u c h a s t m a x , Kel L o w er , a n d Kel U p p er m u st b e r e p ort e d 
wit h t h e s a m e pr e ci si o n a s t h e a ct u al s a m p li n g ti m e: r o u n d e d off t o 3 d e ci m al di git s.
C o n c e ntr ati o n v er s u s ti m e d at a: r e p ort e d a s t h e y a p p e ar i n c orr e s p o n di n g d at a s et.
E x pl or at or y R el ati o n s hi p b et w e e n Pl a s m a e x p o s ur e, a n d Bi o m ar k er
( E x p o s ur e- R e s p o n s e r el ati o n s hi p)
A n y p o s si bl e c orr el ati o n b et w e e n pl a s m a e x p o s ur e ( C m a x , or A U C0-t ) a n d bi o m ar k er s ( e g, c h a n g e fr o m 
b a s eli n e  i n c yt o ki n e s, or  ot h er c o a g ul ati o n/i nfl a m m at or y bi o m ar k er s) u si n g  D a y 7 if  a v ail a bl e,  m a y b e  
e x pl or e d a p pl yi n g e x p o s ur e-r e s p o n s e s c att er pl ot s. F urt h er c orr el ati o n a n al y si s ( e g, utili zi n g a c o m bi n ati o n 
of S p e ar m a n a n d P e ar s o n c orr el ati o n) m a y b e a p pli e d if e x p o s ur e-r e s p o n s e s c att er pl ot s r e v e al a n y r o b u st 
r el ati o n s hi p s. T a bl e s will b e t h e n pr o d u c e d f or c al c ulat e d c orr el ati o n c o effi ci e nt, c o nfi d e n c e i nt er v al s f or 
P e ar s o n c o effi ci e nt i n a d diti o n t o p- v al u e, t o d e m o n str at e t h e v ali dit y of c orr el ati o n.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 3 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 3 of 5 6
P h ar m a c o d y n a mi c s
Bi o m ar k er  l e v el s  p ot e nti all y  i n cl u di n g,  b ut  n ot  li mit e d  t o,  c yt o ki n e s  ( e g,  C-r e a cti v e  pr ot ei n,  i nt erl e u ki n  
[I L]-1 β ,  I L- 6,  t u m or  n e cr o si s  f a ct or-α ,  a n d  I F N-γ ),  a n d  ot h er c o a g ul ati o n/i nfl a m m at or y  bi o m ar k er s  ( e g,  
D- di m er a n d f erriti n) will b e s u m m ari z e d b y a ct u al v al u e s a n d c h a n g e s fr o m b a s eli n e b y tr e at m e nt gr o u p 
a n d vi sit o n t h e S S. T h e c h a n g e i n bi o m ar k er l e v el s will  b e e v al u at e d wit h a n y c h a n g e of C O VI D- 1 9 cli ni c al 
st at u s b y pr e s e nti n g s u m m ar y t a bl e s of t h e c h a n g e i n bi o m ar k er l e v el s fr o m b a s eli n e str atifi e d b y C O VI D- 1 9 
st at u s b y tr e at m e nt gr o u p.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 4 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 4 of 5 6
S af et y
T h e p o p ul ati o n u s e d f or s af et y a n al y s e s will b e t h e S af et y S et ( S S). S af et y will b e a s s e s s e d b a s e d o n
a d v er s e e v e nt ( A E) or a d v er s e dr u g r e a cti o n s ( A D R) r e p ort s, cli ni c al l a b or at or y d at a, E C G p ar a m et er s, 
p h y si c al e x a mi n ati o n s, a n d vit al si g n s . 
A d v er s e E v e nt s / A d v er s e Dr u g R e a cti o n s
All A E s will b e c o d e d u si n g t h e m o st r e c e nt M e d D R A V er si o n. 
E a c h A E will b e a s si g n e d a gr a d e w hi c h r ef er s t o t h e s e v erit y of t h e A E b a s e d o n t h e C o m m o n T er mi n ol o g y 
Crit eri a  f or  A d v er s e  E v e nt s  v er si o n  5. 0.  T h e  C o m m o n  T er mi n ol o g y  Crit eri a  f or  A d v er s e  E v e nt s  v 5. 0  
di s pl a y s gr a d e s 1 t hr o u g h 5 wit h u ni q u e cli ni c al d e s c ri pti o n s of t h e s e v erit y f or e a c h A E. T a bl e s f or t h e 
cl a s sifi c ati o n of t h e A E s e v erit y a n d r el ati o n s hi p t o t h e dr u g ar e pr o vi d e d i n T a bl e s 6 a n d 7 i n S e cti o n 1 2. 6. 1 
of t h e pr ot o c ol. 
W h e n c h a n g e s i n t h e s e v erit y of a n A E o c c ur m or e fr e q u e ntl y t h a n o n c e a d a y, t h e m a xi m u m s e v erit y f or 
t h e e v e nt s h o ul d b e n ot e d i n t h e e C R F. If t h e s e v erit y c at e g or y c h a n g e s o v er a n u m b er of d a y s, t h e n t h o s e 
c h a n g e s s h o ul d b e r e c or d e d s e p ar at el y ( wit h di sti n ct o n s et d at e s) i n t h e e C R F: t h e a s s e s s m e nt of a n A E 
i n s e v er al r e c or d s will b e call e d a s ‘ e pi s o d e s’ of o n e A E. 
A tr e at m e nt- e m er g e nt A E ( T E A E) i s a n A E t h at st art s or w or s e n s at a n y ti m e aft er i niti ati o n of st u d y dr u g 
u ntil t h e e n d of t h e f oll o w- u p p eri o d at D a y 6 0. E v e n t s wit h mi s si n g o n s et d at e s will b e c o n si d er e d a s 
T E A E s. If a p ati e nt e x p eri e n c e s > 1 o c c urr e n c e of t h e s a m e A E, t h e o c c urr e n c e wit h t h e gr e at e st s e v erit y 
a n d t h e cl o s e st a s s o ci ati o n wit h t h e st u d y dr u g will b e u s e d i n t h e c orr e s p o n di n g s u m m ar y t a bl e s. I n c a s e 
t h at  f or  o n e  A E, s e v er al  A E  e pi s o d e s  wit h  e g  c h a n gin g  s e v erit y  ar e  r e p ort e d,  a n  a g gr e g ati o n  of  all  
r e s p e cti v e e pi s o d e s t o o n e A E will b e p erf or m e d pri or t o s u m m ari z ati o n. T h e w or st s e v erit y a n d t h e w or st 
r el ati o n s hi p will b e a s si g n e d t o t h e a g gr e g at e d A E. 
Li sti n g s pr e s e nti n g all A E s i n cl u di n g all e pi s o d e s of o n e A E  will b e pr o d u c e d f or T E A E s a n d n o n- T E A E s 
wit h t h e fl a g gi n g of S A E s. Li sti n g s of s eri o u s T E A E s, T E A E s l e a di n g t o st u d y dr u g wit h dr a w al, a n d T E A E s 
l e a di n g t o d e at h will b e pr e s e nt e d i n t h e t a bl e s e cti o n of t h e o ut p ut s. A d diti o n all y, i n t h e li sti n g T E A E s 
