Clinical trial NCT04446377
Conditions: COVID-19 Disease
Keywords: COVID-19 SARS-CoV-2 Apilimod Dimesylate LAM-002A Coronavirus AI Therapeutics
Sponsor: OrphAI Therapeutics
Start date: 2020-07-15; Completion date: 2021-04-19
Enrollment: 142 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a clinical trial to evaluate the efficacy of LAM-002A compared to placebo treatment in adults with a confirmed SARS-CoV-2 infection who are receiving standards supportive care in an outpatient setting.

Detailed description:
This is a Phase II randomized, double-blind, placebo-controlled, clinical study to evaluate the efficacy of LAM-002A compared to placebo treatment in adults with a confirmed SARS-CoV-2 infection who are receiving standard supportive care in an outpatient setting.

Study eligibility will be assessed during screening. All study participants must sign a written informed consent and satisfy the inclusion and exclusion criteria for the study. Confirmation of SARS-CoV-2 infection, medical history, and current medication will be assessed for each consenting participant at screening.

Study participants will be randomized in a 1:1 ratio, to receive study therapy (either LAM-002A, 125 mg \[5 capsules/dose\]) PO BID or placebo \[5 capsules/dose\] PO BID) for 10 days. Participants who experience an adverse event (AE) considered to be related to study therapy may have a decrease in study dose of LAM-002A to 100 mg \[4 capsules/dose\]) PO BID or placebo \[4 capsules/dose\] PO BID). After the start of treatment on Day 1, participants will be followed at Days 4,6,8,11,22, and 28. Days 6,8, and 22 will be phone visits. Participants can withdraw from the study therapy or study participation at any time.

The study will incorporate an interim safety analysis after the first 30 participants (15 on LAM-002A and 15 on placebo) have completed treatment and have been followed up for 11 days post-first dose. Recruitment and randomization will continue while this analysis is conducted. Recommendations from an independent Data Safety Monitoring Board (DSMB) will be used for decisions of early termination or study design adaptations.

Non-parametric and parametric statistical analysis will be conducted, as appropriate. For the comparison of the LAM-002A active arm and the control arm for the primary endpoint and secondary endpoints of drug effect, appropriate methods will be employed. Baseline subject characteristics, study therapy administration/compliance, safety, supportive care administration, and pharmacokinetics will be analyzed descriptively.

Arms: arm 1: LAM-002A (Apilimod Dimesylate) 125mg in five 25-mg capsules BID for 10 days arm 2: (microcrystalline cellulose) in 5 capsules BID for 10 days
Interventions: intervention 1: Apilimod Dimesylate Capsule intervention 2: Placebo
Intervention descriptions: intervention 1: LAM-002A is formulated in capsules containing 25 mg of apilimod dimesylate. The capsule is Swedish orange, Size 0. intervention 2: Microcrystalline cellulose in Swedish orange, Size 0 capsules

Protocol documents:
Prot_SAP_000.pdf: 
Clinical Study Protocol 
 
Protocol Title: 
A Phase II Randomized, Double-Blind, 
Placebo-Controlled, Study of LAM-002A 
for the Prevention of Progression of 
COVID-19 
Protocol Number: 
LAM-002A-CVD-CLN01 
Protocol Date: 
16 October 2020 
NCT: 
NCT04446377 
 


 
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Clinical Study Protocol 
Protocol Title 
A Phase II Randomized, Double-Blind, Placebo-Controlled, 
Study of LAM-002A for the Prevention of Progression of 
COVID-19 
Study Sponsor 
AI Therapeutics, Inc.  
530 Old Whitfield St 
Guilford CT, 06437 
Investigational Product 
LAM-002A 
Protocol Number 
LAM-002A-CVD-CLN01 
Developmental Phase 
Phase II 
US IND Number 
148521 
Protocol Versions (Date) 
Version 1 (22 June 2020) 
Version 2 (10 July 2020) 
Version 3 (31 August 2020) 
Version 4 (16 October 2020) 
 
 
Confidentiality Statement 
This document contains confidential information belonging to AI Therapeutics, Inc. Except as may be 
otherwise permitted in writing, by accepting or reviewing these materials, it is agreed that this 
information should not be disclosed to others (except if required by applicable law or regulation) and 
should not be used for unauthorized purposes.  


Investigational Drug: LAM-002A 
 
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Study Personnel 
Information regarding sponsor-designated study personnel are described in the Pharmacy 
Manual. 
 
