Clinical trial NCT04532931
Conditions: COVID-19
Keywords: COVID-19 Pyramax Pyronaridine Artesunate Chloroquine Zinc Amodiaquine Favipiravir Nitazoxanide Sofosbuvir Daclatasvir
Sponsor: Shin Poong Pharmaceutical Co. Ltd.
Start date: 2020-09-03; Completion date: 2021-08-23
Enrollment: 192 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This exploratory study is a randomized, single center, open label study of four different experimental treatment arms versus standard of care for the treatment of SARS-CoV-2 infection in symptomatic outpatients with mild disease at the time of enrollment.

Detailed description:
This phase 2, exploratory study will be an adaptive, randomized, open label, trial for treatment of individuals in an outpatient settings with mild SARS-CoV-2 infection. The primary outcome is focused on the evaluation of efficacy of the proposed experimental drugs in reducing upper respiratory viral shedding, defined as viral clearance (i.e., negative swab) on Day 7. Key secondary outcomes focus on other measures of viral shedding, safety evaluation, progression to LRTI (defined by resting blood oxygen saturation level \[SpO2\] \<93% sustained for two readings two hours apart and presence of subjective dyspnoea or cough), disease severity, clinical resolution rate, and cumulative incidence of hospitalization or mortality at Day 28.

Arms: arm 1: 500 mg oral tablets. Two tablets taken at 6-hour intervals as needed, in all treatment arms (in addition to any investigative treatment) arm 2: Fixed dose combination tablets containing 100 mg artesunate and 270 mg amodiaquine. Participants received two tablets once daily for 3 days arm 3: Fixed dose combination tablets containing 180 mg pyronaridine and 60 mg artesunate, given once daily for 3 days. Participants weighing 45 to \<65 kg received 3 tablets per dose, those ≥65 kg received 4 tablets per dose arm 4: Free combination of favipiravir 200 mg and 400 mg tablets and nitazoxanide 500 mg tablets. Participants received favipiravir as a loading dose of 1600 mg twice daily for 1 day followed by 600 mg twice daily for 6 days, and nitazoxanide 1000 mg twice daily, with food, for 7 days arm 5: Fixed dose combination tablets containing 400 mg sofosbuvir and 60 mg daclatasvir. Participants received 1 tablet once daily for 7 days
Interventions: intervention 1: Paracetamol intervention 2: Artesunate-amodiaquine intervention 3: Pyronaridine-artesunate intervention 4: Favipiravir plus Nitazoxanide intervention 5: Sofosbuvir/daclatasvir
Intervention descriptions: intervention 1: SOC - 2 tablets (1000 mg) to be taken 6-hourly as needed intervention 2: SOC plus artesunate-amodiaquine (ASAQ) - 2 tablets (200/540 mg artesunate/amodiaquine) daily for 3 days intervention 3: SOC plus pyronaridine-artesunate (PA) Weight 45 to \<65 kg: 3 tablets (540/180 mg pyronaridine/artesunate) daily for 3 days Weight ≥65 kg: 4 tablets (720/240 mg pyronaridine/artesunate) daily for 3 days intervention 4: SOC plus favipiravir plus nitazoxanide (FPV-NTZ) Favipiravir: 1600 mg 12-hourly for 1 day then 600 mg 12-hourly for 6 days Nitazoxanide: 2 tablets (1000 mg) 12-hourly for 7 days intervention 5: SOC plus sofosbuvir/daclatasvir (SOF/DCV)

1 tablet (400 mg/60 mg sofosbuvir/daclatasvir) daily for 7 days

Protocol documents:
Prot_000.pdf: 
  
 
 
 
 
 
 
SP-PA-COV-202 
 
 
A phase 2, exploratory, single center, randomized, open label, adaptive clinical trial to 
compare the safety and efficacy of four different experimental drug regimens to standard 
of care for the treatment of symptomatic outpatients with COVID-19 
 
 
Short Title: 
COVID-19 Treatment South Africa 
Phase: 
2 
Protocol Version and Approval Date: 
Version 4, 17 Nov 2020 
Sponsor: 
Shin Poong Pharm. Co., Ltd. 
161 Yoksam-ro, Gangnam-gu 
Seoul, 06246 
Republic of Korea 
Funder: 
Medicines for Malaria Venture 
ICC – Block G, 3rd Floor 
20, Route de Pré-Bois 
PO Box 1826 
1215 Geneva 15 
Switzerland 
Principal Investigator: 
Professor Francois Venter PhD, FCP, DTM&H, Dip HIV 
Divisional Director: Ezintsha, Wits Reproductive Health 
& HIV Institute 
University of the Witwatersrand 
5th Floor, Building D 
Sunnyside Office Park 
32 Princess of Wales Terrace 
Parktown, Johannesburg 
 
 
 
CONFIDENTIAL 
Property of Shin Poong Pharm. Co., Ltd. 
May not be used, divulged, published, or otherwise disclosed without consent 




20 Nov 2020
Stephan Duparc
20 Nov 2020


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TABLE OF CONTENTS 
INVESTIGATOR SIGNATURE PAGE ............................................................................................................... 2 
SPONSOR / FUNDER SIGNATORY APPROVAL PAGE ..................................................................................... 3 
ABBREVIATIONS AND TERMS ..................................................................................................................... 6 
SYNOPSIS 
 ....................................................................................................................................... 8 
1. 
SCHEDULE OF ACTIVITIES ................................................................................................................... 15 
2. 
INTRODUCTION ................................................................................................................................. 18 
2.1 
Background ........................................................................................................................................... 19 
2.2 
Study Rationale ..................................................................................................................................... 19 
2.2.1 
COVID-19 and antiviral approaches ............................................................................................. 19 
2.2.2 
Drug selection .............................................................................................................................. 20 
2.2.3 
Dose selection ............................................................................................................................. 22 
2.2.4 
Study design ................................................................................................................................ 23 
2.2.5 
Pharmacokinetic-pharmacodynamic assessments ...................................................................... 23 
2.3 
Benefit/Risk Assessment ....................................................................................................................... 23 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................................................. 24 
4. 
STUDY DESIGN ................................................................................................................................... 25 
4.1 
Overall Design ....................................................................................................................................... 25 
4.2 
Participant and Study Completion ........................................................................................................ 26 
5. 
STUDY POPULATION .......................................................................................................................... 26 
5.1 
Inclusion Criteria ................................................................................................................................... 27 
5.2 
Exclusion Criteria ................................................................................................................................... 27 
5.3 
Co-enrollment Guidelines ..................................................................................................................... 28 
6. 
TREATMENTS ..................................................................................................................................... 28 
6.1 
Treatments Administered ..................................................................................................................... 28 
6.2 
Risks to the Participants ........................................................................................................................ 29 
6.2.1 
Management of participants to limit risks of SARS-CoV-2 transmission ..................................... 30 
6.3 
Dose Modification and Toxicity Management ...................................................................................... 31 
6.4 
Method of Treatment Assignment ........................................................................................................ 32 
6.5 
Blinding ................................................................................................................................................. 32 
6.6 
Preparation / Handling / Storage / Accountability ................................................................................ 32 
6.7 
Treatment Compliance .......................................................................................................................... 32 
6.8 
Concomitant Therapy ............................................................................................................................ 32 
6.8.1 
Prohibited medications ............................................................................................................... 32 
6.8.2 
Precautionary medications .......................................................................................................... 33 
6.9 
Treatment After the End of the Study .................................................................................................. 34 
7. 
DISCONTINUATION/WITHDRAWAL CRITERIA ..................................................................................... 34 
7.1 
Discontinuation of Study Treatment ..................................................................................................... 34 
7.2 
Withdrawal from the Study................................................................................................................... 34 
7.3 
Lost to Follow-up ................................................................................................................................... 35 
8. 
STUDY ENCOUNTERS ......................................................................................................................... 35 
8.1 
Screening Evaluation: Day 0 (-1 day window) ....................................................................................... 35 
8.2 
Enrollment/Randomization/Start of Treatment: Day 1 ........................................................................ 36 
8.3 
Treatment Continuation and Follow-Up: Day 2 to Day 14 (±2)............................................................. 37 
8.4 
Late Follow-Up: Day 21 (±2) .................................................................................................................. 39 
8.5 
End-of-Study: Day 28 ............................................................................................................................ 39 
9. 
STUDY ASSESSMENTS AND PROCEDURES ........................................................................................... 40 
9.1 
Efficacy Assessments ............................................................................................................................. 40 
9.1.1 
Mid-nasal swab and saliva specimen .......................................................................................... 40 
9.1.2 
Participant surveys ...................................................................................................................... 41 
9.1.3 
WHO Ordinal Scale for Clinical Improvement ............................................................................. 41 
9.2 
Adverse Events ...................................................................................................................................... 41 
9.2.1 
Definition ..................................................................................................................................... 42 
9.2.2 
Serious adverse events ................................................................................................................ 42 
9.2.3 
Treatment-related AEs and SAEs ................................................................................................. 43 


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9.3 
Treatment of Overdose ......................................................................................................................... 43 
9.4 
Pregnancy .............................................................................................................................................. 43 
9.5 
Other Safety Assessments ..................................................................................................................... 43 
9.6 
Serological and Other Assessments ...................................................................................................... 44 
9.7 
PK Assessments ..................................................................................................................................... 44 
9.8 
Biohazard Containment ........................................................................................................................ 45 
10. DATA MANAGEMENT ........................................................................................................................ 45 
11. STATISTICAL CONSIDERATIONS .......................................................................................................... 45 
11.1 Sample Size Determination ................................................................................................................... 45 
11.2 Populations for Analyses ....................................................................................................................... 46 
11.3 Statistical Analyses ................................................................................................................................ 46 
11.3.1 
Efficacy analyses .......................................................................................................................... 47 
11.3.2 
Secondary endpoints ................................................................................................................... 47 
11.3.3 
Exploratory endpoints ................................................................................................................. 48 
11.3.4 
Combined study analysis ............................................................................................................. 48 
12. STUDY MONITORING ......................................................................................................................... 48 
12.1 Safety Review Team .............................................................................................................................. 48 
12.2 Independent Monitor ........................................................................................................................... 48 
12.3 Data Monitoring Committee ................................................................................................................. 49 
12.4 Scientific Advisory Committee .............................................................................................................. 49 
13. ETHICAL CONSIDERATIONS ................................................................................................................ 49 
13.1 Regulatory and Ethical Considerations ................................................................................................. 49 
13.2 Informed Consent Process .................................................................................................................... 50 
13.3 Study Records........................................................................................................................................ 50 
13.4 Confidentiality ....................................................................................................................................... 50 
13.5 Blood Volume ........................................................................................................................................ 51 
14. REFERENCES ...................................................................................................................................... 52 
APPENDICES 
 ....................................................................................................................................... 56 
APPENDIX 1: 
STUDY GOVERNANCE ...................................................................................................... 56 
APPENDIX 2: 
CONTACT DETAILS ........................................................................................................... 57 
APPENDIX 3:  
THE INFLUENZA PATIENT-REPORTED OUTCOME INSTRUMENT (FLU-PRO© PLUS) .............. 60 
APPENDIX 4: 
DAILY SURVEY ................................................................................................................. 62 
APPENDIX 5: 
WHO ORDINAL SCALE FOR CLINICAL IMPROVEMENT ....................................................... 65 
APPENDIX 6: 
PROHIBITED CONCOMITANT MEDICATIONS ..................................................................... 66 
 
 
 


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ABBREVIATIONS AND TERMS 
Term 
Definition 
ACE2 
Angiotensin-converting enzyme 2 
ACT 
Artemisinin-based combination therapy 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AQ 
Amodiaquine 
ASAQ 
Artesunate-amodiaquine 
AST 
Aspartate aminotransferase 
COVID-19 
Coronavirus disease 
DAIDS 
Division of Acquired Immunodeficiency Syndrome 
DEAQ 
Desethylamodiaquine 
DMC 
Data Monitoring Committee 
EC50 
Half-maximal effective concentration 
eCRFs 
Electronic case report forms 
Eligible 
Qualified for enrollment into the study based upon inclusion/exclusion criteria 
FLU-PRO 
Influenza patient-reported outcome 
FPV-NTZ 
Favipiravir plus nitazoxanide 
GCP 
Good Clinical Practice 
IATA 
International Air Transport Association 
ICF 
Informed consent form 
IMP 
Investigational medicinal product 
IRB 
Institutional Review Board 
IVRS 
Interactive voice response system 
IWRS 
Interactive web response system 
LRTI 
Lower respiratory tract infection 
MERS-CoV 
Middle East respiratory syndrome coronavirus 
Mpro 
Main protease 
NSAID 
Non-steroidal anti-inflammatory drug 
PA 
Pyronaridine-artesunate 
Participant(s) 
Term used throughout the protocol to denote the enrolled individual(s) 
PBPK 
Physiologically based pharmacokinetics 
PCR 
Polymerase chain reaction 
PK 
Pharmacokinetic(s) 
PPE 
Personal protection equipment 
PY 
Pyronaridine 
QTcF 
QT-interval corrected for heart rate in accordance with Fridericia’s formula 
PKPD 
Pharmacokinetic-pharmacodynamic 
RCT 
Randomized controlled trial 
RdRp 
RNA-dependent RNA-polymerase 
RNA 
Ribonucleic acid 
RR 
Respiratory rate 
RT-PCR 
Reverse transcription polymerase chain reaction 
SAE 
Serious adverse event 


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SAHPRA 
South African Health Products Regulatory Authority 
SARS-CoV 
Severe acute respiratory syndrome coronavirus 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SmPC 
Summary of product characteristics 
SoA 
Schedule of activities 
SOC 
Standard of care 
SOF/DCV 
Sofosbuvir/daclatasvir 
SpO2 
Oxygen saturation 
TdP 
Torsades de pointes 
ULN 
Upper limit of normal 
WHO 
World Health Organization 
 
 
 


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SYNOPSIS 
Title 
A phase 2, exploratory, single center, randomized, open label, adaptive clinical 
trial to compare the safety and efficacy of four different experimental drug 
regimens to standard of care for the treatment of symptomatic outpatients with 
COVID-19. 
Short Title 
COVID-19 Treatment South Africa 
Rationale 
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes 
mild illness confined to the upper respiratory tract in approximately 80% of 
people but can cause severe lower respiratory tract infection (LRTI) in 20%, 
particularly among those in high-risk groups, defined by advanced age (>60 years) 
and presence of comorbidities (e.g., cardiopulmonary disease, hypertension, 
diabetes mellitus, obesity, renal disease). Progression to LRTI appears to 
frequently result in hospitalization for supplemental oxygen therapy and may 
lead to a need for ventilator respiratory support and ultimately death. Given the 
rapid spread of the SARS-CoV-2 pandemic, interventions that avert adverse 
patient outcomes and reduce the strain on the medical system are urgently 
needed. In addition, prolonged viral shedding has been noted after infection, 
especially soon after infection; therapeutic strategies that can effectively reduce 
viral shedding, and potentially onward transmission, have the potential to shift 
the trajectory of the pandemic. 
 
As of the beginning of May 2020, no therapeutic agents had been approved for 
the treatment of COVID-19, although many scientists and researchers have 
proposed a number of potentially suitable existing drugs based on in vitro, pre-
clinical, or limited clinical studies. These agents have potential benefits but also 
have inherent risks and limitations (e.g., adverse reactions and scalability of 
supply). There is an urgent need for controlled and adequately powered clinical 
studies in relevant patient populations to guide policy makers, regulators and 
other clinical trialists on prioritized drugs, including a path toward future 
evaluations as data become available. This study intends to rapidly provide data 
to inform early decision-making and/or support combined analysis with other 
concurrently run studies. 
 
Our understanding of the viral pathogenesis of SARS-CoV-2 remains limited. 
However, it appears that the virus cell entry depends on the binding of the viral 
spike (S) proteins to cellular receptors, and on S protein priming by host cell 
proteases. SARS-CoV-2, like SARS-CoV, uses the same receptor angiotensin 
converting enzyme 2 (ACE2) on pulmonary epithelial cells for entry and the 
transmembrane serine protease 2 for S protein priming [1]. The receptor binding 
domain of lineage B betacoronaviruses is a single, continuous domain that 
contains all of the structural information necessary to interact with the host 
receptor. Fusion is mediated at the cell membrane, delivering the viral 
nucleocapsid inside the cell for subsequent replication. A recent retrospective 
analysis of 85 patients with laboratory-confirmed COVID-19 also indicated that 
SARS-CoV-2 infects human kidney tubules and induces acute tubular damage in 
some patients [2], and 2–11% of patients exhibit liver comorbidities [3]. COVID-
19 has also been associated with multiple direct and indirect cardiovascular 
complications including acute myocardial injury, myocarditis, arrhythmias, and 
venous thromboembolism [4,5]. Therefore, therapeutic options that provide 
antiviral concentrations of drug(s) within the systemic circulation as well as other 
affected organs are likely to be required. 
 
Medications to treat and/or prevent SARS-CoV-2 need to inhibit aspects of the 
viral life cycle, ultimately blocking replication. Already-approved and available 


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medications are ideal for immediate evaluation for SARS-CoV-2 infection 
treatment and prevention. Clinical studies are already ongoing for SARS-CoV-2 
using 
various 
repurposed 
antiviral 
medicines 
(https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-
research-on-novel-coronavirus-2019-ncov). 
 
Drugs were selected for this study on the basis of an analysis of the human 
pharmacokinetics of all agents reported to have anti-SARS-CoV-2 activity in vitro. 
Specifically, the human maximum plasma concentration (Cmax) and predicted 
(calculated) maximum lung concentration after administration of the licensed 
doses were used to assess whether concentrations would exceed those required 
to inhibit at least 50% of SARS-CoV-2 replication in vitro (EC50) for at least some 
of the dosing interval. The full analysis has been published [6] and was 
supplemented by in-house data for 4-aminoquinolines available at MMV [7]. 
 
All study drugs, with the exception of pyronaridine, were predicted to provide 
concentrations with at least some antiviral activity in plasma, with favipiravir and 
nitazoxanide providing the greatest plasma ratios over their reported activity (see 
figure beneath). 
 
 
 
Similarly, based on the calculated lung concentrations, all study drugs were also 
predicted to reach concentrations with some activity in lung, but predicted lung 
exposures for amodiaquine and pyronaridine were estimated to be profoundly 
higher than the reported anti-SARS-CoV-2 EC50 (see figure beneath). For 
amodiaquine, desethylamodiaquine and pyronaridine, this is supported by PBPK 
simulations which predict a high distribution of the compounds into the lungs. 
 
 
 
These data alone support the rationale for assessing these agents in combination 
for COVID-19 therapy. 
 
This phase 2, exploratory study will be an adaptive, randomized, open label, trial 
for treatment of individuals in an outpatient settings with mild SARS-CoV-2 
infection. The primary outcome is focused on the evaluation of efficacy of the 
proposed experimental drugs in reducing upper respiratory viral shedding, 
defined as viral clearance (i.e., negative swab) on Day 7. Key secondary outcomes 
focus on other measures of viral shedding, safety evaluation, progression to LRTI 


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(defined by resting blood oxygen saturation level [SpO2] <93% sustained for two 
readings two hours apart and presence of subjective dyspnea or cough), disease 
severity, clinical resolution rate, and cumulative incidence of hospitalization or 
mortality at Day 28. 
 
Assessment of an initial virological impact will inform further evaluation in a 
subsequent, separate, confirmatory, phase 3 trial to evaluate the efficacy of 
promising experimental drugs in terms of clinical outcomes. 
Design 
This exploratory study is a randomized, single center, open label study of four 
different experimental treatment arms versus standard of care for the 
treatment of SARS-CoV-2 infection in symptomatic outpatients with mild 
disease at the time of enrolment.  
Population 
Women and men from 18 to 65 years of age, inclusive, with self-reported 
symptoms of COVID-19 for no more than 72 hours prior to screening AND who 
test positive for SARS-CoV-2 at screening or during the 2 days prior to screening, 
will be enrolled. The eligibility criteria have been set to identify participants with 
mild COVID-19 disease in accordance with national guidelines [8]. 
 
The following eligibility criteria will be used to select study participants. 
 
Inclusion criteria: 
1. Age from 18 to 65 years of age, inclusive, at the time of signing the 
informed consent form. 
2. Willing and able to provide informed consent. 
3. Women of reproductive potential must be using a highly effective method 
of contraception for at least 28 days prior to enrolment and must be able 
and willing to continue its use throughout the duration of the study. 
4. Men must agree to use condoms when engaging in heterosexual sex during 
the study and for the period up to 91 days after the last dose of study 
medication. Men who are not randomized to a treatment arm including 
favipiravir (or another arm identified as having teratogenic potential 
through semen) will no longer need to adhere to this after randomization. 
5. Laboratory confirmed SARS-CoV-2 infection, and any of the following self-
reported symptoms with onset no more than 72 hours prior to screening 
informed consent, and still present at randomization: fever or chills, cough, 
myalgia, sore throat, headache, conjunctivitis, shortness of breath, nausea, 
diarrhea, new onset of anosmia or ageusia, or other symptoms recognized 
in local and international guidelines as typical of mild COVID-19. 
6. Body weight ≥45 kg. 
7. Access to reliable video conference, telephone, direct/text messaging, or 
other device permitting real-time, reliable information transfer. 
 
Exclusion criteria: 
1. Pregnant or lactating women. 
2. Known hypersensitivity or specific contraindications to the use of any of the 
active drugs in the treatment arms or similar compounds. 
3. Duration of self-reported symptoms of COVID-19 for more than 96 hours or 
four calendar days (whichever is greater) prior to randomisation. 
4. Signs of respiratory distress prior to randomization, including: 
o 
respiratory rate >24 breaths/min 
o 
SpO2 <95% in room air. 
5. Resting pulse rate ≥120 beats/min. 
6. High likelihood of hospitalization in the opinion of the attending clinician. 
7. QTcF >470 msec for females, or >450 msec for males, at screening. 
8. Serum potassium < 3.5 mmol/L at screening. 


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9. History of clinically significant cardiovascular disease (including 
arrhythmias, QT-interval prolongation, torsades de pointes (TdP), history of 
coronary artery disease with graft or stent procedures/surgery, cardiac 
failure [class 2 or higher using the New York Heart Association functional 
classification]). 
10. Known chronic kidney disease (Stage IV or receiving dialysis). 
11. Known cirrhosis (Child-Pugh Class B or greater). 
12. Known macular degeneration, or other known retinal diseases, or 4-
aminoquinolone-induced visual impairment. 
13. Currently receiving, or recently received (within 60 days prior to 
randomization) treatment with any of the drugs in the experimental 
treatment arms (Arms B to E). 
14. Currently receiving, or recently received (within 30 days prior to 
randomization) treatment with any antimalarial drugs. 
15. Currently on treatment with drugs with known arrhythmogenic potential, 
or those known to induce significant QT-interval prolongation or TdP, as 
detailed in Appendix 6. 
16. Currently on treatment for tuberculosis (or on treatment with rifampicin for 
any other indication), or on treatment with a protease inhibitor-based 
antiretroviral regimen, or efavirenz, or carbamazepine. 
17. Inability/unlikely to be in the study area for the duration of the 28 day 
follow-up period. 
18. Any surgical or medical condition which might significantly alter the 
absorption, distribution, metabolism, or excretion of drugs, or which may 
jeopardize the safety of the volunteer or the objectives of the study. The 
Investigator should make this determination in consideration of the 
volunteer’s medical history. 
19. Personnel (e.g. investigator, sub-investigator, research assistant, 
pharmacist, study coordinator or anyone mentioned in the delegation log) 
directly involved in the conduct of the study. 
20. Participant is judged by the Investigator to be at significant risk of failing to 
comply with the provisions of the protocol as to cause harm to self or 
seriously interfere with the validity of the study results. 
 
Volunteers may be re-screened if they are found not to have COVID-19 at the 
time of the initial screening, but develop a further, and separate acute illness 
suggestive of COVID-19 at a later stage again. 
 
Participants will be counseled about the preliminary in vitro data on the activity 
of the planned treatment arms against SARS-CoV-2 and equipoise regarding 
efficacy in humans, given that there are only limited data from an uncontrolled 
study at this time. 
Interventions 
The following treatment arms are planned:  
• Arm A: Standard of care (SOC) 
• Arm B: SOC plus artesunate-amodiaquine (ASAQ) 
• Arm C: SOC plus pyronaridine-artesunate (PA) 
• Arm D: SOC plus favipiravir plus nitazoxanide (FPV-NTZ) 
• Arm E: SOC plus sofosbuvir/daclatasvir (SOF/DCV) 
 
Based on the availability of the investigational drugs, a decision may be made to 
proceed with fewer than five arms initially, and to commence the remaining arms 
as soon as the relevant investigational products are available. 
 
Current standard of care (SOC) will serve as the control arm and will also be 
provided to all participants in accordance with local guidelines which are subject 


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to change. Any changes to recommended SOC will be discussed by the study 
scientific advisory committee to determine the impact on existing assessments 
and treatment arms. At the time of drafting this protocol, SOC comprises 
paracetamol 1 g 6-hourly taken orally as needed. Other optional symptomatic 
therapies (e.g., throat lozenges) may also be provided based on availability and 
need, and participants will be advised to rest. 
Objectives and 
Endpoints 
Primary Objective 
• To test the efficacy of each 
treatment regimen compared to 
SOC alone in reducing SARS-CoV-2 
viral shedding. 
Primary Endpoint 
• Incidence of SARS-CoV-2 clearance 
(defined as the proportion of 
participants with a negative SARS-
CoV-2 RT-PCR test) on Day 7. 
Secondary Objectives 
• To test the efficacy of each 
treatment regimen compared to 
SOC alone in reducing SARS-CoV-2 
viral shedding as determined by 
viral culture 
Secondary Endpoints 
• Incidence of SARS-CoV-2 clearance 
on Day 7 (defined as the 
proportion of participants with 
negative SARS-CoV-2 viral cultures 
on both Day 7 and Day 10 in the 
subset of participants for whom 
these assessments are performed 
and results are available) 
• To test the efficacy of each 
treatment regimen compared to 
SOC alone in reducing late SARS-
CoV-2 viral shedding 
• Incidence of SARS-CoV-2 clearance 
(defined as the proportion of 
participants with negative SARS-
CoV-2 RT-PCR tests) on Days 10, 
14, 21 and 28 
• To test the efficacy of each 
treatment compared to SOC alone 
in reducing the duration of SARS-
CoV-2 viral shedding 
• Time to clearance of SARS-CoV-2, 
defined as a negative SARS-CoV-2 
RT-PCR test (samples collected 
Days 0, 3, 7, 10, 14, 21 and 28) 
• To test whether each treatment 
regimen is associated with 
decreased viral shedding over 14 
days compared to SOC alone 
• Estimated viral load of SARS-CoV-2 
detected by quantitative RT-PCR 
• To test whether each treatment 
regimen decreases the resolution 
rate for symptomatic SARS-CoV-2 
infection/COVID-19 disease 
compared to SOC alone 
• Proportion of days with fever after 
randomization 
• Proportion of days with respiratory 
symptoms after randomization 
• FLU-PRO© Plus questionnaire 
scores and FLU-PRO© Plus Global 
Additional Daily Diary Items over 
the first 14 days 
• To test the safety of each 
treatment regimen compared to 
SOC alone for treatment of 
outpatients with SARS-CoV-2 
infection 
• Serious adverse events (including 
death and hospitalization) 
• Adverse events resulting in 
treatment discontinuation 
• Adverse events considered related 
to the investigational products 


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• To test the efficacy of each 
treatment regimen compared to 
SOC alone to prevent progression 
to LRTI 
• LRTI, defined by resting SpO2<93% 
sustained for 2 readings 2 hours 
apart AND presence of subjective 
dyspnea or cough 
• To test whether each treatment 
regimen has an effect on disease 
severity compared to SOC alone 
• Maximum score on WHO Ordinal 
Scale for Clinical Improvement 
during study participation 
• To test the efficacy of each 
treatment regimen compared to 
SOC alone in reducing 
hospitalization  
• Cumulative incidence of 
hospitalization at Day 28 
• To test whether each treatment 
regimen has an effect on the 
duration of hospitalization among 
persons who become hospitalized 
with COVID-19 disease, compared 
to SOC 
• Days of hospitalization 
• To test the efficacy of each 
treatment regimen compared to 
SOC alone in reducing mortality. 
• Cumulative incidence of mortality, 
measured at Day 28 or later if 
participant is hospitalized at the 
time of Day 28. 
Exploratory Objectives 
• To investigate drug exposure of 
the study drugs in patients with 
COVID-19 
Exploratory Endpoints 
• Plasma/whole blood Cmin 
concentrations on Day 3 (Arms B 
and C) and Day 7 (Arms B to E) 
• To explore the relationship 
between efficacy and plasma or 
whole blood concentrations of the 
study drugs for each treatment 
regimen 
• Viral clearance 
• Categorical secondary endpoints 
related to efficacy 
• Plasma/whole blood Cmin 
concentrations on Day 7 
• To explore the immune response 
in symptomatic patients infected 
with SARS-CoV-2 
• Seroconversion as assessed by 
means of a validated serological 
assay still to be determined 
 
• To explore the relationship 
between sample RT-PCR results, 
their cycle threshold values, and 
corresponding viral culture results 
for SARS-CoV-2. 
• SARS CoV-2 qualitative and 
quantitative RT-PCR results and 
cycle threshold values from all 
relevant time points, and viral 
culture results from screening, Day 
7 and Day 10 in the subset of 
participants for whom viral culture 
is performed. 
Sample Size 
Assuming that the percentage of participants with viral clearance by Day 7 is 20% 
in the control arm (Arm A), a sample size of 50 participants per arm will provide 
at least 80% power to detect an increase in viral clearance to 50% for a new 
treatment. This assumes a two-sided, 5% type 1 error rate and a loss to follow up 
rate of 20%. The assumptions for this calculation are supported by a published 
analysis of a trial of favipiravir (FPV) versus lopinavir/ritonavir (LPV/RTV), where 
the percentage with viral clearance by Day 7 was 65% for favipiravir versus 20% 
for LPV/RTV [9]. Issues of multiplicity have not been considered in this 
exploratory study. 


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The aim of this exploratory study is to demonstrate similar high proportions of 
viral clearance for new candidate treatments. Demonstration of these benefits in 
any study treatment arms would justify taking these forward into a subsequent, 
separate, confirmatory, phase 3 trial, while dropping those arms which fail to 
achieve an improved rate of viral clearance versus the control treatment. 
Duration 
Twenty-eight days of clinical follow-up per participant unless follow-up of an 
unresolved serious adverse event necessitates an extended follow-up period. 
Site 
Administrative Institution: 
Ezintsha, Wits Reproductive Health & HIV Institute (Wits RHI) 
University of the Witwatersrand 
5th Floor, Building D 
Sunnyside Office Park 
32 Princess of Wales Terrace 
Parktown, Johannesburg 
 
Main Site: 
Building C 
Sunnyside Office Park 
32 Princess of Wales Terrace 
Parktown, Johannesburg 
 
Satellite Site: 
Charlotte Maxeke Johannesburg Academic Hospital 
Area 585, Level 8, Jubilee Road 
Johannesburg, 2193 
South Africa 


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1. 
SCHEDULE OF ACTIVITIES 
Procedure 
Screen
-ing 
Enroll-
ment 
Treatment and Follow-Up Period 
(Including self-quarantine as required in accordance with local guidelinesa) 
Late Follow-Up 
EOS 
Day 
0 (-1)b 
Day  
1 
Day  
2 
Day  
3 (+1) 
Days  
4-6 
Day  
7 (±1) 
Days  
8-9 
Day 
10 (±1) 
Days 
11-13 
Day 
14 (±2) 
Days 
15-20 
Day 
21 (±2) 
Day  
28 (±2)c 
Screening informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Duration of COVID-19 symptoms 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy and lactation status and urine 
pregnancy testd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Mid-nasal swab and saliva specimene 
Xf 
 
 
Xg 
 
Xg 
 
Xg 
 
Xg 
 
Xg 
Xg 
Blood for serum potassium 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense 48-hour “Flu Pack”h 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and exclusion criteriai 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Main informed consent, optional storage consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Past and current medical conditions 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications, including contraception 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical examination, including weight and height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Vital signs (temperature, pulse, RR, SpO2) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
ECG, including assessment of QTcF intervalj 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
Xk 
 
 
 
 
 
 
 
 
 
 
 
Blood collection for serologyl 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
Optional blood collection for samples for storagem 
 
X 
 
 
 
 
 
 
 
 
 
 
X 
Participant collected daily vitals (temperature, 
pulse and respiratory rate)n 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Participant collected daily SpO2o 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Completion of daily surveyp 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Completion of FLU-PRO© Plus questionnaireq 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
WHO Ordinal Scale for Clinical Improvementr 
 
X 
 
 
 
X 
 
 
 
X 
 
X 
X 
Study therapy 
 
Xs 
Xs 
Xs 
Xs 
Xs 
 
 
 
 
 
 
 
PK sampling 
 
 
 
Xt 
 
Xu 
 
 
 
 
 
 
 
Contact with study clinician or staffv 
X 
X 
X 
X 
(Xw) 
X 
(Xw) 
X 
(Xw) 
X 
(Xw) 
X 
X 
Adverse event reviewx 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Return of unused IMP and empty containers 
 
 
 
 
 
 
 
 
 
 
 
 
Xy 


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EOS: end of study; PK: pharmacokinetics; SOC: standard of care; SpO2: oxygen saturation; RR: respiratory rate; WHO: World Health Organization. 
Note: Participants who stop study product should continue study participation off study product with continued evaluations as per the schedule of activities. The reason for study 
product discontinuation should be recorded. 
a Current local guidelines specify a quarantine duration for patients with mild COVID-19 of 10 days from onset of symptoms provided resolution of fever has occurred and other 
symptoms are improving [8]. Instructions to participants will be updated if the local guidelines are updated without amending the protocol. 
b Screening will be conducted at the study site. A window period of -1 day may apply as long as COVID-19 symptoms are not present for more than 96 hours or 4 calendar days 
(whichever is greater) prior to randomization. Study personnel will wear personal protective equipment during all interactions, and participants and study personnel will be 
instructed to adhere to local guidance for COVID-19-related safety measures. Screening (Day 0) and Day 1 evaluations may occur on the same calendar day depending on the 
availability of the RT-PCR test results. 
c For participants who are hospitalized at the time of the scheduled Day 28 visit, the last visit will be approximately 3 days after discharge. 
d Urine pregnancy test for women of reproductive potential only. 
e Or other specimen depending on best practice recommendations and the availability of a suitable, validated assay. 
f Participants that have tested positive for SARS-CoV-2 infection (RT-PCR) in the 2 days prior to screening and have laboratory confirmation of this require a mid-nasal swab and 
saliva specimen (or other specimen as identified) for RT-PCR quantification and viral culture of SARS-CoV-2 at screening only. 
g Participants will be visited by laboratory personnel or a study team member or community healthcare worker (CHW), or may report to the site if the quarantine period has been 
completed, to facilitate this. Laboratory personnel/study personnel/CHWs will wear personal protective equipment during all required interactions, and participants and 
laboratory personnel/study personnel/CHWs will be instructed to adhere to local guidance for COVID-19-related safety measures. Qualitative RT-PCR for SARS-CoV-2 will be 
performed at all time points. Quantitative RT-PCR will be performed at all time points up to and including Day 14. Viral culture will be performed at Day 7 and Day 10 only. 
h 48-Hour “flu pack” to be dispensed to all participants in accordance with local standard operating procedures and current national treatment guideline.  
i Eligibility criteria related to age, duration of COVID-19 symptoms, pregnancy status, qualitative RT-PCR and potassium results will be assessed on Day 0 or when the Day 0 results 
are available; all other eligibility criteria will be assessed on Day 1 after completion of the relevant assessments. 
j Using a validated method. 
k Participants who meet all eligibility criteria will be randomized to receive study treatment. Study treatment packs will be dispensed or delivered to participants, or collected by 
participants from the site. 
l Blood samples (5 mL at each time point) will be collected for serological testing in accordance with emerging, validated assays from randomized participants. 
m Blood samples (up to 20 mL at each time point) will be collected from randomized participants providing optional consent for this. Samples will be stored at -70 °C for a period of 
up to 2 years. The samples will be used for future testing in accordance with emerging disease-related data, and suitable, validated assays. 
n The Day 1 assessments will be performed by randomized participants under observation of the site personnel. Assessments will be recorded utilizing a mobile phone/tablet 
application, or other device, or diary, or during a telephonic or in person interaction (once the quarantine period has completed) with the site personnel. Assessments may be 
performed by study personnel if an in person visit is conducted after completion of the quarantine period. 
o The Day 1 assessment will be performed by randomized participants under observation of the site personnel. To be measured after at least 5 minutes resting in a sitting or supine 
position. Participants with an SpO2 <93% will repeat the assessment 2 hours later. If the repeat assessment is <93%, they will contact the site immediately to report this. All 
results will be recorded utilizing a mobile phone/tablet application, or other device, or diary, or during a telephonic or in person interaction (once the quarantine period has 
completed) with the site personnel. 
p To be recorded during a telephonic or in person (once the quarantine period has completed) interaction with the site personnel, or utilizing a mobile phone/tablet application, or 
other device, or diary. The daily survey will consist of the FLU-PRO© Plus Global Additional Daily Diary Items (related to general well-being, overall severity of symptoms, and 


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ability to perform usual daily activies) as well as other general daily diary questions related to study drug administration, recording of vital signs and SpO2 measurements, 
review of concomitant medications, and information related to possible adverse events. 
q The Influenza Patient-Reported Outcome instrument (FLU-PRO© Plus). To be recorded during a telephonic or in person (once the quarantine period has completed) interaction 
with the site personnel, or utilizing a mobile phone/tablet application, or other device, or diary. 
r To be performed by study team personnel. The Day 1 assessment should be performed prior to the first dose of IMP. 
s To be taken as prescribed, for up to 7 days depending on the treatment arm to which the participant is randomized. Includes SOC for all treatment arms. 
t A Day 3 PK sample will be drawn from participants in the ASAQ and PA arms in accordance with the timing in Section 9.7. 
u A Day 7 PK sample will be drawn from all participants in the experimental arms (Arms B to E) in accordance with the timing in Section 9.7. 
v To be performed utilizing a web-conference, telephone call or text/direct messaging, or in person if the quarantine period has been completed. 
w These evaluations will be as needed/requested by study participant. 
x Serious adverse events, adverse events resulting in treatment discontinuation, and all other AEs, including those judged by the site Investigator to be related to the administered 
treatment regimens. 
y Or anytime from Day 7 if an earlier contact visit takes place. 