st arti n g  i n  t h e  tr e at m e nt  p eri o d  a n d  T E A E s  st arti n g  i n  t h e  f oll o w- u p  p eri o d  or  st arti n g  aft er  t h e  i niti al  
tr e at m e nt h a s st o p p e d will b e fl a g g e d 
A n o v er all s u m m ar y will b e pr o vi d e d of t h e n u m b er a n d p er c e nt a g e of p ati e nt s r e p orti n g A E s, T E A E s, 
tr e at m e nt-r el at e d T E A E s, s eri o u s T E A E s, tr e at m e nt-r el at e d s eri o u s T E A E s, T E A E s l e a di n g t o st u d y dr u g 
wit h dr a w al a n d T E A E s l e a di n g t o d e at h. I n t h e o v er al l s u m m ar y, a d diti o n all y, t h e n u m b er a n d p er c e nt a g e 
of p ati e nt s  wit h at l e a st o n e s e v er e T E A E, wit h at l e a st o n e m o d er at e T E A E b ut n o s e v er e T E A E a n d wit h 
o nl y mil d T E A E s will b e pr o vi d e d. F or p ati e nt s wit h  a n y s eri o u s T E A E a n d f or p ati e nt s wit h a n y r el at e d 
s eri o u s T E A E e x p o s ur e- a dj u st e d e v e nt s r at e s will b e  c al c ul at e d a n d c o m p ar e d b et w e e n tr e at m e nt gr o u p s 
u si n g t h e ri s k r ati o [( 3 0 0 m g M P 1 0 3 2 BI D pl u s S o C) / ( pl a c e b o pl u s S o C)] wit h r e s p e cti v e 9 5 % CI. T hi s 
c o m p ari s o n will al s o b e p erf or m e d f or t h e r at e of r e- h o s pit ali z ati o n w hi c h i s c o n si d er e d a s eri o u s A E.
T h e n u m b er a n d p er c e nt a g e of p ati e nt s  wit h T E A E s  / tr e at m e nt-r el at e d T E A E s / s eri o u s T E A E s / a n d 
T E A E s l e a di n g t o st u d y dr u g wit h dr a w al will b e s u m m ari z e d b y S O C a n d P T f or e a c h tr e at m e nt gr o u p, a n d 
t ot al. I n t h e s e t a bl e s, t h e i n ci d e n c e of T E A E s b y S O C a n d P T will al s o b e i n cl u d e d. T E A E s will al s o b e 
s u m m ari z e d b y S O C a n d P T f or m a xi m u m i nt e n sit y a n d m a xi m u m r el ati o n s hi p t o st u d y dr u g f or e a c h 
tr e at m e nt gr o u p a n d t ot al. A d diti o n all y, s e p ar at e t a bl e s of T E A E s b y S O C a n d P T will b e pr o vi d e d f or 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 5 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 5 of 5 6
T E A E s st arti n g i n t h e tr e at m e nt p eri o d a n d f or T E A E s st ar ti n g i n t h e f oll o w- u p p eri o d or aft er t h e st u d y dr u g 
a d mi ni str ati o n h a s st o p p e d.
L a b or at or y E v al u ati o n s
Cli ni c al l a b or at or y d at a of l o c al l a b or at ori e s will b e pr e s e nt e d i n s e p ar at e t a bl e s f or e a c h l a b or at or y t e st 
t y p e ( h e m at ol o g y, bl o o d c h e mi str y, c o a g ul ati o n, uri n al y si s). E a c h l a b or at or y p ar a m et er will b e pr e s e nt e d 
wit h t h e n u m b er a n d p er c e nt a g e of p ati e nt s wit h v al u e s b el o w, wit hi n, or a b o v e t h e n or m al r a n g e at e a c h 
ti m e p oi nt b y tr e at m e nt gr o u p a n d o v er all. A d diti o nall y, a s hift t a bl e of t h e n u m b er a n d p er c e nt a g e of 
p ati e nt s wit h n or m al a n d a b n or m al, a n d cli ni c all y si g nifi c a nt a b n or m al v al u e s at e a c h s c h e d ul e d p o st-
b a s eli n e  vi sit  c o m p ar e d  t o  t h e  n or m al,  a b n or m al,  a n d  cli ni c all y  si g nifi c a nt  a b n or m al  c at e g ori z ati o n  at  
b a s eli n e  will  b e  pr o vi d e d  b y tr e at m e nt  gr o u p.  A  li st i n g  of  cli ni c all y si g nifi c a nt  a b n or m al  v al u e s  will  b e  
pr o vi d e d i n t h e t a bl e s s e cti o n. 
S u m m ar y t a bl e s of a ct u al v al u e s a n d c h a n g e s fr o m b a s eli n e c a n b e pr e s e nt e d f or c o nti n u o u s l a b or at or y 
p ar a m et er s o nl y aft er ‘ n or m ali z ati o n’ of t h e l o c al l a b or at or y a s s e s s m e nt a s s u p p o s e d b y C h u a n g- St ei n ( s e e 
r ef er e n c e 1 a n d 2) u si n g o n e r ef er e n c e l ab or at or y b a s e d o n t h e f oll o wi n g f or m ul a 
w h er e  s  =  t h e  tr a n sf or m e d  i n di vi d u al  l a b or at or y  v al u e  c o n si d eri n g  t h e  n or m al  r a n g e  of  t h e  r ef er e n c e  
l a b or at or y, x = t h e ori gi n al l a b or at or y v al u e, Lx a n d U x ar e t h e l o w er a n d u p p er li mit s or n or m al r a n g e of t h e 
l o c al l a b or at or y f or t h e r e s p e cti v e p ar a m et er, Ls a n d U s ar e t h e l o w er a n d u p p er li mit s of t h e s el e ct e d 
r ef er e n c e l a b or at or y. F or c al c ul ati n g s u m m ar y st ati sti c s, r e s ult s of < x or < = x will b e i m p ut e d a s x/ 2 a n d 
r e s ult s of > x or > = x will b e i m p ut e d a s x.
Pr e g n a n c y t e st r e s ult s will b e li st e d o nl y f or r a n d o mi z e d f e m al e p ati e nt s.
Vit al Si g n s 
Vit al si g n s will i n cl u d e s y st oli c bl o o d pr e s s ur e ( m m H g) , di a st oli c bl o o d pr e s s ur e ( m m H g), h e art r at e ( b e at s 
p er mi n ut e, b p m), r e s pir ati o n r at e ( br e at h s p er mi n ut e), S p O 2, a n d b o d y t e m p er at ur e (° C). S u m m ar y t a bl e s 
of t h e a ct u al v al u e s a n d c h a n g e s fr o m b a s eli n e will b e pr o vi d e d f or e a c h vit al si g n p ar a m et er at e a c h 
s c h e d ul e d vi sit b y tr e at m e nt gr o u p, a n d i n t ot al. 
A d diti o n all y, b o d y w ei g ht a n d B MI will b e s u m m ari z e d wi t h a ct u al v al u e s a n d c h a n g e fr o m b a s eli n e at e a c h 
s c h e d ul e d vi sit b y tr e at m e nt gr o u p, a n d i n t ot al.
Vit al si g n s d at a, b o d y w ei g ht a n d B MI will  b e li st e d f or r a n d o mi z e d p ati e nt s.
E C G