 


Investigational Drug: LAM-002A 
 
Study Protocol: LAM-002A-CVD-CLN01 
AI Therapeutics, Inc. 
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Version 4 (16 October 2020) 
AI Therapeutics, Inc. Approval Page 
Title 
A Phase II Randomized, Double-Blind, Placebo-Controlled, Study 
of LAM-002A for the Prevention of Progression of COVID-19. 
Protocol Number 
LAM-002A-CVD-CLN01 
Version (Date) 
Version 4 (16 October 2020) 
By signing this document, it is confirmed on behalf of AI Therapeutics, Inc., that this study 
will be conducted and reported in compliance with the protocol, accepted standards of Good 
Clinical Practice (GCP), and all applicable regulatory requirements. 
 
 
 
16 October 2020 
Langdon L Miller, MD 
Clinical Advisor 
AI Therapeutics, Inc. 
 
Date 
 


Investigational Drug: LAM-002A 
 
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Principal Investigator Approval Page 
Title 
A Phase II Randomized, Double-Blind, Placebo-Controlled, Study of 
LAM-002A for the Prevention of Progression of COVID-19  
Protocol Number 
LAM-002A-CVD-CLN01 
Version (Date) 
Version 4 (16 October 2020) 
I have reviewed the protocol. On behalf of my institution, I agree to conduct the study as 
outlined in the study protocol and in compliance with Good Clinical Practices (GCP) and all 
applicable regulatory requirements. 
 
 
 
 
Principal Investigator Signature 
 
Date 
 
 
 
Principal Investigator Printed Name 
 
 
Institution: 
 
Address: 
 
 
 


Investigational Drug: LAM-002A 
 
Study Protocol: LAM-002A-CVD-CLN01 
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Table of Contents 
1. 
PROTOCOL SYNOPSIS AND SCHEDULE OF 
ACTIVITIES .................................................................................................................14 
2. 
INTRODUCTION ........................................................................................................21 
2.1. 
Study Rationale ...............................................................................................................21 
2.2. 
Background .....................................................................................................................22 
2.2.1. 
LAM-002A Mechanism of Action ..................................................................................22 
2.2.2. 
Human Experience with LAM-002A ..............................................................................22 
2.3. 
Benefit/Risk Assessment ................................................................................................23 
3. 
STUDY OBJECTIVES ................................................................................................25 
3.1. 
Primary Objective ...........................................................................................................25 
3.2. 
Secondary Objectives .....................................................................................................25 
3.2.1. 
Safety and Tolerability ....................................................................................................25 
3.2.2. 
Clinical Efficacy .............................................................................................................25 
3.2.3. 
Clinical Status .................................................................................................................25 
3.2.4. 
Oxygen Saturation ..........................................................................................................25 
3.3. 
Exploratory Objectives ...................................................................................................26 
3.3.1. 
Pharmacokinetic ..............................................................................................................26 
3.3.2. 
Viral Clearance ...............................................................................................................26 
3.3.3. 
Pharmacodynamic Objectives .........................................................................................26 
3.3.4. 
Genetic Evaluation Objectives ........................................................................................26 
4. 
STUDY ENDPOINTS ..................................................................................................27 
4.1. 
Primary Endpoint ............................................................................................................27 
4.2. 
Secondary Endpoints ......................................................................................................27 
4.2.1. 
Safety and Tolerability ....................................................................................................27 
4.2.2. 
Clinical Efficacy .............................................................................................................27 
4.2.3. 
Clinical Status .................................................................................................................27 
4.2.4. 
Oxygen Saturation ..........................................................................................................27 
4.3. 
Exploratory Endpoints ....................................................................................................28 
4.3.1. 
Pharmacokinetics ............................................................................................................28 
4.3.2. 
Viral Clearance ...............................................................................................................28 
4.3.3. 
Pharmacodynamics .........................................................................................................28 
4.3.4. 
Immunogenicity Endpoints .............................................................................................28 
4.3.5. 
Genetic Endpoints ...........................................................................................................28 
5. 
STUDY DESIGN AND CONDUCT ............................................................................30 
5.1. 
Study Design ...................................................................................................................30 
5.2. 
Study Conduct.................................................................................................................30 
5.3. 
Rationale for Study Design .............................................................................................31 
5.4. 
Justification for Dose ......................................................................................................32 
6. 
STUDY POPULATION ...............................................................................................35 
6.1. 
Inclusion Criteria ............................................................................................................35 
6.2. 
Exclusion Criteria ...........................................................................................................36 