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2. 
INTRODUCTION 
This is a randomized, single center, open label, adaptive, exploratory trial for the treatment of severe 
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in adults with mild disease not requiring 
hospital admission. The trial will compare four different experimental treatment arms to SOC. 
Assessments will be conducted to assess the effect of each dosing regimen in decreasing viral shedding. 
Evaluations include SARS-CoV-2 viral shedding, progression to lower respiratory tract infection (LRTI), and 
safety and tolerability. A plasma or whole blood sample will be collected from each participant on Day 7 
in order to assess plasma concentrations at the primary endpoint, and on Day 3 from participants in the 
artesunate-amodiaquine and pyronaridine-artesunate arms. 
Enrolment to each of the planned, currently identified study arms (Arms A to E) will commence as soon 
as the relevant drugs are available after study initiation (i.e., different treatment arms may be opened up 
at different times depending on the availability of the IMPs). 
Up to 250 eligible adults (18 to 65 years of age) will be randomized in an equal allocation ratio to receive 
one of the following therapies: 
• 
Arm A: Standard of care (SOC) 
• 
Arm B: SOC plus artesunate-amodiaquine (ASAQ) 
• 
Arm C: SOC plus pyronaridine-artesunate (PA) 
• 
Arm D: SOC plus favipiravir plus nitazoxanide (FPV-NTZ) 
• 
Arm E: SOC plus sofosbuvir/daclatasvir (SOF/DCV). 
Current SOC will be provided to all participants in accordance with local guidelines which are subject to 
change. Any changes to recommended SOC will be discussed by the study Scientific Advisory Committee 
to determine the impact on existing assessments and treatment arms. At the time of drafting this protocol, 
SOC comprises paracetamol 1 g 6-hourly taken orally as needed. Other optional symptomatic therapies 
(e.g., throat lozenges) may also be provided based on availability and need, and participants will be 
advised to rest. 
During the study, participants will take the IMP associated with the treatment arm to which they are 
randomized, and will perform the following: 
• 
Complete daily vital signs assessments (temperature, pulse rate and respiratory rate). Participants will 
also measure SpO2 daily and evaluate themselves for symptoms and signs of LRTI. 
• 
Complete surveys that will include questions about general well-being, respiratory and systemic 
symptoms, adherence to the study medication dosing schedule, review of adverse events (AEs) and 
concomitant medications, and other issues which may emerge as important to track on a daily basis. 
Additional assessments (collection of mid-nasal swabs and saliva samples [or other specimen depending 
on best practice recommendations and the availability of suitable, validated assays] for qualitative and 
quantitative reverse transcription polymerase chain reaction [RT-PCR] and viral culture detection of SARS-
CoV-2, AE evaluation, PK sampling and clinical improvement assessment) will be performed by study team 
personnel or laboratory personnel. 


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2.1 
Background 
SARS-CoV-2 is a coronavirus novel to the human population and discovered in December 2019; it is 
currently the cause of a global pandemic [11,12,13]. The World Health Organization (WHO) named the 
novel coronavirus SARS-CoV-2 and the disease caused by the virus COVID-19. 
SARS-CoV-2 has spread rapidly across the world, with the first case confirmed in South Africa on 5 March 
2020. As of 30 June 2020, there were 151,209 confirmed cases in South Africa, with 2,657 deaths [14]. 
Despite scale up in screening and testing, accurate reporting is limited by availability of diagnostic testing. 
WHO declared the COVID-19 pandemic a Public Health Emergency of International Concern on 30 January 
2020 [15], and a pandemic on 11 March 2020 [16]. The United States declared a national emergency on 
13 March 2020 [17], and South Africa declared a national state of disaster on 15 March 2020 [18]. 
Severe pneumonitis and most deaths have occurred in the elderly or in persons with underlying 
pulmonary or cardiac comorbidities, hypertension or diabetes. In healthy adults, including pregnant 
women, infection with SARS-CoV-2 can be asymptomatic, or cause a febrile, self-limited respiratory 
infection in the majority of cases. The disease can be severe, however, in a small percentage of patients. 
Infection appears less symptomatic in children and younger adults [19]. Manifestations of COVID-19 in 
persons with comorbidities, such as HIV infection, tuberculosis or chronic malaria, are not well-
characterized. Nevertheless, the burden of this pandemic to the global health and economic systems is 
expected to be substantial. No acquired immunity to this novel viral infection appears to exist in the 
human population globally, and no effective treatment or preventative agent is licensed at this time. 
As with many infectious epidemics, household contacts, first responders, caregivers, and medical 
personnel attending persons with COVID-19 are at high risk of infection. The incubation time requires 14 
days of quarantine for exposed individuals not wearing personal protective equipment [20], and on 
3 March 2020, WHO declared a global shortage of personal protective equipment, leaving doctors, nurses, 
and other frontline workers dangerously ill-equipped to care for COVID-19 patients [21]. Extensive 
absences from the care network and health system will degrade the ability to care not only for those with 
COVID-19 but also for routine healthcare issues as well. At the height of local epidemic, the already 
stretched health care system is expected to become overburdened with patients with respiratory illness. 
To date, rigorous self-isolation and lockdown have been required to contain SARS-CoV-2, leading entire 
societies to abruptly stop normal life. Interventions are urgently needed to stop viral spread and to 
decrease the morbidity and mortality associated with the infection. The ability to stop viral replication to 
prevent transmission of the virus and to prevent LRTI, which is associated with need for hospitalization 
and possibly mechanical ventilatory support, will be of benefit to the individual, the hospital system, and 
the health of the public. 
2.2 
Study Rationale 
2.2.1 
COVID-19 and antiviral approaches 
SARS-CoV-2 is a novel betacoronavirus of zoonotic origin, similar to the coronaviruses severe acute 
respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-
CoV). Based on current evidence, case fatality rate for SARS-CoV-2 is about 3%, which is significantly lower 
than that of SARS-CoV (10%) and MERS-CoV (40%) [22]. However, SARS-CoV-2 has potentially higher 
transmissibility (R0: 1.4 to 5.5) than both SARS-CoV (R0: 2 to 5) and MERS-CoV (R0: <1). 
Our understanding of the viral pathogenesis of SARS-CoV-2 remains limited. However, it appears that the 
virus cell entry depends on the binding of the viral spike (S) proteins to cellular receptors, and on S protein 


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priming by host cell proteases. SARS-CoV-2, like SARS-CoV, uses the same receptor angiotensin converting 
enzyme 2 (ACE2) on pulmonary epithelial cells for entry and the transmembrane serine protease 2 for 
S protein priming [1]. The receptor binding domain of lineage B betacoronaviruses is a single, continuous 
domain that contains all of the structural information necessary to interact with the host receptor. Fusion 
is mediated at the cell membrane, delivering the viral nucleocapsid inside the cell for subsequent 
replication. A recent retrospective analysis of 85 patients with laboratory-confirmed COVID-19 also 
indicated that SARS-CoV-2 infects human kidney tubules and induces acute tubular damage in some 
patients [2], and 2–11% of patients exhibit liver comorbidities [3]. COVID-19 has also been associated with 
multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, 
arrhythmias, and venous thromboembolism [4,5]. Therefore, therapeutic options that provide antiviral 
concentrations of drug(s) within the systemic circulation as well as other affected organs are likely to be 
required. 
Medications to treat and/or prevent SARS-CoV-2 need to inhibit aspects of the viral life cycle, ultimately 
blocking replication. Already-approved and available medications are ideal for immediate evaluation for 
SARS-CoV-2 infection treatment and prevention. Clinical studies are already ongoing for SARS-CoV-2 using 
various repurposed antiviral medicines (https://www.who.int/emergencies/diseases/novel-coronavirus-
2019/global-research-on-novel-coronavirus-2019-ncov). 
2.2.2 
Drug selection 
Drugs were selected for this study on the basis of an analysis of the human pharmacokinetics of all agents 
reported to have anti-SARS-CoV-2 activity in vitro. Specifically, for all drugs considered with the exception 
of SOF/DCV, the human maximum plasma concentration (Cmax) and predicted maximum lung 
concentration after administration of the licensed doses were used to assess whether concentrations 
would exceed those required to inhibit at least 50% of SARS-CoV-2 replication in vitro (EC50). The full 
analysis has been published [6] and was supplemented by in-house data for 4-aminoquinolines available 
at MMV [7]. 
 
 
Figure 1:  Anti-SARS-CoV-2 activity in plasma (a) and lung (b) for various drug candidates 
 
These drugs, with the exception of pyronaridine, were predicted to provide concentrations with at least 
some antiviral activity in plasma, with favipiravir and nitazoxanide providing the greatest plasma ratios 
over their reported activity (Figure 1a). Similarly, based on the calculated lung concentrations, these drugs 
were also predicted to reach concentrations with some activity in lung, but predicted lung exposures for 
a) 
b) 


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amodiaquine and pyronaridine were estimated to be profoundly higher than the reported anti-SARS-CoV-
2 EC50 (Figure 1b)  
These data alone support the rationale for assessing these agents in combination for COVID-19 therapy. 
Additional rationale is as follows. 
2.2.2.1 
Artesunate-amodiaquine (Arm B) and pyronaridine-artesunate (Arm C) 
Amodiaquine (AQ), desethylamodiaquine (DEAQ, primary active metabolite of AQ), and pyronaridine (PY) 
are active against SARS-CoV-2 (Vero76 cell assay) in vitro with plasma/blood EC50 of 1.8 µM, <0.3 µM and 
0.7 µM, respectively [7]. Moreover, PBPK modelling of lung penetration indicates AQ, DEAQ and PY to be 
well-distributed to lungs, with a Cmax lung/plasma ratio of 13 for AQ and 40 for DEAQ, and Cmax lung/blood 
ratio of 44 for PY, supporting the selection of these compounds for this trial [7]. 
In contrast with AQ and PY, the available data on the activity of artesunate against SARS-CoV-2 are limited 
[23,24]. The inclusion of artesunate in treatment arms B and C is therefore largely driven by the availability 
of AQ and PY as existing fixed-dose combinations with artesunate (ASAQ and PA) with established safety, 
tolerability and efficacy in malaria. 
2.2.2.2 
Favipiravir and nitazoxanide (Arm D) 
Favipiravir has already demonstrated benefits as a therapeutic agent for COVID-19 in a randomized 
controlled trial [10]. 
Nitazoxanide, is a thiazolide antiparasitic medicine used for the treatment of cryptosporidiosis and 
giardiasis that cause diarrhea [25,26], and also has reported activity against anaerobic bacteria, protozoa 
and other viruses [27]. Importantly, rapid deacetylation of nitazoxanide in blood means that the major 
systemic species of the drug in vivo is tizoxanide, which has not yet been studied for anti-SARS-CoV-2 
activity. Notwithstanding, tizoxanide has been shown to exhibit similar in vitro inhibitory activity to 
nitazoxanide for rotaviruses [28], hepatitis B and C viruses [29,30], other coronaviruses, noroviruses [31] 
and influenza viruses [32,33]. As another respiratory virus, previous work on influenza may be useful to 
gain insight into the expected impact of nitazoxanide for SARS-CoV-2. Accordingly, the drug has been 
shown to selectively block the maturation of the influenza hemagglutinin glycoprotein at the post-
translational stage [33,34] and a previous phase 2b/3 trial demonstrated a reduction in symptoms and 
viral shedding at a dose of 600 mg twice daily compared to placebo in patients with uncomplicated 
influenza [35]. Other potential benefits of nitazoxanide in COVID-19 may derive from its impact upon the 
innate immune response that potentiates the production of type 1 interferons [33,36] and 
bronchodilation of the airways through inhibition of TMEM16A ion channels [37]. 
No significant adverse drug-drug interactions are expected when favipiravir and nitazoxanide are 
administered together (https://www.covid19-druginteractions.org/). 
2.2.2.3 
Sofosbuvir / daclatasvir (Arm E) 
The combination of sofosbuvir 400mg once daily and daclatasvir 60g once daily is normally used to treat 
hepatitis C and has an excellent safety profile. 
SARS-CoV-2 replication and transcription depends on a number of key enzymes, notably RNA-dependent 
RNA-polymerase (RdRp), Main Protease (Mpro) and Helicase. The structure of SARS-CoV-2 RdRp and Mpro 
have been analyzed and published in high resolution and are attractive targets against which to model 
antiviral drugs [38,39]. Some in silico [40,41] and in vitro [42,43] studies of sofosbuvir and daclatasvir have 


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predicted that these and other nucleoside/nucleotide analogues will bind strongly to the SARS-CoV-2 
RdRp enzyme and inhibit its function [40,43]. This is the same proposed mechanism of action of both 
remdesivir and favipiravir. 
One study predicts sofosbuvir and remdesivir both would have equal binding energy to SARS-CoV-2 RdRp 
of -7.5Kcal/mol. Another study predicts molecular docking score to SARS-CoV-2 RdRp of -4.41Kcal/mol 
and -5.16Kcal/mol, respectively with a binding energy of -34.1Kcal/mol and -36.3Kcal/mol, respectively 
[44]. 
However, in silico results are not always concurrent, as computer models use different formulas and make 
different assumptions, and in vitro analyses use different cell lines and have different laboratory 
conditions. One deep learning model suggested that daclatasvir would have a binding strength to SARS-
CoV-2 RdRp of 23.31Kd which is similar to remdesivir (20.17Kd) [45]. However, another modelling study 
comparing the binding strength of 88 antiviral drugs with SARS-CoV-2 Mpro, found daclatasvir to be one 
of the weakest binders to the enzyme (MolDock Score -45.44) [46]. 
Pharmacokinetics 
Whilst the IC50 of remdesivir is thought to be 0.85 +/- 0.41 μM [47] the IC50 of sofosbuvir and daclatasvir 
in SARS-Cov-2 has not yet been published. One study found that sofosbuvir failed to prevent COVID-19-
induced cellular death in vitro [48]. Sofosbuvir and daclatasvir are both licensed for use in hepatitis C virus 
(HCV) [48]. The IC50 of sofosbuvir across HCV genotypes is thought to range from 0.7 to 2.6 µM [49]. 
Knowledge of sofosbuvir pharmacokinetics in other viruses is crucial in guiding sufficient dosing regimens 
against SARS-CoV-2 and ensuring the success of repurposed antivirals. Many studies in silico, in vitro and 
in animals have shown sofosbuvir to have action against other members of the Flaviviridae and 
Togaviridae family (other positive-strand RNA viruses) such as yellow fever, Zika, dengue and Chikungunya 
(CHIKV) viruses [50,51,52,53]. Sofosbuvir inhibited yellow fever viral replication in vitro with an EC50 of 
around 5 μM [50]. In another study, sofosbuvir showed inhibition of three Zika virus strains in Huh-7 and 
Jar cells, with EC50 of 1 μM to 5 μM [51]. Furthermore, sofosbuvir possesses anti-dengue activity and 
demonstrated aggressive in vitro reduction of viral yield with an EC90 of 0.4 μM in HepG2 cells [52]. Ferreira 
et. al. [53] investigated the pharmacology of sofosbuvir on CHIKV-infected astrocytes and Huh-7 
hepatoma cells in vitro, demonstrating that sofosbuvir inhibits CHIKV replication (EC50 17 ± 5 μM and 2.7 
± 0.5 μM, respectively). Results from these studies highlight sofosbuvir’s broad potential antiviral activity. 
In the light of the mentioned evidence it is reasonable to believe that sofosbuvir could be effective in 
treating COVID-19. In Iran, there are currently eight registered randomized clinical trials looking at the 
effectiveness of sofosbuvir in combination with daclatasvir or ledipasvir for treatment against COVID-19, 
with a total sample size of 510. Results from these are expected from May 2020 onwards [54]. Six out of 
the eight trials are assessing the combination of sofosbuvir/daclatasvir. 
2.2.3 
Dose selection 
Assessment of human maximum plasma concentrations and modelling of predicted maximum lung 
concentrations of candidate drugs was done based on the doses for which these drugs are currently 
licensed (with respect to their known therapeutic indications). Therefore, the safety and tolerability are 
well understood at these doses and they are deemed appropriate for this study. 
The adult dose of nitazoxanide for diarrhea in immunocompetent patients with amebiasis, 
cryptosporidiosis, or giardiasis is 500 mg twice daily with food. However, for diarrhea in AIDS patients, 
1000 mg twice daily with food can be used for 14 days or until diarrhea resolves. This 1000 mg twice daily 


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dose has been selected for this study on the basis that modelling suggests a higher proportion of patients 
will achieve plasma and lung exposures above the EC90 target at this dose [55]. 
2.2.4 
Study design 
In the absence of approved drug therapies for the treatment of COVID-19, this phase 2, exploratory trial 
aims to efficiently evaluate and prioritize multiple candidate therapeutics selected for clinical evaluation 
based on their known safety in humans, available pre-clinical activity against SARS-CoV-2, 
pharmacokinetic properties, and potential ease of delivery to low-resource settings.  
The study offers an approach where an initial assessment of potential benefit can be made before 
enrolling a large number of participants in a confirmatory clinical trial with selected treatment(s). The 
overarching goal of the proposed study is to evaluate the effect of the proposed experimental drugs on 
viral shedding. Assessment of an initial virological impact will inform further evaluation in a subsequent, 
confirmatory, phase 3 trial to evaluate the efficacy of promising experimental drugs on clinical outcomes 
such as prevention of lower respiratory tract infection, duration of hospitalization, and mortality. 
2.2.5 
Pharmacokinetic-pharmacodynamic assessments 
PK assessments in initial trials are critical to garner essential information about the exposure-response 
relationship for COVID-19 treatment and prevention. Given ethical concerns regarding the exposure of 
study personnel to highly infectious patients, intense PK sampling is not possible in the context of this 
study. Minimum plasma (or whole blood in the case of pyronaridine) concentrations (Cmin) are well 
understood to be the best PK surrogate parameters for assessing PKPD effects in viral infections due to 
the speed at which viruses replicate in the presence of subtherapeutic drug concentrations. The sampling 
strategy in this study has therefore been developed to maximize the value of isolated samples. Minimum 
concentration (Cmin) on Day 7 will be assessed in all participants in the experimental arms to coincide with 
the primary endpoint, and on Day 3 in participants in the ASAQ and PA arms. 
2.3 
Benefit/Risk Assessment 
COVID-19 disease can be unpredictable in its severity. An 18.7% mortality rate has been observed among 
hospitalized cases in South Africa [56]. The elderly (>60 years of age) and those with medical comorbidities 
(e.g., cardiopulmonary disease, hypertension, diabetes mellitus and renal disease) are at highest risk of 
poor outcomes [11,12,13]. Transmission in younger persons, however, amplifies infection in communities, 
putting susceptible persons at risk. There is no proven drug for treatment of those with COVID-19 disease, 
although preliminary data for remdesivir is promising.  
All of the planned interventions have been demonstrated to be tolerable and safe at the proposed, 
clinically tested doses. Participants will also be provided with standard of care treatment in accordance 
with local, existing guidelines, which will also serve as a control arm. 
QT-interval prolongation is associated with the 4-aminoquinolone compounds. For this reason, patients 
at high risk of developing QT-interval prolongation (those with a history of arrhythmias or other significant 
cardiovascular disease, those with QT-interval prolongation at baseline, those with low serum potassium 
levels at baseline, and those on treatment with other drugs known to cause QT-interval prolongation) will 
be excluded at screening. Concomitant administration of other drugs known to cause significant QT-
interval prolongation is also prohibited during the study. 


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Thus, the potential benefit-to-risk ratio for testing the proposed interventions as treatment, is favorable 
in this population. 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
• To test the efficacy of each treatment regimen 
compared to SOC alone in reducing SARS-CoV-2 
viral shedding. 
• Incidence of SARS-CoV-2 clearance (defined as the 
proportion of participants with a negative SARS-
CoV-2 RT-PCR test) on Day 7. 
Secondary 
• To test the efficacy of each treatment regimen 
compared to SOC alone in reducing SARS-CoV-2 
viral shedding determined by viral culture 
• Incidence of SARS-CoV-2 clearance on Day 7 
(defined as the proportion of participants with 
negative SARS-CoV-2 viral cultures on both Day 7 
and Day 10 in the subset of participants for whom 
these assessments are performed and results are 
available) 
• To test the efficacy of each treatment regimen 
compared to SOC alone in reducing late SARS-CoV-
2 viral shedding 
• Incidence of SARS-CoV-2 clearance (defined as the 
proportion of participants with negative SARS-CoV-
2 RT-PCR tests) on Days 10, 14, 21 and 28 
• To test the efficacy of each treatment compared to 
SOC alone in reducing the duration of SARS-CoV-2 
viral shedding 
• Time to clearance of SARS-CoV-2, defined as a 
negative SARS-CoV-2 RT-PCR test (samples 
collected Days 0, 3, 7, 10, 14, 21 and 28) 
• To test whether each treatment regimen is 
associated with decreased viral shedding over 14 
days compared to SOC alone 
• Estimated viral load of SARS-CoV-2 detected by 
quantitative RT-PCR 
• To test whether each treatment regimen decreases 
the resolution rate for symptomatic SARS-CoV-2 
infection/COVID-19 disease compared to SOC 
alone 
• Proportion of days with fever after randomization 
• Proportion of days with respiratory symptoms 
after randomization 
• FLU-PRO© Plus questionnaire scores and FLU-PRO© 
Plus Global Additional Daily Diary Items over the 
first 14 days 
• To test the safety of each treatment regimen 
compared to SOC alone for treatment of 
outpatients with SARS-CoV-2 infection 
• Serious adverse events (including death and 
hospitalization) 
• Adverse events resulting in treatment 
discontinuation 
• Adverse events considered related to the 
investigational products 
• To test the efficacy of each treatment regimen 
compared to SOC alone to prevent progression to 
LRTI 
• LRTI, defined by resting SpO2<93% sustained for 2 
readings 2 hours apart AND presence of subjective 
dyspnea or cough 
• To test whether each treatment regimen has an 
effect on disease severity compared to SOC alone 
• Maximum score on WHO Ordinal Scale for Clinical 
Improvement during study participation 
• To test the efficacy of each treatment regimen 
compared to SOC alone in reducing hospitalization 
• Cumulative incidence of hospitalization at Day 28 


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• To test whether each treatment regimen has an 
effect on the duration of hospitalization among 
persons who become hospitalized with COVID-19 
disease, compared to SOC 
• Days of hospitalization 
• To test the efficacy of each treatment regimen 
compared to SOC alone in reducing mortality. 
• Cumulative incidence of mortality, measured at 
Day 28 or later if participant is hospitalized at the 
time of Day 28. 
Exploratory 
• To investigate drug exposure of the study drugs in 
patients with COVID-19 
• Plasma/whole blood Cmin concentrations on Day 3 
(Arms B and C) and Day 7 (Arms B to E) 
• To explore the relationship between efficacy and 
plasma or whole blood concentrations of the study 
drugs for each treatment regimen 
• Viral clearance 
• Categorical secondary endpoints related to efficacy 
• Plasma/whole blood Cmin concentrations on Day 7 
• To explore the immune response in symptomatic 
patients infected with SARS-CoV-2 
• Seroconversion as assessed by means of a 
validated serological assay still to be determined 
• To explore the relationship between sample RT-
PCR results, their cycle threshold values, and 
corresponding viral culture results for SARS-CoV-2. 
• SARS CoV-2 qualitative and quantitative RT-PCR 
results and cycle threshold values from all relevant 
time points, and viral culture results from 
screening, Day 7 and Day 10 in the subset of 
participants for whom viral culture is performed. 
 
4. 
STUDY DESIGN 
4.1 
Overall Design 
The overarching goal of this study is to assess the efficacy of interventions to reduce virus shedding among 
adult outpatients with mild SARS-CoV-2 infection. Confirmation of the initial virological impact on the 
clinical progression of COVID-19 should be obtained in a subsequent, separate, phase 3 trial focused on 
prevention of LRTI, and reduction of hospitalization and mortality. 
This is a randomized, single center, open label, exploratory, adaptive trial. The trial will commence four 
experimental interventions (Arms B to E) to assess the efficacy as measured by a reduction in viral 
shedding compared to SOC (Arm A). Participants will be randomized to one of these treatment arms in a 
1:1:1:1:1 ratio. 
Initially, this study will enroll up to 250 eligible adults (18 to 65 years of age inclusive) who have RT-PCR-
confirmed SARS-CoV-2 infection and self-reported symptoms of COVID-19 (50 per arm). The sample size 
calculations and statistical power are detailed in Section 11.1). Eligible participants will be enrolled and 
randomized in an equal allocation ratio to study treatment arms. The recruitment rate will be assessed on 
a weekly basis starting at the end of the second week after the first eligible participant is recruited and 
randomized. The DMC may advise increasing the sample size target, should a higher dropout rate than 
expected be observed. This would be based on a blind review of the pooled, observed recruitment and 
dropout rates, and the final sample size target, if applicable. The interim monitoring plan (written by the 
study Statistician) will define the strategy for potential sample size re-assessment (based on the the 
observed overall dropout rate) in order to preserve the pre-specified power of 80%. If this study 
demonstrates high rates of viral clearance for new candidate treatments, demonstration of these benefits 


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would then justify taking selected treatments into a subsequent, separate, phase 3, confirmatory trial 
with a larger sample size, powered on a new endpoint of clinical recovery. 
Other unspecified additional treatment modalities may be incorporated into this protocol, based on 
emerging data. These will be added through protocol amendments, which will define additional sample 
size needs and any potential change to randomization (e.g., changing the randomization ratio, 
continuation/discontinuation of any of the existing arms, etc.). Details regarding sample size calculation, 
statistical power, and statistical methods are provided in Section 10. 
Participants will be counseled about the preliminary in vitro data on the activity of the experimental 
interventions against SARS-CoV-2, and equipoise regarding efficacy in humans, given that there are only 
limited data available at this time. This counselling will be serially updated as new, clear data become 
available. 
Blood samples will be drawn from participants for SARS-CoV-2 antibody testing using emerging, validated 
assays. Blood samples will also be collected from participants offering optional consent for storage and 
future testing defined by emerging disease-related data and hypotheses and suitable, validated assays. 
An amendment to this protocol will be drafted to describe the assessment of other outcomes based on 
emerging data in this rapidly developing field. 
An independent DMC will be convened for this study with expertise in COVID-19 or respiratory viruses, 
emerging epidemics, as well as biostatistics. The purpose of the DMC is to monitor the study for social 
harms, safety and efficacy. The DMC will also review the blinded sample size re-assessment plan and 
proposed sample size changes in a blinded manner if required. 
4.2 
Participant and Study Completion 
As an initial target, 250 participants will be randomly assigned to one of the five study treatment arms (at 
least 50 participants per treatment arm). This sample size target may increase based on blinded sample 
size re-assessment. 
A participant is considered to have completed the study if he/she has completed all phases of the study 
including the last scheduled procedure shown in the Schedule of Activities (SoA) in Section 1. 
The study will be considered complete when sufficient number of participants have completed the study 
to enable appropriate evaluation of the primary endpoint. 
5. 
STUDY POPULATION 
Women and men from 18 to 65 years of age, inclusive, with self-reported symptoms of COVID-19 for no 
more than 72 hours prior to screening informed consent and who test positive for SARS-CoV-2 at 
screening or during the two days prior to screening, will be enrolled. The eligibility criteria have been set 
to identify participants with mild COVID-19 disease in accordance with national guidelines [8]. 
Potential participants will be recruited from surrounding COVID-19 testing stations and from patients 
presenting to local healthcare facilities. Volunteers who are interested in participating in the trial may be 
consented for pre-screening to assess potential eligibility. Those eligible for screening, will be invited to 
participate in the informed consent process as described in Section 13.2. Written or electronic informed 
consent will be obtained prior to any screening procedures. 
Prospective approval of protocol deviations to recruitment and enrollment criteria (also known as 
protocol waivers or exemptions) is not permitted. 


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The following eligibility criteria will be used to select study participants. 
5.1 
Inclusion Criteria 
Participants are eligible to be included in the study if all of the following criteria apply: 
1. Age from 18 to 65 years of age, inclusive, at the time of signing the informed consent. 
2. Willing and able to provide informed consent. 
3. Women of reproductive potential must be using a highly effective method of contraception for at 
least 28 days prior to enrolment and must be able and willing to continue its use throughout the 
duration of the study. 
4. Men must agree to use condoms when engaging in heterosexual sex during the study and for the 
period up to 91 days after the last dose of study medication. Men who are not randomized to a 
treatment arm including favipiravir (or another arm identified as having teratogenic potential 
through semen) will no longer need to adhere to this after randomization. 
5. Laboratory confirmed SARS-CoV-2 infection, and any of the following self-reported symptoms with 
onset no more than 72 hours prior to screening informed consent, and still present at 
randomization: fever or chills, cough, myalgia, sore throat, headache, conjunctivitis, shortness of 
breath, nausea, diarrhea, new onset of anosmia or ageusia, or other symptoms recognized in local 
and international guidelines as typical of mild COVID-19. 
6. Body weight ≥45 kg. 
7. Access to reliable video conference, telephone, direct/text messaging, or other device permitting 
real-time, reliable information transfer. 
5.2 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria are met: 
1. Pregnant or lactating women. 
2. Known hypersensitivity or specific contraindications to the use of any of the active drugs in the 
treatment arms, or similar compounds. 
3. Duration of self-reported symptoms of COVID-19 for more than 96 hours or four calendar days 
(whichever is greater) prior to randomisation. 
4. Signs of respiratory distress prior to randomization, including: 
o 
respiratory rate >24 breaths/min 
o 
SpO2 <95% in room air. 
5. Resting pulse rate ≥120 beats/min. 
6. High likelihood of hospitalization in the opinion of the attending clinician. 
7. QTcF >470 msec for females, or >450 msec for males, at screening. 
8. Serum potassium <3.5 mmol/L at screening. 
9. History of clinically significant cardiovascular disease (including arrhythmias, QT-interval 
prolongation, torsades de pointes (TdP), history of coronary artery disease with graft or stent 
procedures/surgery, cardiac failure [class 2 or higher using the New York Heart Association 
functional classification]). 
10. Known chronic kidney disease (Stage IV or receiving dialysis). 
11. Known cirrhosis (Child-Pugh Class B or greater). 
12. Known macular degeneration, or other known retinal diseases, or 4-aminoquinolone-induced visual 
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13. Currently receiving, or recently received (within 60 days prior to randomization) treatment with any 
of the drugs in the experimental treatment arms (Arms B to E). 
14. Currently receiving, or recently received (within 30 days prior to randomization) treatment with any 
antimalarial drugs. 
15. Currently on treatment with drugs with known arrhythmogenic potential, or those known to induce 
significant QT-interval prolongation or TdP, as detailed in Appendix 6. 
16. Currently on treatment for tuberculosis (or on treatment with rifampicin for any other indication), or 
on treatment with a protease inhibitor-based antiretroviral regimen, or efavirenz, or 
carbamazepine. 
17. Inability/unlikely to be in the study area for the duration of the 28 day follow-up period. 
18. Any surgical or medical condition which might significantly alter the absorption, distribution, 
metabolism, or excretion of drugs, or which may jeopardize the safety of the volunteer or the 
objectives of the study. The Investigator should make this determination in consideration of the 
volunteer’s medical history. 
19. Personnel (e.g. investigator, sub-investigator, research assistant, pharmacist, study coordinator or 
anyone mentioned in the delegation log) directly involved in the conduct of the study. 
20. Participant is judged by the Investigator to be at significant risk of failing to comply with the 
provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study 
results. 
Volunteers may be re-screened if they are found not to have COVID-19 at the time of the initial screening, 
but develop a further, and separate acute illness suggestive of COVID-19 at a later stage again. 
5.3 
Co-enrollment Guidelines 
Participants may be co-enrolled in other research studies, provided that these are observational studies 
where no interventions are offered only. Any other exception requires approval of the Principal 
Investigator; if a participant clinically worsens, such as requiring hospitalization, such an exception will be 
automatically granted for participation in other offered treatment studies. The study team should be 
consulted for co-enrollment in studies that do not meet this guidance or if there are questions about 
eligibility for co-enrollment. For any co-enrolled study, the total volume of blood samples collected across 
the two studies should not exceed 480 mL over any eight week period. 
6. 
TREATMENTS 
Study treatment is defined as any investigational treatment or marketed product to be administered to a 
study participant according to the study protocol. 
6.1 
Treatments Administered 
The following treatments are planned: 
Arm A: 
Study Treatment Name 
Paracetamol (SOC) 
Dosage Formulation 
Tablet 500 mg 
Route of Administration 
Oral 
Dosing Instructions 
2 tablets (1000 mg) to be taken 6-hourly as needed 


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Arm B: 
SOC as described in Arm A plus experimental treatment as follows: 
Study Treatment Name 
Artesunate-amodiaquine (ASAQ) 
Dosage Formulation 
100/270 mg artesunate/amodiaquine fixed dose combination, uncoated tablets 
Route of Administration 
Oral 
Dosing Instructions 
2 tablets (200/540 mg artesunate/amodiaquine) daily for 3 days 
Arm C: 
SOC as described in Arm A plus experimental treatment as follows: 
Study Treatment Name 
Pyronaridine-artesunate (PA) 
Dosage Formulation 
180/60 mg pyronaridine tetraphosphate/artesunate fixed dose combination, film-
coated tablets 
Route of Administration 
Oral 
Dosing Instructions 
For participants with body weight 45 to <65 kg: 
3 tablets (540/180 mg  
 
 
 
 
 
 
 
 
pyronaridine/artesunate) daily 
 
 
 
 
 
 
 
 
for 3 days 
For participants with body weight ≥65 kg 
 
4 tablets (720/240 mg  
 
 
 
 
 
 
 
 
pyronaridine/artesunate) daily 
 
 
 
 
 
 
 
 
for 3 days 
Arm D: 
SOC as described in Arm A plus experimental treatment as follows: 
Study Treatment Name 
Drug 1: Favipiravir 
Drug 2: Nitazoxanide 
Dosage Formulation 
200 mg and 400 mg film-coated tablets  
500 mg tablets 
Route of Administration 
Oral 
Oral 
Dosing Instructions 
1600 mg 12-hourly for 1 day,  
then 
600 mg 12-hourly for 6 days 
2 tablets (1000 mg) 12-hourly for 7 days; 
to be taken with food. 
Arm E: 
SOC as described in Arm A plus experimental treatment as follows: 
Study Treatment Name 
Sofosbuvir/daclatasvir 
Dosage Formulation 
400mg/60 mg sofosbuvir/daclatasvir fixed dose combination, film coated tablets 
Route of Administration 
Oral 
Dosing Instructions 
1 tablet (400 mg/60 mg sofosbuvir/daclatasvir) daily for 7 days 
6.2 
Risks to the Participants 
Administration of IMP in this study will be for a short duration (up to 7 days) at doses that are well-
described and have been shown to be well-tolerated in clinical studies. Risks to participants are therefore 
expected to be well-controlled.  