T h e o v er all i nt er pr et ati o n of E C G at s cr e e ni n g will b e s u m m ari z e d b y tr e at m e nt gr o u p a n d o v er all a n d li st e d
f or all r a n d o mi z e d p ati e nt s.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 6 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 6 of 5 6
P h y si c al E x a mi n ati o n
A b n or m al  p h y si c al  e x a mi n ati o n  r e s ult s  will  b e  s u m m ari z e d  b y  pr e s e nti n g  n u m b er  a n d  p er c e nt a g e  of  
p ati e nt s  f or  e a c h  b o d y  s y st e m  b y  tr e at m e nt  gr o u p  a n d  o v er all  f or  all  s c h e d ul e d  vi sit s.  All  p h y si c al  
e x a mi n ati o n d at a will b e li st e d f or t h e r a n d o mi z e d p ati e nt s.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 7 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 7 of 5 6
H e alt h E c o n o mi c s
N ot a p pli c a bl e.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 8 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 8 of 5 6
I nt eri m A n al y s e s or I D M C s
T h er e will b e n o i nt eri m a n al y si s i n t h e st u d y.
A n i n d e p e n d e nt D M C will b e e st a bli s h e d b y t h e s p o n s or or d e si g n e e t o r e vi e w a c c u m ul ati n g st u d y d at a at 
r e g ul ar i nt er v al s ( a s p er t h e D M C c h art er) t hr o u g h o ut t he st u d y t o e n s ur e t h e s af et y of p ati e nt s a n d r e vi e w 
o v er all st u d y c o n d u ct. A d diti o n al d at a m a y b e r e vi e w e d t h at ar e r el at e d t o effi c a c y, b ut t h e D M C will o nl y 
b e r e vi e wi n g d at a f or ri s k- b e n efit p ur p o s e s. M e m b er s will i n cl u d e e x p ert s i n dr u g s af et y a n d/ or m e di c al 
s p e ci ali st  a n d  bi o st ati sti c s,  w h o  ar e  n ot  p arti ci p ati n g  i n  t hi s  st u d y a n d  d o  n ot  h a v e  affili ati o n  wit h  t h e  
i n v e sti g at or s or t h e s p o n s or. T h e D M C c a n r e c o m m e nd i n writi n g t o t h e s p o n s or w h et h er t o c o nti n u e, 
m o dif y, or st o p t h e cli ni c al st u d y o n t h e b a si s of s af et y c o n si d er ati o n s. T h e pr e- s p e cifi e d st u d y st o p pi n g 
r ul e s f or t h e tri al ar e d efi n e d a s f oll o w s: 
d e at h ( n ot i n cl u di n g di s e a s e pr o gr e s si o n) i n a n y p ati e nt i n w h o m t h e c a u s e of d e at h i s j u d g e d t o 
b e r el at e d t o t h e st u d y dr u g b y i n v e sti g at or
t h e o c c urr e n c e i n a n y p ati e nt of a S A E w h o s e c a u s al r el ati o n s hi p (i e, wit h o ut a pl a u si bl e alt er n ati v e 
e x pl a n ati o n) t o t h e st u d y dr u g i s j u d g e d t o b e r el at e d b y i n v e sti g at or
t w o o c c urr e n c e s of a cli ni c all y si g nifi c a nt Gr a d e 3 or hi g h er l a b or at or y a b n or m alit y a s s e s s e d t o b e 
r el at e d t o t h e st u d y dr u g b y i n v e sti g at or.
T h e D M C’ s s p e cifi c d uti e s will b e f ull y d e s cri b e d i n a D M C c h art er. T h e li st of t h e o ut p ut s t h at  will b e 
pr o d u c e d f or t h e D M C will b e att a c h e d  t o t h e c h art er. A n u n bli n d e d t e a m fr o m S y n e o s H e alt h Bi o st ati sti c s 
will p erf or m t h e a n al y s e s a s d e s cri b e d i n S e cti o n 4. 4 of t hi s S A P t o m ai nt ai n t h e bli n di n g of t h e st u d y.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 4 9 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 4 9 of 5 6
C h a n g e s fr o m A n al y si s Pl a n n e d i n Pr ot o c ol
N ot a p pli c a bl e
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 0 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 5 0 of 5 6
R ef er e n c e Li st
1.  
C h u a n g- St ei n  C.  S u m m ari zi n g  l a b or at or y  d at a  wit h  diff er e nt  r ef er e n c e  r a n g e s  i n  m ulti- c e nt er  
cli ni c al tri al s. Dr u g I nf or m ati o n J o ur n al 1 9 9 2; 2 6( 1): 7 7- 8 4.
2.  
C h u a n g- St ei n C. S o m e i s s u e s c o n c er ni n g t h e n or m ali z ati o n of l a b or at or y d at a b a s e d o n r ef er e n c e 
r a n g e s. Dr u g I nf or m ati o n J o ur n al 2 0 0 1; 3 5( 1): 1 5 3- 1 5 6. 
3. I C H E 9 ( R 1) a d d e n d u m o n e sti m a n d s a n d s e n siti vit y a n al y si s i n cli ni c al tri al s t o t h e g ui d eli n e o n 
st ati sti c al pri n ci pl e s f or cli ni c al tri al s. St e p 5;  D at e f or c o mi n g i nt o eff e ct: 3 0 J ul 2 0 2 0; E M A.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 1 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 5 1 of 5 6
Pr o gr a m mi n g C o n si d er ati o n s
G e n er al C o n si d er ati o n s
A s e p ar at e S A S pr o gr a m will b e cr e at e d f or e a c h o ut p ut
E a c h o ut p ut will b e st or e d i n a s e p ar at e fil e
O ut p ut fil e s will b e d eli v er e d i n W or d f or m at or p ort a bl e d o c u m e nt f or m at p df
N u m b eri n g of T F L s will f oll o w I C H E 3 g ui d a n c e 
T a bl e, Fi g ur e, a n d Li sti n g F or m at
G e n er al
All T F L s will b e pr o d u c e d i n l a n d s c a p e f or m at o n A 4 p a p er si z e, u nl e s s ot h er wi s e s p e cifi e d.
All T F L s will b e pr o d u c e d u si n g t h e C o uri er N e w f o nt, si z e 8 w hi c h i s t h e s m all e st a c c e pt a bl e p oi nt 
si z e f or t h e R e g ul at or y A ut h oriti e s
T h e d at a di s pl a y s f or T F L s will h a v e a mi ni m u m bl a n k 1-i n c h m ar gi n o n all 4 si d e s
H e a d er s a n d f o ot er s f or fi g ur e s will b e i n C o uri er N e w f o nt, si z e 8  w hi c h i s t h e s m all e st a c c e pt a bl e 
p oi nt si z e f or t h e R e g ul at or y A ut h oriti e s