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7. 
STUDY DRUG ALLOCATION ..................................................................................38 
7.1. 
Randomization ................................................................................................................38 
7.2. 
Blinding ..........................................................................................................................38 
8. 
STUDY DRUG INFORMATION, ADMINISTRATION, 
AND SUPPORT ............................................................................................................39 
8.1. 
Blinded Study Drug (LAM-002A and Placebo) .............................................................39 
8.1.1. 
Description ......................................................................................................................39 
8.1.2. 
Source .............................................................................................................................39 
8.1.3. 
Packaging and Labelling .................................................................................................39 
8.1.4. 
Shipping, Storage, and Stability......................................................................................39 
8.1.5. 
Dispensing.......................................................................................................................39 
8.1.6. 
Return and Compliance Assessment ...............................................................................39 
8.1.7. 
Accountability .................................................................................................................40 
8.1.8. 
Overdose Precautions ......................................................................................................40 
8.1.9. 
Inadvertent Exposure Precautions ...................................................................................40 
8.2. 
Study Drug Administration .............................................................................................40 
8.2.1. 
Drug Administration .......................................................................................................40 
8.2.2. 
Fed/Fasting Status ...........................................................................................................41 
8.2.3. 
Dose Schedule Interruptions and Vomited Doses ..........................................................41 
8.2.4. 
Dose Modification Recommendations ............................................................................41 
8.3. 
Emergency Unblinding ...................................................................................................42 
8.4. 
Supportive Care ..............................................................................................................42 
8.4.1. 
General Recommendations .............................................................................................42 
8.4.2. 
Antibiotics, Antifungals, and Antivirals .........................................................................42 
8.4.3. 
Anti-SARS-CoV-2 Therapies .........................................................................................43 
8.4.4. 
Anticoagulants ................................................................................................................43 
8.4.5. 
Antidiarrheals ..................................................................................................................43 
8.4.6. 
Antiemetics .....................................................................................................................43 
8.4.7. 
Antihistamine, Antiinflammatory, or Antipyretic, Drugs ...............................................44 
8.4.8. 
Corticosteroids ................................................................................................................44 
8.4.9. 
Drugs with Drug-Drug Interaction Potential ..................................................................44 
8.4.10. Drugs Known to Prolong the QT Interval .......................................................................44 
8.4.11. Hematopoietic Support ...................................................................................................44 
8.4.12. Cardiopulmonary Support ...............................................................................................44 
8.5. 
Study Restrictions ...........................................................................................................45 
8.5.1. 
Breast Feeding ................................................................................................................45 
8.5.2. 
Contraception/Reproduction ...........................................................................................45 
8.5.3. 
Diet ..................................................................................................................................46 
8.6. 
Duration of Study Drug Administration and Study Participation ..................................46 
9. 
SAFETY ASSESSMENT .............................................................................................47 
9.1. 
Definitions ......................................................................................................................47 
9.1.1. 
Adverse Event .................................................................................................................47 
9.1.2. 
Serious Adverse Event ....................................................................................................48 
9.1.3. 
Unexpected Adverse Event .............................................................................................48 
9.1.4. 
Treatment-Emergent Adverse Event ...............................................................................49 
9.1.5. 
Adverse Events of Special Interest .................................................................................49 