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Since both COVID-19 and many drugs are known to be associated with liver injury, all participants will be 
advised of the clinical signs and symptoms of hepatotoxicity and will be requested to report the 
emergence of any of these urgently. 
In evaluating individual risks to participants, the relevant Summaries of Product Characteristics (SmPCs) 
for each IMP should be reviewed. Documented risks related to different components of the treatment 
arms include, but are not limited to, the following. 
Artesunate-amodiaquine: 
Amodiaquine has been shown to prolong the QT-interval in some patients. 
Pyronaridine-artesunate: 
PA has been associated with a transient increase in transaminases in a small number of patients treated 
for acute malaria and in Caucasian, healthy volunteers. No associated clinical signs and symptoms of 
hepatotoxicity have been observed or reported. 
Favipiravir: 
Early embryonic deaths and teratogenicity have been observed in pre-clinical studies with favipiravir. 
Participants will be counselled with regard to this prior to study participation and will be required to agree 
to use of suitable contraception (Section 5.1). Women of reproductive potential will require a negative 
urine pregnancy test to be eligible for study participation. 
Nitazoxanide: 
No specific risks to participants are predicted at the proposed dose to be administered during this study. 
Sofosbuvir: 
Cases of severe bradycardia and heart block have been observed when sofosbuvir-containing regimens 
are used in combination with amiodarone, which is an exclusion criterion for participation in this study. 
Daclatasvir: 
Cases of severe bradycardia and heart block have been observed when daclatasvir-containing regimens 
are used in combination with amiodarone, which is an exclusion criterion for participation in this study. 
Diabetics may experience improved glucose control, potentially resulting in symptomatic hypoglycemia, 
after initiating treatment. 
6.2.1 
Management of participants to limit risks of SARS-CoV-2 transmission 
To limit the transmission of SARS-CoV-2, the following measures will be employed: 
• 
Participants will engage in visits and site personnel contact using telemedicine, telephone or 
text/direct messaging as far as is possible. 
• 
For any necessary physical interactions, study and laboratory personnel will be instructed to wear 
personal protection equipment (PPE) at all times, and participants and laboratory/study personnel 
will be instructed to adhere to national and regional guidance for COVID-19-related safety measures. 
• 
The organization of each study site will be in accordance with national and regional guidelines for 
limiting the spread of COVID-19, and will be such that contact between persons with potential SARS-
CoV-2 infection and other patients is restricted. 


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• 
To limit exposure in waiting rooms and pharmacies, daily vital signs will be self-monitored by 
participants and medications will be delivered to participants at homes where possible. 
• 
To limit community exposure to trial participants infected with SARS-CoV-2, participants will be 
required to self-quarantine in accordance with national and regional guidelines for the required 
duration and transported to study site with a study vehicle in line with national infection control 
guidelines. 
6.3 
Dose Modification and Toxicity Management 
If any study therapy dose is missed, it should be taken as soon as possible. If it is less than 4 hours before 
the next dose is scheduled, the missed dose should be skipped and documented as such in the participant 
daily survey. 
Modification for toxicities is discussed below. Only toxicities related to study medications provided 
through the study will be considered in this section. 
Grade 1 or 2 
Participants who develop Grade 1 or 2 toxicity (per Division of Acquired Immunodeficiency Syndrome 
[DAIDS] Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1, July 
2017 [https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf]) that is considered by 
the site Investigator to be related to the study medication, may continue study treatment at the discretion 
of the site Investigator with close follow up. If a participant chooses to discontinue study treatment, the 
site should notify the Safety Review Team within 7 days. These participants will remain on study, off study 
treatment, and have all evaluations performed. 
Grade 3 
• 
Participants who develop a Grade 3 toxicity thought by the site Investigator to be related to study 
drug should have study product withheld, and the site should consult with the Safety Review Team 
via the Medical Monitor. The participant should be re-evaluated every 2 days until the AE returns to 
Grade ≤2, at which time study drug may be reintroduced at the discretion of the site Investigator in 
consultation with the Safety Review Team. 
• 
Participants experiencing a Grade 3 toxicity requiring permanent discontinuation of study product 
should be followed up weekly until resolution of the toxicity. These participants will remain on study, 
off study treatment, and have all evaluations performed per the SoA. 
Grade 4 
• 
Participants who develop a Grade 4 toxicity will have study product permanently discontinued, and 
the site should notify the Principal Investigator and the Safety Review Team via the Medical Monitor 
within 72 hours. 
• 
Participants experiencing Grade 4 toxicity requiring permanent discontinuation of study product 
should be followed up weekly until resolution of the AE or return to baseline. These participants will 
remain on study, off study treatment, and have all evaluations performed per the SoA. 
Specific Management of Toxicities Related to Study Drugs 
All possible drug toxicities will be managed on a case-by-case basis. Grade 2 and above toxicities will be 
discussed with one of the study physicians in their role as a site Investigator. All Grade 3 and above 


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toxicities will be reported to the Principal Investigator and Medical Monitor. Case management and 
follow-up will, at a minimum, be in accordance with the above-mentioned guidelines. 
All AEs (whether or not considered drug-related) will be reported during the study, and all serious adverse 
events (SAEs) and suspected, unexpected, serious adverse reactions (SUSARs) will be reported in 
accordance with applicable regulations and requirements (Section 9.2.2). 
6.4 
Method of Treatment Assignment 
Participants will be randomized using a centralized, automated randomization system (IVRS/IWRS) to one 
of the five treatment arms (Arms A to E) in a 1:1:1:1:1 ratio. The randomization plan will be adaptive based 
on treatment arms available for participant allocation and will be overseen by the study Statistician. 
6.5 
Blinding 
No blinding will be performed to conceal treatment identification for the study. The study will be open-
label to participants and study personnel. 
6.6 
Preparation / Handling / Storage / Accountability 
Drugs should be stored at room temperature, as per package insert. Records must be maintained that 
document receipt, release for dosing, disposal, or return to the Sponsor. 
Details of all drug-related procedures surrounding shipping, receipt, storage, handling, preparation, 
dispensing and accountability will be documented in the Pharmacy Manual. 
6.7 
Treatment Compliance 
Study drug (and home monitoring kits) will either be dispensed to participants at the site or delivered to 
participants at their homes. In cases where study supplies are delivered, participants will be contacted to 
ensure that they received the box of study supplies and took their first dose of medication. All participants 
will be asked to complete a daily survey to gather information regarding treatment administration. 
Medication errors, including under-dosing, will be recorded in the survey. 
Consultation via tele-medicine, text/direct messaging, or telephone will be available to provide support 
to the participant to complete study procedures. 
6.8 
Concomitant Therapy 
Participants will be asked about concomitant medications at the screening/baseline evaluation visit. 
During the study, participants will be asked to complete a daily survey that includes information regarding 
any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or herbal 
supplements) that the participant receives during the study. At each contact, the Investigator should 
question the participant about any medication taken.  
6.8.1 
Prohibited medications 
Participants will be advised to consult the study clinician before commencing any new concomitant 
medications during the study. 


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The use of the following drugs is prohibited during the study (Appendix 6): 
• 
Drugs with known arrhythmogenic potential, or known to induce significant QT-interval prolongation 
or TdP (detailed in Appendix 6) 
• 
Protease inhibitor-based antiretroviral regimens, or efavirenz 
• 
Rifampicin 
• 
Carbamazepine. 
6.8.2 
Precautionary medications 
Use of medications classified as precautionary is not study prohibitory but will be discussed with the study 
clinician and the participant. The study clinician will review all previous and concomitant medications 
taken by study participants to evaluate possible drug-drug interactions and ensure that unacceptable risks 
do not result from these. The relevant SmPCs for the applicable study drugs and previous/concomitant 
medications will be used as a reference. 
Known interactions to be considered include, but are not limited to, the following: 
Artesunate-amodiaquine:  
Drugs known to prolong the QT interval should be used with caution. In the absence of clinical data, ASAQ 
is not recommended to be administered concomitantly with drugs known to inhibit CYP2A6 (e.g., 
methoxsalen, pilocarpine, tranylcypromine) and/or CYP2C8 (e.g., trimethoprim, ketoconazole, ritonavir, 
saquinavir, lopinavir, gemfibrozil, montelukast). 
Pyronaridine-artesunate: 
Caution is advised when co-administering PA with metoprolol given in cardiac failure. A possible dose 
adjustment of metoprolol may be required. Dihydroartemisinin administration may result in a slight 
decrease in CYP1A2 activity. Caution is therefore, advised when PA is administered concomitantly with 
medicinal products metabolized by this enzyme that have a narrow therapeutic index, such as 
theophylline. 
Favipiravir: 
Favipiravir should be used with caution when administered together with pyrazinamide, repaglinide, 
theophylline, and famciclovir. 
Nitazoxanide: 
Caution should be used when administering nitazoxanide concurrently with other highly plasma protein-
bound drugs with narrow therapeutic indices. 
Sofosbuvir: 
Medicinal products that are strong (e.g., carbamazepine, phenobarbital, phenytoin, rifampicin and St 
John's wort) or moderate (e.g., modafinil, oxcarbazepine and rifapentine ) P-glycoprotein (P-gp) inducers 
in the intestine may decrease sofosbuvir plasma concentration leading to reduced therapeutic effect. Co-
administration with such medicinal products is not recommended. The concomitant administration of 
protease inhibitors can result in increased plasma concentrations of sofosbuvir and is not recommended. 


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Daclatasvir: 
Strong inducers of CYP3A4 and P-gp (e.g., phenytoin, carbamazepine, oxcarbazepine, phenobarbital, 
rifampicin, rifabutin, rifapentine, systemic dexamethasone, and St John’s wort) may lead to lower 
exposure and loss of efficacy of daclatasvir. The concomitant administration of protease inhibitors can 
result in increased plasma concentrations of daclatasvir and is not recommended. 
Daclatasvir is an inhibitor of P-gp, organic anion transporting polypeptide (OATP) 1B1, OCT1 and breast 
cancer resistance protein (BCRP). Administration of daclatasvir may increase systemic exposure to 
medicinal products that are substrates of P-gp, OATP 1B1, OCT1 or BCRP, which could increase or prolong 
their therapeutic effect and adverse reactions. Caution should be used if the medicinal product has a 
narrow therapeutic range. 
6.9 
Treatment After the End of the Study 
No additional treatment will be provided at the end of the study. 
7. 
DISCONTINUATION/WITHDRAWAL CRITERIA 
7.1 
Discontinuation of Study Treatment 
Study treatment will be discontinued for the following reasons: 
• 
Hospitalization (at the discretion of the inpatient provider, hospitalized participants may continue to 
receive study treatment if maintained on the originally randomized treatment regimen) 
• 
Requirement for prohibited concomitant medications or other contraindication to study product 
• 
Occurrence of an AE requiring discontinuation of study product 
• 
Request by participant to terminate study treatment 
• 
Clinical reasons believed by the physician to be life-threatening or place the participant at undue risk, 
even if not addressed in Section 6.3. 
Participants who stop study product should continue study participation off study product with continued 
evaluations as per the SoA. The reason for study product discontinuation should be recorded. 
Hospitalized participants will be followed through hospitalization and the last visit will be within 3 days of 
discharge if this occurs after Day 28. 
7.2 
Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his/her own request or may be withdrawn 
at any time for the following reasons: 
o 
At the request of the primary care provider if he/she thinks the study is no longer in the best 
interest of the participant 
o 
Participant is judged by the Investigator to be at significant risk of failing to comply with the 
provisions of the protocol as to cause harm to self or seriously interfere with the validity of the 
study results 
o 
At the discretion of the Institutional Review Board/Ethics Committee or government agencies as 
part of their duties, Investigator, or industry supporter. 


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• 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain and 
continue to use any data collected before such withdrawal of consent. 
• 
If a participant withdraws from the study, he/she may request destruction of any samples taken and 
not tested. This must be documented by the Investigator in the site study records. 
• 
If possible and agreed to by the participant, assessments detailed for the EOS visit on Day 28 (SoA) 
should be completed at the time of study discontinuation if a participant withdraws from the study. 
7.3 
Lost to Follow-up 
A participant will be considered lost to follow-up if he/she is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to comply with required study procedures: 
• 
The site must attempt to contact the participant as soon as possible and counsel the participant on 
the importance of maintaining the assigned procedure schedule and ascertain whether or not the 
participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the Investigator or designee must make every effort 
to regain contact with the participant (where possible, 3 telephone calls and, if necessary, a visit to 
the participant’s place of residence by a member of the study team). These contact attempts should 
be documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have withdrawn from 
the study with a primary reason of lost to follow-up. 
8. 
STUDY ENCOUNTERS 
The current COVID-19 pandemic has placed a significant burden on the healthcare system. Contact 
between study participants and study personnel will be limited as far as is possible. Study personnel will 
be instructed to wear PPE during all interactions, and participant and study personnel will be instructed 
to adhere to national and regional guidance for COVID-19-related safety measures. 
For this study, data collection will be self-conducted where possible to minimize the impact of non-ill 
participants within the healthcare system and the risks of SARS-CoV-2 transmission. If the participant is 
assessed as eligible during the screening visit, contact between study participants and study personnel 
will occur via tele-medicine, text/direct messaging or telephone as far as is possible. 
Participants will be instructed to seek clinical care should they manifest any signs or symptoms of LRTI 
requiring medical intervention and notify their physician about trial participation. Any participant who’s 
clinical condition deteriorates during the study, will be hospitalised if required in accordance with the 
national guidelines for clinical management of patients with COVID-19 [8]. 
8.1 
Screening Evaluation: Day 0 (-1 day window) 
Presenting patients will be assessed for study eligibility through screening conducted at the site. 
Day 0 evaluations and procedures are as follows: 
• 
Screening informed consent for all eligibility assessments to be conducted on Day 0 (may be taken 
electronically) 
• 
Collection of demographic information 


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• 
Collection of information on the duration of COVID-19 symptoms 
• 
Pregnancy and lactation status, and a urine pregnancy test for women of reproductive potential 
(women will be considered to be of reproductive potential unless they have been surgically sterilized 
[by hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy or tubal ligation], or 
are post-menopausal [age-appropriate spontaneous amenorrhea for ≥12 months in the absence of 
oral contractive use for >12 months) 
• 
Collection of a mid-nasal swab and saliva sample (or other sample depending on best practice 
recommendations) for RT-PCR detection and quantification of SARS-CoV-2 and viral culture 
• 
Collection of blood sample for serum potassium concentration 
• 
Dispensing of a 48-hour “flu pack” for symptomatic management of COVID-19 symptoms 
(paracetamol 1 g 6-hourly to be taken orally as needed and other optional symptomatic therapies 
[e.g., throat lozenges] based on availability and need). 
Once available, participants will be contacted to inform them of their test results, and those with a positive 
SARS-CoV-2 RT-PCR test result, a serum potassium ≥ 3.5 mmol/L, and otherwise eligible in terms of 
assessments conducted on Day 0, will be invited to return for an enrollment visit on Day 1. 
8.2 
Enrollment/Randomization/Start of Treatment: Day 1 
Patients who present for the Day 1 visit will be invited to take part in the study (pending additional 
confirmation of eligibility), and to provide informed consent for this and the remaining eligibility 
assessments in accordance with the main study informed consent form (ICF) prior to any further 
procedures being conducted. The main study informed consent may be taken electronically. 
Eligibility will continue to be assessed at the Enrollment Visit on Day 1 in accordance with the following 
assessments: 
• 
Collection of past and current medical conditions 
• 
Collection of concomitant medication information, including contraception usage 
• 
Weight and height assessment 
• 
Abbreviated, symptom-directed, physical examination to include as least the following: 
o 
General examination 
o 
Heart and lungs 
• 
Vital signs (temperature, pulse, and respiratory rate) 
• 
SpO2 assessment 
• 
ECG, including assessment of QTcF-interval 
• 
Check of inclusion and exclusion criteria. 
Thereafter, the following will be conducted for patients meeting all eligibility criteria: 
• 
Participants will be randomized to one of the treatment arms in accordance with the study 
randomization schedule. 
• 
Each participant will receive a monitoring kit containing a thermometer and an SpO2 monitor. 


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• 
Participants will be instructed as to how to: 
o 
Measure daily vital signs (temperature, pulse and respiratory rate) 
o 
Measure daily SpO2 (and repeat SpO2 if the scheduled reading is <93%) 
o 
Complete the FLU-PRO© Plus questionnaire 
o 
Complete the daily survey (comprising the FLU-PRO© Plus Global Additional Daily Diary Items and 
other general daily diary questions). 
• 
A mobile data collection application will be installed on the participant’s mobile device (for 
participants that have their own, compatible, mobile device). 
• 
A blood sample will be collected for: 
o 
SARS-CoV-2 serology 
o 
Storage for future testing (only in participants providing optional consent for this). 
• 
Participants will perform the following assessments under observation of the site personnel (and 
record data using telemedicine or relay this to the site personnel for transcribing): 
o 
Vital signs (temperature, pulse and respiratory rate) 
o 
SpO2 measurement 
o 
The FLU-PRO© Plus questionnaire 
o 
The daily survey (comprising the FLU-PRO© Plus Global Additional Daily Diary Items and other 
general daily diary questions). 
• 
A study team member will complete the WHO Ordinal Scale for Clinical Improvement survey. 
• 
IMP for the full course of treatment will be dispensed to participants (either at the study site, or via 
courier or study personnel delivery). Participants will be instructed to commence their study 
treatment on the same day. 
Prior to completion of the visit, the following will be done: 
• 
Participants will be instructed to seek clinical care at any stage throughout the study should they 
develop signs or symptoms of respiratory distress. If needed, direct hospital referral may be facilitated 
by the site personnel in accordance with the national guidelines for clinical management of patients 
with COVID-19 [8]. 
• 
Participants will be advised that, at any stage during the study, they may request additional contact, 
including via telemedicine or telephone, with the study clinician or staff to discuss developing 
symptoms or AEs, or if they need to clarify study procedures. 
Screening, enrollment and randomization procedures (Day 0 and Day 1) can take place on the same 
calendar day in the unlikely event that the RT-PCR result is available rapidly. 
8.3 
Treatment Continuation and Follow-Up: Day 2 to Day 14 (±2) 
A study team member will be available via telemedicine, text/direct messaging, or telephone to provide 
support for completion of study procedures.  


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On Relevant Study Treatment Days: 
• 
Participants will take their study treatment until completion as per the dosing schedule described in 
Section 6.1. 
On Days 2 to 14 (±2) inclusive: 
• 
Participants will complete the following assessments (and record data using telemedicine, 
telephonically or via text/direct messaging): 
o 
Vital signs (temperature, pulse and respiratory rate) 
o 
SpO2 measurement 
o 
The FLU-PRO© Plus questionnaire 
o 
The daily survey (comprising the FLU-PRO© Plus Global Additional Daily Diary Items and other 
general daily diary questions). 
On Day 2: 
• 
Contact with the study clinician or staff will be conducted via telemedicine or telephone. Participants 
will be clinically assessed for signs and symptoms of respiratory distress and will have in person 
assessment of AEs. 
On Days 3 (±1), 7 (±1), 10 (±1), and 14 (±2): 
• 
Contact with the study clinician or staff will be conducted via telemedicine or telephone, or may be in 
person if the relevant quarantine period has been completed in accordance with local guidelines. 
Participants will be clinically assessed for signs and symptoms of respiratory distress and will have in 
person assessment of AEs. 
• 
Participants will be visited by a study team member, laboratory personnel or a CHW, or may report to 
the site if the relevant quarantine period has been completed, for collection of a mid-nasal swab and 
saliva sample (or other sample depending on best practice recommendations) for RT-PCR detection 
and quantification of SARS-CoV-2 (Days 3, 7, 10 and 14) and viral culture (Days 7 and 10). 
On Days 3 and 7: 
• 
Participants in the ASAQ and PA treatment arms will have a plasma and/or whole blood PK sample 
collected on Day 3 prior to the last dose of IMP and approximately 24 hours after the previous IMP 
dose. 
• 
Participants in the experimental treatment arms (Arms B to E) will have a single plasma and/or whole 
blood PK sample collected on Day 7 prior to their last dose of IMP (if relevant) and relative to the 
previous dose of IMP administered as follows: 
o 
24 (±2) hours post-dose for SOF/DCV 
o 
96 (±2) hours post dose for ASAQ, PA 
o 
12 (±1) hours post dose for FPV-NTZ. 
On Days 7 (±1) and 14 (±2): 
• 
A study team member will complete the WHO Ordinal Scale for Clinical Improvement survey. 


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8.4 
Late Follow-Up: Day 21 (±2) 
The following will be performed: 
• 
Contact with the study clinician or staff will be conducted via telemedicine or telephone. Participants 
will be clinically assessed for signs and symptoms of respiratory distress and will have in person 
assessment of AEs. As needed, additional contact with the study clinician or staff will be conducted at 
the request of the participant (e.g., if developing concerning symptoms or an AE) or if needed to clarify 
study procedures or follow-up symptoms. 
• 
Participants will complete the following assessments (and record data using telemedicine, 
telephonically or via text messaging): 
o 
Vital signs (temperature, pulse and respiratory rate) 
o 
The FLU-PRO© Plus questionnaire 
o 
The daily survey (comprising the FLU-PRO© Plus Global Additional Daily Diary Items and other 
general daily diary questions). 
• 
Participants will report to the site, or be visited by a study team member, laboratory personnel or a 
CHW for collection of a mid-nasal swab and saliva sample (or other sample depending on best practice 
recommendations) for RT-PCR detection of SARS-CoV-2. 
• 
A study team member will complete the WHO Ordinal Scale for Clinical Improvement survey. 
A study team member will be available via telemedicine, text/direct messaging, or telephone to provide 
support for completion of study procedures. 
8.5 
End-of-Study: Day 28 
The following will be performed: 
• 
Contact with the study clinician or staff will be conducted via telemedicine or telephone or in person. 
Participants will be clinically assessed for signs and symptoms of respiratory distress and will have in 
person assessment of AEs. 
• 
Participants will complete the following assessments (and record data using telemedicine, 
telephonically, via text messaging or in person): 
o 
Vital signs (temperature, pulse and respiratory rate); these may be assessed by the site personnel 
if an in person visit is conducted 
o 
The FLU-PRO© Plus questionnaire 
o 
The daily survey (comprising the FLU-PRO© Plus Global Additional Daily Diary Items and other 
general daily diary questions). 
• 
Participants will report to the site or be visited by a study team member or CHW for the following: 
o 
Collection of a mid-nasal swab and saliva sample (or other sample depending on best practice 
recommendations) for RT-PCR detection of SARS-CoV-2 
o 
Collection of blood for SARS-CoV-2 serology 
o 
Collection of blood for storage for future testing (only in participants providing optional consent 
for this). 


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• 
A study team member will complete the WHO Ordinal Scale for Clinical Improvement survey. 
• 
Unused IMP, empty IMP containers and SpO2 monitors will either be returned to the site by the 
participant, or collected by courier or a member of the study team (if not already returned at an earlier 
time point). 
For participants who are hospitalized on Day 28, the Day 28 procedures will be performed within 3 days 
after discharge from the hospital. 
A study team member will be available via telemedicine, text/direct messaging, or telephone to provide 
support for completion of study procedures. 
Clinical outcomes will be confirmed through appropriate health records, if possible. 
Participant reimbursement may be performed in accordance with local standards. 
9. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in the SoA. 
• 
Protocol waivers or exemptions are not allowed. 
• 
Immediate safety concerns should be discussed with the Sponsor (via the Medical Monitor or 
chairperson of the SRT) immediately upon occurrence or awareness to determine if the participant 
should continue or discontinue study treatment. 
• 
All screening and enrollment evaluations (demographic data, duration of COVID-19 symptoms, 
pregnancy and lactation status, mid-nasal swab and saliva sample, confirmation of positive SARS-CoV-
2 result, serum potassium, medical history, previous and concomitant medication usage, weight and 
height, abbreviated, symptom-directed physical examination, study personnal assessment of vital 
signs and SpO2, and ECG and QTcF evaluation) must be completed prior to randomization, and 
reviewed to confirm that potential participants meet all eligibility criteria. The Investigator will 
maintain a screening log to record details of all participants screened and to confirm eligibility or 
record reasons for screening failure, as applicable. 
• 
Procedures conducted as part of the participant’s routine clinical management and obtained before 
signing of the informed consent form (ICF) may be utilized for screening or baseline purposes provided 
that the procedures meet the protocol-specified criteria and were performed within the time frame 
defined in the SoA. 
• 
Blood samples will only be collected for SARS-CoV-2 serological assays (in accordance with emerging, 
suitable and validated assays), for a screening serum potassium assessment, for a maximum of two 
PK samples, and for storage for future testing (in participants offering optional consent for this only). 
The maximum amount of blood collected from any participant over the duration of the study is 
expected to be 71 mL but should not exceed 480 mL even if additional safety assessments are 
required. 
9.1 
Efficacy Assessments 
9.1.1 
Mid-nasal swab and saliva specimen 
Mid-nasal swabs and saliva specimens (or other site depending on best practice recommendations and 
the availability of suitable, validated assays) will be collected from all potentially eligible volunteers at 


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screening on Day 0 for viral detection (and quantification and viral culture if the participant is 
subsequently enrolled). Additional mid-nasal swabs and saliva samples will be collected on Days 3, 7, 10, 
14, 21 and 28. Participants will report to the site or be visited by a study team member, laboratory 
personnel or a CHW to facilitate swab collection. 
Swab kits may contain either viral transport media, 0.9% saline, or phosphate-buffered saline, which have 
been shown to be equivalent for storage of SARS-CoV-2 samples based on validated assays [57]. Saliva 
samples will be collected in suitable sterile containers. Previous testing has demonstrated that respiratory 
viral ribonucleic acid (RNA) is stable in room temperature for up to 1 week. 
Swabs will be subjected to RNA amplification and tested for SARS-CoV-2. Qualitative assays will be 
performed at all time points. Additional quantitative assays for viral load will be performed at screening 
and on Days 3, 7, 10 and 14. Viral culture will be performed on samples from enrolled participants 
collected at screening, Day 7 and Day 10. 
Further details regarding mid-nasal swab and saliva sample (or other biological samples depending on the 
availability of suitable, validated assays) collection, handling and processing, as well as the testing 
laboratory, assays and methods to be used, will be documented in the Laboratory Manual. 
9.1.2 
Participant surveys 
Participants will be asked to complete the the following surveys during the study: 
• 
The FLU-PRO© Plus questionnaire [58,59,60] to assess the symptomatic extent of their illness 
(Appendix 3) 
• 
The daily survey (Appendix 4) that includes: 
o 
The FLU-PRO© Plus Global Additional Daily Diary Items (related to general well-being, overall 
severity of symptoms, and ability to perform usual daily activies) 
o 
General daily diary items (related to study drug administration, recording of vital signs and SpO2 
measurements, review of concomitant medications, and information related to possible adverse 
events). 
These surveys will be completed electronically using telemedicine, or telephonically during an interview 
with a study team member. 
9.1.3 
WHO Ordinal Scale for Clinical Improvement 
A study team member will complete the WHO Ordinal Scale for Clinical Improvement (Appendix 5) after 
contact (via telemedicine or telephone) on relevant study days. 
9.2 
Adverse Events 
Participants will be asked to complete the daily survey (Appendix 4) that includes information on any 
symptoms that they are experiencing. In addition, AE review by a staff member (via telemedicine, 
telephone, or text/direct messaging) will be performed. 
All AEs must be recorded on the electronic case report forms (eCRFs). 
AEs will be recorded from the time of informed consent until the end-of-study visit (Day 28). SAEs 
occurring after the reporting period that the Investigator becomes aware of must be reported as 
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9.2.1 
Definition 
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant 
administered a pharmaceutical product, which does not necessarily have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory 
findings), symptom, or disease temporally associated with the use of an investigational product, whether 
or not considered related to the product. 
AEs may include the onset of new illnesses and the exacerbation of pre-existing medical conditions. An 
AE can include an undesirable medical condition occurring at any time, including baseline or washout 
periods, even if no study treatment has been administered. 
9.2.2 
Serious adverse events 
An SAE is defined as any untoward medical occurrence that: 
• 
Results in death 
• 
Is life-threatening (immediate risk of death) 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization (with the exception of 
hospitalization due to progressive COVID-19 disease) 
• 
Results in persistent or significant disability/incapacity 
• 
Results in a congenital anomaly/birth defect 
• 
Is an important medical event that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the participant or may require intervention to prevent one of the 
other outcomes listed in the definition above. 
All AEs that are recorded must have their severity graded. To grade AEs, sites should refer to the DAIDS 
AE Grading Table, corrected Version 2.1, July 2017, which can be found on the DAIDS Regulatory Support 
Center website at https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf. 
The Investigator will report all SAEs to the Sponsor through the Qualified Person for Pharmacovigilance 
(QPPV) within 24 hours of the site personnel becoming aware of the event. The report should be in writing 
by email or fax with the Medical Monitor on copy and documented on a standard SAE Reporting Form. In 
addition to this, fatal or life-threatening SAEs must be reported immediately to the QPPV, irrespective of 
the extent of available AE information.  
Qualified Person Responsible for Pharmacovigilance: 
Dr Robert Miller 
Email:   
 
 
 
 
 
safety @artemidapharma.com 
Tel/Fax: 
 
 
 
 
 
+44 203 291 3032 
For all SAEs, the Investigator is obligated to pursue and provide information in accordance with the 
timeframes for reporting specified above. In addition, an Investigator may be requested to obtain specific 
additional follow-up information in an expedited fashion. This information may be more detailed than 
that captured on the AE case report form. In general, this will include a description of the AE in sufficient 
detail to allow for a complete medical assessment of the case and independent determination of possible 
causality. Information on other possible causes of the event, such as concomitant medications and 
illnesses must be provided. In the case of a participant death, a summary of autopsy findings (if available) 
must be submitted as soon as possible to the QPPV. 


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The Local Ethics Committee and Regulatory Authority will be notified of all SAEs in accordance with their 
requirements. 
Reporting and follow-up procedures are described in the Safety Management Plan. 
9.2.3 
Treatment-related AEs and SAEs 
A treatment-related AE is defined as any new AE that begins, or any preexisting condition that worsens in 
severity, after at least 1 dose of study treatment has been administered and is considered by the 
Investigator to be related to the study medication. 
All AEs and SAEs should have attribution recorded as treatment- or not treatment-related, in the judgment 
of the site Investigator. 
9.3 
Treatment of Overdose 
Overdose of any of the study interventions (including SOC) should be managed according to the product 
labeling information. Study drug overdose, including misuse or abuse of the product and medication 
errors, should be reported in the eCRF in the clinician notes. 
9.4 
Pregnancy 
All women of reproductive potential will be offered effective contraception for the duration of the study. 
While all efforts will be undertaken to prevent pregnancy among participants, or pregnancy in partners of 
male participants in Arm D, should a participant or partner of a participant from any study arm become 
pregnant during the study, she will be counselled (or invited for counselling if she is a participant’s partner) 
regarding the risks associated with known or potentially teratogenic study drugs, and undergo an 
informed consent process to confirm her continued participation in the study (if appropriate), and 
willingness to be followed through the pregnancy.  
Pregnancies occurring in participants enrolled in this study, or their partners, must be reported and 
followed to outcome. Reporting should be performed using a standard Pregnancy Reporting Form. The 
reporting procedure follows that described for SAEs in Section 9.2.2. 
Pregnancy alone is not regarded as an AE unless there is a possibility that the study drug may have 
interfered with the effectiveness of a contraceptive medication. Elective abortions without complications 
should not be considered AEs unless they were therapeutic abortions. Hospitalization for normal delivery 
of a healthy newborn should not be considered an SAE. Pregnancy is not considered an SAE unless there 
is an associated outcome that meets one or more of the SAE criteria. Spontaneous abortions should 
always be reported as SAEs. 
Any pregnancy outcome considered to be an SAE should be reported within the timelines and using the 
procedures described in Section 9.2.2. 
9.5 
Other Safety Assessments 
ECG, including assessment of QTcF-interval (using a suitable, validated method) and serum potassium will 
be performed at screening to exclude patients at high risk of QT-interval prolongation from participation 
in the study. 
During the study, safety will be assessed through vital signs monitoring, SpO2 monitoring, and participant 
surveys, as shown in the SoA. 