L e g e n d s will b e u s e d f or all fi g ur e s wit h m or e  t h a n o n e v ari a bl e, gr o u p, or it e m di s pl a y e d
T F L s will b e i n bl a c k a n d w hit e ( n o c ol or), u nl e s s ot h er wi s e s p e cifi e d
S p e ci ali z e d t e xt st yl e s, s u c h a s b ol di n g, it ali c s, b or d er s, s h a di n g, a n d s u p er s cri pt e d a n d 
s u b s cri pt e d t e xt, will n ot b e u s e d  i n t h e T F L s, u nl e s s ot h er wi s e s p e cifi e d. O n s o m e o c c a si o n s, 
s u p er s cri pt s 1, 2, or 3 m a y b e u s e d ( s e e b el o w)
O nl y st a n d ar d k e y b o ar d c h ar a ct er s will b e u s e d  i n t h e T F L s. S p e ci al c h ar a ct er s, s u c h a s n o n-
pri nt a bl e c o ntr ol c h ar a ct er s, pri nt er- s p e cifi c, or f o nt- s p e cifi c c h ar a ct er s, will n ot b e u s e d. 
H e x a d e ci m al- d eri v e d c h ar a ct er s wi ll b e u s e d, w h er e p o s si bl e, if t h e y ar e a p pr o pri at e t o h el p 
di s pl a y m at h s y m b ol s ( e g, μ ). C ert ai n s u b s cri pt s a n d s u p er s cri pt s ( e g, c m 2 , Cm a x ) will b e e m pl o y e d 
o n a c a s e- b y- c a s e b a si s
Mi x e d c a s e will b e u s e d f or all titl e s, f o ot n ot e s,  c ol u m n h e a d er s, a n d pr o gr a m m er- s u p pli e d f or m at s, 
a s a p pr o pri at e
H e a d er s
All o ut p ut will h a v e t h e f oll o wi n g h e a d er at t h e t o p l eft of e a c h p a g e: 
o
M etri o P h ar m A G, Pr ot o c ol M P 1 0 3 2- C T 0 5 ( S y n e o s H e alt h st u d y n u m b er < x x x > )
o
Dr aft/ Fi n al R u n < d at e >
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 2 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 5 2 of 5 6
All o ut p ut will h a v e P a g e n of N at t h e t o p or b o tt o m ri g ht c or n er of e a c h p a g e. T F L s ar e i nt er n all y 
p a gi n at e d i n r el ati o n t o t h e t ot al l e n gt h (i e, t h e p a g e n u m b er will a p p e ar s e q u e nti all y a s p a g e n of 
N, w h er e N i s t h e t ot al n u m b er of p a g e s i n t h e t a bl e)
T h e d at e t h e o ut p ut w a s g e n er at e d will a p p e ar al o n g wit h t h e pr o gr a m n a m e a s a f o ot er o n e a c h 
p a g e
Di s pl a y Titl e s
E a c h T F L  will b e i d e ntifi e d b y t h e d e si g n ati o n a n d a n u m er al. (i e, T a bl e 1 4. 1. 1). A d e ci m al s y st e m 
( x. y a n d x. y. z) ar e u s e d t o i d e ntif y T F L s wit h r el at e d c o nt e nt s. T h e titl e will b e c e nt er e d. T h e 
a n al y si s s et will b e i d e ntifi e d o n t h e li n e i m m e di at el y f oll o wi n g t h e titl e a n d will b e e n cl o s e d i n 
p ar e nt h e si s. T h e titl e a n d t a bl e d e si g n ati o n will b e  si n gl e s p a c e d. A s oli d li n e s p a n ni n g t h e m ar gi n s 
will s e p ar at e t h e di s pl a y titl e s fr o m t h e c ol u m n h e a d er s. T h er e will b e o n e bl a n k li n e b et w e e n t h e 
l a st titl e a n d t h e s oli d li n e.
•
T a bl e x. y. z
•
Fir st Li n e of Titl e
•
S e c o n d Li n e of Titl e if N e e d e d
•
( F ull A n al y si s S et)
C ol u m n H e a d er s
C ol u m n h e a di n g s  will b e di s pl a y e d i m m e di at el y b el o w t h e s oli d li n e d e s cri b e d a b o v e i n i niti al 
u p p er- c a s e c h ar a ct er s .
I n t h e c a s e of effi c a c y t a bl e s, t h e v ari a bl e ( or c h ara ct eri sti c) c ol u m n i s o n t h e f ar l eft f oll o w e d b y t h e 
tr e at m e nt gr o u p c ol u m n s a n d t ot al c ol u m n (if a p pli c a bl e). P- v al u e s m a y b e pr e s e nt e d u n d er t h e 
t ot al c ol u m n or i n s e p ar at e p- v al u e c ol u m n (if a ppli c a bl e). Wit hi n-tr e at m e nt c o m p ari s o n s m a y h a v e 
p- v al u e s pr e s e nt e d i n a r o w b e n e at h t h e s u m m ar y st ati sti c s f or t h at tr e at m e nt
F or n u m eri c v ari a bl e s, i n cl u d e ‘u nit ’ i n c ol u m n or r o w h e a di n g w h e n a p pr o pri at e
A n al y si s s et si z e s will b e pr e s e nt e d f or e a c h tr e at m e nt gr o u p i n t h e c ol u m n h e a di n g a s ( N = x x) or i n 
t h e r o w h e a di n g s, if a p pli c a bl e. T hi s i s di sti n ct fr o m t h e ‘ n’ u s e d f or t h e d e s cri pti v e st ati sti c s 
r e pr e s e nti n g t h e n u m b er of p ati e nt s i n t h e a n al y si s s et.
T h e or d er of tr e at m e nt s i n t h e t a bl e s a n d li sti n g s will b e Pl a c e b o fir st i n t h e c a s e of pl a c e b o 
c o ntr oll e d st u di e s a n d A cti v e c o m p ar at or s fir st i n t h e c a s e of a cti v e c o m p ar at or tri al s, f oll o w e d b y a 
t ot al c ol u m n (if a p pli c a bl e)
B o d y of t h e D at a Di s pl a y
1 8. 2. 5. 1.
G e n er al C o n v e nti o n s
D at a i n c ol u m n s of a t a bl e or li sti n g ar e f or m att e d a s f oll o w s:
Al p h a n u m eri c v al u e s will b e l eft-j u stifi e d;
W h ol e n u m b er s ( e g, c o u nt s) will b e ri g ht-j u stifi e d; a n d
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 3 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 5 3  of 5 6  
  N u m b er s c o nt ai ni n g fr a cti o n al p orti o n s will b e d e ci m al ali g n e d. 
1 8. 2. 5. 2. 
T a bl e C o n v e nti o n s 
  U nit s will b e i n cl u d e d w h er e a v ail a bl e 
  F or c at e g ori c al p ar a m et er s, all c at e g ori e s will b e pr e s e nt e d i n t h e t a bl e, e v e n if n = 0 f or all 
tr e at m e nt gr o u p s i n a gi v e n c at e g or y. F or e x a m pl e, t h e fr e q u e n c y distri b uti o n f or s y m pt o m s e v erit y 
w o ul d a p p e ar a s: 
S e v erit y 
R ati n g  
N 
s e v er e 
0 
m o d er at e 
8 
mil d 
3 
 