Investigational Drug: LAM-002A 
 
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9.2. 
Eliciting Adverse Event Information ..............................................................................49 
9.3. 
Recording Adverse Events..............................................................................................49 
9.4. 
Grading of the Severity of an Adverse Event .................................................................50 
9.5. 
Describing Adverse Event Relationship to Study Drug and Study 
Procedures .......................................................................................................................50 
9.6. 
Adverse Event Reporting Period ....................................................................................51 
9.7. 
Study Center Reporting Requirements ...........................................................................51 
9.7.1. 
Adverse Event Reporting Requirements .........................................................................51 
9.7.2. 
Pregnancy ........................................................................................................................53 
9.7.3. 
Contact Information for Reporting an SAE or Pregnancy ..............................................54 
9.8. 
Sponsor Reporting Requirements ...................................................................................54 
10. 
LABORATORY AND OTHER ASSESSMENTS .....................................................55 
10.1. 
Methods and Analytes ....................................................................................................55 
10.2. 
Sample Shipping, Storage, and Retention ......................................................................56 
11. 
EFFICACY ASSESSMENTS ......................................................................................58 
11.1. 
Primary Efficacy Endpoint: Viral Clearance at Day 4 ...................................................58 
11.2. 
Secondary Efficacy Endpoint .........................................................................................58 
11.2.1. Clinical Efficacy .............................................................................................................58 
11.2.2. Hospitalization: Clinical Status.......................................................................................60 
12. 
STATISTICAL CONSIDERATIONS ........................................................................62 
12.1. 
Statistical Hypotheses .....................................................................................................62 
12.2. 
Sample Size Determination ............................................................................................62 
12.3. 
Analysis Sets ...................................................................................................................63 
12.3.1. Intention to Treat (ITT) Population ................................................................................63 
12.3.2. Antiviral Efficacy Analysis Population ..........................................................................63 
12.3.3. Per Protocol (PP) Population ..........................................................................................63 
12.3.4. Safety Population ............................................................................................................63 
12.4. 
Statistical Analyses .........................................................................................................63 
12.4.1. General Considerations ...................................................................................................63 
12.4.2. Comparability of Baseline Characteristics......................................................................63 
12.4.3. Analysis of Primary Outcome: Viral Load in Nasopharyngeal 
Samples at Day 4 ............................................................................................................64 
12.4.4. Analysis of Secondary Outcomes ...................................................................................64 
12.4.5. Exploratory Endpoints ....................................................................................................65 
12.4.6. Subgroup Analyses .........................................................................................................65 
12.4.7. Plan for Missing Data .....................................................................................................65 
12.4.8. Safety and Tolerability Analyses ....................................................................................65 
12.4.9. Other Safety Analyses .....................................................................................................67 
12.5. 
Interim Analyses .............................................................................................................67 
13. 
STUDY ADMINISTRATION AND RESPONSIBILTIES .......................................68 
13.1. 
General Investigator Responsibilities .............................................................................68 
13.2. 
Protocol Compliance.......................................................................................................68 
13.3. 
Compliance with Ethical and Regulatory Guidelines .....................................................68 
13.4. 
Institutional Review Board/Independent Ethics Committee 
(IRB/IEC)........................................................................................................................69 


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13.5. 
Informed Consent ...........................................................................................................70 
13.6. 
Confidentiality ................................................................................................................70 
13.7. 
Study Files and Retention of Records and Biological Samples......................................71 
13.8. 
Subject Screening Log ....................................................................................................72 
13.9. 
Modifications of the Protocol or Informed Consent Documents ....................................72 
13.10. 
Case Report Forms..........................................................................................................72 
13.11. 
Study Drug Accountability .............................................................................................73 
13.12. 
Monitoring ......................................................................................................................74 
13.13. 
Inspections ......................................................................................................................74 
13.14. 
Data Management ...........................................................................................................74 
13.15. 
Clinical Trial Insurance ..................................................................................................75 
13.16. 
Communications with Regulatory Authorities ...............................................................75 
13.17. 
Public Notification of Study Conduct .............................................................................75 
13.18. 
Study Reporting and Publication ....................................................................................75 
13.19. 
Study Discontinuation.....................................................................................................76 
14. 
BIBLIOGRAPHY .........................................................................................................77 
15. 
APPENDICES ...............................................................................................................79 
15.1. 
Strong CYP3A Inhibitors and Inducers ..........................................................................79 
15.2. 
Drugs Known to Prolong the QT Interval and/or Cause Torsades 
De Pointes .......................................................................................................................80 
15.3. 
ECOG Performance Status .............................................................................................84 
15.4. 
Protocol Amendment History .........................................................................................85 
15.4.1. Summary of Changes: Version 2 (10 July 2020) ............................................................85 
15.4.2. Summary of Changes: Version 3 (31 August 2020) .......................................................87 
15.4.3. Summary of Changes: Version 4 (16 October 2020) ......................................................89 
 
 


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LIST OF TABLES 
Table 1: 
Schedule of Activities ....................................................................................... 18 
Table 2. 
Summary of LAM-002A In Vitro Activity Against SARS CoV-2 ................... 34 
Table 3. 
Grading of Adverse Event Severity .................................................................. 50 
Table 4.  
Relationship of Study Drug to Adverse Event .................................................. 51 
Table 5.  
Study Center Reporting Requirements for Adverse Events .............................. 52 
Table 6.  
Laboratory and Other Parameters to Be Assessed ............................................ 56 
Table 7 
National Early Warning Score (NEWS) ........................................................... 60 
Table 8.  
Death Boundary for Study Termination ............................................................ 67 
 
 