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Participants will be asked to complete the FLU-PRO© Plus questionnaire and the daily survey (which 
includes the FLU-PRO© Plus Global Additional Daily Diary Items). Events qualifying as AEs will be recorded 
on the eCRF and reported as described in Section 9.2. 
9.6 
Serological and Other Assessments 
Blood samples will be collected from all randomized participants at baseline on Day 1, and on Day 28 for 
serological testing in accordance with emerging, suitable and validated assays. 
An additional blood sample will also be collected from participants offering optional consent for storage 
of samples at -70 °C for a period of up to 2 years. These samples will be used for future testing in 
accordance with emerging, disease-related data and suitable, validated assays. 
Additional details regarding sample collection, processing and storage will be described in the Laboratory 
Manual. 
9.7 
PK Assessments 
The aim of the PK assessments is to gather essential information about the exposure-response 
relationship for COVID-19 treatment and prevention. The sampling strategy in this study has been 
developed to maximize the value of isolated samples. Minimum concentration (Cmin) on Day 7 will be 
assessed in all participants in the experimental arms (Arms B to E) to coincide with the primary endpoint, 
and on Day 3 in participants in the ASAQ and PA arms (Arms B and C). 
A single plasma and/or whole blood PK sample will be collected on these days. The timing of the sample 
collections will be as follows: 
• 
Day 3 samples for participants in the ASAQ and PA arms will be collected prior to the last dose of IMP 
and approximately 24 hours after the previous IMP dose. 
• 
Day 7 samples for participants in all experimental arms (Arms B to E) will be collected prior to the last 
dose of IMP (if IMP administration is still scheduled for Day 7) and relative to the previous dose of IMP 
administered as follows: 
o 
24 (±2) hours post-dose for SOF/DCV 
o 
96 (±2) hours post dose for ASAQ, PA 
o 
12 (±1) hours post dose for FPV-NTZ. 
The basic requirements for PK sampling are as follows: 
1. Accurate record of the time of IMP administration (for the dose administered prior to the blood 
sampling) (dd:mm:yy; hh:mm) 
2. Accurate recording of the time of blood sampling (dd:mm:yy; hh:mm). 
Blood samples will be collected and processed as outlined in the study-specific Laboratory Manual. 
Additional details regarding storage and shipment will be also be described in the Laboratory Manual. 
Details of PK analytical procedures will be described in the Analytical Plan. 


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9.8 
Biohazard Containment 
As the transmission of SARS-CoV-2 and other respiratory droplet pathogens can occur through contact 
with respiratory droplets and contaminated surfaces, precautions will be employed by all personnel in the 
handling of all specimens for this study. 
All dangerous goods and materials, including diagnostic specimens and infectious substances, must be 
transported using packaging mandated by national and regional regulations.  
Details of these procedures will be described in the Laboratory Manual and will comply with relevant IATA 
Dangerous Goods Regulations. 
10. 
DATA MANAGEMENT 
The Investigator will maintain paper or electronic source documentation for all study participants. 
Participant information will be captured in an eCRF. The Clinical Data Management System will comply 
with regulatory guidelines and requirements for electronic systems. 
Data validation and quality control procedures will be detailed in the Data Management Plan. 
Medical history and AE data will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
version 22.1 or later. Concomitant medications will be coded using the latest 2020 release of the WHO 
Drug Dictionary in effect at the time of study start. 
11. 
STATISTICAL CONSIDERATIONS 
11.1 
Sample Size Determination 
Primary Endpoint of Viral Clearance 
Assuming that the percentage of participants with viral clearance by Day 7 is 20% in the control arm (Arm 
A), a sample size of 50 participants per arm will provide at least 80% power to detect an increase in viral 
clearance to 50% for a new treatment regimen. This assumes a two-sided, 5% type 1 error rate and a loss 
to follow up rate of 20%. The assumptions for this calculation are supported by a published analysis of a 
trial of favipiravir versus lopinavir/ritonavir, where the percentage with viral clearance by Day 7 was 65% 
for favipiravir (FPV) versus 20% for lopinavir/ritonavir (LPV/RTV) [9]. Issues of multiplicity have not been 
considered in this exploratory study. 
 


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Figure 2:  Kaplan-Meier survival curves for time to viral clearance per treatment 
 
The aim of this exploratory study is to demonstrate similar high proportions of viral clearance for new 
candidate treatments. Demonstration of these benefits in any study treatment arms would justify taking 
these specific arms forward into a subsequent, separate, confirmatory, phase 3 trial, with a new endpoint 
of clinical recovery. 
11.2 
Populations for Analyses 
For analysis purposes, the following populations are defined and will be described in greater detail in the 
trial Statistical Analysis Plan: 
Population 
Description 
Safety Analysis Set 
All enrolled participants who receive at least one dose of randomized 
treatment  
Modified Intention to Treat 
(mITT) 
All enrolled participants with confirmed SARS-CoV-2 infection who receive at 
least one dose of randomized treatment  
As Treated 
All enrolled participants who complete the course of randomized treatment 
and have viral load results available on Day 7 
11.3 
Statistical Analyses 
The Statistical Analysis Plan will be developed and finalized before database lock and will describe the 
participant populations to be included in the analyses, the detailed analytical plans with endpoints and 
procedures for accounting for missing, unused, and spurious data. 
An Interim Monitoring Plan will also be developed to describe approaches for re-estimation of sample size 
in order to preserve the pre-specified power of 80%. 
This section presents a brief summary of the planned statistical analyses of the primary and secondary 
endpoints (Section 3). 


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11.3.1 
Efficacy analyses 
Demographic characteristics (age, sex, race) of each study group will be tabulated. 
The mean age (plus range and standard deviation) by sex of the enrolled participants, as a whole and per 
group, will be calculated. 
Primary analyses: The primary analyses will be conducted on the mITT population overall. Participants 
randomized to each active treatment will be compared to participants randomized to SOC (Arm A). The 
primary analysis will make use of all participants randomized to SOC, whether contemporaneously 
enrolled or not. Due to anticipated heterogeneity in risk of disease progression, pre-specified baseline 
variables, including age, body mass index (BMI), and days of symptoms at time of enrollment will be 
included in the model to increase precision. 
Sensitivity analysis: The primary analyses will be repeated, replacing randomization arm by actual 
treatment to account for possible off-label use of and noncompliance to the investigational products. 
Subgroup analyses: All subgroup analyses will be pre-specified in the Statistical Analysis Plan. Any further 
subgroup analyses will be considered ad hoc. 
Missing Data: Due to the design of the study and retention activities, measurable outcomes are expected 
for all participants. However, in the unlikely event of a missing test result, the missing data will be imputed. 
11.3.2 
Secondary endpoints 
All secondary endpoints will be assessed in the mITT population overall and by treatment arm. 
Endpoints related to SpO2 will be calculated for all participants that had SpO2 ≥95% on Day 1. 
11.3.2.1 Safety analyses 
All safety analyses will be performed on the Safety Analysis Set. SAEs, AEs, treatment-related AEs, and 
discontinuations due to AEs will be compared by study group. 
11.3.2.2 Hospitalization 
Hospitalization rates between the groups will be compared using logistic regression stratified by site. 
Number of days hospitalized will be described graphically and by median and interquartile rage. 
11.3.2.3 Disease severity 
Disease severity, as measured by the WHO Ordinal Scale for Clinical Improvement (Appendix 5), will be 
compared between the groups using a proportional odds model. 
11.3.2.4 Symptom resolution 
Days with fever after randomization, respiratory symptoms after randomization, and Sp02<93% after 
randomization will be modeled using Poisson regression stratified by site with an offset for number of 
days of observation. 
Data from the FLU-PRO© Plus questionnaire (Appendix 3) and the FLU-PRO© Plus Global Additional Daily 
Diary Items (Appendix 4) will be analysed in accordance with guidance from Leidos Biomedical Research, 
Inc. Details will be described in the Statistical Analysis Plan. 


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11.3.3 
Exploratory endpoints 
Limited sparse PK sampling will be conducted in all participants in the experimental arms of the study 
using Cmin plasma and/or whole blood concentrations tailored to each of the main study drugs. For the 
majority of drugs this will be conducted on Day 7 only, to minimize exposure of healthcare staff to 
infectious patients through site visits. For long half-life drugs such as pyronaridine and amodiaquine that 
will only be dosed during the first days of the study, an additional plasma and/or whole blood Cmin sample 
will be collected pre-dose on Day 3 to ensure robust quantification of drugs and/or their major circulating 
active metabolite. 
A number of potential analyses are possible with these plasma or whole blood concentration data. 
Correlations of Cmin with time to undetectable virus will be analyzed by Cox regression and the difference 
in proportions for other endpoints can be evaluated using Pearson’s chi-square or Fisher’s exact test (as 
appropriate). If warranted, differences in plasma and whole blood concentrations between individuals 
defined as “responders” versus those defined as “non-responders” to therapy will be assessed using a 
ttest, in the case that differences in response to therapy between participants is evident. 
11.3.4 
Combined study analysis 
This protocol is based on a model protocol for consideration by multiple institutions as they evaluate the 
efficacy of experimental treatments for SARS-CoV-2 infection. Individual participant data from similar 
studies may be pooled into a combined study analysis. De-identified data from the present study will be 
made available for these purposes in accordance with the funder’s open access policy 
(https://www.gatesfoundation.org/how-we-work/general-information/open-access-policy). 
12. 
STUDY MONITORING 
12.1 
Safety Review Team 
The Safety Review Team (SRT) will monitor the conduct of the study through monthly summary reports 
of arms of accrual, baseline characteristics, AEs, laboratory results and protocol deviations. On a weekly 
basis, the Medical Monitor (one of the members of the SRT) will review by-arm summaries of premature 
study discontinuations and premature study treatment discontinuations (and reasons) and AEs. 
A detailed description of the operational aspects of the Safety Review Team will be documented in the 
Safety Review Team Charter. 
12.2 
Independent Monitor 
Study conduct will be monitored by an independent monitor. Monitors will conduct remote monitoring 
and will visit the sites as required. Review of individual participant records, including consent forms, eCRFs, 
supporting data, laboratory specimen records, and endpoints through laboratory and medical records 
(physicians’ progress notes, nurses’ notes, individuals’ hospital charts) will be performed as detailed in 
the Clinical Monitoring Plan, to ensure protection of study participants, compliance with the protocol, and 
accuracy and completeness of records. The monitors also will inspect the sites’ regulatory files to ensure 
that regulatory requirements are being followed, and the sites’ pharmacies to review product storage and 
management. 


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The Clinical Monitoring Plan will describe these activities and will take into consideration necessary 
adaptations to ensure the safety of the monitor with regard to infection control and the fact that physical 
access to sites may be limited. 
12.3 
Data Monitoring Committee 
An independent DMC will be convened for this study with expertise in respiratory viruses, antiviral 
therapies and shedding, and emerging epidemics. A biostatistician will also form part of the DMC. The 
purpose of the DMC is to monitor the study for safety, social harms, and efficacy. The DMC will evaluate 
the progress of the project, including periodic assessments of accrual, retention, safety, performance and 
variation of the project site, and other factors that can affect project implementation. 
The DMC will review and approve modifications to the overall enrollment target based on the observed 
drop-out rate. Due to the anticipated rapid speed of enrollment and the short duration of the study, no 
formal interim analyses for futility will be performed. The DMC will review severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2) endpoints. 
The DMC will conduct interim reviews as specified in the DMC Charter when adequate data have been 
accrued. Meetings will be convened by teleconference. Semi-blinded reports containing participant 
characteristics, AEs, SAEs, and other safety and efficacy data will be sent to the protocol team and DMC 
members the week prior to the DMC meeting. The DMC members will also receive pooled reports of 
accrual and retention rates to enable them to provide recommendations regarding a possible sample size 
increase in an un-biased way. 
The objectives and responsibilities of the DMC, and the DMC operational procedures will be detailed in 
the DMC Charter which will be ratified by the DMC members prior to the study start. 
12.4 
Scientific Advisory Committee 
A scientific advisory committee (SAC) will be established for this study. The scientific advisory committee 
will be consulted in the event of new evidence emerging that could impact the scientific rationale of the 
trial and might require: 
• 
changes to treatment arm drugs or doses or duration of IMP administration, or 
• 
changes to other aspects of the study design. 
13. 
ETHICAL CONSIDERATIONS 
13.1 
Regulatory and Ethical Considerations 
The study will be conducted according to GCP, the Belmont Report, the Declaration of Helsinki, and South 
Africa legal requirements regarding clinical trials. The study protocol and relevant supporting documents 
will be submitted for review and approval by the SAHPRA and the Human Research Ethics Committee 
(HREC) responsible for oversight of research conducted at the study site. The study protocol will be 
registered with the South African National Clinical Trial Registry (www.sanctr.gov.za) / National Human 
Research Ethics Committee (www.ethicsapp.co.za) and www.ClinicalTrial.gov. Six-monthly progress 
reports will be submitted to SAHPRA and HREC for the duration of the study, and as requested. Upon 
completion or premature termination of the study, the Investigator will provide HREC and SAHPRA with a 
summary of the study’s outcome, and any reports required. 


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13.2 
Informed Consent Process 
The principles of informed consent in the current edition of the Declaration of Helsinki will be 
implemented before any protocol-specified procedures or interventions are carried out. The pre-
screening consent form will describe any information that will be gathered or procedures that will be 
followed during pre-screening. The separate screening and main study electronic consent form(s) will 
describe the purpose of the study, the procedures to be followed, and the risks and benefits of 
participation. Consent for storage of samples for future testing will also be requested, but will be optional. 
Failure to provide consent for sample storage will not exclude a volunteer from study participation. In the 
event of a female participant becoming pregnant, consent for follow-up of the pregnancy and outcome 
thereof will be requested. Potential participants will have the opportunity to have any questions answered 
before and after signing either the pre-screening consent form or the ICF. The informed consent process 
and all questions raised will be documented. 
The study staff who conduct the informed consent process will also sign the ICF(s). A copy of the consent 
form(s) will be given to the participant, and this fact will be documented in the participant’s record. 
A participant who is rescreened will sign new ICF(s); eligibility for the study must be re-checked prior to 
enrollment with regard to all other screening procedures. 
13.3 
Study Records 
The study site will establish a standard operating procedure for confidentiality protection. The site will 
ensure that study records including administrative documentation and regulatory documentation as well 
as documentation related to each participant enrolled in the study, including ICFs, locator forms, case 
report forms, notations of all contacts with the participant, and all other source documents are stored in 
a secure manner. 
13.4 
Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a manner 
designed to maintain participant confidentiality. The exceptions are SARS-CoV-2 testing results, which are 
subject to local and national reporting. This may be name-based depending on local requirements. Local 
public health may contact participants diagnosed with SARS-CoV-2 for the purpose of surveillance and 
contact notification. Participants will be informed prior to SARS-CoV-2 testing that results are reportable 
and may lead to contact by local public health if results are positive for infection. 
All records will be kept in a secure storage area with limited access. Clinical information will not be 
released without the written permission of the participant, except as necessary for monitoring, and 
auditing by the regulatory authorities or the Human Research Ethics Committee (HREC). 
The Principal Investigator or designee and all employees and co-workers involved with this study may not 
disclose or use for any purpose other than performance of the study, any data, record, or other 
unpublished confidential information disclosed to those individuals for the purpose of the study. All 
computers are password-protected and records can only be accessed by authorized study staff. 


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13.5 
Blood Volume 
Anticipated blood draws for participants in the experimental treatment arms will amount to the following 
total blood volumes: 
Assessment 
Maximum volume per sample 
Maximum no. of samples 
Total volume 
Serum potassium 
5 mL 
1 
5 mL 
PK 
8 mL 
2 
16 mL 
Serology 
5 mL 
2 
10 mL 
Storage for future testing 
20 mL 
2 
40 mL 
TOTAL 
71 mL 
For participants in the SOC arm (Arm A), no PK samples will be drawn and the anticipated total blood 
volume drawn will therefore be 55 mL.  
Therefore, for all participants, even if the situation arises where multiple additional blood draws for 
unanticipated safety monitoring are required, the total volume drawn should not exceed 480 mL over an 
8 week period. 
 


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59. Powers JH, Bacci ED, Guerrero ML, et al. Evaluation of the performance properties of the 
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APPENDICES 
APPENDIX 1: 
STUDY GOVERNANCE 
The following Investigators and Institutional Affiliations are established. Designees may be provided, as 
appropriate. 
Name 
Role  
Institution 
Francois Venter 
Principal Investigator 
Ezintsha, Wits Reproductive Health & HIV Institute 
University of the Witwatersrand 
5th Floor, Building D 
Sunnyside Office Park 
32 Princess of Wales Terrace 
Parktown, Johannesburg 
South Africa 
Nomathemba Chandiwana 
Lead Investigator 
 
Main Site: 
Building C 
Sunnyside Office Park 
32 Princess of Wales Terrace 
Parktown, Johannesburg 
 
Satellite Site: 
Charlotte Maxeke Johannesburg Academic Hospital 
Area 585, Level 8 
Jubilee Road 
Johannesburg, 2193 
South Africa 
 


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APPENDIX 2: 
CONTACT DETAILS 
Site 
Institution: 
 
 
Ezintsha, Wits Reproductive Health & HIV Institute 
Address: 
 
 
University of the Witwatersrand 
 
 
 
 
5th Floor, Building D 
 
 
 
 
Sunnyside Office Park 
 
 
 
 
32 Princess of Wales Terrace 
 
 
 
 
Parktown, Johannesburg 
Main Site: 
 
 
Building C 
 
 
 
 
Sunnyside Office Park 
 
 
 
 
32 Princess of Wales Terrace 
 
 
 
 
Parktown, Johannesburg 
 
 
 
 
South Africa 
Principal Investigator:  
Professor Francois Venter 
Email:  
 
 
fventer@ezintsha.org 
Telephone: 
 
 
+27 11 084 4983 
Lead Investigator: 
 
Nomathemba Chandiwana 
Email:  
 
 
nchandiwana@ezintsha.org 
Mobile:  
 
 
+27 76 164 3215 
Research Pharmacist: 
 
Lebohang Mphahlele 
Address: 
 
 
Wits RHI Yeoville Research Centre 
 
 
 
 
35 Bedford Street, Cnr Dunbar 
 
 
 
 
Yeoville, 2001 
 
 
 
 
South Africa 
Telephone: 
 
 
+27 11 358 5848 
IRB/Ethics Committee:  
Human Research Ethics Committee 
Research Administrator: 
Ms Jennifer Palmer 
(email: jpalmer@witshealth.co.za)  
Telephone: 
 
 
+27 11 274 9278 
 
Satellite Site 
Satellite Site: 
 
 
Charlotte Maxeke Johannesburg Academic Hospital 
 
 
 
 
Area 585, Level 8 
 
 
 
 
Jubilee Road 
 
 
 
 
Johannesburg, 2193 
 
 
 
 
South Africa 
 


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Sponsor 
Institution: 
 
 
Shin Poong Pharm. Co., Ltd. 
Address: 
 
 
161 Yoksam-Ro, Gangnam-Gu 
 
 
 
 
Seoul, 06246 
 
 
 
 
Republic of Korea 
Project Director: 
 
Jandee Kim 
Email:  
 
 
jdkim@shinpoong.co.kr 
Telephone: 
 
 
+82 10 6263 5261 
 
Funder 
Institution: 
 
 
Medicines for Malaria Venture 
Address: 
 
 
ICC – Block G, 3rd Floor 
 
 
 
 
20, Route de Pré-Bois 
 
 
 
 
PO Box 1826 
 
 
 
 
1215 Geneva 15 
 
 
 
 
Switzerland 
Chief Medical Officer:  
Stephan Duparc 
Email:  
 
 
duparcs@mmv.org 
Telephone: 
 
 
+41 22 555 0351 / +41 79 446 2956 
Project Director: 
 
Farouk Chughlay 
Email:  
 
 
chughlayf@mmv.org 
Telephone: 
 
 
+41 22 555 0355 / +41 79 123 4289 
Clinical Trial Manager:  
Julia Flynn 
Email:  
 
 
flynnj-consultants@mmv.org 
Telephone: 
 
 
+41 79 905 9203 
 
Cinical Research Organisation 
Institution: 
 
 
Triclinium Clinical Development (TCD) 
Address: 
 
 
Design House 
 
 
 
 
121 Amkor Road 
 
 
 
 
Lyttleton Manor 
 
 
 
 
Centurion, 0157 
 
 
 
 
South Africa 
Project Manager: 
 
Fiona Storer 
Email:  
 
 
fiona.storer@tcd-global.com 
Telephone: 
 
 
+27 12 664 1622 / +27 82 853 6791 
 


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Independent Medical Monitor 
Institution: 
 
 
HJ-Clinical Trial Consultancy 
Address: 
 
 
15 Oaklands, Fancourt 
 
 
 
 
George, 6529 
 
 
 
 
South Africa 
Medical Monitor: 
 
Hilary Johnstone 
Email:  
 
 
hjohnstone@hjclinical.com 
Telephone: 
 
 
+27 83 704 4929 
 
Pharmacovigilance 
Institution: 
 
 
Quanticate 
Address: 
 
 
Bevan House  9-11 Bancroft Court 
 
 
 
 
Hitchin 
 
 
 
 
Hertfordshire 
 
 
 
 
SG5 1LH 
 
 
 
 
United Kingdom 
QPPV:  
 
 
Robert Miller, Artemida Pharma 
Email:  
 
 
robert.miller@artemidapharma.com 
Telephone: 
 
 
+44 203 291 3032 / +44 782 655 5254 
 


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APPENDIX 3:  
THE INFLUENZA PATIENT-REPORTED OUTCOME INSTRUMENT (FLU-PRO© Plus) 
To be completed on D1-14, D21 and D28: 
 
 
Copyright © 2014- 2020 Leidos Biomedical Research, Inc.  All Rights Reserved 
 


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Copyright © 2014- 2020 Leidos Biomedical Research, Inc.  All Rights Reserved 
 
 


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APPENDIX 4: 
DAILY SURVEY 
To be completed on D1-14, D21 and D28 
FLU-PRO© Plus GLOBAL ADDITIONAL DAILY DIARY ITEMS: 
Copyright © 2014- 2020 Leidos Biomedical Research, Inc.  All Rights Reserved 
Items to be asked in daily diary through to Day 14, and on Days 21 and 28 along with the FLU-PRO 
symptom items 
1. Overall, how severe were your infection symptoms today? (Please select one response only) 
0 
No flu symptoms today 
1 
Mild 
2 
Moderate 
3 
Severe 
4 
Very severe 
2. Overall, how were your infection symptoms today compared to yesterday? (Please select one 
response only) 
1 
Much better 
2 
Somewhat better 
3 
A little better 
4 
About the same 
5 
A little worse 
6 
Somewhat worse 
7 
Much worse 
3. How much did your infection symptoms interfere with your usual activities today? (Please select one 
response only) 
1 
Not at all 
2 
A little bit 
3 
Somewhat 
4 
Quite a bit 
4. Have you returned to your usual activities today? 
1 
Yes 
0 
No 


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5. In general, how would you rate your physical health today? (Please select one response only) 
5 
Excellent 
4 
Very Good 
3 
Good 
2 
Fair 
1 
Poor 
6. Have you returned to your usual health today? 
1 
Yes 
0 
No 
5 
Very much 
 
GENERAL DAILY DIARY ITEMS: 
1. Have you taken your daily medication since the last survey? 
 
Yes 
 
No 
 
Not applicable 
2. Take your vitals: (time of day: 
: 
 hh:mm) 
• 
Pulse 
 
 
 
 beats per minute 
• 
Temperature 
 
 
 °C 
• 
Respiratory rate 
 
 breaths per minute 
• 
Oxygen saturation level  
 % 
3. Have you taken any other medications? 
 
Yes 
 
No 
If “yes”, describe:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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4. Have you observed any change or new complaint since you last completed the survey? 
 
Yes 
 
No 
If “yes”, describe:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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APPENDIX 5: 
WHO ORDINAL SCALE FOR CLINICAL IMPROVEMENT 
Patient State 
Descriptor 
Score 
Uninfected 
No clinical or virological evidence of infection 
0 
Ambulatory 
No limitation of activities 
1 
 
Limitation of activities 
2 
Hospitalized: mild disease 
Hospitalized, no oxygen therapy 
3 
 
Oxygen by mask or nasal prongs 
4 
Hospitalized: severe disease 
Non-invasive ventilation or high-flow oxygen 
5 
 
Intubation and mechanical ventilation 
6 
 
Ventilation + additional organ support (pressors, RRT, ECMO) 7 
Dead 
Death 
8 
WHO COVID-19 Core Protocol 
SOLIDARITY Trial 
Version 10.0, March 22, 2020 
 
 


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APPENDIX 6: 
PROHIBITED CONCOMITANT MEDICATIONS 
The following drugs are known to induce prolongation of the QT-interval. Their use is not permitted in 
conjunction with the study drugs. Participants using these drugs at baseline, or those anticipated to 
require these during the study, should not be enrolled in the study. 
• 
antiarrhythmics (e.g., amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, 
hydroquinidine, sotalol) 
• 
neuroleptics (e.g., phenothiazines, sertindole, sultopride, chlorpromazine, haloperidol, mesoridazine, 
pimozide, or thioridazine) and antidepressant agents known to cause significant QT-interval 
prolongation (e.g., citalopram, escitalopram) 
• 
certain antimicrobial agents, including agents of the following classes: 
o 
macrolides (e.g,. erythromycin, clarithromycin) 
o 
fluroquinolones (e.g., moxifloxacin, sparfloxacin) 
o 
imidazole and triazole antifungal agents 
o 
pentamidine 
o 
saquinavir 
• 
certain non-sedating antihistamines (e.g., terfenadine, astemizole, mizolastine) 
• 
cisapride 
• 
droperidol 
• 
domperidone 
• 
bepridil 
• 
diphemanil 
• 
probucol 
• 
levomethadyl 
• 
methadone 
• 
vinca alkaloids 
• 
arsenic trioxide. 
Use of the following drugs is not permitted during the study due to potential drug-drug interactions. 
Participants using these drugs at baseline, or those anticipated to require these during the study, should 
not be enrolled in the study. 
• 
protease inhibitor-based antiretroviral regimens 
• 
efavirenz 
• 
rifampicin 
• 
carmabazepine. 

SAP_001.pdf: 
 
SP-PA-COV-202_SAP_amendment_2 
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DATAMAP GmbH 
Page 1 of 105 
 
 
 
 
 
 
 
A PHASE 2, EXPLORATORY, SINGLE CENTER, RANDOMIZED, OPEN LABEL, 
ADAPTIVE CLINICAL TRIAL TO COMPARE THE SAFETY AND EFFICACY OF 
FOUR DIFFERENT EXPERIMENTAL DRUG REGIMENS TO STANDARD OF 
CARE FOR THE TREATMENT OF SYMPTOMATIC OUTPATIENTS WITH COVID-
19 
SP-PA-COV-202 
 
 
 
Statistical Analysis Plan 
 
 
Author 
Daniel Windgassen, Project Biostatistician 
Version 
Version 1, Final amendment 2 
Date of version 
01-Mar-2022 
Approved by 
Wookyung Kim, Deputy Head of Research, Shin Poong Pharm.  Co., Ltd. 
Anne Claire Marrast, Senior Medical Director, MMV 
 
 
 
 


 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
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Signatures 
Author: 
 
 
 
 
 
 
 
 
 
 
DATAMAP GmbH 
(Date) 
(Signature) 
 
Approved by: 
 
 
 
 
 
Wookyung Kim 
Deputy Head of Research 
Shin Poong Pharm. Co., Ltd. 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Date) 
(Signature) 
Anne Claire Marrast 
Senior Medical Director 
MMV 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Date) 
(Signature) 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 3 of 105 
 
Document - History 
Version 
Date 
Responsible 
Change information 
Version 1, Draft 1 
20-Nov-2020 
Daniel Windgassen 
Initial draft version 
Version 1, Draft 2  
10-Dec-2020 
Daniel Windgassen 
Comments from draft 1 incorporated and outputs shells 
added. 
Version 1, Draft 3 
15-Dec-2020 
Daniel Windgassen 
Comments from wider team for draft 2 incorporated 
Version 1, Draft 4 
30-Jun-2021 
Daniel Windgassen 
Comments from wider team for draft 3 incorporated 
Version 1, Draft 5 
23-Jul-2021 
Daniel Windgassen 
Comments from wider team for draft 4 incorporated 
Version 1, final 
05-Aug-2021 
Daniel Windgassen 
Last comments incorporated. Track change mode 
removed. 
Version 1, 
amendment 1  
15-Oct-2021 
Daniel Windgassen 
Minor corrections and clarifications in text and TFL 
shells. 
Added programming notes where necessary. 
Added imputation rule for PK concentration and for viral 
load data. 
Added clarification on calculation of days of symptoms 
at time of enrolment. 
Aligned viral load endpoint with protocol, i.e. removed 
Day 21 and 28. 
Clarified exploratory PK analysis: removed 
corresponding cox regression. Removed visit windows 
for PK as concentrations outside of visit windows 
should not be excluded from the analysis. Added 
corresponding footnotes to PK outputs. 
Version 1, 
amendment 2 
01-Mar-2022 
Daniel Windgassen 
For the subgroups of sero-negative participants and for 
high-risk participants, the following post-hoc analyses 
were added respectively: 
• 
Summary of WHO Ordinal Scale for Clinical 
Improvement 
• 
Kaplan Meier analysis of time to first zero 
WHO Ordinal Scale score for Clinical 
Improvement 
• 
Cox regression analysis of time to first zero 
WHO Ordinal Scale score for Clinical 
Improvement 
 


Statistical Analysis Plan 
 
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Table of Contents 
Abbreviations ........................................................................................................................................... 5 
1. 
Introduction ....................................................................................................................................... 6 
2. 
Definitions and Data Conventions .................................................................................................... 6 
3. 
Analysis Sets .................................................................................................................................... 9 
4. 
General analysis considerations ...................................................................................................... 9 
5. 
Subject Disposition ......................................................................................................................... 10 
6. 
Demographic Data and Baseline Characteristics .......................................................................... 10 
7. 
Prior/ Concomitant Medications ..................................................................................................... 10 
8. 
Efficacy Analysis ............................................................................................................................ 10 
8.1 
Primary variable(s) .................................................................................................................. 10 
8.2 
Secondary and other variable(s) ............................................................................................. 11 
8.2.1 
Incidence of SARS-CoV-2 clearance............................................................................... 11 
8.2.2 
Time to clearance of SARS-CoV-2 .................................................................................. 12 
8.2.3 
Viral load of SARS-CoV-2 ................................................................................................ 12 
8.2.4 
Hospitalization .................................................................................................................. 13 
8.2.5 
Disease severity ............................................................................................................... 13 
8.2.6 
Symptom resolution ......................................................................................................... 15 
8.2.7 
Lower respiratory tract infection ....................................................................................... 15 
8.2.8 
All-cause Mortality............................................................................................................ 15 
9. 
Exposure to Study Drug ................................................................................................................. 16 
10. 
Safety Analysis ........................................................................................................................... 16 
10.1 
Adverse events .................................................................................................................... 16 
10.2 
Vital signs ............................................................................................................................ 17 
11. 
Exploratory Analyses .................................................................................................................. 17 
12. 
Interim Analyses ......................................................................................................................... 18 
13. 
Change to Protocol Specified Analyses ..................................................................................... 18 
14. 
List of Tables and Figures .......................................................................................................... 19 
15. 
List of Data Listings and Statistical Tabulations ......................................................................... 21 
16. 
Output Shells .............................................................................................................................. 23 
17. 
Appendices ............................................................................................................................... 104 
17.1 
FLU-PRO total and domain scoring .................................................................................. 104 
 
 
 


Statistical Analysis Plan 
 
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Abbreviations 
AE 
Adverse event 
ASAQ 
Artesunate-amodiaquine 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body mass index 
CT 
Cycle threshold 
FLU-PRO 
Influenza patient-reported outcome 
FPV-NTZ 
Favipiravir plus nitazoxanide 
MAR 
Missing at random 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intention to Treat 
LRTI 
Lower respiratory tract infection 
LSM 
Least Square Means 
PA 
Pyronaridine-artesunate 
PK 
Pharmacokinetic 
RR 
Respiratory rate 
RT-PCR 
Reverse transcription polymerase chain reaction 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SE 
Standard Error 
SOC 
Standard of care  
SOF/DCV 
Sofosbuvir/daclatasvir 
SpO2 
Oxygen saturation 
TEAEs 
Treatment emergent adverse event 
WHO 
World Health Organization 
 


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1. 
Introduction 
This analysis plan is based on the study protocol SP-PA-COV-202 version 4, dated 17-November-
2020. All analyses will be performed by DATAMAP GmbH, Freiburg, Germany using SAS, version 
9.4 in a Linux environment. 
This is a randomized, single center, open label, adaptive, exploratory trial. The trial is comprising four 
experimental interventions (Arms B to E) to assess the efficacy of each intervention  as measured by a 
reduction in viral shedding compared to standard of care (SOC) (Arm A). Participants are randomized 
to one of these treatment arms in a 1:1:1:1:1 ratio. The overarching goal of this study is to assess the 
efficacy of interventions to reduce virus shedding among adult outpatients with mild SARS-CoV-2 
infection. Additional objectives include clinical outcomes related to SARS-CoV-2 infection and 
tolerability of the interventions. 
2. 
Definitions and Data Conventions 
Study days 
Study days will be calculated as actual date minus date of study drug intake + 1 if the actual date is 
greater or equal to the date of study drug intake. If the actual date is earlier than the date of study drug 
intake the study day will be calculated as actual date minus date of study drug intake + 1. Hence the 
day of the study drug intake will be defined as Day 1. 
Baseline 
Baseline for analysis purposes if not otherwise defined will be the last measurement prior to the first 
study drug administration, or where this is not available, the earliest measurement performed on the 
first day of study drug administration. 
Fever 
Fever is defined as oral body temperature ≥38°C. 
Baseline comorbidities 
Baseline comorbidities will be defined by the participants having none, 1 or more than 1 comorbidity as 
defined in the pre-specified medical history terms in the eCRF. 
Baseline viral load category 
A baseline viral load category will be determined by quantitative RT-PCR results (copies/mL) of the N 
gene. Participants will be assigned to the low/high baseline viral load category based on the median 
baseline viral load of all participants in the mITT Analysis Set. Participants with viral load below the 
median are assigned to the low category, participants with viral load equal to or higher than the 
median are assigned to the high category. 
High-risk participants 
Participants will be assigned in the high-risk category if they have at least one of the following risk factors: 
BMI > 30, baseline comorbidities of at least one or more or aged > 60 years. Otherwise participants are 
assigned to the low risk category. 
 
