MP1032 Treatment in Patients With Moderate to Severe COVID-19

Study Overview
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Brief Summary
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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).

Official Title
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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 Participants With Moderate to Severe COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Drug: MP1032
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participant is admitted to hospital and has a positive severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) test by standard reverse transcription-polymerase chain reaction (RT-PCR) assay or equivalent test Participant has the presence of any symptom(s) suggestive of moderate or severe systemic illness with COVID-19 Key Exclusion Criteria: Participant, in opinion of the investigator, is not likely to survive >=48 hours beyond Day 1 Participant has a diagnosis of asymptomatic COVID-19, mild COVID-19, or critical COVID-19 on Day 1 Participant has a documented medical history of infection with hepatitis A, B, C, or with human immunodeficiency virus (with a detectable viral load and CD4 count <500 cells per micro liter), or a documented active infection with tuberculosis. The Participant has clinically significant electrocardiogram (ECG) abnormalities at screening Other protocol defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MP1032<br>Participants will receive MP1032 300 milligrams (mg) twice daily (BID) with hospital selected SoC for 28 days. | Drug: MP1032<br>* Hard gelatin capsules for oral administration.<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo matched to MP1032 with hospital selected SoC for 28 days. | Drug: Placebo<br>* Placebo capsules matched to MP1032 for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Progression Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale at Day 14 | Disease progression was defined as the percentage of participants who were not alive or who had respiratory failure. Respiratory failure was defined as participants who had a score of 2, 3 or 4 on the NIAID 8-point ordinal scale: The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation 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 - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. | At Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Disease Progression Using NIAID 8-point Ordinal Scale at Day 28 | Disease progression was defined as the percentage of participants who were not alive or who had respiratory failure. Respiratory failure was defined as participants who had a score of 2, 3 or 4 on the NIAID 8-point ordinal scale: The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. | At Day 28 | 
| Percentage of Participants With Disease Resolution at Day 28 | Disease resolution was defined as participants who were alive and had a score of 6, 7, or 8 on the NIAID 8-point ordinal scale. The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. | At Day 28 | 
| All-cause Mortality Rate up to Day 28 | All-cause mortality rate was the percentage of participants in each treatment group who died by Day 28 were reported. | Up to Day 28 | 
| Change From Baseline in Clinical Status Score Related to COVID-19 According to the NIAID 8-point Ordinal Scale at Day 28 | The NIAID 8-point Ordinal Scale is an assessment of the clinical status on a given study day and the scale was defined as follows: 1=Death, 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. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. | Baseline, Day 28 | 
| Percentage of Participants With Disease Resolution at Day 14 | Disease resolution was defined as participants who were alive and had a score of 6, 7, or 8 on the NIAID 8-point ordinal scale. The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. | At Day 14 | 
| All-cause Mortality Rate up to Day 14 and Day 60 | The percentage of participants who died by Day 14 and Day 60 were reported. | Up to Day 14 and Day 60 | 
| Change From Baseline in Clinical Status Score Related to COVID-19 According to the NIAID 8-point Ordinal Scale at Day 14 | The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. The change from baseline in NIAID clinical status score related to COVID-19 at Day 14 were reported. | Baseline, Day 14 | 
| Percentage of Participants Who Required Invasive Ventilation (Mechanical Ventilator and/ ECMO), or Who Died at Day 14 and Day 28 | Percentage of participants who required invasive mechanical ventilation/ECMO or who died by Day 14 and Day 28 were reported. | At Day 14 and Day 28 | 
| Change From Baseline in Clinical Status Score of the NIAID 8-point Ordinal Scale at Each Visit | The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. The change from baseline in NIAID clinical status score at each visit were reported. | Baseline up to Day 60 | 
| Time to (First) Improvement of at Least 1 Category on the NIAID 8-point Ordinal Scale | The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Participants who did not improve at least 1 category on the NIAID scale or died before Day 28 were censored at Day 28. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. | Baseline up to Day 28 | 
| Percentage of Participants With Clinical Status Improvement of at Least 1 Category From Baseline on the NIAID 8-point Ordinal Scale at Day 14 and Day 28 | NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Higher score = improvement in clinical status. Percentage of Participants with Clinical Status Improvement of at least 1 category from baseline on the NIAID 8-point Ordinal Scale at Day 14 and Day 28 were reported. | Baseline, Day 14 and Day 28 | 
| Time to Discharge by Day 28 and Day 60 | Time to discharge i.e., the total duration of participant hospitalization from baseline to discharge at Day 28 and Day 60 was reported. | Baseline, Day 28 and Day 60 | 
| Percentage of Participants Who Were Alive and Tested Negative for COVID-19 at Day 14, Day 28, and Day 60 | Percentage of participants who were alive and tested negative for COVID-19 at Day 14, Day 28, and Day 60 were reported. | At Day 14, Day 28 and Day 60 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | An Adverse Event (AE) was 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. TEAE was defined as any adverse event which starts or worsens at any time after initiation of study drug until the end of the follow-up period at Day 60. An SAE was any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Number of participants with TEAEs and Serious TEAEs were reported. | Day 1 up to Day 60 | 
| Number of Participants With Clinically Significant Change in Vital Sign | Vital sign parameters included of systolic and diastolic blood pressure, heart rate, respiration rate, oxygen saturation (SpO2), and body temperature. Any clinically significant change in vital signs were judged by the investigator. Number of participants with clinically significant change in vital sign values were reported. | Day 1 up to Day 60 | 
| Number of Participants With Clinically Significant Abnormalities in Physical Examinations | Physical examination included examination of respiratory, cardiovascular, dermatological, neurological, and gastrointestinal system. Any clinically significant abnormalities in physical examination were judged by the investigator. Number of participants with clinically significant abnormalities in physical examinations findings were reported. | Baseline up to Day 60 | 
| Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Results | Clinical laboratory tests included biochemistry, hematology and urinalysis. Any clinically significant abnormalities in clinical laboratory results were judged by the investigator. Number of participants with clinically significant abnormalities in laboratory results were reported. | Baseline up to Day 60 | 
| Maximum Observed Plasma Concentration (Cmax) of MP1032 | Cmax of MP1032 in plasma were reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 and Day 7 | 
| Area Under the Plasma Concentration-time Curve From Time Zero to Last Non-zero Concentration (AUC0-t) of MP1032 | AUC0-t of MP1032 in plasma were reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported. | Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 and Day 7 | 
| Apparent Elimination Rate Constant (Kel) of MP1032 | Kel was calculated using negative of the estimated slope of the linear regression of the ln-transformed plasma concentration versus time profile in the terminal elimination phase. Kel of MP1032 in plasma were reported. | Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 | 
| Apparent Body Clearance (CL/F) of MP1032 | Cl/F was estimated as Dose/AUC0-inf. CL/F of MP1032 in plasma was reported. | Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 | 
| Apparent Volume of Distribution (Vz/F) of MP1032 | Vz/F was estimated as Dose/(Kel x AUC0-inf). Vz/F of MP1032 in plasma was reported. | Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 | 
| Plasma Concentration Prior to the Next Dose (Ctrough) of MP1032 | Ctrough of MP1032 in plasma was reported. | Pre-dose concentration (Day 2, Day 7, and Day 8). | 
| Average Observed Plasma Concentration at Steady State of MP1032 | Average observed plasma concentration at steady state of MP1032 was reported. | Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 and Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, MP1032