Investigational Drug: LAM-002A 
 
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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
API 
Active pharmaceutical ingredient 
AST 
Aspartate aminotransferase 
AUC 0-t 
Area under the plasma concentration versus time curve, as determined by a trapezoidal 
method, from time zero to t hours post-dose 
AUC0-24 
Area under the curve 0-24 hours 
AVPU 
Alert, voice, pain, unresponsive 
βHCG 
Beta human chorionic gonadotropin 
BID 
Twice per day 
BIPAP 
Bilevel Positive Airway Pressure 
BTK 
Bruton tyrosine kinase 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
cGMP 
Current Good Manufacturing Practices 
CK 
Creatine kinase 
CLIA 
Clinical Laboratory Improvement Amendments  
Cmax 
Maximal plasma concentration 
CMC 
Chemical Manufacturing and Control 
CNS 
Central Nervous System 
COA 
Certificate of Analysis 
COVID 
Corona virus Disease 
CRF 
Case Report Form 
CRO 
Clinical research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Cardiovascular 
CYP3A4 
Cytochrome P450 3A4 
DNA 
Deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
EBV 
Ebola virus 
ECG 
Electrocardiogram 
eCLCR 
Estimated creatinine clearance 
ECMO 
Extracorporeal membrane oxygenation 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EDC 
Electronic data system 
ELISA 
Enzyme-linked immunosorbent assay 
FDA 
Food and Drug Administration 


Investigational Drug: LAM-002A 
 
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Abbreviation 
Definition 
FSH 
Follicle-stimulating hormone 
GCP 
Good clinical practice 
GLP 
Good Laboratory Practice 
GP 
Glycoprotein 
h or hr 
Hour 
HDPE 
High density polyethylene 
HEPA 
High-efficiency particulate air 
HET 
Heterogeneity of treatment effect 
HIV 
Human immunodeficiency virus 
HPLC 
High-performance liquid chromatography 
IC50 
Inhibitory Concentration 50% 
ICH 
International Conference on Harmonization 
ICU 
Intensive care unit 
IEC 
Independent ethics committee 
IFNγ 
Interferon gamma 
IIG 
Inactive Ingredient 
IL6 
Interleukin 6 
IL-10 
Interleukin 10 
IL-12 
Interleukin 12 
IL-23 
Interleukin 23 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
ITT 
Intent to treat 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
LDH 
Lactate dehydrogenase 
MARV 
Marburg virus 
MedDRA 
Medical Dictionary for Regulatory Activities 
MERS 
Middle East respiratory syndrome  
MERS-CoV 
Middle East respiratory syndrome coronavirus 
mg/kg 
Milligram/kilogram 
mg/kg/day 
Microgram/kilogram/day 
μg 
Microgram 
MH 
Mantel-Haenszel 
μg/mL 
Microgram per milliliter 
mL 
Milliliter 
mL/kg 
Milliliter/kilogram 
Msec 
Millisecond 
n 
Number of Observations 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 


Investigational Drug: LAM-002A 
 
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Abbreviation 
Definition 
NDA 
New Drug Application 
NEWS 
National Early Warning Score 
NHL 
Non-Hodgkins Lymphoma 
NIOSH 
National Institute for Occupational Safety and Health 
nM 
Nanomolar 
NPCI 
Niemann-Pick C1 
NSAID 
Nonsteroidal anti-inflammatory drugs 
PAPR 
Powered air-purifying respirator 
PBMC 
Peripheral blood mononuclear cells 
PCR 
Polymerase chain reaction 
PI 
Phosphatidylinositol 
PI3P 
Phosphatidylinositol 3-phosphate 
PIKfyve 
Phosphatidylinositol-3-phosphate- 5 kinase 
PK  
Pharmacokinetics 
pM 
Pico molar 
PO 
Per os (by mouth) 
PP 
Per protocol 
PPE 
Personal protective equipment 
QD 
Once a day 
QRS 
Combination of three of the graphical deflections seen on a typical electrocardiogram (ECG) 
QT 
Time of start of Q wave until end of T wave in the heart’s electrical cycle 
QTc 
Corrected QT 
QTcF 
QTc by Fridericia 
RBC 
Red blood cell  
RNA 
Ribonucleic acid 
RNAseq 
RNA sequence analysis  
RR 
Respiratory rate, also risk ratio 
RT-PCR 
Reverse transcriptase polymerase chain reaction  
SAC 
Staphylococcus aureus Cowan I strain 
SAE 
Series Adverse Event 
SAP 
Statistical Analysis Plan 
SARS 
Severe acute respiratory syndrome 
SARS-CoV 
Severe acute respiratory syndrome corona virus 
SD 
Standard Deviation 
SoA 
Schedule of activities 
SUSAR 
Suspected unexpected serious adverse reactions 
T 1/2 
Elimination half-life 
TBD 
To be determined 
TdP 
Torsades de Pointes 
TEAE 
Treatment Emergent Adverse Event 
TFEB 
Transcription Factor EB 