  
W h er e p er c e nt a g e s ar e pr e s e nt e d i n t h e s e t a bl e s, z er o p er c e nt a g e s will n o t b e pr e s e nt e d a n d s o 
c o u nt s of 0 will b e pr e s e nt e d a s 0 a n d n ot a s 0 ( 0 %). 
  A n U n k n o w n or Mi s si n g c at e g or y will b e a d d e d t o e a c h p ar a m et er f or w hi c h i nf or m ati o n i s n ot 
a v ail a bl e f or 1 or m or e p ati e nt s 
  U nl e s s ot h er wi s e s p e cifi e d, t h e e sti m at e d m e a n a n d m e di a n f or a s et of v al u e s will b e pri nt e d o ut 
t o 1 m or e si g nifi c a nt di git t h a n t h e ori gi n al v al u e s, a n d st a n d ar d d e vi ati o n s will b e pri nt e d o ut t o 2 
m or e si g nifi c a nt di git s t h a n t h e ori gi n al v al u e s. T h e mi ni m u m a n d m a xi m u m will r e p ort t h e s a m e 
si g nifi c a nt di git s a s t h e ori gi n al v al u e s. F or e x a m pl e, s y st oli c bl o o d pr e s s ur e will b e pr e s e nt e d a s 
f oll o w s: 
• N
 