Time windows for analysis 
To account for potential deviations from the visit schedule and unscheduled assessments, all "by time 
point" summaries will be based on analysis visits, which will be assigned based on a time window 
around the scheduled time point. Please note that the window is only used for the summaries by time 
point. In all participant-specific displays and time to event analyses the exact timing of the 
assessments will be used. If more than one assessment falls into a time window the one closest to the 
target time point will be used for summarization. If two assessments are equally close the later will be 
chosen. The following windows will be used: 
 


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Mid-nasal swab data 
Scheduled time point 
Window 
Baseline 
last assessment prior to or on the 
day of first study drug 
administration  
Day 3 
Day 3 - 4 
Day 7 
Day 6 - 8 
Day 10 
Day 9 - 11 
Day 14 
Day 12 - 16 
Day 21 
Day 19 - 23 
Day 28 
Day 26 - 30 
End of study 
Overall last available assessment 
 
Viral culture data  
Scheduled time point 
Window 
Baseline 
last assessment prior to or on the 
day of first study drug 
administration  
Day 7 
Day 6 - 8 
Day 10 
Day 9 - 11 
 
Vital signs data 
Scheduled time point 
Window 
Baseline 
Screening/enrollment assessment 
by study personnel prior to first 
study drug administration. If it is 
not available, the last assessment 
prior to or on the day of first study 
drug administration will be used. 
Day 2 
Day 2 
Day 3 
Day 4 
Day 3 
Day 4 
Day 5 
Day 5 
Day 6 
Day 6 
Day 7 
Day 7 
Day 8 
Day 8 
Day 9 
Day 9 
Day 10 
Day 10 
Day 11 
Day 11 
Day 12 
Day 12 
Day 13 
Day 13 
Day 14 
Day 14 - 16 
Day 21 
Day 19 - 23 


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Day 28 
Day 26 - 30  
End of study 
Overall last available assessment 
 
FLU-PRO Plus© questionnaire data 
Scheduled time point 
Window 
Baseline 
last assessment prior to or on 
the day of first study drug 
administration  
Day 2 
Day 2 
Day 3 
Day 3 
Day 4 
Day 4 
Day 5 
Day 5 
Day 6 
Day 6 
Day 7 
Day 7 
Day 8 
Day 8 
Day 9 
Day 9 
Day 10 
Day 10 
Day 11 
Day 11 
Day 12 
Day 12 
Day 13 
Day 13 
Day 14 
Day 14 - 16 
Day 21 
Day 19 - 23 
Day 28 
Day 26 - 30  
End of study 
Overall last available 
assessment 
 
WHO Ordinal Scale for Clinical Improvement 
Scheduled time point 
Window 
Baseline 
last assessment prior to or on the 
day of first study drug 
administration 
Day 7 
Day 6 – 8 
Day 14 
Day 12 - 16 
Day 21 
Day19 – 23 
Day 28 
Day 26 – 30 
End of study 
Overall last available assessment 
 
Serology 
Scheduled time point 
Window 
Baseline 
last assessment before dosing 
Day 28 
Day 26 – 30 


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3. 
Analysis Sets 
The following analysis sets are defined: 
Randomized Analysis Set 
All enrolled participants who were randomized. Analyses will be performed by using randomized 
treatment. 
Safety Analysis Set 
All enrolled participants who receive at least one dose of randomized treatment will be included in the 
Safety Analysis Set. Analyses will be performed by using actual treatment. 
Modified Intention to Treat (mITT) Analysis Set 
All enrolled participants with confirmed SARS-CoV-2 infection (based on qualitative RT-PCR, either mid-
nasal swab or saliva/combination sample) who receive at least one dose of randomized treatment will 
be included in the Modified Intention to Treat Analysis Set. Only randomized participants are included 
and randomized treatment will be used in the analysis. The primary analyses and all secondary 
endpoints except for safety analyses will be assessed using the mITT Analysis Set.  
As Treated Analysis Set 
All enrolled participants who complete the course of randomized treatment and have qualitative SARS-
CoV-2 RT-PCR results (either mid-nasal swab or saliva/combination sample) for Day 7 (+/- 1 Day). 
Analyses will be performed by using actual treatment instead of randomized treatment. The As Treated 
analysis set will be used for a sensitivity analysis of the primary analysis. A participant will be considered 
as having completed the course of treatment if he/she took all scheduled experimental treatment doses 
(ASAQ or PA) or if he/she took at least 6 out of 7 scheduled experimental treatment doses (SOF/DCV) 
or 12 out of 14 scheduled experimental treatment doses (FPV-NTZ).  
For FPV-NTZ arm both study drugs, FPV and NTZ, must reach at least 85% compliance. For NTZ the 
rules are based on tablet counts (as detailed above). For FPV the compliance calculated is based on 
the total dose, see section 9. Additionally, for FPV the intake of the loading dose (two times 1600 mg) 
on day 1 must be complete. 
Pharmacokinetic (PK) Analysis Set 
All enrolled participants who were randomized and received at least one dose of treatment and with at 
least one PK result available. 
4. 
General analysis considerations 
Continuous data will be summarised by treatment arm with the number of observations, mean, 
standard deviation, median, minimum and maximum, and quartiles. Categorical data will be 
summarised by number and percentage of participants per treatment arm and overall.  
There will five treatment arms (Arm A to Arm E) with Arm A being standard of care (reference arm) 
and Arm B to Arm E being four different experimental drug regimens. The following treatment arm 
labels will be used in the outputs: 
• 
Label used for treatment arm A: SOC 
• 
Label used for treatment arm B: ASAQ 
• 
Label used for treatment arm C: PA 
• 
Label used for treatment arm D: FPV-NTZ 
• 
Label used for treatment arm E: SOF/DCV 
As treatment for Arm A is to be administered on an as needed basis only, all participants in this arm 
will be considered compliant and to have completed the course of treatment. Since this is an 
exploratory, screening study, multiplicity issues will not be considered.  
The following variables will be used in covariate adjusted analyses: age at baseline (years), sex, BMI 
at baseline, baseline comorbidities, baseline viral load category and days of symptoms at time of 
enrollment. Of these variables age at baseline, sex and BMI at baseline will be non-missing for 
randomized participants. If a participant has no baseline comorbidities recorded, he will be counted in 
the 'None' category. If a patient's CRF item days of symptoms at time of enrolment is missing then it 
will be calculated as the duration from the medical history start date of Covid-19 to the informed 
consent date. 


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All RT-PCR-specific analyses will be using mid-nasal swab results only. 
All analyses of quantitative SARS-CoV-2 RT-PCR (viral load) are based on the N gene. 
5. 
Subject Disposition 
Summary tables of participant disposition will be provided for the Randomized Analysis Set by treatment 
arm and overall. The following data will be displayed: 
• 
The number and percentage of participants randomized, treated, completed, prematurely 
withdrawn. 
• 
The number and percentage by reasons for withdrawal. 
The number and percentage of participants in each analysis set will be summarized by treatment arm 
and overall. The reasons leading to exclusion from any analysis set will be presented as well. 
All protocol deviations will be summarized by treatment arm and overall. 
6. 
Demographic Data and Baseline Characteristics 
Participant demographic data and baseline characteristics will be summarised by treatment arm and 
overall for the mITT Analysis Set. Standard summary statistics will be used, as appropriate. The 
following summaries will be generated: 
• 
Participant demographics: sex, age (additionally split by sex), race, body weight, height, BMI. 
• 
Baseline characteristics: 
o 
Temperature, pulse rate, respiratory rate (RR), SpO2, number of days with symptoms 
at time of enrollment and WHO Ordinal Scale score for Clinical Improvement. 
• 
Medical and surgical history terms will be coded according to the Medical Dictionary for 
Regulatory Activities (MedDRA) version 23.0 or later and will be summarised by primary system 
organ class and preferred term by treatment regimen and overall. Medical histories of COVID-
19 will not be included in this analysis. Additionally, a table containing only comorbidities pre-
specified in the CRF will be displayed. 
Physical examination findings will be listed. 
7. 
Prior/ Concomitant Medications 
Prior medications will be those that were taken prior to study entry and were stopped prior to the day of 
first study drug intake. Concomitant medications will be those that were given from the day of first study 
drug intake until study termination, irrespective of whether they started before the first study drug intake 
and continued into the study or whether they were newly started on or after first study drug intake. Prior 
and concomitant medications will be coded according to the latest release of the WHO drug dictionary 
in effect at the time of study start.  
Prior and concomitant medications will be summarized separately by Anatomical / Therapeutical / 
Chemical (ATC) class 3 and preferred term. 
All prior and concomitant medications will be listed by participant. These will include ATC classification 
and WHO preferred terms. 
Prior and concomitant medication will be summarized for the Safety Analysis Set. 
8. 
Efficacy Analysis 
8.1 
Primary variable(s) 
The mITT Analysis Set will be used for the primary analysis. 
The primary efficacy variable is incidence of SARS-CoV-2 clearance defined as the proportion of 
participants with a negative SARS-CoV-2 RT-PCR test on Day 7. The analysis will be performed using 
a log-binomial model. SARS-CoV-2 RT-PCR test on Day 7 (yes/no) will be the response variable. 
Treatment, age at baseline (years), sex, BMI at baseline, baseline comorbidities, baseline viral load 
category and days of symptoms at time of enrollment will be used as covariates. The analysis will be 


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repeated using a crude log-binomial regression model without any covariate adjustment. The main 
conclusions will be drawn from the adjusted analysis. 
If the log-binomial model specified above does not converge a generalized linear regression with a log 
link, Poisson distribution, instead of Binomial distribution, will be used. If neither model converges a 
Normal distribution instead of a Poisson distribution will be used.  
Estimates, two-sided 95% confidence intervals and corresponding p-values will be provided for the 
adjusted risk ratios that compare each experimental arm against the standard of care arm.  
Participants who discontinue the study prior to the day 7 assessment of SARS-CoV-2 RT-PCR test 
because of an adverse event are counted as having a positive SARS-CoV-2 RT-PCR test on Day 7. 
Values from participants who discontinue the study prior to the day 7 assessment of SARS-CoV-2 RT-
PCR test due to other reasons remain missing. Other participants with a missing Day 7 assessment will 
be imputed as positive. A time window from Day 5 to Day 9 will be used for the day 7 assessment. 
In the first sensitivity analysis all participants who discontinue prior to the day 7 SARS-CoV-2 RT-PCR 
test are imputed as having a positive of SARS-CoV-2 RT-PCR test on Day 7. As a second sensitivity 
analysis the primary analysis will be repeated using the As Treated Analysis Set. Actual treatment 
received instead of randomized treatment will be utilized in the analysis. 
 
Additionally, the number and percentage of participants with negative SARS-CoV-2 RT-PCR test at Day 
7 will be displayed. 
Subgroup analyses will be done for all covariates. The covariates age and days of symptoms at time of 
enrollment will be categorized according to the respective median of the covariate based on all patients 
in the mITT Analysis Set. The following subgroup analysis will be performed 
• 
Age group at baseline (low: age (years) <= median, high: age (years) > median) 
• 
Sex (male, female) 
• 
BMI at baseline (low: BMI <= 30, high: BMI > 30) 
• 
Baseline comorbidities (none, one or more) 
• 
Baseline viral load category (low, high) 
• 
Days of symptoms at time of enrollment (low: days of symptoms at time of enrollment <= median, 
high: days of symptoms at time of enrollment > median). 
• 
Baseline risk category (low, high) 
The primary regression model will be calculated for each subgroup variable by adding an interaction 
between the treatment arm and the respective subgroup variable. The p-value of the interaction will be 
displayed as well as the overall and the by-subgroup risk ratios comparing each experimental arm 
against the standard of care arm and the respective 95% CIs. In case the respective subgroup variable 
was defined by categorizing a continuous variable, the continuous variable will be replaced by the 
categorized version in the model. 
8.2 
Secondary and other variable(s) 
All secondary endpoints will be assessed in the mITT Analysis Set. All analyses will be done by 
treatment arm, and overall if applicable. 
8.2.1 
Incidence of SARS-CoV-2 clearance 
Analyses based on viral culture 
The incidence of SARS-CoV-2 clearance on Day 7 (defined as the proportion of participants with 
negative SARS-CoV-2 viral cultures on both Day 7 and Day 10 in the subset of participants for whom 
these assessments are performed and results are available) will be analyzed using a log-binomial 
regression model in which the response variable will be SARS-CoV-2 clearance on Day 7 (yes/no). 
Treatment, age at baseline (years), sex, BMI at baseline, baseline comorbidities, baseline viral load 
category, and days of symptoms at time of enrollment will be used as covariates. Similar to the primary 
analysis, if the log-binomial model specified above does not converge a generalized linear regression 
with a log link, Poisson distribution, instead of binomial distribution, will be used. If neither model 
converges a normal distribution instead of a Poission distribution will be used. 
Participants who discontinue the study prior to Day 7 will be excluded from the analysis. If a positive 
result is present either at Day 7 or Day 10 while the other assessment is missing, the outcome will be 


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classified as positive overall. If a negative result is present at either Day 7 or Day 10 while the other 
assessment is missing (or both or missing), the participant will be excluded from the analysis.  
Additionally, the number and percentage of participants with SARS-CoV-2 clearance on Day 7 
determined by viral culture will be displayed. 
Only patients with positive viral culture at baseline are included in the analyses above. 
 
Analyses based on SARS-CoV-2 RT-PCR test 
The incidence of SARS-CoV-2 clearance (defined as the proportion of participants with negative of 
SARS-CoV-2 RT-PCR test) on Days 3, 10, 14, 21 and 28 will be analyzed similarly to the primary efficacy 
variable.  
Separate log-binomial regressions will be used to analyze the categorical variable SARS-CoV-2 
clearance (yes/no) at each time point. Treatment, age at baseline (years), sex, BMI at baseline, baseline 
comorbidities, baseline viral load category and days of symptoms at time of enrollment will be used as 
covariates. In case of non-convergence a poisson regression, similar to the primary analysis, will be 
used. If the Poisson regression does not converge, a Normal distribution will be used instead. 
If the result at Day X (3, 10, 14 21, or 28) is missing then the result at Day X will be classified as positive 
if the test at the preceding visit was positive or if any subsequent test was positive. However, if the 
preceding test was negative and there were no subsequent positive tests, then the result will be 
classified as negative.  
Additionally, the number and percentage of participants with negative of SARS-CoV-2 RT-PCR test will 
be displayed for Days 3, 10, 14, 21 and 28. 
8.2.2 
Time to clearance of SARS-CoV-2 
Kaplan Meier analysis will be performed for the time to clearance of SARS-CoV-2, defined as the time 
to first negative qualitative SARS-CoV-2 RT-PCR test (collected post-baseline on Days 3, 7, 10, 14, 21 
and 28) without any subsequent positive qualitative SARS-CoV-2 RT-PCR test. 
Data from participants who do not experience the defined event will be censored as follows: 
• 
Participants who withdraw from the study early due to any reason will be censored on the day 
of the last available of SARS-CoV-2 RT-PCR test measurement 
• 
Participants who continue in the study but have all remaining SARS-CoV-2 RT-PCR tests 
missing from a given point in time onward will be censored on the day of the last available 
SARS-CoV-2 RT-PCR test measurement 
• 
Participants without any post-baseline SARS-CoV-2 RT-PCR data will be censored at Day 1 
(duration of 1 day) 
Kaplan-Meier estimates and corresponding 2-sided 95% confidence intervals will be provided for time 
to clearance of SARS-CoV-2 until Day 7, Day 14, Day 21 and Day 28. The 25th, 50th and 75th percentiles 
of time to clearance and corresponding 2-sided 95% confidence intervals will be presented. 
Kaplan-Meier curves for time to clearance of SARS-CoV-2 will be generated including the p-value of the 
log-rank test. 
Time to first negative qualitative SARS-CoV-2 RT-PCR test without any subsequent positive qualitative 
SARS-CoV-2 RT-PCR test will also be analysed using Cox proportional hazards regression model. 
Covariates will be the same as in the regression model for the primary analysis. Hazard ratios, 
comparing each experimental arm against the standard of care arm, and the associated 95% confidence 
intervals will be presented. 
 
The Kaplan Meier analysis and the Cox regression analysis will be repeated using quantitative RT-PCR 
based on the N gene instead of qualitative RT-PCR. The time to first quantitative SARS-CoV-2 RT-PCR 
test with zero count without any subsequent count above zero will be analysed.  
 
The Kaplan-Meier analyses using quantitative RT-PCR will be repeated in the subset of participants with 
high viral load at baseline and high-risk participants respectively. 
8.2.3 
Viral load of SARS-CoV-2 
Descriptive statistics for the log10 transformed viral load of SARS-CoV-2 detected by quantitative RT-
PCR based on the N gene and corresponding change from baseline will be presented by time point 


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(Baseline, Day 3, Day 7, Day 10, Day 14). For the descriptive analysis and the mixed-effect linear model 
viral load values of 0 will be imputed with half of the lower limit of quantification (LLOQ) before log10 
transformation. The lower limit of quantification is 20 copies/ml.  
The covariate adjusted mean change from baseline for log10 transformed viral loads for each treatment 
arm will be obtained from a mixed-effect linear model for repeated measures (MMRM) with treatment, 
age at baseline (years), sex, BMI at baseline, baseline comorbidities, baseline viral load category, days 
of symptoms at time of enrollment and treatment-by-visit interaction as fixed effects. An unstructured 
covariance matrix will be assumed for the within subject repeated measurements, and Kenward-Rogers 
type degrees of freedom will be used. If the model fails to converge with unstructured covariance matrix, 
either a compound symmetry (first choice) or first order autoregressive (AR1) (second choice) 
covariance structure will be used. 
The SAS procedure PROC MIXED will be used for analysis. Results will be presented with least-square 
mean (LSM) change, standard error (SE) and associated two-sided 95% confidence interval for 
treatment effects and LSM, SE, associated two-sided 95% confidence interval, and two-sided p value 
for treatment contrasts of each experimental arm versus the standard of care arm. 
 
The model above will be repeated using the subset of high-risk participants. 
 
A spaghetti plot which displays the individual log10 transformed viral loads of SARS-CoV-2 (detected 
by quantitative RT-PCR) of each participant from baseline until Day 28 by treatment arm will be 
presented.  
8.2.4 
Hospitalization 
The response variable hospitalization up to day 28 (yes/no) will be analyzed using logistic regression. 
Treatment, age at baseline (years), sex, BMI at baseline, baseline comorbidities, baseline viral load 
category and days of symptoms at time of enrollment will be used as covariates. Estimates, two-sided 
95% confidence intervals and corresponding p-values will be provided for the adjusted odds ratios that 
compare each experimental arm against the standard of care arm.  
Time to first hospitalization (in days) will be analysed using Kaplan-Meier methodology. 
Data from participants who do not experience the defined event will be censored as follows: 
• 
Participants who withdraw from the study early due to any reason will be censored on the day 
of study termination. 
Kaplan-Meier estimates and corresponding 2-sided 95% confidence intervals will be for Day 7, Day 14, 
Day 21 and Day 28. The 25th, 50th and 75th percentiles of time to first hospitalization and corresponding 
2-sided 95% confidence intervals will be presented. 
Kaplan-Meier curves for time to clearance of SARS-CoV-2 will be generated including the p-value of the 
log-rank test. 
Time to first hospitalization will also be analysed using Cox proportional hazards regression model. 
Covariates will be the same as in the regression model for the primary analysis. Hazard ratios, 
comparing each experimental arm against the standard of care arm, and the associated 95% confidence 
intervals will be presented. 
The cumulative incidence of hospitalization at Day 28, defined by the number of participants hospitalized 
up to and including Day 28 divided by the number of participants in the mITT Analysis Set, will be 
presented. The p-value of fisher's exact test will be provided for comparison of each experimental arm 
against the standard of care arm. 
Number of days hospitalized will be described graphically using a bar chart and will be summarized 
using standard statistics for continuous data as well as interquartile range. 
In general, only hospitalizations related to COVID-19 are analysed. Patients hospitalized within the first 
24h after first study drug intake will be excluded from the analysis. 
8.2.5 
Disease severity 
Disease severity as measured by the WHO Ordinal Scale for Clinical Improvement (Appendix 5) will be 
compared between the treatment arms using a longitudinal proportional odds model.  


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The response variable WHO Ordinal Scale score for Clinical Improvement measured at the post-
baseline time points Day 7, Day 14, Day 21 and Day 28 is ordered from score 0 to 8 (0 < 1 < 2 < … < 
8). Time point, treatment and treatment-by-time point interaction will be included as fixed-effect factors. 
Baseline age (in years), sex, baseline BMI, baseline WHO Ordinal Scale score, baseline comorbidities, 
baseline viral load category and days of symptoms at time of enrollment will be included as covariates. 
Participant-specific intercepts will be included as random effects. The estimated adjusted odds ratios 
comparing each experimental arm against the standard of care arm at each time point (Day 7, Day 14, 
Day 21 and Day 28) together with the associated two-sided 95% confidence intervals will be provided. 
The analysis will be performed with an assumption of missing at random (MAR) for missing data in the 
response variable. The proportional odds assumption will be investigated. If the assumption does not 
hold the results of the analysis have to be interpreted with caution.  
If convergence problems arise due to the high number of categories of the response variable then a 
condensed response variable, patient state, will be used instead of the WHO Ordinal Scale score for 
Clinical Improvement. The score categories would be condensed as follows: 
WHO Ordinal Scale score 
for Clinical Improvement 
Patient state 
0 
0 
1, 2 
1 
3, 4 
2 
5, 6, 7 
3 
8 
4 
If convergence problems persist for condensed response variables then patients will be classified into 
two categories (any post-baseline worsening by at least 1 category of the WHO ordinal scale score 
compared to baseline, no worsening of at least 1 category at any time point post-baseline compared to 
baseline). Using this classification, a logistic regression model, using the same covariates as in the 
primary analysis, will be calculated. Estimates, two-sided 95% confidence intervals and corresponding 
p-values will be provided for the adjusted odds ratios that compare each experimental arm against the 
standard of care arm.   
Summary statistics for the maximum score on WHO Ordinal Scale for Clinical Improvement during study 
participation will be presented and results for each participant will be listed. The proportion of patients 
whose worst post-baseline WHO Ordinal Scale score improved, stayed equal or worsened compared to 
baseline will be provided. 
 
Time to first zero WHO Ordinal Scale score (in days) defined as time to first zero score without any 
subsequent non-zero score will be analysed using Kaplan-Meier methodology. Participants with a WHO 
Ordinal Scale score of zero at baseline will be excluded from the analysis. 
Data from participants who do not experience the defined event will be censored as follows: 
• 
Participants who withdraw from the study early due to any reason will be censored on the day 
of last available WHO Ordinal Scale for Clinical Improvement assessment. 
• 
Participants who continue in the study but have all remaining WHO Ordinal Scale for Clinical 
Improvement assessments missing from a given point in time onward will be censored on the 
day of the last available WHO Ordinal Scale for Clinical Improvement assessment. 
• 
Participants without any post-baseline WHO Ordinal Scale for Clinical Improvement 
assessment data will be censored at Day 1 (duration of 1 day). 
Kaplan-Meier estimates and corresponding 2-sided 95% confidence intervals will be for Day 7, Day 14, 
Day 21 and Day 28. The 25th, 50th and 75th percentiles of time to first zero score and corresponding 2-
sided 95% confidence intervals will be presented. 
Kaplan-Meier curves will be generated including the p-value of the log-rank test. 


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Time to first zero WHO Ordinal Scale Score (as defined above) will also be analysed using Cox 
proportional hazards regression model. Covariates will be the same as in the regression model for the 
primary analysis. Hazard ratios, comparing each experimental arm against the standard of care arm, 
and the associated 95% confidence intervals will be presented. 
 
8.2.6 
Symptom resolution 
The number of days with fever after randomization, the number of days with respiratory symptoms 
(chest/respiratory FLU-PRO domain score >0) after randomization, and the number of days with 
Sp02<93% after randomization will be modeled using Poisson regression with an offset for number of 
days of observation (i.e. number of days with corresponding daily vitals/chest/respiratory FLU-PRO 
domain score data non-missing after randomization). Treatment, baseline viral load category and 
baseline comorbidities will be included as factor, age at baseline (years), sex, BMI at baseline and days 
of symptoms at time of enrollment will be included as covariates. Estimates of incidence rates (number 
of events per 100 person-days) and corresponding two-sided 95% confidence intervals will be presented 
for each experimental arm and the standard of care arm. Additionally, the incidence rate ratios (IRR) 
and corresponding two-sided 95% confidence intervals will be provided that compare each experimental 
arm against the standard of care arm.  
The endpoint relating to SpO2 will be calculated for all participants that had SpO2 ≥95% at baseline. 
SpO2 assessments <93% are only counted if they are confirmed by a repeat assessment which must 
be between 1 and 12 hours after the initial SpO2 reading. The analysis for SpO2 will be done once only 
for plausible SpO2 values and once for all available SpO2 values. Implausible SpO2 values are defined 
as values below 87% with no associated difficulty in breathing or chest tightness (as determined by 
medical review of FLU-PRO and other eCRF data). 
The FLU-PRO© Plus questionnaire will be measured daily during the first 14 days, at Day 21 and at Day 
28. The questionnaire is composed of 32 items. From these items six domain scores for the body areas 
Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, and Body/Systemic can be computed ranging 
from 0 (symptom free) to 4 (very severe symptoms). A total score is calculated as well. The domain 
scores and the total score will be calculated for each time point. The derivation rules for the domain 
score and the total score can be found in Section 17.1. The domain scores and the total score and their 
corresponding changes from baseline will be displayed by time point with the number of observations, 
mean, standard deviation, median, minimum and maximum, and quartiles. 
Both the FLU-PRO© Plus questionnaire and the FLU-PRO© Plus Global Additional Daily Diary Items, 
including daily survey items not related to vital signs, will be listed for each participant. 
8.2.7 
Lower respiratory tract infection 
Lower respiratory tract infection (LRTI) is defined by resting SpO2<93% sustained for 2 readings 2 hours 
apart and presence of either subjective dyspnea or cough (or both). The repeat SpO2 assessment must 
be between 1 and 12 hours after the initial SpO2 reading. In order to identify the LRTIs all possible 
cases are first determined programmatically using only the SpO2 readings. Medical review will then 
review these possible cases in conjunction with clinical symptoms and decide whether the LRTI 
definition is fulfilled or not.  
The cumulative incidence of LRTI at Day 28, defined by the number of participants developing LRTI up 
to and including Day 28 divided by the number of participants in the mITT Analysis Set that had SpO2 
≥95% at baseline, will be presented. Corresponding two-sided 95% CIs, calculated according to the 
Wilson method without continuity correction, will be displayed. 
The above analysis will be done once only for plausible SpO2 values and once for all available SpO2 
values. Plausible values are defined in Section 8.2.6. 
8.2.8 
All-cause Mortality  
The cumulative incidence of all-cause mortality at Day 28 defined by the number of participants who 
died up to and including Day 28 divided by the number of participants in the mITT Analysis Set will be 
presented. Participants who are hospitalized at the time of Day 28 and die later also count to the 
numerator. Corresponding two-sided 95% CIs, calculated according to the Wilson method without 
continuity correction, will be displayed. 


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9. 
Exposure to Study Drug 
The study drug compliance will be presented using standard summary statistics for each experimental 
treatment arm for the Safety Analysis Set. Additionally, compliance will be categorized using <85% and 
>=85% and the corresponding number and percentage will be displayed. The compliance will only be 
calculated and displayed for the experimental treatments, as Paracetamol follows no clear dosing 
regimen and is taken as needed to the maximum allowed daily dose.   
Compliance is calculated by using the total number of tablets actually taken divided by the total 
scheduled number of tablets based on the participant's randomized treatment arm multiplied with 100. 
The total number of tablets actually taken is derived as the total number of tablets dispensed minus the 
total number of tablets returned. The total scheduled number of tablets for each experimental treatment 
arm can be found in the table 1 below. For experimental arm D the compliance for NTZ is calculated as 
detailed above. For FPV the compliance is calculated as the total dose actually taken divided by the 
total planned dose multiplied with 100. The total dose actually taken is derived as the sum of the total 
number of tablets actually taken (see derivation above) multiplied with corresponding dosage 
formulation (200 mg or 400 mg). The total planned dose for FPV is 10400 mg. The compliance for each 
drug is presented separately. 
 
Table 1 
Treatment 
arm 
Study 
drug 
Total daily 
number of 
scheduled tablets 
Arm B 
ASAQ 
6 
Arm C 
PA 
9 
(body 
weight 
>=45 kg - < 65 kg) 
12 (body weight 
>= 65 kg) 
Arm D 
 
FPV 
Based 
on 
total 
planned 
dose 
(10400 mg). 
NTZ 
28 
Arm E 
SOF/DCV 
7 
 
Details on the administration of the investigational drug, including number of tablets dispensed, number 
of tablets returned, date, time and compliance of dosing will be listed by participant. The listing will be 
done for the Safety Analysis Set. 
PK analyses with respect to exposure to study drug are detailed in section 11. 
10. 
Safety Analysis 
All safety analyses will be performed on the Safety Analysis Set by treatment arm and overall. 
10.1 
Adverse events 
All treatment emergent adverse events (TEAEs), i.e., adverse events (AEs) which newly started or 
increased in intensity on or after the day of first study drug administration will be considered for 
summarization. Adverse events will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA) version 23.0 or later. The severity grading of AEs will be done according to the 
DAIDS AE Grading Table, corrected Version 2.1, July 2017.   
TEAEs will be summarized by presenting the number and percentage of participants having at least 
one TEAE, having a TEAE in each primary system organ class and having each individual TEAE 
(preferred term). 
The number and percentage of participants and the numbers of events will be presented by primary 
system organ class and preferred term for the following summaries: 


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• 
TEAEs. 
• 
Serious TEAEs. 
• 
Study drug related TEAEs/serious TEAEs.  
• 
TEAEs/serious TEAEs leading to study drug discontinuation. 
• 
TEAEs leading to death. 
• 
TEAEs leading to hospitalization. 
Additionally, TEAEs will be summarized with number and percentage of participants and the numbers 
of events by primary system organ class, preferred term and maximum severity. For summaries by 
maximum severity the following applies: if a participant reported more than one adverse event with the 
same preferred term, the adverse event with the greatest severity will be presented. If a participant 
reported more than one adverse event within the same primary system organ class, the participant will 
be counted only once with the greatest severity at the system organ class level. 
For the legal requirements of ClinicalTrials.gov a summary of treatment emergent adverse events which 
are not serious adverse events with an incidence greater than 5% in at least one treatment arm will be 
provided by primary system organ class and preferred term on the Safety Analysis Set. 
 
All information obtained on AEs will be displayed in appropriate data listings by treatment arm and 
participant. 
10.2 
Vital signs 
Absolute values and changes from baseline in vital signs (temperature (°C), pulse (beats/min), 
respiratory rate (breaths/min) and SpO2 (%)) will be summarized by time point with the number of 
observations, mean, standard deviation, median, minimum and maximum, and quartiles. 
11. 
Exploratory Analyses 
All exploratory analyses relating to PK will be performed using the PK Analysis Set. All other exploratory 
analyses will be performed using the mITT Analysis Set. 
 
Drug exposure 
Plasma/whole blood Cday 3 and Cday 7 concentrations on Day 3 (Arms B and C) and Day 7 (Arms B to E) 
will be displayed by treatment arm for each component using summary statistics. Concentrations below 
the lower limit of quantification (LLOQ) will be imputed with LLOQ/2. 
 
Relationship between efficacy and plasma or whole blood concentrations of the study drugs 
Plasma or blood concentrations of each component at Day 3 (Cday 3, for ASAQ and PA arms) and/or Day 
7 (Cday 7, for all participants in the experimental arms), will be displayed using a scatter plot. Participants 
will be displayed by SARS-CoV-2 clearance on Day 7 (as defined for the primary endpoint) and 
exploratory arm. Concentrations below the lower limit of quantification (LLOQ) will be imputed with 
LLOQ/2. 
 
Immune response 
Seroconversion as assessed by means of a validated serological assay will be a qualitative outcome 
(positive, negative). A shift table comparing baseline and Day 28 results will be displayed. 
 
Relationship between sample RT-PCR results, their cycle threshold values, and corresponding 
viral culture results for SARS-CoV-2 
The proportion of participants with low viral load (log10 viral load < 6) on Day 7 will be analyzed similarly 
to the primary analysis using a log-binomial regression adjusted for the same covariates. If the log-
binomial model specified above does not converge a generalized linear regression with a log link, 
poisson distribution, instead of binomial distribution, will be used. If neither model converges a Normal 
distribution instead of a Poisson distribution will be used. 
Estimates, two-sided 95% confidence intervals and corresponding p-values will be provided for the 
adjusted risk ratios that compare each experimental arm against the standard of care arm.  


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A shift table of the baseline qualitative SARS-CoV-2 RT-PCR results versus each post-baseline time 
point by treatment arm will be generated. 
Additionally, corresponding viral culture results from screening, Day 7 and Day 10 in the subset of 
participants for whom viral culture is performed will be displayed. 
 
Descriptive statistics for the log10 transformed mean viral load of SARS-CoV-2 and corresponding 
change from baseline will be presented by time point (Baseline, Day 3, Day 7, Day 10, Day 14, Day 21, 
Day 28). The mean viral load result will be calculated as the mean viral load result detected by 
quantitative RT-PCR of the S-gene, N-gene and ORF1ab gene. Only results based on nasal-swabs will 
be used. Mean viral load values of 0 will be imputed with half of the lower limit of quantification (LLOQ) 
before log10 transformation, i.e. the imputed value will be 10 copies/ml, before log10 transformation. 
The mixed-effect linear model for repeated measures described in section 8.2.3 will be repeated using 
the above derivation of log10 transformed mean viral load. 
 
The incidence of SARS-CoV-2 clearance on Day 10 (defined as the proportion of participants with 
negative SARS-CoV-2 viral cultures on Day 10 in the subset of participants for whom this assessment 
is performed and results are available) will be analyzed using a log-binomial regression model in which 
the response variable will be SARS-CoV-2 clearance on Day 10 (yes/no). Treatment, age at baseline 
(years), sex, BMI at baseline, baseline comorbidities, baseline viral load category, and days of 
symptoms at time of enrollment will be used as covariates. Similar to the primary analysis, if the log-
binomial model specified above does not converge a generalized linear regression with a log link, 
Poisson distribution, instead of Binomial distribution, will be used. If neither model converges a Normal 
distribution instead of a Poission distribution will be used. 
Participants who discontinue the study prior to Day 10 will be excluded from the analysis. If a result is 
missing at Day 10 the participant will be excluded from the analysis.  
Only patients with positive viral culture at baseline are included in the analyses above. 
12. 
Interim Analyses 
No formal interim analyses for futility will be performed. 
An independent DMC will be convened for this study after approximately 75 and 150 patients have 
reached Day 7 with expertise in respiratory viruses, antiviral therapies and shedding, emerging 
epidemics and medical statistics. Details regarding the objectives and responsibilities of the DMC, and 
the DMC operational procedures are described in the DMC Charter.  
There may be a potential sample size adjustment based on the dropout rate after approximately 150 
participants have been recruited and have safety and viral clearance data for Day 7. The sample size 
adjustment will be performed by the trial statistician and verified by the DMC statistician. The details of 
the sample size adjustment are described in the Interim Monitoring Plan. 
Processing of data and reports to be generated for the DMC, except for the sample size adjustment, are 
not described in the SAP.  
13. 
Change to Protocol Specified Analyses 
Due to the now well-described varying sensitivity of SARS-CoV-2 RT-PCR assays and the high 
incidence of false negative results, the analysis of time to clearance of SARS-CoV-2 will only consider 
viral clearance to be present if all subsequent RT-PCR results remain negative. 
For the subgroups of sero-negative participants and for high-risk participants, the following post-hoc 
analyses were added: 
• 
Summary of WHO Ordinal Scale for Clinical Improvement 
• 
Kaplan Meier analysis of time to first zero WHO Ordinal Scale score for Clinical Improvement 
• 
Cox regression analysis of time to first zero WHO Ordinal Scale score for Clinical Improvement. 