Investigational Drug: LAM-002A 
 
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Abbreviation 
Definition 
Th1 
T-helper lymphocyte type 1 
TLR 
Toll-like receptor 
TLS 
Tumor Lysis Syndrome 
Tmax 
Time to maximum concentration 
UK 
United Kingdom 
US 
United States 
vs. 
Versus 
 


Investigational Drug: LAM-002A 
 
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1. 
PROTOCOL SYNOPSIS AND SCHEDULE OF ACTIVITIES 
Study Title 
A Phase II Randomized, Double-Blind, Placebo-controlled, Study of 
LAM-002A for the Prevention of Progression of COVID-19  
Study Number 
LAM-002A-CVD-CLN01 
Investigational 
Medicinal Product 
LAM-002A (Apilimod dimesylate capsules) 
Clinical Phase 
Phase II 
Sponsor 
AI Therapeutics, Inc. 
530 Old Whitfield Street 
Guilford, Connecticut 06437 
Study Objective(s) 
Primary Objective: 
• To evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 with a 
baseline viral load >105 copies/mL as measured by SARS-CoV-2 clearance as determined 
by a quantitative RT-PCR (qRT-PCR) test from nasopharyngeal samples at Day 4 
(72 hours ± 4 hours after the first dose of the study drug). 
Secondary Objective(s): 
• To evaluate the safety and tolerability of LAM-002A administration in the treatment of 
subjects with mild COVID-19. 
• To evaluate the efficacy of LAM-002A in preventing COVID-19 disease progression in 
subjects who have proven infection with the SARS-CoV-2 virus as determined by a 
validated test; disease progression is defined as the occurrence of any of the following:  
o Death at Day 28 
o Hospitalization at Day 28 
• To evaluate change in COVID-19 clinical status, as defined by the ordinal scale, of 
subjects treated with LAM-002A compared to placebo at Day 28, in subjects who become 
hospitalized and continue LAM-002A/placebo treatment. 
• To compare the proportion of subjects at or above 95% oxygen saturation (O2 sat) between 
LAM-002A versus placebo treatment groups as measured on Days 1, 4, and 11.  


Investigational Drug: LAM-002A 
 
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Exploratory Objective(s):  
• To potentially evaluate the pharmacokinetics of LAM-002A in subjects with mild 
COVID-19. 
• To potentially evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 
with a baseline viral load >105 copies/mL as measured by SARS-CoV-2 clearance as 
determined by qRT-PCR test from saliva samples at Day 4. 
• To potentially evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 
with a baseline viral load >105 copies/mL as measured by SARS-CoV-2 clearance as 
determined by a qRT-PCR test from saliva samples at Day 11. 
• To potentially evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 
with a baseline viral load >105 copies/mL as measured by SARS-CoV-2 clearance as 
determined by a qRT-PCR test from saliva samples at Day 28. 
• To potentially evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 
with a baseline viral load >105 copies/mL as measured by SARS-CoV-2 clearance as 
determined by a qRT-PCR test from saliva samples at all available days based on AUC 
analysis.  
• To potentially evaluate the difference in proportion of subjects with a SARS-CoV-2 viral 
load <LLOQ between the LAM-002A and the placebo arm as measured by a qRT-PCR 
test from nasopharyngeal samples at Day 4. 
• To potentially evaluate the effect of LAM-002A on target engagement biomarkers. 
• To potentially evaluate the effect of LAM-002A on pro- and anti-inflammatory cytokine 
levels and target engagement biomarkers in COVID-19 subjects. 
• To potentially evaluate viral resistance by comparing genomic sequence of SARS-CoV-2 
before and after LAM-002A treatment. 
• To potentially evaluate the effect of SARS-CoV-2 genetic variants on LAM-002A 
efficacy. 
• To potentially evaluate the effect of germline DNA sequence polymorphisms on 
LAM-002A safety and efficacy. 
Study Design: 
This is a Phase II randomized, double-blind, placebo-controlled, clinical study to evaluate the 
efficacy of LAM-002A compared to placebo treatment in adults with a confirmed 
SARS-CoV-2 infection who are receiving standard supportive care in an outpatient setting.  
Study eligibility will be assessed during screening. All study participants must sign a written 
informed consent and satisfy the inclusion and exclusion criteria for the study. Written 
documentation confirming SARS-CoV-2 infection via a validated test, medical history, and 
current medication will be assessed for each consenting participant at screening. 
Study participants will be randomized in a 1:1 ratio, to receive study therapy (either 
LAM-002A, 125 mg [5 capsules/dose]) PO BID or placebo [5 capsules/dose] PO BID) for 
10 days. Nasopharyngeal swabs for quantification of baseline viral load will be performed on 
Day 1, however, results will not be available before administration of treatment. Subjects who 
experience an AE considered to be related to study therapy may have a decrease in study dose 
to LAM-002A, 100 mg [4 capsules/dose]) PO BID or placebo [4 capsules/dose] PO BID). 