• 
 
X X
 
• M e a n
 
• X X X. X
 
• St d
 D e v
 
•  
   X. X X 
• M e di a n
 
• X X X. X
 
• Mi ni m u m
 
• X X X
 
• M a xi m u m
 
• X X X
 
 
  P- v al u e s will b e o ut p ut i n t h e f or m at: ‘0. x x x ’, w h er e x x x i s t h e v al u e r o u n d e d t o 3 d e ci m al pl a c e s. 
E v er y p- v al u e l e s s t h a n 0. 0 0 1 will b e pr e s e nt e d a s < 0. 0 0 1. If t h e p- v al u e ar e l e s s t h a n 0. 0 0 0 1, t h e n 
pr e s e nt a s < 0. 0 0 0 1. P- v al u e s a b o v e  0. 9 9 9 will b e pr e s e nt e d a s > 0. 9 9 9 
  P er c e nt a g e v al u e s will b e pri nt e d t o o n e d e ci m al pl a c e, i n p ar e nt h e s e s wit h n o s p a c e s, o n e s p a c e 
aft er t h e c o u nt ( e g, 7 ( 1 2. 8 %), 1 3 ( 5. 4 %)). U nl e s s ot h er wi s e n ot e d, f or all p er c e nt a g e s, t h e n u m b er 
of p ati e nt s i n t h e a n al y si s s et f or t h e tr e at m e nt gr o u p w h o h a v e a n o b s er v ati o n will b e t h e 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 4 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s  
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5 
 