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14. 
List of Tables and Figures 
Table 14.1.1 Participant disposition by treatment arm and overall (Randomized Analysis Set) ........... 24 
Table 14.1.2 Analysis sets by treatment arm and overall (Randomized Analysis Set) ......................... 25 
Table 14.1.3 Summary of participants excluded from analysis sets by treatment arm and overall 
(Randomized Analysis Set) ................................................................................................................... 26 
Table 14.1.4 Demographic characteristics by treatment arm and overall (mITT Analysis Set) ............ 27 
Table 14.1.5 Baseline characteristics by treatment arm and overall (mITT Analysis Set) .................... 31 
Table 14.1.6 Medical and surgical history by treatment arm and overall, MedDRA primary system 
organ class and preferred term (mITT Analysis Set)............................................................................. 34 
Table 14.1.7 Comorbidities of interest for SARS-CoV-2 infection by treatment arm and overall, 
MedDRA primary system organ class and preferred term (mITT Analysis Set) ................................... 35 
Table 14.1.8 Prior medications by ATC class and WHO preferred term by treatment arm and overall, 
ATC class and preferred term (Safety Analysis Set) ............................................................................. 36 
Table 14.2.1.1 Primary analysis of incidence of SARS-CoV-2 clearance on Day 7 based on RT-PCR 
(mITT Analysis Set) ............................................................................................................................... 37 
Table 14.2.1.2 Sensitivity analysis #1 for incidence of SARS-CoV-2 clearance on Day 7 based on RT-
PCR (mITT Analysis set) ....................................................................................................................... 37 
Table 14.2.1.3 Sensitivity analysis #2 for incidence of SARS-CoV-2 clearance on Day 7 based on RT-
PCR (As Treated Analysis set) .............................................................................................................. 37 
Table 14.2.1.4 Primary analysis of incidence of SARS-CoV-2 clearance on Day 7 based on RT-PCR 
by subgroup (mITT Analysis Set) .......................................................................................................... 38 
Table 14.2.1.5 Incidence of SARS-CoV-2 clearance on Day 7 based on viral culture (mITT Analysis 
Set) ........................................................................................................................................................ 39 
Table 14.2.1.6 Incidence of SARS-CoV-2 clearance on Day 3, 10, 14, 21 and 28 based on RT-PCR 
(mITT Analysis Set) ............................................................................................................................... 40 
Table 14.2.2.1 Kaplan Meier analysis of time to SARS-CoV-2 clearance based on qualitative RT-PCR 
(mITT Analysis Set) ............................................................................................................................... 41 
Table 14.2.2.2 Kaplan Meier analysis of time to SARS-CoV-2 clearance based on quantitative RT-
PCR (mITT Analysis Set) ...................................................................................................................... 43 
Table 14.2.2.3 Kaplan Meier analysis of time to SARS-CoV-2 clearance based on quantitative RT-
PCR (mITT Analysis Set - high-risk participants) .................................................................................. 44 
Table 14.2.2.4 Kaplan Meier analysis of time to SARS-CoV-2 clearance based on quantitative RT-
PCR (mITT Analysis Set – high baseline viral load) ............................................................................. 44 
Table 14.2.2.5 Cox regression analysis of time to SARS-CoV-2 clearance based on qualitative RT-
PCR (mITT Analysis Set) ...................................................................................................................... 45 
Table 14.2.2.6 Cox regression analysis of time to SARS-CoV-2 clearance based on quantitative RT-
PCR (mITT Analysis Set) ...................................................................................................................... 45 
Table 14.2.2.7 Cox regression analysis of time to SARS-CoV-2 clearance based on quantitative RT-
PCR (mITT Analysis Set – high-risk participants) ................................................................................. 46 
Table 14.2.2.8 Cox regression analysis of time to SARS-CoV-2 clearance based on quantitative RT-
PCR (mITT Analysis Set – high baseline viral load) ............................................................................. 46 
Figure 14.2.2.1 Kaplan-Meier curves for time to SARS-CoV-2 clearance based on qualitative RT-PCR 
(m-ITT Analysis Set) .............................................................................................................................. 47 
Figure 14.2.2.2 Kaplan-Meier curves for time to SARS-CoV-2 clearance based on quantitative RT-
PCR (m-ITT Analysis Set) ..................................................................................................................... 48 
Figure 14.2.2.3 Kaplan-Meier curves for time to SARS-CoV-2 clearance based on quantitative RT-
PCR (m-ITT Analysis Set – high-risk participants) ................................................................................ 48 
Figure 14.2.2.4 Kaplan-Meier curves for time to SARS-CoV-2 clearance based on quantitative RT-
PCR (m-ITT Analysis Set – high baseline viral load) ............................................................................ 48 
Table 14.2.3.1 Summary of log10 viral load of SARS-CoV-2 by treatment arm and overall and time 
point (mITT Analysis Set) ...................................................................................................................... 49 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
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Table 14.2.3.2 Repeated measure analysis of log10 viral load of SARS-CoV-2 change from baseline 
(mITT Analysis Set) ............................................................................................................................... 51 
Table 14.2.3.3 Repeated measure analysis of log10 viral load of SARS-CoV-2 change from baseline 
(mITT Analysis Set – high-risk participants) .......................................................................................... 51 
Figure 14.2.3.1 Spaghetti plot of log10 viral load of SARS-CoV-2 based quantitative RT-PCR by 
treatment arm (mITT Analysis Set) ....................................................................................................... 52 
Table 14.2.4.1 Logistic regression for hospitalization up to Day 28 (mITT Analysis Set) ..................... 53 
Table 14.2.4.2 Summary of hospitalization data by treatment arm and overall (mITT Analysis Set) ... 54 
Table 14.2.4.3 Kaplan Meier analysis of time to first hospitalization (mITT Analysis Set) .................... 55 
Table 14.2.4.4 Cox regression analysis of time to first hospitalization  (mITT Analysis Set) ................ 56 
Figure 14.2.4.1 Kaplan-Meier curves for time to first hospitalization (mITT Analysis Set).................... 56 
Table 14.2.5.1 Summary of WHO Ordinal Scale for Clinical Improvement by treatment arm and overall 
(mITT Analysis Set) ............................................................................................................................... 57 
Table 14.2.5.2 Proportional odds model for disease severity for Day 7, 14, 21, and 28 (mITT Analysis 
Set) ........................................................................................................................................................ 58 
Table 14.2.5.3 Logistic regression for disease severity (mITT Analysis Set) ....................................... 59 
Table 14.2.5.4 Kaplan Meier analysis of time to first zero WHO Ordinal Scale score for Clinical 
Improvement (mITT Analysis Set) ......................................................................................................... 60 
Table 14.2.5.5 Cox regression analysis of time to first zero WHO Ordinal Scale score for Clinical 
Improvement (mITT Analysis Set) ......................................................................................................... 61 
Table 14.2.5.6 Summary of WHO Ordinal Scale for Clinical Improvement by treatment arm and overall 
(mITT Analysis Set – sero-negative participants) .................................................................................. 61 
Table 14.2.5.7 Summary of WHO Ordinal Scale for Clinical Improvement by treatment arm and overall 
(mITT Analysis Set – high-risk participants) .......................................................................................... 61 
Table 14.2.5.8 Kaplan Meier analysis of time to first zero WHO Ordinal Scale score for Clinical 
Improvement (mITT Analysis Set – sero-negative participants) ........................................................... 61 
Table 14.2.5.9 Kaplan Meier analysis of time to first zero WHO Ordinal Scale score for Clinical 
Improvement (mITT Analysis Set – high-risk participants) .................................................................... 62 
Table 14.2.5.10 Cox regression analysis of time to first zero WHO Ordinal Scale score for Clinical 
Improvement (mITT Analysis Set – sero-negative participants) ........................................................... 62 
Table 14.2.5.11 Cox regression analysis of time to first zero WHO Ordinal Scale score for Clinical 
Improvement (mITT Analysis Set – high-risk participants) .................................................................... 62 
Figure 14.2.5.1 Kaplan-Meier curves for time to first zero WHO Ordinal Scale score for Clinical 
Improvement (mITT Analysis set).......................................................................................................... 62 
Table 14.2.6.1 Poisson regression for proportion of days with fever after randomization (mITT Analysis 
Set) ........................................................................................................................................................ 63 
Table 14.2.6.2 Poisson regression for proportion of days with respiratory symptoms after 
randomization (mITT Analysis Set) ....................................................................................................... 64 
Table 14.2.6.3 Poisson regression for proportion of days with SpO2<93% after randomization (mITT 
Analysis Set) .......................................................................................................................................... 65 
Table 14.2.6.4 Summary of FLU-PRO Plus questionnaire scores and changes from baseline by 
treatment arm and overall (mITT Analysis Set) ..................................................................................... 66 
Table 14.2.7.1 Cumulative incidence of lower respiratory tract infection by treatment arm and overall 
(mITT Analysis Set) ............................................................................................................................... 68 
Table 14.2.8.1 Cumulative incidence of all-cause mortality by treatment arm and overall (mITT 
Analysis Set) .......................................................................................................................................... 69 
Table 14.3.1.1 Compliance by treatment arm (Safety Analysis Set)..................................................... 70 
Table 14.3.2.1 Concomitant medications by treatment arm and overall, ATC class and WHO preferred 
term (Safety Analysis Set) ..................................................................................................................... 71 
Table 14.3.3.1 Summary of treatment emergent adverse events by MedDRA primary system organ 
class and preferred term by treatment arm and overall (Safety Analysis Set) ...................................... 72 


Statistical Analysis Plan 
 
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Page 21 of 105 
 
Table 14.3.3.2 Summary of serious treatment emergent adverse events by MedDRA primary system 
organ class and preferred term by treatment arm and overall (Safety Analysis Set) ............................ 73 
Table 14.3.3.3 Summary of treatment emergent adverse events considered to be study drug related 
by MedDRA primary system organ class and preferred term by treatment arm and overall (Safety 
Analysis Set) .......................................................................................................................................... 73 
Table 14.3.3.4 Summary of serious treatment emergent adverse events considered to be study drug 
related by MedDRA primary system organ class and preferred term by treatment arm and overall 
(Safety Analysis Set) ............................................................................................................................. 73 
Table 14.3.3.5 Summary of treatment emergent adverse events leading to study drug discontinuation 
by MedDRA primary system organ class and preferred term by treatment arm and overall (Safety 
Analysis Set) .......................................................................................................................................... 73 
Table 14.3.3.6 Summary of serious treatment emergent adverse events leading to study drug 
discontinuation by MedDRA primary system organ class and preferred term by treatment arm and 
overall (Safety Analysis Set) .................................................................................................................. 73 
Table 14.3.3.7 Summary of treatment emergent adverse events leading to death by MedDRA primary 
system organ class and preferred term by treatment arm and overall (Safety Analysis Set) ............... 73 
Table 14.3.3.8 Summary of treatment emergent adverse events leading to hospitalization by MedDRA 
primary system organ class and preferred term by treatment arm and overall (Safety Analysis Set) .. 73 
Table 14.3.3.9 Summary of treatment emergent adverse events by MedDRA primary system organ 
class, preferred term, maximal severity and treatment arm and overall (Safety Analysis Set) ............. 74 
Table 14.3.3.10 Non-serious adverse events (threshold >5%) by MedDRA primary system organ 
class, preferred term and treatment arm (Safety Analysis Set) ............................................................ 75 
Table 14.3.4.1 Summary of vital signs including changes from baseline by treatment arm and overall 
and time point (Safety Analysis Set) ..................................................................................................... 76 
Table 14.3.5.1 Shift table of serology by treatment arm (mITT Analysis Set) ....................................... 78 
Table 14.3.5.2 Summary of PK parameter by treatment arm and overall (PK Analysis Set) ............... 79 
Table 14.3.5.3 Incidence of low viral load on Day 7 (mITT Analysis Set) ............................................. 80 
Table 14.3.5.4 Shift table of viral culture data by treatment arm, overall and time point (mITT Analysis 
Set) ........................................................................................................................................................ 81 
Table 14.3.5.5 Shift table of qualitative SARS-CoV-2 RT-PCR by treatment arm (mITT Analysis Set) 82 
Table 14.3.5.6 Summary of log10 mean viral load of SARS-CoV-2 by treatment arm and overall, time 
point (mITT Analysis Set) ...................................................................................................................... 83 
Table 14.3.5.7 Repeated measure analysis of log10 mean viral load of SARS-CoV-2 change from 
baseline (mITT Analysis Set) ................................................................................................................. 83 
Table 14.3.5.8 Incidence of SARS-CoV-2 clearance on Day 10 based on viral culture (mITT Analysis 
Set) ........................................................................................................................................................ 83 
Figure 14.3.5.1 Scatter plot of plasma or blood concentrations at Day 3 and/or Day 7 by SARS-CoV-2 
clearance on Day 7 and exploratory arm (PK Analysis Set) ................................................................. 84 
Listing 14.3.1.1 Listing of adverse events leading to death (Safety Analysis Set) ................................ 85 
Listing 14.3.1.2 Listing of serious treatment-emergent adverse events (Safety Analysis Set) ............. 85 
Listing 14.3.1.3 Listing of treatment-emergent adverse events leading to study discontinuation (Safety 
Analysis Set) .......................................................................................................................................... 85 
Listing 14.3.1.4 Listing of treatment-emergent adverse events with action taken related to study 
treatment (Safety Analysis Set) ............................................................................................................. 85 
 
15. 
List of Data Listings and Statistical Tabulations 
Appendix 16.2.1.1 Study completion (Randomized Analysis Set) ........................................................ 86 
Appendix 16.2.1.2 Screening failures (All screened subjects) .............................................................. 87 
Appendix 16.2.2.1 Protocol deviation (Randomized Analysis Set) ....................................................... 88 
Appendix 16.2.3.1 Analysis Sets (Randomized Analysis Set) .............................................................. 89 


Statistical Analysis Plan 
 
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Appendix 16.2.4.1 Demographic data and informed consent (Randomized Analysis Set)................... 90 
Appendix 16.2.4.2 Medical and surgical history (Randomized Analysis Set) ....................................... 91 
Appendix 16.2.4.3 Physical examination (Randomized Analysis Set) .................................................. 92 
Appendix 16.2.4.4 Randomization (Randomized Analysis Set) ............................................................ 93 
Appendix 16.2.5.1 Drug accountability (Safety Analysis Set) ............................................................... 94 
Appendix 16.2.5.2 Pharmacokinetic concentration data (PK Analysis Set) .......................................... 95 
Appendix 16.2.6.1 Mid-nasal swab and saliva specimen data, viral culture and SARS-CoV-2 serology 
(Randomized Analysis Set) ................................................................................................................... 96 
Appendix 16.2.6.2 Hospitalizations (Randomized Analysis Set) ........................................................... 97 
Appendix 16.2.6.3 FLU-PRO Plus (Randomized Analysis Set) ............................................................ 98 
Appendix 16.2.6.4 FLU-PRO Plus Global additional daily diary items (Randomized Analysis Set) ..... 99 
Appendix 16.2.6.5 WHO Ordinal Scale for Clinical Improvement (Randomized Analysis Set) .......... 100 
Appendix 16.2.7.1 Treatment emergent adverse events (Safety Analysis Set) .................................. 101 
Appendix 16.2.7.2 Vital signs (Safety Analysis Set) ........................................................................... 102 
Appendix 16.2.7.3 Prior and concomitant medications (Safety Analysis Set) .................................... 103 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 23 of 105 
 
16. 
Output Shells 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 24 of 105 
 
Table 14.1.1 Participant disposition by treatment arm and overall (Randomized Analysis Set) 
             (Page x of y) 
 
 
SOC 
(N=xx) 
n (%) 
ASAQ 
(N=xx) 
n (%) 
PA 
(N=xx) 
n (%) 
FPV-NTZ 
(N=xx) 
n (%) 
SOF/DCV 
(N=xx) 
n (%) 
Overall 
(N=xx) 
n (%) 
 
 
 
 
 
 
 
Participants randomized 
xx (100.0) 
xx (100.0) 
xx (100.0) 
xx (100.0) 
xx (100.0) 
xx (100.0) 
Participants randomized but not  
treated 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Primary reason for discontinuation  
 
 
 
 
 
 
  Reason 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Reason 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ... 
 
 
 
 
 
 
Participants treated 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Participants treated but 
discontinued prior to study end 
 
 
 
 
 
 
  Primary reason for discontinuation  
 
 
 
 
 
 
  Reason 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Reason 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  ... 
 
 
 
 
 
 
Participants completed 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Percentages are based on the number participants in the Randomized Analysis Set. 
 
 
 
Programming note: Display only reasons for discontinuation with non-zero counts. 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 25 of 105 
 
Table 14.1.2 Analysis sets by treatment arm and overall (Randomized Analysis Set) 
             (Page x of y) 
 
 
SOC 
n (%) 
ASAQ 
n (%) 
PA 
n (%) 
FPV-NTZ 
n (%) 
SOF/DCV 
n (%) 
Overall 
n (%) 
 
 
 
 
 
 
 
Randomized Analysis Set 
xx (100.0) 
xx (100.0) 
xx (100.0) 
xx (100.0) 
xx (100.0) 
xx (100.0) 
Safety Analysis Set 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
mITT Analysis Set 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
As Treated Analysis Set 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
PK Analysis Set 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Percentages are based on the number of participants in the Randomized Analysis Set. 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 26 of 105 
 
Table 14.1.3 Summary of participants excluded from analysis sets by treatment arm and overall (Randomized Analysis Set) 
             (Page x of y) 
 
 
 
 
SOC 
(N=xx) 
n (%) 
ASAQ 
(N=xx) 
n (%) 
PA 
(N=xx) 
n (%) 
FPV-NTZ 
(N=xx) 
n (%) 
SOF/DCV 
(N=xx) 
n (%) 
Overall 
(N=xx) 
n (%) 
 
 
 
 
 
 
 
Excluded from the Safety 
Analysis Set (*) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
 
 
Excluded from the mITT 
Analysis Set (**) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
 
 
Excluded from the As Treated 
Analysis Set 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
   Reasons for exclusion (***) 
 
 
 
 
 
 
      Reason 1 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
      Reason 2 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
      Reason 3 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
   Participants with more than 
one reason 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
 
 
Excluded from the PK Analysis 
Set (****) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
 
 
Percentages are based on the number of participants in the Randomized Analysis Set. 
 (*) Enrolled, randomized participants who did not receive study drug. 
 (**) Enrolled, randomized participants who did not receive study drug or did not have confirmed SARS-CoV-2 infection at baseline.  
 (***) Reasons are not mutually exclusive. 
(****) Enrolled, randomized participants who received study drug who had no PK data. 
 
 
Programming note: Sort reasons by descending frequency in the total column. 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 27 of 105 
 
Table 14.1.4 Demographic characteristics by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
 
Variable/ 
   Statistic/Category 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
 
 
 
 
 
 
 
Sex, n (%) 
 
 
 
 
 
 
   Male 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Female 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Race 
 
 
 
 
 
 
   Black African 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Coloured 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   White 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Asian or Indian 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Age (years) 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
   Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
   Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
   Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
In case of missing values for categorical variables a missing category will be displayed. 
Body mass index = weight in kg / (height in m)**2 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 28 of 105 
 
Table 14.1.4 Demographic characteristics by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
Variable/ 
   Statistic/Category 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
 
 
 
 
 
 
 
Age (years) by sex, n (%) 
 
 
 
 
 
 
   Male 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
      Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
      Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
      Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
   Female 
 
 
 
 
 
 
      n 
xx 
xx 
xx 
xx 
xx 
xx 
      Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
      Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
      Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
      Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
      Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
In case of missing values for categorical variables a missing category will be displayed. 
Body mass index = weight in kg / (height in m)**2 
 
 
 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 29 of 105 
 
Table 14.1.4 Demographic characteristics by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
Variable/ 
   Statistic/Category 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
 
 
 
 
 
 
 
Body weight (kg) 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
   Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
   Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
   Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
Height (cm) 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
   Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
   Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
   Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
BMI (kg/m**2) 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
   Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
   Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
   Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 30 of 105 
 
In case of missing values for categorical variables a missing category will be displayed. 
Body mass index = weight in kg / (height in m)**2 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 31 of 105 
 
Table 14.1.5 Baseline characteristics by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
 
Variable/ 
   Statistic/Category 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
 
 
 
 
 
 
 
Temperature (degree C) 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
   Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
   Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
   Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
Pulse rate (beats/min) 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
   Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
   Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
   Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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Table 14.1.5 Baseline characteristics by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
 
Variable/ 
   Statistic/Category 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
 
 
 
 
 
 
 
Respiratory rate 
(breaths/min) 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
   Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
   Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
   Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
SpO2 (%) 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
   Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
   Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
   Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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DATAMAP GmbH 
Page 33 of 105 
 
Table 14.1.5 Baseline characteristics by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
 
Variable/ 
   Statistic/Category 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
 
 
 
 
 
 
 
Days of symptoms at time of 
enrollment 
 
 
 
 
 
 
   n 
xx 
xx 
xx 
xx 
xx 
xx 
   Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Standard deviation 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
x.xx 
   Minimum 
xx 
xx 
xx 
xx 
xx 
xx 
   Q1 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Median 
xx.x 
xx 
xx 
xx 
xx 
xx 
   Q3 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Maximum 
xx 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
WHO Ordinal Scale for Clinical 
Improvement, n (%) 
 
 
 
 
 
 
   0 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   6 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   7 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   8 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
Programming note: For WHO ordinal scale present only categories with count > 0. 


Statistical Analysis Plan 
 
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Table 14.1.6 Medical and surgical history by treatment arm and overall, MedDRA primary system organ class and preferred term (mITT 
Analysis Set) 
            (Page x of y) 
 
Primary system organ 
class 
SOC 
(N=xx) 
n (%) 
ASAQ 
(N=xx) 
n (%) 
PA 
(N=xx) 
n (%) 
FPV-NTZ 
(N=xx) 
n (%) 
SOF/DCV 
(N=xx) 
n (%) 
Overall 
(N=xx) 
n (%) 
   Preferred term 
 
 
 
 
 
 
 
At least one medical 
history 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Primary system organ 
class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Primary system organ 
class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
A participant with multiple events within a primary system organ class is counted only once for that system organ class. 
A participant with multiple events within a preferred term is counted only once for that preferred term. 
Medical history related to COVID-19 disease are not reported in this table. 
MedDRA version xx.x has been used for coding. 
 
Programming note: Sort primary system organ classes alphabetically. Sort preferred terms within system organ classes by descending 
frequency in the "overall" column. The total n within each cohort will be used as denominator. 


Statistical Analysis Plan 
 
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Table 14.1.7 Comorbidities of interest for SARS-CoV-2 infection by treatment arm and overall, MedDRA primary system organ class and 
preferred term (mITT Analysis Set) 
            (Page x of y) 
 
Primary system organ 
class 
SOC 
(N=xx) 
n (%) 
ASAQ 
(N=xx) 
n (%) 
PA 
(N=xx) 
n (%) 
FPV-NTZ 
(N=xx) 
n (%) 
SOF/DCV 
(N=xx) 
n (%) 
Overall 
(N=xx) 
n (%) 
   Preferred term 
 
 
 
 
 
 
 
At least one 
comorbitity 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Primary system organ 
class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Primary system organ 
class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
A participant with multiple events within a primary system organ class is counted only once for that system organ class. 
A participant with multiple events within a preferred term is counted only once for that preferred term. 
Only comorbidities pre-specified on the CRF are presented. 
MedDRA version xx.x has been used for coding. 
 
Programming note: Sort primary system organ classes alphabetically. Sort preferred terms within system organ classes by descending 
frequency in the "overall" column. The total n within each cohort will be used as denominator. 
 


Statistical Analysis Plan 
 
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Table 14.1.8 Prior medications by ATC class and WHO preferred term by treatment arm and overall, ATC class and preferred term 
(Safety Analysis Set) 
             (Page x of y) 
 
 
ATC class/ 
   Preferred term 
SOC 
(N=xx) 
n (%) 
ASAQ 
(N=xx) 
n (%) 
PA 
(N=xx) 
n (%) 
FPV-NTZ 
(N=xx) 
n (%) 
SOF/DCV 
(N=xx) 
n (%) 
Overall 
(N=xx) 
n (%) 
 
 
 
 
 
 
 
At least one 
medication 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
ATC class 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
ATC class 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Preferred term 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A participant can have more than one prior medication. 
Medications were coded using the World Health Organizational-Drug Dictionary (WHO-DD) version xx. 
 
Programming note: Use ATC class 3. Sort ATC classes alphabetically. Sort preferred terms within ATC classes by descending frequency 
in the overall column. The total n within each cohort will be used as denominator. 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 37 of 105 
 
 
 
 
Table 14.2.1.1 Primary analysis of incidence of SARS-CoV-2 clearance on Day 7 based on RT-PCR (mITT Analysis Set)  
 
 
 
 
 
Covariate adjusted analysis* 
 
Crude analysis* 
Treatment arm 
N 
n/M (%) 
Comparison 
Risk 
ratio 
95% CI 
p-value 
 
Risk 
ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
 
 
 
 
SOC 
xx 
xx/xx (xx.x) 
 
 
 
 
 
 
 
 
ASAQ 
xx 
xx/xx (xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
xx.x 
(xx.x, xx.x) 
x.xxx 
PA  
xx 
xx/xx (xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
xx.x 
(xx.x, xx.x) 
x.xxx 
FPV-NTZ  
xx 
xx/xx (xx.x) 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
xx.x 
(xx.x, xx.x) 
x.xxx 
SOF/DCV  
xx 
xx/xx (xx.x) 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants with SARS-CoV-2 clearance on Day 7 based on RT-PCR test. 
M = number of evaluable participants for Day 7. 
The covariate adjusted regression model contains treatment arm, age at baseline (years), sex, baseline BMI, baseline 
comorbidities, baseline viral load category and days of symptoms at time of enrollment as covariates. 
The crude analysis repeats the regression model without any covariate adjustment. 
A risk ratio > 1 favors the treatment arm in the numerator of the ratio (= higher proportion of SARS-CoV-2 clearance). 
Model specification: * = log link and binomial distribution, # = log link and poisson distribution, § = log link and normal 
distribution.  
 
Table 14.2.1.2 Sensitivity analysis #1 for incidence of SARS-CoV-2 clearance on Day 7 based on RT-PCR (mITT Analysis set)  
 
Programming note: Same layout as table 14.2.1.1. 
All participants who discontinue prior to the day 7 SARS-CoV-2 RT-PCR test are imputed as having a positive of SARS-CoV-2 RT-PCR test 
on Day 7. 
 
Table 14.2.1.3 Sensitivity analysis #2 for incidence of SARS-CoV-2 clearance on Day 7 based on RT-PCR (As Treated Analysis set)  
 
Programming note: Same layout as table 14.2.1.1. 
 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
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Page 38 of 105 
 
Table 14.2.1.4 Primary analysis of incidence of SARS-CoV-2 clearance on Day 7 based on RT-PCR by subgroup (mITT Analysis Set)  
 
Subgroup 
 
Treatment 
arm 
N 
n/M (%) 
Comparison 
Risk 
ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
 
 
Age group 
at 
baseline* 
Overall 
SOC  
xx xx/xx (xx.x)  
 
 
 
 
 
ASAQ 
xx xx/xx (xx.x) ASAQ / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
PA  
xx xx/xx (xx.x) PA / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
FPV-NTZ  
xx xx/xx (xx.x) FPV-NTZ / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
SOF/DCV  
xx xx/xx (xx.x) SOF/DCV / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
 
 
 
Interaction effect 
 
 
x.xxx 
 
 
 
 
 
 
 
 
 
 
Low (<= 
median) 
SOC  
xx xx/xx (xx.x)  
 
 
 
 
 
ASAQ 
xx xx/xx (xx.x) ASAQ / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
PA  
xx xx/xx (xx.x) PA / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
FPV-NTZ  
xx xx/xx (xx.x) FPV-NTZ / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
SOF/DCV  
xx xx/xx (xx.x) SOF/DCV / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
 
 
High (> 
median) 
SOC  
xx xx/xx (xx.x)  
 
 
 
 
 
ASAQ 
xx xx/xx (xx.x) ASAQ / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
PA  
xx xx/xx (xx.x) PA / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
FPV-NTZ  
xx xx/xx (xx.x) FPV-NTZ / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
SOF/DCV  
xx xx/xx (xx.x) SOF/DCV / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 39 of 105 
 
 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants with SARS-CoV-2 clearance on Day 7 based on RT-PCR. 
M = number of evaluable participants for Day 7. 
The regression model for each subgroup contains all covariates from the primary analysis and the 
interaction between the respective subgroup variable and the treatment arm. 
A risk ratio > 1 favors the treatment arm in the numerator of the ratio (= higher proportion of SARS-
CoV-2 clearance). 
Model specification: * = log link and binomial distribution, # = log link and poisson distribution, § 
= log link and normal distribution. 
 
Programming note: Display subgroup analysis for all other subgroup variables (sex, BMI at baseline, baseline comorbidities, baseline 
viral load category, days of symptoms at time of enrollment, baseline risk category) on the following pages. Use new page for each 
subgroup. For subgroup variables categorized by median, display median value in brackets. For the subgroup analysis of baseline risk 
category this variable is also used as covariate. In general use the same covariates as in the primary efficacy endpoint model. In 
case a subgroup analysis is done for a categorized version of a continuous variable the categorized version is used as covariate 
(instead of the continuous version). 
 
Table 14.2.1.5 Incidence of SARS-CoV-2 clearance on Day 7 based on viral culture (mITT Analysis Set) 
 
Treatment arm 
N 
n/M (%) 
Comparison* 
Risk ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
SOC 
xx 
xx/xx (xx.x) 
 
 
 
 
ASAQ 
xx 
xx/xx (xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
PA  
xx 
xx/xx (xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
FPV-NTZ  
xx 
xx/xx (xx.x) 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
SOF/DCV  
xx 
xx/xx (xx.x) 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants with SARS-CoV-2 clearance on Day 7 based on viral culture. 
M = number of evaluable participants for Day 7. 
The regression model contains treatment arm, age at baseline (years), sex, baseline BMI, 
baseline comorbidities, baseline viral load category and days of symptoms at time of 
enrollment as covariates. 
A risk ratio > 1 favors the treatment arm in the numerator of the ratio (= higher proportion 
of SARS-CoV-2 clearance). 
Model specification: * = log link and binomial distribution, # = log link and poisson 
distribution, § = log link and normal distribution. 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 40 of 105 
 
Table 14.2.1.6 Incidence of SARS-CoV-2 clearance on Day 3, 10, 14, 21 and 28 based on RT-PCR (mITT Analysis Set) 
 
Time point 
Treatment arm 
N 
n/M (%) 
Comparison 
Risk ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
 
Day 3* 
 
 
 
 
 
 
 
 
SOC 
xx 
xx/xx (xx.x) 
 
 
 
 
 
ASAQ 
xx 
xx/xx (xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
PA  
xx 
xx/xx (xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
FPV-NTZ  
xx 
xx/xx (xx.x) 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
SOF/DCV  
xx 
xx/xx (xx.x) 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
Day 10 
 
 
 
 
 
 
 
 
SOC  
xx 
xx/xx (xx.x) 
 
 
 
 
 
ASAQ 
xx 
xx/xx (xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
PA  
xx 
xx/xx (xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
FPV-NTZ  
xx 
xx/xx (xx.x) 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
SOF/DCV  
xx 
xx/xx (xx.x) 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
Etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants with SARS-CoV-2 clearance at respective time point based on RT-PCR test. 
M = number of evaluable participants for respective time point. 
The regression model contains treatment arm, age at baseline (years), sex, baseline BMI, baseline comorbidities, 
baseline viral load category and days of symptoms at time of enrollment as covariates. 
A risk ratio > 1 favors the treatment arm in the numerator of the ratio (= higher proportion of SARS-CoV-2 
clearance). 
Model specification: * = log link and binomial distribution, # = log link and poisson distribution, § = log link 
and normal distribution. 
Programming note: Display table for time points Day 3, Day 10, Day 14, Day 21 and Day 28. 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 41 of 105 
 
Table 14.2.2.1 Kaplan Meier analysis of time to SARS-CoV-2 clearance based on qualitative RT-PCR (mITT Analysis Set) 
               (Page x of y) 
 
 
 
 
 
Statistic 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
 
 
 
 
 
 
Available observations 
xx 
xx 
xx 
xx 
xx 
Number of participants with  
SARS-CoV-2 clearance 
xx 
xx 
xx 
xx 
xx 
Number of censored observations 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
SARS-CoV-2 clearances over time (days) 
 
 
 
 
  25th percentile (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  Median (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  75th percentile (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
 
 
 
 
 
 
% SARS-CoV-2 clearance estimate (95% CI)  
 
 
 
 
 
  Day 7 
xx.x (xx.x, 
xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  Day 14 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
  Day 21 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
  Day 28 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
 
 
 
 
 
 
Estimates are based on Kaplan-Meier methodology. 
Participants who did not experience the event of interest are considered censored according to the censoring rules detailed in Appendix 
16.1.9.  
Time to SARS-CoV-2 clearance is defined as the time to first negative qualitative SARS-CoV-2 RT-PCR test without any subsequent 
positive qualitative SARS-CoV-2 RT-PCR test. 
SARS-Cov-2 clearance over time: presents the time point (in days) by which the estimated cumulative probability of SARS-CoV-2 is 25%, 
50% and 75% and the corresponding two-sided 95% confidence interval. 
% SARS-CoV-2 clearance estimate: presents the estimated cumulative probability of SARS-CoV-2 clearance by Day 7/14/21/28 and the 
corresponding two-sided 95% confidence interval.  


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 42 of 105 
 
n.e. = not estimable. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 43 of 105 
 
Table 14.2.2.2 Kaplan Meier analysis of time to SARS-CoV-2 clearance based on quantitative RT-PCR (mITT Analysis Set) 
               (Page x of y) 
 
 
Statistic 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
 
 
 
 
 
 
Available observations 
xx 
xx 
xx 
xx 
xx 
Number of participants with  
SARS-CoV-2 clearance 
xx 
xx 
xx 
xx 
xx 
Number of censored observations 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
SARS-CoV-2 clearances over time (days) 
 
 
 
 
  25th percentile (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  Median (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  75th percentile (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
 
 
 
 
 
 
% SARS-CoV-2 clearance estimate (95% CI)  
 
 
 
 
 
  Day 7 
xx.x (xx.x, 
xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  Day 14 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
  Day 21 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
  Day 28 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
 
 
 
 
 
 
Estimates are based on Kaplan-Meier methodology. 
Participants who did not experience the event of interest are considered censored according to the censoring rules detailed in 
Appendix 16.1.9.  
Time to SARS-CoV-2 clearance is defined as the time to first quantitative SARS-CoV-2 RT-PCR test with zero count without any 
subsequent count above zero. 
SARS-Cov-2 clearance over time: presents the time point (in days) by which the estimated cumulative probability of SARS-CoV-2 is 
25%, 50% and 75% and the corresponding two-sided 95% confidence interval. 
% SARS-CoV-2 clearance estimate: presents the estimated cumulative probability of SARS-CoV-2 clearance by Day 7/14/21/28 and the 
corresponding two-sided 95% confidence interval.  