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After the start of treatment on Day 1, subjects will be followed at Days 4, 6, 8, 11, 22, and 28. 
Subjects can withdraw from the study therapy or study participation at any time. 
The study will incorporate an interim safety analysis after the first 30 subjects (15 on 
LAM-002A and 15 on placebo) have completed treatment and have been followed up for 
11 days post-first dose. Recruitment and randomization will continue while this analysis is 
conducted. An additional interim analysis will be conducted at 50% of total enrollment. 
Recruitment and randomization will continue while this analysis is conducted. 
Recommendations from an independent DSMB will be used for decision of early termination 
or design adaptations. 
Primary analysis of antiviral efficacy will be conducted in the subgroup of randomized 
participants with a baseline viral load > 105 copies/mL. As existing data on viral load is 
preliminary, this baseline may be adjusted as detailed in the statistics section. Non-parametric 
and parametric statistical analysis will be conducted as appropriate. For the comparison of the 
LAM-002A active arm and the control arm for the primary endpoint and secondary endpoints 
of drug effect, appropriate methods will be employed. Baseline subject characteristics, study 
therapy administration/compliance, safety, supportive care administration, and 
pharmacokinetics will be analyzed descriptively. 


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Product Description: 
LAM-002A (apilimod dimesylate) is a first-in-class inhibitor of phosphatidylinositol-3-
phosphate 5-kinase (PIKfyve) that has demonstrated in vitro anti-viral activity against 
SARS-COV-2 infected cells.  
Each Size 0 capsule of the active drug contains 25 mg of LAM-002A (equivalent to 17.1 mg 
of apilimod free base). Inactive components in the capsules are microcrystalline cellulose, 
silicified microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, colloidal 
silicon dioxide, and magnesium stearate.  
Each Size 0 capsule of the placebo is identical in appearance to capsules containing the active 
drug.  Each placebo capsules contains microcrystalline cellulose as the inactive ingredient. 
All inactive excipients are within the limits of FDA’s Inactive Ingredient (IIG) limit 
requirements.  
Study Activities: 
The specific study procedures and timing of activities to be conducted for each subject 
enrolled in the study are presented in tabular form in Table 1. Physical examinations, other 
clinical evaluations, and additional laboratory studies or more frequent assessments may be 
performed consistent with appropriate medical care for the subject, but these data will not 
necessarily be collected unless specified in Table 1.  
Missed or delayed procedures or evaluations should be performed as close to the originally 
scheduled date/time as possible. Based on the medical monitor’s judgment, an exception can 
be made when rescheduling becomes medically unnecessary because it is too close in time to 
the next scheduled procedure or evaluation. In that case, the missed evaluation may be omitted 
after consultation with the medical monitor. 


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Table 1: 
Schedule of Activities  
Procedures 
Screening  
[a] 
Intervention Period 
 [Days] 
Follow-up 
Period [Days] 
Early 
Termi-
nation 
1 
2 
3 
4 
5 
6    
Phone 
Visit 
7 
8    
Phone 
Visit 
9 
10 
11 
22   
Phone 
Visit 
28 
Visit Days 
(Window) 
 [b] 
 
 
(72 
hours ± 
4 hours) 
 
 
 
 
 
 
 
(±2) (±2) 
General Eligibility/Safety Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent [c] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment criteria [d] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics [e] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history [f] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG performance status [g] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, weight [h] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs/oxygen saturation (NEWS) [i] 
X 
X 
 
 
X 
 
X 
 
X 
 
 
X 
 
X 
X 
AE review [j] 
X 
X 
 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
Concomitant medication review [k] 
X 
X 
 