 
T hi s d o c u m e nt i s c o nfi d e nti al. 
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2 
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0 
Fili n g r e q uir e m e nt s: T M F 
P a g e 5 4  of 5 6  
d e n o mi n at or. P er c e nt a g e s aft er z e r o c o u nt s will n ot b e di s pl a y ed a n d p er c e nt a g e s e q u ati n g t o 
1 0 0 % will b e pr e s e nt e d a s 1 0 0 %, wit h o ut d e ci m al pl a c e s  
  T a b ul ar di s pl a y of d at a f or m e di c al hi st or y, pri or/ c o n c o mit a nt m e di c ati o n s, a n d all t a b ul ar di s pl a y s 
of a d v er s e e v e nt d at a will b e pr e s e nt e d b y t h e b o d y s y st e m, tr e at m e nt cl a s s, or S O C wit h t h e 
hi g h e st o c c urr e n c e i n t h e a cti v e tr e at m e nt gr o u p i n d e cr e a si n g or d er, a s s u mi n g all t er m s ar e 
c o d e d. Wit hi n t h e b o d y s y st e m, dr u g cl a s s a n d S O C, m e di c al hi st or y ( b y pr ef err e d t er m), dr u g s ( b y 
A T C 1 c o d e), a n d a d v er s e e v e nt s ( b y pr ef err e d t er m) will b e di s pl a y e d i n d e cr e a si n g or d er. If 
i n ci d e n c e f or m or e t h a n 1 t er m i s i d e nti c al, t h e y will t h e n b e s ort e d al p h a b eti c all y. Mi s si n g 
d e s cri pti v e st ati sti c s or p- v al u e s t h at c a n n ot b e e sti m at e d will b e r e p ort e d a s ‘-’ 
  T h e p er c e nt a g e of p ati e nt s will n or m all y b e c al cul at e d a s a pr o p orti o n of t h e n u m b er of p ati e nt s 
a s s e s s e d i n t h e r el e v a nt tr e at m e nt gr o u p ( or o v er all) f or t h e a n al y si s s et pr e s e nt e d. H o w e v er, 
c ar ef ul c o n si d er ati o n i s r e q uir e d i n m a n y i n st a n c e s d u e t o t h e c o m pli c at e d n at ur e of s el e cti n g t h e 
d e n o mi n at or, u s u all y t h e a p pr o pri at e n u m b er of p a ti e nt s e x p o s e d. D et ail s will b e d e s cri b e d i n 
f o ot n ot e s or pr o gr a m mi n g n ot e s, a s n e c e s s ar y 
  F or c at e g ori c al s u m m ari e s ( n u m b er a n d p er c e nt a g e of p ati e nt s) w h er e a p ati e nt c a n b e i n cl u d e d i n 
m or e t h a n o n e c at e g or y, a f o ot n ot e or pr o gr a m m i n g n ot e will b e a d d e d d e s cri bi n g w h et h er t h e 
p ati e nt i s i n cl u d e d i n t h e s u m m ar y st ati sti c s f or all r e l e v a nt c at e g ori e s or j u st 1 c at e g or y a s w ell a s 
t h e s el e cti o n crit eri a 
  W h er e a c at e g or y wit h a s u b h e a di n g ( s u c h a s s y ste m or g a n cl a s s) h a s t o b e s plit o v er m or e t h a n 
o n e p a g e, o ut p ut t h e s u b h e a di n g f oll o w e d b y ‘( c o nt)’ at t h e t o p of e a c h s u b s e q u e nt p a g e. T h e 
o v er all s u m m ar y st ati sti c s f or t h e s u b h e a di n g s h o ul d  o nl y b e o ut p ut o n t h e fir st r el e v a nt p a g e 
1 8. 2. 5. 3. 
Li sti n g C o n v e nti o n s 
  Li sti n g s will b e s ort e d f or pr e s e nt ati o n i n ord er of tr e at m e nt gr o u p s a s a b o v e, p ati e nt n u m b er, 
vi sit/ c oll e cti o n d a y, a n d vi sit/ c oll e cti o n ti m e 
  Mi s si n g d at a will b e r e pr e s e nt e d o n p ati e nt li sti n g s a s eit h er a h y p h e n (‘-’) wit h a c orr e s p o n di n g 
f o ot n ot e (‘- = u n k n o w n or n ot e v al u at e d’), or a s ‘N/ A ’, wit h t h e f o ot n ot e ‘N/ A = n ot a p pli c a bl e ’, 
w hi c h e v er i s a p pr o pri at e 
  D at e s will b e pri nt e d i n S A S D A T E 9.f or m at (‘D D _ M M M _ Y Y Y Y ’: 0 1 J U L 2 0 0 0). Mi s si n g p orti o n s of 
d at e s will b e r e pr e s e nt e d o n p ati e nt li sti n g s a s d a s h e s (-- J U L 2 0 0 0). D at e s t h at ar e mi s si n g 
b e c a u s e t h e y ar e n ot a p pli c a bl e f or t h e p ati e nt will b e o ut p ut a s ‘N/ A ’, u nl e s s ot h er wi s e s p e cifi e d 
  All o b s er v e d ti m e v al u e s will b e pr e s e nt e d u si ng a 2 4- h o ur cl o c k H H: M M or H H: M M: S S f or m at ( e g, 
1 1: 2 6: 4 5, or 1 1: 2 6). Ti m e will o nl y b e r e p ort e d if it w a s m e a s ur e d a s p art of t h e st u d y 
  U nit s will b e i n cl u d e d w h er e a v ail a bl e 
1 8. 2. 5. 4. 
Fi g ur e C o n v e nti o n s 
  U nl e s s ot h er wi s e s p e cifi e d, f or all fi g ur e s, st u d y vi sit s will b e di s pl a y e d o n t h e X- a xi s a n d e n d p oi nt 
( e g, tr e at m e nt m e a n c h a n g e fr o m b a s eli n e) v al u e s will b e di s pl a y e d o n t h e Y- a xi s 
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 5 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 5 5 of 5 6
F o ot n ot e s
A s oli d li n e s p a n ni n g t h e m ar gi n s will s e p ar at e t h e b o d y of t h e d at a di s pl a y fr o m t h e f o ot n ot e s. 
All f o ot n ot e s will b e l eft j u stifi e d wit h si n g l e-li n e s p a ci n g i m m e di at el y b el o w t h e s oli d li n e 
u n d er n e at h t h e d at a di s pl a y
F o ot n ot e s will al w a y s b e gi n wit h ‘N ot e: ’ if a n i nf or m ati o n al f o ot n ot e, or 1, 2, 3, et c. if a r ef er e n c e 
f o ot n ot e. E a c h n e w f o ot n ot e will st art o n a n e w li n e,  w h er e p o s si bl e
P ati e nt s p e cifi c f o ot n ot e s ar e a v oi d e d, w h er e p o s si bl e
F o ot n ot e s will b e u s e d s p ari n gl y a n d a d d v al u e t o t h e T F L. If m or e t h a n si x li n e s of f o ot n ot e s ar e 
pl a n n e d, t h e n a c o v er p a g e i s str o n gl y r e c o m m e n d e d t o b e u s e d t o di s pl a y f o ot n ot e s, a n d o nl y 
t h o s e e s s e nti al t o c o m pr e h e n si o n of t h e d at a will b e r e p e at e d o n e a c h p a g e
T h e l a st li n e of t h e f o ot n ot e s e cti o n will b e a st a n d ar d s o ur c e li n e t h at i n di c at e s t h e n a m e of t h e 
pr o gr a m u s e d t o pr o d u c e t h e d at a di s pl a y, t h e d at e  t h e pr o gr a m w a s r u n, a n d t h e li sti n g s o ur c e (i e, 
‘ Pr o gr a m: m y pr o gr a m.s a s Li sti n g s o ur c e: 1 6. x. y. z’)
S o ur c e s a n d / or cr o s s-r ef er e n c e s i n f o ot n ot e s will u s e t h e k e y w or d pr efi x (i n si n g ul ar f or m) f or 
e a c h r ef er e n c e a n d will b e s e p ar at e d b y a c o m m a w h e n m ulti pl e cr o s s-r ef er e n c e s ar e di s pl a y e d
E x a m pl e
Li sti n g s o ur c e: Li sti n g 1 6. 2. 4. 1. 1, Li sti n g 1 6. 2. 4. 1. 2, Li sti n g 1 6. 2. 4. 2. 1
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 6 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