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 44 of 105 
 
n.e. = not estimable. 
 
 
Table 14.2.2.3 Kaplan Meier analysis of time to SARS-CoV-2 clearance based on quantitative RT-PCR (mITT Analysis Set - high-risk 
participants) 
               (Page x of y) 
 
Programming note: Use same layout as table 14.2.2.2. Use mITT Analysis Set restricted to the subset of high-risk participants. 
 
 
Table 14.2.2.4 Kaplan Meier analysis of time to SARS-CoV-2 clearance based on quantitative RT-PCR (mITT Analysis Set – high baseline 
viral load) 
               (Page x of y) 
 
Programming note: Use same layout as table 14.2.2.2. Use mITT Analysis Set restricted to the subset of participants with high viral 
load at baseline. 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
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Page 45 of 105 
 
Table 14.2.2.5 Cox regression analysis of time to SARS-CoV-2 clearance based on qualitative RT-PCR (mITT Analysis Set) 
 
Treatment arm 
N 
n/M (%) 
Comparison 
Hazard ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
SOC 
xx 
xx/xx (xx.x) 
 
 
 
 
ASAQ 
xx 
xx/xx (xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
PA  
xx 
xx/xx (xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
FPV-NTZ  
xx 
xx/xx (xx.x) 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
SOF/DCV  
xx 
xx/xx (xx.x) 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants with SARS-CoV-2 clearance based on RT-PCR test. 
M = number of evaluable participants. 
Time to SARS-CoV-2 clearance is defined as the time to first negative qualitative SARS-CoV-2 RT-
PCR test without any subsequent positive qualitative SARS-CoV-2 RT-PCR test. 
The cox regression model contains treatment arm, age at baseline (years), sex, baseline BMI, 
baseline comorbidities, baseline viral load category and days of symptoms at time of enrollment 
as covariates. 
A hazard ratio > 1 favors the treatment arm in the numerator of the ratio (= higher probability 
of SARS-CoV-2 clearance). 
 
 
Table 14.2.2.6 Cox regression analysis of time to SARS-CoV-2 clearance based on quantitative RT-PCR (mITT Analysis Set) 
 
Programming note: Use same layout as table 14.2.2.5. 
 
Footnotes: 
N = number of participants in the respective treatment arm. 
n = number of participants with SARS-CoV-2 clearance based on RT-PCR test. 
M = number of evaluable participants. 
Time to SARS-CoV-2 clearance is defined as the time to first quantitative SARS-CoV-2 RT-PCR test with zero count without any subsequent 
count above zero. 
The cox regression model contains treatment arm, age at baseline (years), sex, baseline BMI, baseline comorbidities, baseline viral 
load category and days of symptoms at time of enrollment as covariates. 
A hazard ratio > 1 favors the treatment arm in the numerator of the ratio (= higher probability of SARS-CoV-2 clearance). 
 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 46 of 105 
 
Table 14.2.2.7 Cox regression analysis of time to SARS-CoV-2 clearance based on quantitative RT-PCR (mITT Analysis Set – high-risk 
participants) 
 
Programming note: Use same layout as table 14.2.2.6. Use mITT Analysis Set restricted to the subset of high-risk participants. 
 
Table 14.2.2.8 Cox regression analysis of time to SARS-CoV-2 clearance based on quantitative RT-PCR (mITT Analysis Set – high 
baseline viral load) 
 
Programming note: Use same layout as table 14.2.2.6. Use mITT Analysis Set restricted to the subset of participants with high viral 
load at baseline. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 47 of 105 
 
Figure 14.2.2.1 Kaplan-Meier curves for time to SARS-CoV-2 clearance based on qualitative RT-PCR (m-ITT Analysis Set) 
 
 
 
Programming note: Figure layout will be similar to the above. Display the following treatment arms: SOC, ASAQ, PA, FPV-NTZ, SOF/DCV. 
Use different colors and line styles to differentiate between survival curves. Use x-axis label: Study day following first study drug 
intake. Use y-axis label: Cumulative probability of SARS-CoV-2 clearance. Display x-axis until Day 28. Time until SARS-CoV-2 clearance 
will be truncated after Day 28 in order to avoid a sudden drop in number of participants at risk. Also display the p-value of the 
log-rank test. 
 
Footnotes: 
Time to SARS-CoV-2 clearance is defined as the time to first negative qualitative SARS-CoV-2 RT-PCR test without any subsequent 
positive SARS-CoV-2 RT-PCR test. 
Participants who did not experience the event of interest are considered censored according to the censoring rules detailed in the 
SAP. 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 48 of 105 
 
Figure 14.2.2.2 Kaplan-Meier curves for time to SARS-CoV-2 clearance based on quantitative RT-PCR (m-ITT Analysis Set) 
 
Programming note: Same layout as figure 14.2.2.1. 
 
Footnotes: 
Time to SARS-CoV-2 clearance is defined as the time to first quantitative SARS-CoV-2 RT-PCR test with zero count without any subsequent 
count above zero. 
Participants who did not experience the event of interest are considered censored according to the censoring rules detailed in the 
SAP. 
 
Figure 14.2.2.3 Kaplan-Meier curves for time to SARS-CoV-2 clearance based on quantitative RT-PCR (m-ITT Analysis Set – high-risk 
participants) 
 
Programming note: Use same layout as figure 14.2.2.2. Use mITT Analysis Set restricted to the subset of high-risk participants. 
 
Figure 14.2.2.4 Kaplan-Meier curves for time to SARS-CoV-2 clearance based on quantitative RT-PCR (m-ITT Analysis Set – high 
baseline viral load) 
 
Programming note: Use same layout as figure 14.2.2.2. Use mITT Analysis Set restricted to the subset of participants with high viral 
load at baseline. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 49 of 105 
 
Table 14.2.3.1 Summary of log10 viral load of SARS-CoV-2 by treatment arm and overall and time point (mITT Analysis Set) 
             (Page x of y) 
 
Time point 
   Statistic 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
Base 
Post 
Change 
Base 
Post 
Change 
Base 
Post 
Change 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
 
 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
   Mean 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   SD 
xx.xxx 
 
 
xx.xxx 
 
 
xx.xxx 
 
 
   Minimum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
   Q1 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Median 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Q3 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Maximum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
Day 3 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
xx (xx.x) xx xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
Day 7 
 
 
 
 
 
 
 
 
 
  etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Base = Baseline, Post = Post-baseline, Change = Post-baseline - baseline. 
At each visit, only participants with a value at both baseline and the respective day are included. 
Analysis is based on quantitative RT-PCR. 
Viral load values (copies/mL) are log10 transformed. 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 50 of 105 
 
Table 14.2.3.1 Summary of log10 viral load of SARS-CoV-2 by treatment arm and overall and time point (mITT Analysis Set) 
             (Page x of y) 
 
Time point 
   
Statistic 
FPV-NTZ 
(N=xx) 
SOF/DCF 
(N=xx) 
Overall 
(N=xx) 
Base 
Post 
Change 
Base 
Post 
Change 
Base 
Post 
Change 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
   n (%) 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
   Mean 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   SD 
xx.xxx 
 
 
xx.xxx 
 
 
xx.xxx 
 
 
   Minimum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
   Q1 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Median 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Q3 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Maximum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
Day 3 
 
 
 
 
 
 
 
 
 
   n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
Day 7 
 
 
 
 
 
 
 
 
 
  Etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Base = Baseline, Post = Post-baseline, Change = Post-baseline - baseline. 
At each visit, only participants with a value at both baseline and the respective day are included. 
Analysis is based on quantitative RT-PCR. 
Viral load values (copies/mL) are log10 transformed. 
Programming note: Present this table for time points Baseline, Day 3, Day 7, Day 10, Day 14and End of study. 
 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 51 of 105 
 
Table 14.2.3.2 Repeated measure analysis of log10 viral load of SARS-CoV-2 change from baseline (mITT Analysis Set) 
             (Page x of y) 
 
 
 
Test 
Reference 
Comparison of LSmean change 
Test vs Ref. 
(Comparison) 
Time 
point 
n 
LSmean 
change 
(SE) 
95% CI 
n 
LSmean 
change 
(SE) 
95% CI 
Diff. 
Test– Ref. 
(SE) 
95% CI 
2-sided 
p-value 
 
 
 
 
 
 
 
 
 
 
 
ASAQ (N=xx)  
vs 
SOC (N=xx) 
Day 3 
xx 
xx.x 
(xx.xx) 
(xx.x, 
xx.x) 
xx 
xx.x 
(xx.xx) 
(xx.x, 
xx.x) 
xx.x 
(xx.xx) 
(xx.x, xx.x) 
x.xxx 
 
Day 7 
xx 
xx.x 
(xx.xx) 
(xx.x, 
xx.x) 
xx 
xx.x 
(xx.xx) 
(xx.x, 
xx.x) 
xx.x 
(xx.xx) 
(xx.x, xx.x) 
x.xxx 
 
Day 10 
xx 
xx.x 
(xx.xx) 
(xx.x, 
xx.x) 
xx 
xx.x 
(xx.xx) 
(xx.x, 
xx.x) 
xx.x 
(xx.xx) 
(xx.x, xx.x) 
x.xxx 
 
Day 14 
xx 
xx.x 
(xx.xx) 
(xx.x, 
xx.x) 
xx 
xx.x 
(xx.xx) 
(xx.x, 
xx.x) 
xx.x 
(xx.xx) 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants with available data on respective time point. 
The mixed-effect linear model for repeated measures includes treatment, age at baseline (years), sex, BMI at 
baseline, baseline comorbidities, baseline viral load category, days of symptoms at time of enrollment and 
treatment-by-visit interaction as fixed effects. 
 
Programming note: Continue table on next pages for comparison of PA vs SOC, FPV-NTZ vs SOC and SOF/DCV vs SOC. 
 
Table 14.2.3.3 Repeated measure analysis of log10 viral load of SARS-CoV-2 change from baseline (mITT Analysis Set – high-risk 
participants) 
             (Page x of y) 
 
Programming note: Use same layout as table 14.2.3.2. Produce table for mITT Analysis Set in the subset of high-risk participants.  


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 52 of 105 
 
Figure 14.2.3.1 Spaghetti plot of log10 viral load of SARS-CoV-2 based quantitative RT-PCR by treatment arm (mITT Analysis Set) 
 
Programming note: Display the individual log10 transformed viral load of SARS-CoV-2 (detected by quantitative RT-PCR based on N gene) 
of each participant from baseline until Day 28. Display a separate panel for each treatment arm. No visit windowing approach is 
applied. Viral load values are log10 transformed for the analysis. Use "Viral load (log10 copies/mL)" as y-axis label.  


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 53 of 105 
 
Table 14.2.4.1 Logistic regression for hospitalization up to Day 28 (mITT Analysis Set) 
             (Page x of y) 
 
 
Treatment arm 
N 
n/M (%) 
Comparison 
Odds ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
SOC 
xx 
xx/xx (xx.x) 
 
 
 
 
ASAQ 
xx 
xx/xx (xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
PA  
xx 
xx/xx (xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
FPV-NTZ  
xx 
xx/xx (xx.x) 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
SOF/DCV  
xx 
xx/xx (xx.x) 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants hospitalized up to Day 28. 
M = number of evaluable participants. 
The logistic regression model contains treatment arm, age at baseline (years), sex, baseline 
BMI, baseline comorbidities, baseline viral load category and days of symptoms at time of 
enrollment as covariates. 
An odds ratio > 1 suggests a higher chance of hospitalization in the treatment arm of the 
numerator of the ratio. 
Only hospitalizations related to COVID-19 are analysed. 
 
 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 54 of 105 
 
Table 14.2.4.2 Summary of hospitalization data by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
Variable 
   Statistic/Category 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
 
 
 
 
 
 
 
Cumulative incidence 
of hospitalization at 
Day 28, n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
p-value (Fisher's 
exact test) 
 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
 
 
 
 
 
 
 
 
Number of days 
hospitalized 
 
 
 
 
 
 
   n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Interquartile range 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
 
 
 
 
 
 
 
Interquartile range is defined as Q3-Q1. 
Cumulative incidence of hospitalization at Day 28 is defined as the number of participants hospitalized up to and including Day 28 
divided by the number of participants in the mITT Analysis Set. 
Only hospitalizations related to COVID-19 are analysed. 
p-values of fisher's exact test comparing cumulative incidence of each experimental arm against the standard of care arm is displayed. 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 55 of 105 
 
Table 14.2.4.3 Kaplan Meier analysis of time to first hospitalization (mITT Analysis Set) 
               (Page x of y) 
 
 
Statistic 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
 
 
 
 
 
 
Available observations 
xx 
xx 
xx 
xx 
xx 
Number of participants with  
hospitalization 
xx 
xx 
xx 
xx 
xx 
Number of censored observations 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
Hospitalizations over time (days) 
 
 
 
 
  25th percentile (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  Median (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  75th percentile (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
 
 
 
 
 
 
% Hospitalization estimate (95% CI)  
 
 
 
 
 
  Day 7 
xx.x (xx.x, 
xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  Day 14 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
  Day 21 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
  Day 28 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
 
 
 
 
 
 
Estimates are based on Kaplan-Meier methodology. 
Participants who did not experience the event of interest are considered censored according to the censoring rules detailed in Appendix 
16.1.9.  
Hospitalizations over time: presents the time point (in days) by which the estimated cumulative probability of hospitalization is 
25%, 50% and 75% and the corresponding two-sided 95% confidence interval. 
% SARS-CoV-2 clearance estimate: presents the estimated cumulative probability of hospitalization by Day 7/14/21/28 and the 
corresponding two-sided 95% confidence interval.  
n.e. = not estimable. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 56 of 105 
 
Table 14.2.4.4 Cox regression analysis of time to first hospitalization  (mITT Analysis Set) 
 
Programming note: Use same layout as table 14.2.2.3. 
 
Footnotes: 
N = number of participants in the respective treatment arm. 
n = number of participants hospitalized up to Day 28. 
M = number of evaluable participants 
The cox regression model contains treatment arm, age at baseline (years), sex, baseline BMI, baseline comorbidities, baseline viral 
load category and days of symptoms at time of enrollment as covariates. 
A hazard ratio > 1 favors the treatment arm in the denominator of the ratio (= lower probability of hospitalization). 
 
 
Figure 14.2.4.1 Kaplan-Meier curves for time to first hospitalization (mITT Analysis Set) 
 
Programming note: Use same figure layout as figure 14.2.2.1. Display the following treatment arms: SOC, ASAQ, PA, FPV-NTZ, SOF/DCV. 
Use different colors and line styles to differentiate between survival curves. Use x-axis label: Days following first study drug 
intake. Use y-axis label: Cumulative probability of hospitalization. Display x-axis until Day 28. Time to hospitalization will be 
truncated after Day 28 in order to avoid a sudden drop in number of participants at risk. Also display the p-value of the log-rank 
test. 
 
Footnotes: 
Participants who did not experience the event of interest are considered censored according to the censoring rules detailed in the 
SAP. 
 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 57 of 105 
 
Table 14.2.5.1 Summary of WHO Ordinal Scale for Clinical Improvement by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
Variable 
   Statistic 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
 
 
 
 
 
 
 
Maximum score of WHO 
Ordinal Scale for 
Clinical Improvement 
post-baseline 
 
 
 
 
 
 
  n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
  Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
  Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
  Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
Worst WHO Ordinal 
Scale for Clinical 
Improvement post-
baseline compared to 
baseline 
 
 
 
 
 
 
  Improved     
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No change 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Worsened 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Missing 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Percentages are based on the total number of participants in the corresponding treatment arm. 
 


Statistical Analysis Plan 
 
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Table 14.2.5.2 Proportional odds model for disease severity for Day 7, 14, 21, and 28 (mITT Analysis Set) 
             (Page x of y) 
 
 
Time point 
Treatment arm 
N 
Comparison 
Adjusted 
odds ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
Day 7 
 
 
 
 
 
 
 
SOC  
xx 
 
 
 
 
 
ASAQ 
xx 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
PA  
xx 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
FPV-NTZ  
xx 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
SOF/DCV  
xx 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
Day 14 
 
 
 
 
 
 
 
SOC 
xx 
 
 
 
 
 
ASAQ 
xx 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
PA  
xx 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
FPV-NTZ  
xx 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
SOF/DCV  
xx 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
Etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
Disease severity is measured by WHO Ordinal Scale score for Clinical Improvement (ordered from 
0<1<2<...<8). 
The longitudinal proportional odds model includes time point, treatment and treatment-by-time point 
interaction as fixed-effect factors. Baseline age (in years), sex, baseline BMI, baseline WHO 
Ordinal Scale score, baseline comorbidities, baseline viral load category and days of symptoms at 
time of enrollment are included as covariates. Participant-specific intercepts will be included as 
random effects. 
An adjusted odds ratio > 1 suggests a higher chance of more severe disease at the corresponding 
time point in the treatment arm of the numerator of the ratio. 
 
Programming note: Display table for time points Day 7, Day 14, Day 21 and Day 28. If the condensed response variable needs to be 
used due to convergence issues of the original model, change footnote " Disease severity is measured by WHO Ordinal Scale score for 
Clinical Improvement (ordered from 0<1<2<...<8)." to " Disease severity is measured by patient state (0<1<2<3<4).".  , derived from 
WHO Ordinal Scale score for Clinical Improvement.".  


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 59 of 105 
 
Table 14.2.5.3 Logistic regression for disease severity (mITT Analysis Set) 
             (Page x of y) 
 
 
Treatment arm 
N 
n/M (%) 
Comparison 
Odds ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
SOC  
xx 
xx/xx (xx.x) 
 
 
 
 
ASAQ 
xx 
xx/xx (xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
PA  
xx 
xx/xx (xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
FPV-NTZ  
xx 
xx/xx (xx.x) 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
SOF/DCV  
xx 
xx/xx (xx.x) 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants with WHO ordinal scale score worsening at any post-baseline time 
point by at least 1 category compared to baseline. 
M = number of evaluable participants. 
The logistic regression model contains treatment arm, age at baseline (years), sex, baseline 
BMI, baseline comorbidities, baseline viral load category and days of symptoms at time of 
enrollment as covariates. 
An odds ratio > 1 suggests a higher chance of severe disease in the treatment arm of the 
numerator of the ratio. 
 
Programming note: This analysis is only required if the proportional odds model from table 14.2.5.2 does not converge. 
 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 60 of 105 
 
Table 14.2.5.4 Kaplan Meier analysis of time to first zero WHO Ordinal Scale score for Clinical Improvement (mITT Analysis Set) 
               (Page x of y) 
 
 
Statistic 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
 
 
 
 
 
 
Available observations 
xx 
xx 
xx 
xx 
xx 
Number of participants with zero WHO Scale 
score 
xx 
xx 
xx 
xx 
xx 
Number of censored observations 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
Zero scores over time (days) 
 
 
 
 
  25th percentile (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  Median (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  75th percentile (Two-sided 95% CI) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
 
 
 
 
 
 
% zero scores estimate (95% CI)  
 
 
 
 
 
  Day 7 
xx.x (xx.x, 
xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
xx.x  
(xx.x, xx.x) 
  Day 14 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
  Day 21 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
  Day 28 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
xx.x (xx.x, 
xx.x) 
 
 
 
 
 
 
Estimates are based on Kaplan-Meier methodology. 
Participants who did not experience the event of interest are considered censored according to the censoring rules detailed in Appendix 
16.1.9.  
Time to first zero WHO Ordinal Scale score is defined as time to first zero score without any subsequent non-zero score. 
Zero scores over time: presents the time point (in days) by which the estimated cumulative probability of a zero WHO Ordinal Scale 
score is 25%, 50% and 75% and the corresponding two-sided 95% confidence interval. 
% zero score estimate: presents the estimated cumulative probability of a zero WHO Ordinal Scale score by Day 7/14/21/28 and the 
corresponding two-sided 95% confidence interval. 
n.e. = not estimable. 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 61 of 105 
 
Table 14.2.5.5 Cox regression analysis of time to first zero WHO Ordinal Scale score for Clinical Improvement (mITT Analysis Set) 
 
Programming note: Use same layout as table 14.2.2.5. 
 
Footnotes: 
N = number of participants in the respective treatment arm. 
n = number of participants with WHO Ordinal Scale score. 
M = number of evaluable participants. 
The cox regression model contains treatment arm, age at baseline (years), sex, baseline BMI, baseline comorbidities, baseline viral 
load category and days of symptoms at time of enrollment as covariates. 
A hazard ratio > 1 favors the treatment arm in the numerator of the ratio (= higher probability of having zero WHO Ordinal Scale 
score). 
 
 
Table 14.2.5.6 Summary of WHO Ordinal Scale for Clinical Improvement by treatment arm and overall (mITT Analysis Set – sero-negative 
participants) 
             (Page x of y) 
 
Programming note: Use same layout as table 14.2.5.1. Produce table for mITT Analysis Set in the subset of sero-negative 
participants. Sero-negative participants can be selected using ADMB.PARAMCD='COVSER' and ADMB.ABLFL='Y' and ADMB.MITTFL='Y' and 
ADMB.AVAL=0. 
 
 
Table 14.2.5.7 Summary of WHO Ordinal Scale for Clinical Improvement by treatment arm and overall (mITT Analysis Set – high-risk 
participants) 
             (Page x of y) 
 
Programming note: Use same layout as table 14.2.5.1. Produce table for mITT Analysis Set in the subset of high-risk participants. 
High-risk participants can be selected using ADSL.HGRKCATN=2. 
 
 
Table 14.2.5.8 Kaplan Meier analysis of time to first zero WHO Ordinal Scale score for Clinical Improvement (mITT Analysis Set – 
sero-negative participants) 
               (Page x of y) 
 
Programming note: Use same layout as table 14.2.5.4. Produce table for mITT Analysis Set in the subset of sero-negative 
participants. Sero-negative participants can be selected using ADMB.PARAMCD='COVSER' and ADMB.ABLFL='Y' and ADMB.MITTFL='Y' and 
ADMB.AVAL=0. 
 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 62 of 105 
 
Table 14.2.5.9 Kaplan Meier analysis of time to first zero WHO Ordinal Scale score for Clinical Improvement (mITT Analysis Set – 
high-risk participants) 
               (Page x of y) 
 
Programming note: Use same layout as table 14.2.5.4. Produce table for mITT Analysis Set in the subset of high-risk participants. 
High-risk participants can be selected using ADSL.HGRKCATN=2. 
 
 
Table 14.2.5.10 Cox regression analysis of time to first zero WHO Ordinal Scale score for Clinical Improvement (mITT Analysis Set – 
sero-negative participants) 
 
Programming note: Use same layout as table 14.2.5.5. Produce table for mITT Analysis Set in the subset of sero-negative 
participants. Sero-negative participants can be selected using ADMB.PARAMCD='COVSER' and ADMB.ABLFL='Y' and ADMB.MITTFL='Y' and 
ADMB.AVAL=0. 
 
 
Table 14.2.5.11 Cox regression analysis of time to first zero WHO Ordinal Scale score for Clinical Improvement (mITT Analysis Set – 
high-risk participants) 
 
Programming note: Use same layout as table 14.2.5.5. Produce table for mITT Analysis Set in the subset of high-risk participants. 
High-risk participants can be selected using ADSL.HGRKCATN=2. 
 
 
Figure 14.2.5.1 Kaplan-Meier curves for time to first zero WHO Ordinal Scale score for Clinical Improvement (mITT Analysis set) 
 
Programming note: Use same figure layout as figure 14.2.2.1. Display the following treatment arms: SOC, ASAQ, PA, FPV-NTZ, SOF/DCV. 
Use different colors and line styles to differentiate between survival curves. Use x-axis label: Days following first study drug 
intake. Use y-axis label: Cumulative probability of zero WHO Ordinal Scale score. Display x-axis until Day 28. Time to first zero WHO 
Ordinal Scale score will be truncated after Day 28 in order to avoid a sudden drop in number of participants at risk. Also display 
the p-value of the log-rank test. 
 
Footnotes: 
Participants who did not experience the event of interest are considered censored according to the censoring rules detailed in the 
SAP. 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 63 of 105 
 
Table 14.2.6.1 Poisson regression for proportion of days with fever after randomization (mITT Analysis Set) 
             (Page x of y) 
 
Treatment 
arm 
N 
No. of days 
with fever 
No. of days 
observation 
Raw rate 
Rate 
estimate 
95% CI 
Comparison 
Rate ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
 
 
 
 
SOC  
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
 
 
 
 
ASAQ 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
PA  
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
FPV-NTZ  
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
FPV-NTZ / 
SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
SOF/DCV  
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
SOF/DCV / 
SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
Raw rate is calculated as the number of days with fever / number of days of observation x 100. 
Rate estimate is derived by means of a Poisson regression model, adjusted to a 100 day period. 
The Poisson regression model contains treatment arm, age at baseline (years), sex, baseline BMI, baseline comorbidities, baseline 
viral load category and days of symptoms at time of enrollment as covariates. For each participant the number of days of observation 
(i.e. days where temperature is non-missing) is used as offset. 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 64 of 105 
 
Table 14.2.6.2 Poisson regression for proportion of days with respiratory symptoms after randomization (mITT Analysis Set) 
             (Page x of y) 
 
Treatment 
arm 
N 
No. of days with 
respiratory 
symptoms 
No. of days 
observation 
Raw rate 
Rate 
estimate 
95% CI 
Comparison 
Rate ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
 
 
 
 
SOC  
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
 
 
 
 
ASAQ 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
PA  
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
FPV-NTZ  
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
FPV-NTZ / 
SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
SOF/DCV  
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, 
xx.x) 
SOF/DCV / 
SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
Raw rate is calculated as the number of days with respiratory symptoms / number of days of observation x 100. 
Rate estimate is derived by means of a Poisson regression model, adjusted to a 100 day period. 
The Poisson regression model contains treatment arm, age at baseline (years), sex, baseline BMI, baseline comorbidities, baseline viral 
load category and days of symptoms at time of enrollment as covariates. For each participant the number of days of observation (i.e. days 
where chest/respiratory FLU-PRO domain score is non-missing) is used as offset. 
Respiratory symptom is defined as a chest/respiratory FLU-PRO domain score >0. 
 
 


Statistical Analysis Plan 
 
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SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 65 of 105 
 
Table 14.2.6.3 Poisson regression for proportion of days with SpO2<93% after randomization (mITT Analysis Set) 
             (Page x of y) 
 
Type of 
analysis 
Treatment 
arm 
N 
m 
No. of days 
with SpO2<93% 
No. of days 
observation 
Raw rate 
Rate 
estimate 
95% CI 
Comparison 
Rate 
ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
 
 
 
 
 
 
All SpO2 values 
 
 
 
 
 
 
 
 
 
SOC  
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
 
 
 
 
 
ASAQ 
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
PA  
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
PA / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
FPV-NTZ  
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
FPV-NTZ / 
SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
SOF/DCV  
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
SOF/DCV / 
SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
Restricted to plausible SpO2 values* 
 
 
 
 
 
 
 
 
 
SOC  
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
 
 
 
 
 
ASAQ 
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
PA  
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
PA / SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
FPV-NTZ  
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
FPV-NTZ / 
SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
SOF/DCV  
xx 
xx 
xx 
xx 
xx.x  
xx.x  
(xx.x, xx.x) 
SOF/DCV / 
SOC 
xx.x 
(xx.x, 
xx.x) 
x.xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
m is the number of participants in the mITT Analysis Set of the corresponding treatment arm that have SpO2 >=95% on baseline. 
Raw rate is calculated as the number of days with SpO2<93% / number of days of observation x 100. 
Rate estimate is derived by means of a Poisson regression model, adjusted to a 100 day period. 
The Poisson regression model contains treatment arm, age at baseline (years), sex, baseline BMI, baseline comorbidities, baseline viral load 
category and days of symptoms at time of enrollment as covariates. For each participant the number of days of observation (i.e. days where 
SpO2<93% is non-missing) is used as offset. 
The analysis includes only participants that had SpO2 >=95% on baseline. 
*Only plausible SpO2 values are used in the analysis. Days without any plausible SpO2 value are not counted towards no. of days of 
observation. 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 66 of 105 
 
Table 14.2.6.4 Summary of FLU-PRO Plus questionnaire scores and changes from baseline by treatment arm and overall (mITT Analysis 
Set) 
             (Page x of y) 
 
Score: Domain score - Nose 
Time point 
   Statistic 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
Base 
Post 
Change 
Base 
Post 
Change 
Base 
Post 
Change 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
 
 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
   Mean 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   SD 
xx.xxx 
 
 
xx.xxx 
 
 
xx.xxx 
 
 
   Minimum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
   Q1 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Median 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Q3 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Maximum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
xx (xx.x) xx xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
Day 3 
 
 
 
 
 
 
 
 
 
  etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Base = Baseline, Post = Post-baseline, Change = Post-baseline - baseline. 
At each visit, only participants with a value at both baseline and the respective day are included. 
 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 67 of 105 
 
Table 14.2.6.4 Summary of FLU-PRO Plus questionnaire scores and changes from baseline by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
Score: Domain score - Nose 
Time point 
   Statistic 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
Base 
Post 
Change 
Base 
Post 
Change 
Base 
Post 
Change 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
 
 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
   Mean 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   SD 
xx.xxx 
 
 
xx.xxx 
 
 
xx.xxx 
 
 
   Minimum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
   Q1 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Median 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Q3 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Maximum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
xx (xx.x) xx xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
Day 3 
 
 
 
 
 
 
 
 
 
  etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Base = Baseline, Post = Post-baseline, Change = Post-baseline - baseline. 
At each visit, only participants with a value at both baseline and the respective day are included. 
 
Programming note: Present this table for time points Baseline, Day 2, Day 3, ..., Day 13, Day 14, Day 21, Day 28 and End of study and 
for each domain score and the overall score, i.e. Domain score – Nose, Domain score – Throat, Domain score – Eyes, Domain score – 
Chest/Respiratory, Domain score - Gastrointestinal, Domain Score – Body/Systemic and Total score. 
 


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Table 14.2.7.1 Cumulative incidence of lower respiratory tract infection by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
 
Type of 
analysis 
  Variable 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
n/m (%) 
95% CI 
n/m (%) 
95% CI 
n/m (%) 
95% CI 
n/m (%) 
95% CI 
n/m (%) 
95% CI 
n/m (%) 
95% CI 
 
 
 
 
 
 
 
 
 
 
 
 
 
All SpO2 values 
 
 
 
 
 
 
 
 
 
  Cumulative   
 incidence  
  of LRTI at  
  Day 28 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Restricted to plausible SpO2 values* 
 
 
 
 
 
 
 
 
 
  Cumulative   
 incidence  
  of LRTI at  
  Day 28 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
xx/xx 
(xx.x) 
(xx.x, 
xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lower respiratory tract infection (LRTI) is defined by resting SpO2<93% sustained for 2 readings 2 hours apart and presence of either 
subjective dyspnea or cough (or both). It is only defined for participants with SpO2 ≥95% on Day 1. 
m is the number of participants in the mITT Analysis Set of the corresponding treatment arm that have SpO2 ≥95% on Day 1. 
The cumulative incidence of LRTI at Day 28 is defined by the number of participants developing LRTI up to and including Day 28 divided by 
the number of participants in the mITT Analysis Set that had SpO2 ≥95% on Day 1. 
Two-sided 95% confidence intervals are calculated according to the Wilson method without continuity correction. 
*Only plausible SpO2 values are used in the analysis. 
 


Statistical Analysis Plan 
 
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Table 14.2.8.1 Cumulative incidence of all-cause mortality by treatment arm and overall (mITT Analysis Set) 
             (Page x of y) 
 
 
Variable 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
n (%) 
95% CI 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cumulative 
incidence of 
all-cause 
mortality at 
Day 28 
xx (xx.x) (xx.x, 
xx.x) 
xx (xx.x) 
(xx.x, 
xx.x) 
xx (xx.x) 
(xx.x, 
xx.x) 
xx (xx.x) 
(xx.x, 
xx.x) 
xx (xx.x) 
(xx.x, 
xx.x) 
xx (xx.x) 
(xx.x, 
xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
The cumulative incidence of all-cause mortality at Day 28 defined by the number of participants who died up to and including Day 28 divided 
by the number of participants in the mITT Analysis Set will be presented. Participants who are hospitalized at the time of Day 28 and die 
later also count to the numerator.  
The two-sided 95% confidence intervals are calculated according to the Wilson method without continuity correction. 
 
 
 
 


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Table 14.3.1.1 Compliance by treatment arm (Safety Analysis Set) 
             (Page x of y) 
 
Variable 
   Statistic 
ASAQ 
(N=xx) 
PA 
(N=xx) 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
FPV 
NTZ 
 
 
 
 
 
 
Compliance 
 
 
 
 
 
   n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
Compliance category, n (%) 
 
 
 
 
 
   <85% 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   >=85% 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   >=85% and loading dose  
   complete* 
 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The compliance is only calculated and displayed for the experimental treatments. 
* Only applicable to FPV. Refers to the participant taking the full loading dose on Day 1. 
Analyses is performed according to actual treatment. 
 
 
 


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Table 14.3.2.1 Concomitant medications by treatment arm and overall, ATC class and WHO preferred term (Safety Analysis Set) 
Programming note: Same layout as table 14.1.8. Replace prior with concomitant in the footnotes. Use ATC class 3. 


Statistical Analysis Plan 
 
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Table 14.3.3.1 Summary of treatment emergent adverse events by MedDRA primary system organ class and preferred term by treatment arm 
and overall (Safety Analysis Set) 
             (Page x of y) 
 
 
Primary system organ class 
SOC 
 (N=xx) 
ASAQ 
 (N=xx) 
PA 
 (N=xx) 
FPV-NTZ 
(N=xxx) 
SOF/DCV 
(N=xxx) 
Overall 
(N=xxx) 
   Preferred term 
n (%) /# events n (%) /# events n (%) /# events n (%) /# events 
n (%) /# events 
n (%) /# 
events 
 
 
 
 
 
 
 
At least one adverse event 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
 
 
 
 
 
 
 
Primary system organ class 
1 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
   Preferred term 1 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
   Preferred term 2 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
 
 
 
 
 
 
 
Primary system organ class 
2 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
   Preferred term 1 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
   Preferred term 2 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
xx (xx.x) / xx 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
N = number of participants in the Safety Analysis set. 
n = number of participants with at least one event. 
Analyses is performed according to actual treatment. 
A participant with more than one adverse events within a primary system organ class is counted only once for that 
class. 
# events: number of events  
MedDRA version xx.x has been used for coding. 
 
 
 
Programming note: Sort primary system organ classes alphabetically. Sort preferred terms within system organ classes by descending 
frequency in the overall group. 
 


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Table 14.3.3.2 Summary of serious treatment emergent adverse events by MedDRA primary system organ class and preferred term by 
treatment arm and overall (Safety Analysis Set) 
             (Page x of y) 
 
Programming note: Same layout as table 14.3.3.1. 
 
Table 14.3.3.3 Summary of treatment emergent adverse events considered to be study drug related by MedDRA primary system organ class 
and preferred term by treatment arm and overall (Safety Analysis Set) 
             (Page x of y) 
 
Programming note: Same layout as table 14.3.3.1. 
 
Table 14.3.3.4 Summary of serious treatment emergent adverse events considered to be study drug related by MedDRA primary system 
organ class and preferred term by treatment arm and overall (Safety Analysis Set) 
             (Page x of y) 
 
Programming note: Same layout as table 14.3.3.1. 
 
Table 14.3.3.5 Summary of treatment emergent adverse events leading to study drug discontinuation by MedDRA primary system organ 
class and preferred term by treatment arm and overall (Safety Analysis Set) 
             (Page x of y) 
 
Programming note: Same layout as table 14.3.3.1. 
 
Table 14.3.3.6 Summary of serious treatment emergent adverse events leading to study drug discontinuation by MedDRA primary system 
organ class and preferred term by treatment arm and overall (Safety Analysis Set) 
             (Page x of y) 
 
Programming note: Same layout as table 14.3.3.1. 
 
Table 14.3.3.7 Summary of treatment emergent adverse events leading to death by MedDRA primary system organ class and preferred term 
by treatment arm and overall (Safety Analysis Set) 
             (Page x of y) 
 
Programming note: Same layout as table 14.3.3.1. 
 
Table 14.3.3.8 Summary of treatment emergent adverse events leading to hospitalization by MedDRA primary system organ class and 
preferred term by treatment arm and overall (Safety Analysis Set) 
             (Page x of y) 


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Programming note: Same layout as table 14.3.3.1. 
 
Table 14.3.3.9 Summary of treatment emergent adverse events by MedDRA primary system organ class, preferred term, maximal severity 
and treatment arm and overall (Safety Analysis Set) 
               (Page x of y) 
 
 
Primary 
system 
organ class 
 
Preferred 
term 
 
 
Maximal 
severity 
SOC 
(N=xx) 
n (%) /# events 
ASAQ 
(N=xx) 
n (%)/# events 
PA 
(N=xx) 
n (%)/# events 
FPV-NTZ 
(N=xx) 
n (%)/# events 
SOF/DCV 
(N=xx) 
n (%)/# events 
Overall 
(N=xx) 
n (%)/# events 
 
 
 
 
 
 
 
 
 
At least 
one AE 
All PTs 
Any grade 
xxx (xx.x) / xx 
xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx 
 
 
Grade 1 
xxx (xx.x) / xx 
xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx 
 
 
Grade 2 
xxx (xx.x) / xx 
xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx 
 
 
Grade 3 
xxx (xx.x) / xx 
xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx 
 
 
Grade 4 
xxx (xx.x) / xx 
xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx 
 
 
Grade 5 
xxx (xx.x) / xx 
xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx 
 
 
 
 
 
 
 
 
 
Primary SOC  All PTs 
Any grade 
xxx (xx.x) / xx 
xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx 
 
 
Grade 1 
xxx (xx.x) / xx 
xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx 
 
 
 
 
 
 
 
 
 
 
Preferred 
term 1 
Total 
xxx (xx.x) / xx 
xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx xxx (xx.x) / xx 
 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
N: number of participants in the Safety Analysis Set. 
n: number of participants with at least one event. 
If a participant reported more than one adverse event within the same category, the worst severity was summarized. A participant with more 
than one adverse event within a primary system organ class is counted only once for that class. 
# events: For Grade 1 to 5 only the events with the worst severity per patient are counted. For Any Grade all events are 
counted. 
MedDRA version xx.x has been used for coding. 
Programming note: Sort primary system organ classes alphabetically. Sort preferred terms within system organ classes by descending 
frequency in the overall group. 
 


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Table 14.3.3.10 Non-serious adverse events (threshold >5%) by MedDRA primary system organ class, preferred term and treatment arm 
(Safety Analysis Set) 
             (Page x of y) 
 
MedDRA version xx.x has been used for coding. 
Total number of patients affected by non-serious AE are those patients who had at least one PT that met the threshold criteria. 
Preferred terms with a frequency greater than 5% in any treatment arm were printed. 
Only non-serious treatment emergent adverse events are included. 
 
Programming note: Same layout as table 14.3.3.1. 
 
 


Statistical Analysis Plan 
 
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Table 14.3.4.1 Summary of vital signs including changes from baseline by treatment arm and overall and time point (Safety Analysis 
Set) 
             (Page x of y) 
 
Parameter: Oral temperature (degrees C) 
Time point 
   Statistic 
SOC 
(N=xx) 
ASAQ 
(N=xx) 
PA 
(N=xx) 
Base 
Post 
Change 
Base 
Post 
Change 
Base 
Post 
Change 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
 
 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
   Mean 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   SD 
xx.xxx 
 
 
xx.xxx 
 
 
xx.xxx 
 
 
   Minimum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
   Q1 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Median 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Q3 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Maximum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
xx (xx.x) xx xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
Day 3 
 
 
 
 
 
 
 
 
 
  etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Base = Baseline, Post = Post-baseline, Change = Post-baseline - baseline. 
At each visit, only participants with a value at both baseline and the respective day are included. 
 


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Table 14.3.4.1 Summary of vital signs including changes from baseline by treatment arm and overall and time point (Safety Analysis 
Set) 
             (Page x of y) 
 
Parameter: Oral temperature (degrees C) 
Time point 
   Statistic 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Overall 
(N=xx) 
Base 
Post 
Change 
Base 
Post 
Change 
Base 
Post 
Change 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
 
 
xx (xx.x) 
 
 
xx (xx.x) 
 
 
   Mean 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   SD 
xx.xxx 
 
 
xx.xxx 
 
 
xx.xxx 
 
 
   Minimum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
   Q1 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Median 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Q3 
xx.xx 
 
 
xx.xx 
 
 
xx.xx 
 
 
   Maximum 
xx.x 
 
 
xx.x 
 
 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
Day 2 
 
 
 
 
 
 
 
 
 
   n (%) 
xx 
(xx.x) 
xx (xx.x) xx xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
Day 3 
 
 
 
 
 
 
 
 
 
  etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Base = Baseline, Post = Post-baseline, Change = Post-baseline - baseline. 
At each visit, only participants with a value at both baseline and the respective day are included. 
 
Programming note: Present table for time points Day 1, Day 2, Day 3, ..., Day 13, Day 14, Day 21, Day 28 and End of study. Display 
table for parameter Oral temperature (degrees C), Pulse (beats/min), Respiratory rate (breaths/min) and SpO2 (%). 


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Table 14.3.5.1 Shift table of serology by treatment arm (mITT Analysis Set) 
             (Page x of y) 
 
 
 
Day 28 
Treatment 
Baseline 
Negative 
Positive 
Missing 
Total 
Result 
n 
(%) 
n 
(%) 
n 
(%) 
n 
(%) 
n 
(%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC (N=xx) 
Negative 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Positive 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
ASAQ (N=xx) 
Negative 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Positive 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
PA (N=xx) 
Negative 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Positive 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FPV-NTZ (N=xx) 
Negative 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Positive 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
SOF/DCV (N=xx) 
Negative 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Positive 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
Percentage is based on baseline total N for each treatment arm. 
 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 79 of 105 
 
Table 14.3.5.2 Summary of PK parameter by treatment arm and overall (PK Analysis Set) 
             (Page x of y) 
 
Parameter 
   Statistic 
ASAQ 
(N=xx) 
PA 
(N=xx) 
  Artesunate 
 
Dihydroarte
misinin 
 
Amodiaquine 
 
N-Desethyl 
Amodiaquine 
 
Pyronaridine 
  
Artesunate 
 
Dihydroartem
isinin 
 
 
 
 
 
 
 
 
Cday3 (ng/mL) 
 
 
 
 
 
 
 
   n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Geometric mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
Cday7 (ng/mL) 
 
 
 
 
 
 
 
   n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx xx.x) 
xx (xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Geometric mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
PK analysis is only done for experimental arms, hence the SOC arm is not displayed. 
Only for ASAQ and PA arms PK assessments were done at Day 3 additionally. 
Concentrations below the lower limit of quantification (LLOQ) were imputed with LLOQ/2. 
No visit windowing approach was applied. 
 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 80 of 105 
 
Table 14.3.5.2 Summary of PK parameter by treatment arm and overall (PK Analysis Set) 
             (Page x of y) 
 
 
 
 
 
Table 14.3.5.3 Incidence of 
low viral load on Day 7 (mITT 
Analysis Set) 
 
Treatment arm 
N 
n/M (%) 
Comparison* 
Risk ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
SOC  
xx 
xx/xx (xx.x) 
 
 
 
 
ASAQ 
xx 
xx/xx (xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
PA  
xx 
xx/xx (xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
FPV-NTZ  
xx 
xx/xx (xx.x) 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
SOF/DCV  
xx 
xx/xx (xx.x) 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
Parameter 
   Statistic 
FPV-NTZ 
(N=xx) 
SOF/DCV 
(N=xx) 
Favipiravir 
 
Nitazoxanide 
 
Tizoxanide 
Sofosbuvir 
 
Daclatasvir 
 
 
 
 
 
 
Cday3 (ng/mL) 
 
 
 
 
 
   n (%) 
 
 
 
 
 
   Mean 
 
 
 
 
 
   Geometric mean 
 
 
 
 
 
   SD 
 
 
 
 
 
   Minimum 
 
 
 
 
 
   Q1 
 
 
 
 
 
   Median 
 
 
 
 
 
   Q3 
 
 
 
 
 
   Maximum 
 
 
 
 
 
 
 
 
 
 
 
Cday7 (ng/mL) 
 
 
 
 
 
   n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx xx.x) 
xx (xx.x) 
   Mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Geometric mean 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   SD 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
xx.xxx 
   Minimum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
   Q1 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Median 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Q3 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
xx.xx 
   Maximum 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
PK analysis is only done for experimental arms, hence the SOC arm is not displayed. 
Only for ASAQ and PA arms PK assessments were done at Day 3 additionally. 
Concentrations below the lower limit of quantification (LLOQ) were imputed with LLOQ/2. 
No visit windowing approach was applied. 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 81 of 105 
 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants with low viral load on Day 7. 
M = number of evaluable participants for Day 7. 
Low viral load is defined as log10 viral load < 6. 
The regression model contains treatment arm, age at baseline (years), sex, baseline BMI, 
baseline comorbidities, baseline viral load category and days of symptoms at time of 
enrollment as covariates. 
A risk ratio > 1 favors the treatment arm in the numerator of the ratio (= higher proportion 
of low viral load on Day 7). 
Model specification: * = log link and binomial distribution, # = log link and poisson 
distribution, § = log link and normal distribution. 
 
 
Table 14.3.5.4 Shift table of viral culture data by treatment arm, overall and time point (mITT Analysis Set) 
             (Page x of y) 
 
Programming note: Use same layout as table 14.3.5.5. Present time points Baseline, Day 7 and Day 10. 
 
Footnotes: 
Base = Baseline, Post = Post-baseline, Change = Post-baseline - baseline. 
At each visit, only participants with a value at both baseline and the respective day are included. 
Analysis is based on viral culture data. 
 


Statistical Analysis Plan 
 
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SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 82 of 105 
 
Table 14.3.5.5 Shift table of qualitative SARS-CoV-2 RT-PCR by treatment arm (mITT Analysis Set) 
             (Page x of y) 
 
Time point: Day 3 
Treatment 
Baseline 
Not detected 
Detected 
Missing 
Total 
Result 
n 
(%) 
n 
(%) 
n 
(%) 
n 
(%) 
n 
(%) 
 
 
 
 
 
 
 
 
 
 
 
 
SOC (N=xx) 
Not detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
ASAQ (N=xx) 
Not detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
PA (N=xx) 
Not detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FPV-NTZ (N=xx) 
Not detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
SOF/DCV (N=xx) 
Not detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Detected 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Missing 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
Total 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
xx 
(xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
Percentage is based on baseline total N for each treatment arm. 
 
Programming note: Present the table for time points Day 3, 10, 14, 21 and 28.  
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 83 of 105 
 
Table 14.3.5.6 Summary of log10 mean viral load of SARS-CoV-2 by treatment arm and overall, time point (mITT Analysis Set) 
 
Base = Baseline, Post = Post-baseline, Change = Post-baseline - baseline. 
At each visit, only participants with a value at both baseline and the respective day are included. 
Analysis is based on RT-PCR. 
Mean viral load values (copies/mL) are calculated across the S-gene, N-gene and ORF1ab gene. Mean viral load values are then log10 
transformed. 
 
Programming note: Use layout similar to table 14.2.3.1.  
 
Table 14.3.5.7 Repeated measure analysis of log10 mean viral load of SARS-CoV-2 change from baseline (mITT Analysis Set) 
             (Page x of y) 
 
Programming note: Use layout similar to table 14.2.3.2.  
 
Table 14.3.5.8 Incidence of SARS-CoV-2 clearance on Day 10 based on viral culture (mITT Analysis Set) 
 
Treatment arm 
N 
n/M (%) 
Comparison* 
Risk ratio 
95% CI 
p-value 
 
 
 
 
 
 
 
SOC 
xx 
xx/xx (xx.x) 
 
 
 
 
ASAQ 
xx 
xx/xx (xx.x) 
ASAQ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
PA  
xx 
xx/xx (xx.x) 
PA / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
FPV-NTZ  
xx 
xx/xx (xx.x) 
FPV-NTZ / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
SOF/DCV  
xx 
xx/xx (xx.x) 
SOF/DCV / SOC 
xx.x 
(xx.x, xx.x) 
x.xxx 
 
 
 
 
 
 
 
N = number of participants in the respective treatment arm. 
n = number of participants with SARS-CoV-2 clearance on Day 10 based on viral culture. 
M = number of evaluable participants for Day 10. 
The regression model contains treatment arm, age at baseline (years), sex, baseline BMI, 
baseline comorbidities, baseline viral load category and days of symptoms at time of 
enrollment as covariates. 
A risk ratio > 1 favors the treatment arm in the numerator of the ratio (= higher proportion 
of SARS-CoV-2 clearance). 
Model specification: * = log link and binomial distribution, # = log link and poisson 
distribution, § = log link and normal distribution. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 84 of 105 
 
Figure 14.3.5.1 Scatter plot of plasma or blood concentrations at Day 3 and/or Day 7 by SARS-CoV-2 clearance on Day 7 and 
exploratory arm (PK Analysis Set) 
             (Page x of y) 
 
Programming note: Present plasma or blood concentrations on y-axis. Separate x-axis by "SARS-CoV-2 D7 clearance" and "No SARS-CoV-2 
D7 clearance". Create a separate scatter plot panel for each experimental arm. Use different symbols for different PK components. For 
ASAQ and PA display data for Cday3 and Cday7 either next to each other on the x-axis or use different symbols. For other experimental 
arms only display Cday7. 
Footnotes: 
Patients with missing Cday3 and/or Cday7 concentrations are excluded. 
PK analysis is only done for experimental arms, hence participants from SOC arm are not included. 
No visit windowing approach was applied. 
Concentrations below the lower limit of quantification (LLOQ) were imputed with LLOQ/2. LLOQ(Amodiaquine)=0.156 ng/mL, LLOQ(Artesunate, 
N-Desethyl Amodiaquine)=1.56 ng/mL, LLOQ(Daclatasvir)= 15.6 ng/mL, LLOQ(Dihydroartemisinin)= 3.91 ng/mL, LLOQ(Favipiravir)= 391 ng/mL, 
LLOQ(Nitazoxanide, Tizoxanide)= 100 ng/mL, LLOQ(Pyronaridine)=0.977 ng/mL, LLOQ(Sofosbuvir)=2.5 ng/mL. 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 85 of 105 
 
Listing 14.3.1.1 Listing of adverse events leading to death (Safety Analysis Set) 
Programming note: Use shell of Appendix 16.2.7.1 
 
Listing 14.3.1.2 Listing of serious treatment-emergent adverse events (Safety Analysis Set) 
Programming note: Use shell of Appendix 16.2.1.7 
 
Listing 14.3.1.3 Listing of treatment-emergent adverse events leading to study discontinuation (Safety Analysis Set) 
Programming note: Use shell of Appendix 16.2.7.1 
 
Listing 14.3.1.4 Listing of treatment-emergent adverse events with action taken related to study treatment (Safety Analysis Set) 
Programming note: Action taken related to study treatment is either "Dose reduced", "Drug interrupted" or "Drug withdrawn". Use shell 
of Appendix 16.2.7.1 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 86 of 105 
 
Appendix 16.2.1.1 Study completion (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Age/ 
 
 
 
Any hospitalizations 
Participant 
Sex/ 
 
Study termination   
during study period 
ID 
Race 
Participant status 
date 
Primary reason for discontinuation 
due to COVID-19?* 
 
 
 
 
 
 
xxxxx 
xx/F/Bl 
Completed study 
ddMMMyyyy / x 
 
No 
xxxxx 
xx/M/Bl 
Randomized: 
Discontinued prior 
to study end 
ddMMMyyyy / x 
xxxxxxxxxxxxxxxxxxxx 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
* Randomized participants only.  
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort within treatment arm by participant ID. Start a new page for each treatment arm. Derive hospitalization column 
by checking if participant has record in HO with HOOCCUR="Y".If yes, then populate with Yes, else with No. 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 87 of 105 
 
Appendix 16.2.1.2 Screening failures (All screened subjects) 
                  (Page x of y) 
 
 
Age/ 
 
 
Participant 
Sex/ 
Study termination   
ID 
Race 
date 
Primary reason for discontinuation 
 
 
 
 
xxxxx 
xx/F/Bl 
ddMMMyyyy 
 
xxxxx 
xx/M/Bl 
ddMMMyyyy 
xxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Only screening failures are displayed. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort by participant ID. Display all participants with the DS.DSTERM as primary reason for discontinuation where 
DS.DSSTATUS='NOT RANDOMIZED: SCREEN FAILURE'. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 88 of 105 
 
Appendix 16.2.2.1 Protocol deviation (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Participant 
ID 
Age/ 
Sex/ 
Race 
 
 
Date occurred/day 
 
 
Date reported/day 
 
Protocol deviation 
category 
Protocol 
deviation 
description 
 
 
 
 
 
 
xxxxx 
xx/F/Bl 
ddMMMyyyy / xx 
ddMMMyyyy / xx 
xxxxxx 
xxxxxxx 
xxxxx 
xx/M/Bl 
 
 
 
 
 
 
 
 
 
 
Etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort within treatment arm by participant ID. Start a new page for each treatment arm. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 89 of 105 
 
Appendix 16.2.3.1 Analysis Sets (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Participant 
ID 
Age/ 
Sex/ 
Race 
 
Randomized 
Analysis Set 
 
Safety Analysis 
Set 
Modified Intention to 
Treat Analysis Set 
As Treated 
Analysis Set 
Pharmacokinetic 
Analysis Set 
 
 
 
 
 
 
 
xxxxx 
xx/F/Bl 
Yes 
Yes 
Yes 
No 
No 
xxxxx 
xx/M/Bl 
Yes 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
 
Etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort within treatment arm by participant ID. Start a new page for each treatment arm. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 90 of 105 
 
Appendix 16.2.4.1 Demographic data and informed consent (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
 
Participant 
ID 
 
Age/ 
Sex/ 
Race 
 
Language 
of FLU-
PRO 
Date/time of 
pre-screening 
informed 
consent 
Date/time 
of 
informed 
consent 
Date/time 
of  
enrollment 
informed 
consent 
 
 
Height 
(cm) 
 
Body 
weight 
(kg) 
 
BMI 
(kg/m**2) 
 
Race: 
Other, 
specify 
Days of 
symptoms at 
time of 
enrollment 
 
 
 
 
 
 
 
 
 
 
 
xxxx 
xx/ 
F/ 
Black 
 
ddMMMyyyy/ 
hh:mm 
ddMMMyyyy
/hh:mm 
ddMMMyyyy/
hh:mm 
xxx 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xx/ 
M/ 
Black 
 
ddMMMyyyy/ 
hh:mm 
ddMMMyyyy
/hh:mm 
ddMMMyyyy/
hh:mm 
xxx 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI = Weight (kg)/[Height (m)]**2. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort within treatment arm by participant ID. Start a new page for each treatment arm. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 91 of 105 
 
Appendix 16.2.4.2 Medical and surgical history (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
Participant 
ID 
Age/ 
Sex/ 
Race 
Pre-
specifi
ed term 
Medical / surgical 
history as reported 
 
Preferred term 
   Primary system organ class 
Start date/day 
End date/day 
 
 
 
 
 
 
 
xxxx 
xx/ 
F/ 
Black 
No 
xxx 
Xxxxxxx 
   xxxxxx 
ddMMMyyyy/xx 
ddMMMyyyy/xx 
 
xx/ 
M/ 
Black 
Yes 
 
Xxxxxxx 
   xxxxxx 
ddMMMyyyy/xx 
Ongoing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort within treatment arm by participant ID. Start a new page for each treatment arm. If medical history was ticked 
as 'Ongoing at study end' then 'Ongoing' should be displayed instead of End date/day. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 92 of 105 
 
Appendix 16.2.4.3 Physical examination (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Participant 
ID 
Age/ 
Sex/ 
Race 
 
Collection date/day/ 
time/hours since 1st dose 
 
Body system or 
part 
 
 
Exam finding 
 
 
If abnormal: 
specify 
 
 
 
 
 
 
xxxx 
xx/ 
F/ 
Black 
ddMMMyyyy/xx/hh:mm/xx.x 
General appearance 
 
 
 
 
ddMMMyyyy/xx/hh:mm/xx.x 
Skin 
 
 
xxxx 
xx/ 
M/ 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort within treatment arm by participant ID, collection date/time and body system or part. Start a new page for 
each treatment arm.  


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 93 of 105 
 
Appendix 16.2.4.4 Randomization (Randomized Analysis Set) 
                  (Page x of y) 
 
Participant 
ID 
Age/Sex/Race 
Randomization 
date/time 
 
Randomization 
number 
 
Randomized 
treatment arm 
 
Actual 
treatment arm 
 
Re-screened? 
Randomized 
manually? 
 
 
 
 
 
 
 
 
xxxx 
xx/F/Black 
ddMMMyyyy/hh:
mm 
xxx 
SOC 
SOC 
 
 
 
 
 
 
 
 
 
 
xxxx 
xx/M/White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort within randomized treatment arm and participant ID. Start a new page for each treatment arm. Display re-
screened column using SUPPDS.QNAM="DSRESCRN" and randomized manually column using SUPPDS.QNAM="MANYN". 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 94 of 105 
 
Appendix 16.2.5.1 Drug accountability (Safety Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Age/ 
 
 
 
Drug 
 
 
 
Type 
 
 
Date/ 
day 
 
 
No. of 
tablets  
 
 
 
Compliance* 
Par. 
Sex/ 
ID 
Race 
 
 
 
 
 
 
 
xxxx 
xx/F/
Bl 
Paracetamol 
Dispense 
ddMMMyyyy/ xx 
xx 
 
 
 
xxx 
Return 
ddMMMyyyy/ xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Compliance is only calculated for experimental treatments. 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
 
Programming note: Sort within treatment arm by participant ID, drug, type (first dispense, then return), date. Display compliance 
only for experimental treatments. If there are multiple rows or dispense/return, show compliance in last row. 
Start a new page for each treatment arm. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 95 of 105 
 
Appendix 16.2.5.2 Pharmacokinetic concentration data (PK Analysis Set) 
                  (Page x of y) 
 
Treatment arm: ASAQ 
 
 
Age/ 
 
 
 
PK parameter 
(unit) 
 
 
 
Sample date/day/time 
 
 
 
Concentration 
Date/day/time 
of 
IMP dose administ. 
prior 
to 
blood 
sampling 
Samples stored and 
processed 
appropriately 
Par. 
Sex/ 
ID 
Race 
 
 
 
 
 
 
 
xxxx 
xx/F/Bl 
xxx (xx) 
ddMMMyyyy/xx/hh:mm 
xxx 
ddMMMyyyy/xx/hh:mm 
Yes 
 
 
 
ddMMMyyyy/xx/hh:mm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
 
Programming note: Sort within treatment arm by participant ID, PK parameter and date/time. Display only experimental arms as no PK 
parameter. Present only available data. 
Start a new page for each treatment arm. 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 96 of 105 
 
Appendix 16.2.6.1 Mid-nasal swab and saliva specimen data, viral culture and SARS-CoV-2 serology (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Participant 
ID 
Age/ 
Sex/ 
Race 
 
Visit  
 
Category 
 
Specimen material 
type 
 
Collection date/day/ 
time/hours since 1st dose 
 
Parameter 
 
Result 
 
Unit 
 
 
 
 
 
 
 
 
 
xxxx 
xx/ 
F/ 
Black 
Day 2 
SINGLE PLEX 
RT-PCR 
NASOPHARYNGEAL SWAB 
ddMMMyyyy/xx/hh:mm/xx.x 
 
Positive 
 
 
 
 
 
 
ddMMMyyyy/xx/hh:mm/xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxx 
xx/ 
M/ 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort within treatment arm by participant ID, collection date/time, category, specimen and parameter. Start a new 
page for each treatment arm. Present data from MB domain. Present unit if available in separate column. For category column use 
MB.MBCAT and for specimen material type use MB.MBSPEC. 
 
 
 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 97 of 105 
 
Appendix 16.2.6.2 Hospitalizations (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
Participant 
ID 
Age/ 
Sex/ 
Race 
Date of 
admission/day 
Date of 
discharge/day 
Maximum WHO Ordinal 
Scale for Clinical 
Improvement during 
Admission period 
 
 
 
 
 
xxxx 
xx/ 
F/ 
Black 
ddMMMyyyy/xx 
ddMMMyyyy/xx 
xx 
 
 
ddMMMyyyy/xx 
ddMMMyyyy/xx 
 
 
 
 
 
 
xxxx 
xx/ 
M/ 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, 
Ot=Other. 
 
Programming note: Sort within treatment arm by participant ID and date of admission. Start a new page for each treatment arm.  
 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 98 of 105 
 
Appendix 16.2.6.3 FLU-PRO Plus (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Age/ 
 
 
 
 
 
Part. 
Sex/ 
 
 
 
 
 
ID 
Race 
Date/day/ 
time/hours 
since 1st dose 
 
Visit 
Question 
Item 
Answer 
 
 
 
 
 
 
 
xxxx 
xx/F/Bl ddMMMyyyy/xx/ 
hh:mm/xx.x 
Baseline 
Please rate the extent to which you 
had each symptom during the past 24 
hours 
Runny or 
dripping nose 
Somewhat 
 
 
 
 
 
xxx 
 
 
 
 
 
 
xxx 
 
 
 
 
 
 
... 
 
 
 
 
 
In the past 24 hours, how often have 
you had any of the following symptoms? 
Sneezing 
Never 
 
 
 
 
 
xxx 
 
Etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration.   
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
 
Programming note: Sort within treatment arm by participant ID and date/time, and question. Start a new page for each treatment arm.  
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 99 of 105 
 
Appendix 16.2.6.4 FLU-PRO Plus Global additional daily diary items (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Age/ 
 
 
 
 
Part. 
Sex/ 
 
 
 
 
ID 
Race 
Date/day/ 
Visit 
Question 
Answer 
 
 
 
 
 
 
xxxx 
xx/F/Bl ddMMMyyyy/xx 
 
Overall, how severe were your 
infection symptoms today? 
Mild 
 
 
 
 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc... 
 
 
 
 
 
 
 
 
 
 
 
* Time point displays the mapped time window for analysis. 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
 
Programming note: Sort within treatment arm by participant ID and date/time, and question. Present all FLU-PRO Plus global additional 
daily diary items and also the following questions from general daily diary items: 'Have you taken your daily medication since survey', 
'Have you taken any other medication?' (Show also SUPPFA.FADESC if answer is yes as "Yes, FADESC") and ' Have you observed any change 
or new complaint since you last completed the survey?' (Show also SUPPFA.FADESC if answer is yes as "Yes, FADESC"). 
Start a new page for each treatment arm.  
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 100 of 105 
 
Appendix 16.2.6.5 WHO Ordinal Scale for Clinical Improvement (Randomized Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Participant ID 
 
Age/Sex/Race 
Date/day/ 
time/hours since 1st dose 
 
Visit 
 
Score 
 
 
 
 
 
xxxx 
xx/F/Bl 
ddMMMyyyy/xx/ 
hh:mm/xx.x 
Baseline  
2 
 
 
ddMMMyyyy/xx/ 
hh:mm/xx.x 
Day 7 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Etc... 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
 
Programming note: Sort within treatment arm by participant ID and date/time. Start a new page for each treatment arm.  
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 101 of 105 
 
Appendix 16.2.7.1 Treatment emergent adverse events (Safety Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Age/ 
Adverse event 
 
 
Start date/ 
day 
 
 
Outcome 
date/day 
 
 
Severity* 
Related  
 
 
 
 
Par. 
Sex/ 
INVESTIGATOR TERM/ 
To study 
Action 
 
 
If SAE: Serious 
ID 
Race 
  Preferred term/SOC 
Treatment? 
Taken** Outcome SAE 
due to? 
 
 
 
 
 
 
 
 
 
 
 
xxxx 
xx/F/
Bl 
XXXXXXXXXXXX/ 
xxxxxxxxxxx/xxxx 
ddMMMyyyy/ 
xx 
ddMMMyyy/ 
xx 
Grade 1 
Not related 
1 
Unknown 
Yes 
Life-threatening 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
* The severity of AEs is assessed according to the DAIDS AE grading Table, corrected Version 2.1, July 2017. 
** Action taken: 1 = Not applicable, 2 = Unknown , 3 = No change, 4 = Dose reduced, 5 = Drug interrupted, 6 = Drug withdrawn. If action 
taken = Drug withdrawn then the day of drug withdrawal is given in brackets. 
MedDRA version xx.x has been used for coding. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
 
Programming note: Sort within treatment arm by participant ID, AE start date. If action taken = Drug withdrawn, display corresponding 
numerical code and in in brackets the day on which the drug was withdrawn (AEENDY). 
Start a new page for each treatment arm.  


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 102 of 105 
 
Appendix 16.2.7.2 Vital signs (Safety Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
Participant 
ID 
Age/ 
Sex/ 
Race 
Date/day/ 
time/hours 
since 1st 
dose 
 
 
Visit 
 
 
Pulse (bpm) 
 
Temperature 
(degree C) 
Respiratory 
rate (breaths 
per minute) 
 
 
SpO2 (%)  
SpO2 <93%? 
 
 
 
 
 
 
 
 
 
xxxx 
xx/ 
F/ 
Black 
ddMMMyyyy/xx 
/hh:mm/xx.x 
Baseline 
xx 
xx.x 
xx 
xx 
No 
 
 
ddMMMyyyy/xx 
/hh:mm/xx.x 
Day 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxx 
xx/ 
M/ 
White 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
Programming note: Sort within treatment arm by participant ID, parameter and collection date/time. Display all vital sign parameters. 
Start a new page for each treatment arm.  


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 103 of 105 
 
Appendix 16.2.7.3 Prior and concomitant medications (Safety Analysis Set) 
                  (Page x of y) 
 
Treatment arm: SOC 
 
 
Age/ 
Treatment 
 
 
 
 
 
 
Part. 
Sex/ 
INVESTIGATOR TERM 
Date/day 
Date/day 
 
 
 
Type 
ID 
Race 
  Preferred term/ATC class 
started 
stopped 
Dose 
(unit) 
Frequency 
Route 
 
 
 
 
 
 
 
 
 
 
xxxx 
xx/F/Bl Xxxxxxxxxxxxxxxx 
  xxxxxxxxxxxxxx/xxxxxxxx 
ddMMMyyy 
/xx 
ddMMMyyyy 
/xx 
xxx 
xxx 
xxx 
Prior 
 
 
Xxxxxxxxxxxxxxxx 
  xxxxxxxxxxxxxx/xxxxxxxx 
ddMMMyyy 
/xx 
ddMMMyyyy 
/xx 
xxx 
xxx 
xxx 
Concomitant 
xxxx 
xx/F/Bl Xxxxxxxxxxxxxxxx 
  xxxxxxxxxxxxxx/xxxxxxxx 
ddMMMyyyy 
/xx 
ddMMMyyyy 
/xx 
xxx 
xxx 
xxx 
Prior 
 
 
 
 
 
 
 
 
 
Etc... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Day 1 defined as the day of first study drug administration. 
Medications were coded using the World Health Organizational-Drug Dictionary (WHO-DD) version xx. 
|M=Male, F=Female, As=Asian or Indian, Bl=Black African, Wh=White, Ot=Other. 
 
 
Programming note: Sort within treatment arm by participant ID and start date. Start a new page for each treatment arm. For Frequency 
and Route: if the 'Other, specify' item is used, use that for presentation. 
 
 
 
 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 104 of 105 
 
17. 
Appendices 
17.1 
FLU-PRO total and domain scoring 
The derivation of FLU-PRO Total and domain scores (including rules for handling missing data) according to the FLU-PRO user manual version 1.2 are provided 
in the table 2 below. 
Table 2 
Domain 
Items 
Scoring 
Minimum Data 
R
i
Nose 
Runny or dripping nose 
Congested or stuffy 
nose Sneezing 
Sinus pressure 
Arithmetic mean 
of 4 items within 
Nose domain 
Daily score for 3 of 4 items 
must be present to 
calculate domain score 
Throat 
Scratchy or itchy throat 
Sore or painful throat 
Difficulty swallowing 
Arithmetic mean 
of 3 items within 
Throat domain 
Daily score for 2 of 3 items 
must be present to 
calculate domain score 
Eyes 
Teary or watery eyes 
Sore or painful eyes 
Eyes sensitive to light 
Arithmetic mean 
of 3 items within 
Eyes domain 
Daily score for 2 of 3 items 
must be present to 
calculate domain score 
Chest/Respiratory 
Trouble breathing 
Chest congestion 
Chest tightness 
Dry or hacking cough 
Wet or loose cough 
Coughing 
Coughed up mucus or 
phlegm 
Arithmetic mean 
of 7 items within 
Chest/Respirato
ry 
domain 
Daily score for 5 of 7 items 
must be present to 
calculate domain score 


Statistical Analysis Plan 
 
SP-PA-CoV-202 
 
SP-PA-COV-202_SAP_amendment_2 
SOP 401, Template 1, Version 9 
DATAMAP GmbH 
Page 105 of 105 
 
Gastrointestinal 
Felt nauseous 
Stomachache 
How many times did 
you vomit? How many 
times did you have 
diarrhea? 
Arithmetic mean 
of 4 items within 
Gastrointes
tinal domain 
Daily score for 3 of 4 items 
must be present to 
calculate domain score 
Body/Systemic 
Headache 
Head congestion 
Felt dizzy 
Lack of appetite 
Sleeping more than 
usual 
Body aches or pains 
Weak or tired 
Chills or shivering 
Felt cold 
Felt hot 
Arithmetic 
mean of 11 
items within 
Body/Systemic 
domain 
Daily score for 8 of 11 
items must be present to 
calculate domain score 
Total 
All above 32 items 
Arithmetic mean 
of all 32 items 
within FLU-PRO 
In the presence of 
missing data, the above 
conditions for the 
calculation of all domain 
scores must be met in 
order to calculate the 
FLU-PRO total score.