St ati sti c al A n al y si s Pl a n f or I nt er v e nti o n al St u di e s
S p o n s or: M etri o P h ar m A G; Pr ot o c ol N o.: M P 1 0 3 2- C T 0 5
T hi s d o c u m e nt i s c o nfi d e nti al.
S A P T e xt V er si o n: 2. 0, 3 1- A u g- 2 0 2 2
C o ntr oll e d D o c u m e nt I D: 
, Eff e cti v e D at e 3 1- A u g- 2 0 2 0
Fili n g r e q uir e m e nt s: T M F
P a g e 5 6 of 5 6
Q u alit y C o ntr ol
S A S pr o gr a m s ar e d e v el o p e d t o pr o d u c e o ut p ut s u c h a s  a n al y si s d at a s et s, s u m m ar y t a bl e s, d at a li sti n g s, 
fi g ur e s or st ati sti c al a n al y s e s. A n o v er vi e w of t h e d e v el o p m e nt of pr o gr a m s i s d et ail e d i n S y n e o s H e alt h 
D e v el o pi n g St ati sti c al Pr o gr a m s S O P ( 3 9 0 7).
S y n e o s  H e alt h  D e v el o pi n g  St ati sti c al  Pr o gr a m s  S O P  ( 3 9 0 7),  C o n d u cti n g  t h e  Tr a n sf er  of  Bi o st ati sti c al  
D eli v er a bl e s S O P ( 3 9 0 8) a n d t h e S A S Pr o gr a m mi n g a n d V ali d ati o n Pl a n d e s cri b e s t h e q u alit y c o ntr ol 
pr o c e d ur e s t h at ar e p erf or m e d f or all S A S pr o gr a m s a n d o ut p ut. Q u alit y c o ntr ol i s d efi n e d h er e a s t h e 
o p er ati o n al t e c h ni q u e s a n d a cti viti e s  u n d ert a k e n t o v erif y t h at t h e S AS pr o gr a m s pr o d u c e t h e o ut p ut b y 
c h e c ki n g f or t h eir l o gi c, effi ci e n c y a n d c o m m e n ti n g a n d b y r e vi e w of t h e pr o d u c e d o ut p ut.
Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 7 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C CI


Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 8 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
P P D


Metri o P har m A G 
M P 1 0 3 2
M P 1 0 3 2- C T 0 5 
Fi nal
0 7- Fe b- 2 0 2 3
T his d oc u me nt is c o nfi de ntial.
Pa ge 5 9 of 5 9
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
P P D