 
X 
 
X 
 
X 
 
 
X 
X 
X 
X 
12-lead ECG [l] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment, Randomization, Study Drug Administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Submit randomization form [m] 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study drug administration in clinic [n] 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dispensing of study drug [o] 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Self-administration of study drug by subject [p] 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
LAM-002A return/compliance and diary check [q] 
 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
X 
Laboratory/Disease Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient COVID-19 symptoms diary completed (r) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum or urine pregnancy test [s] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for DNA and RNA isolation [t] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nasopharyngeal swabs for viral load analysis and infectious disease diagnostic 
(Biofire or equivalent) [u] 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Saliva for SARS-CoV-2 viral load, sequence, and target engagement analysis [v] 
 
X 
 
 
X 
 
 
 
 
 
 
X 
 
X 
 
Blood for hematology [w] 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Serum chemistry [x] 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Blood for cytokine analysis/target engagement [y] 
 
X 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
Plasma for pharmacokinetics [z] 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Secondary clinical endpoint assessment [aa] 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
See footnotes on next page 
 


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Table 1: 
Schedule of Activities  
Footnotes:   
Note: For pharmacokinetic assessments to be performed at specified times postdose on Day 1, the acceptable margin for actual time is as follows for hours (± minutes): 1 (±15) 
and 2 (±15). For scheduled visits after Day 1, permitted visit windows are indicated in the table.  
a. The screening and baseline visits can occur on the same day. Day 1 of the study is the day the subject takes the first dose of study drug after randomization. 
b. Hematology and serum chemistry collected during Screening need not be repeated on Day 1. 
c. Written informed consent will be obtained before performance of any study procedures that are not part of routine medical care. 
d. Adverse changes in inclusion/exclusion criteria before randomization should be discussed with the medical monitor before randomization. Optional confirmatory SARS CoV-2 
rapid viral test for patients who do not have documentation of positive infection. These rapid SARS CoV-2 viral tests will be supplied by the site and only conducted after the ICF 
is signed. 
e. Demographics to include sex, age, race, ethnicity. 
f. Medical history to include recording of COVID-19 history, previous therapy for COVID-19, past and ongoing medical conditions, substance use (smoking, alcohol), and 
cardiovascular history. 
g. Performance status will be assessed at Screening using the ECOG scale: Grade 1: Fully active, able to carry on all pre-disease performance without restriction; Grade 2: Restricted 
in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work; Grade 3: Ambulatory and capable of all 
self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; Grade 4: Capable of only limited self-care; confined to bed or chair more than 
50% of waking hours; completely disabled. Cannot carry on any self-care; totally confined to bed or chair. 
h. Height (in centimeters) and weight (in kilograms) will be obtained at Screening only.  
i. Vital signs (respiratory rate, blood pressure, pulse, temperature, and oxygen saturation via pulse oximetry) will be obtained with the subject resting in a seated upright position 
while breathing room air or with supplemental oxygen (if required). National Early Warning Score (NEWS) score will be derived from respiratory rate, oxygen saturation, 
supplemental oxygen use, temperature, systolic blood pressure, heart rate, and AVPU (alert, voice, pain, unresponsive). Assessments will be performed on Day 1 (predose), Day 4, 
Day 11 and Day 28 during site visits. 
j. AEs will be described using concise medical terminology, including whether the AE is serious, the date of AE onset, the date of AE resolution, the severity of the AE based on the 
CTCAE, Version 5.0, a description of relatedness of the AE to study drug or to a study procedure, the action taken due to the AE, and the outcome of the AE. AEs will be collected 
beginning once ICF is executed and include any changes from medical history.  Day 6, Day 8, and Day 22 assessments will be done via telephone 
k. Concomitant medication assessments should include information regarding all prescription, nonprescription, and alternative medications (health foods). Use of any other drugs 
intended as therapy for COVID-19 (e.g. antivirals, antimalarials, BTK inhibitors, anti-IL-6 antibodies) or supportive care (e.g. antidiarrheals, NSAIDs, antiemetics, supplemental 
oxygen) should be noted. Information on concomitant medications used during Screening or since the last assessment will be assessed on each designated day. Day 6, 8, and 22 
assessments will be done via telephone 
l. 12-lead ECG will be obtained with the subject resting in a supine position at Screening. An ECG obtained within 30 days prior to the Screening visit is acceptable. 
m. At Screening, obtain a subject number.  On Day 1, randomize the subject and obtain a study drug bottle number. 
n. The first dose of blinded study drug (LAM-002A or placebo) will be administered to the subject in the study center (with recording of the date and actual clock time of the 
LAM-002A administration). Depending on the time of administration (AM vs PM), the follow-up visit times will be determined as AM or PM. 
o. Study personnel will dispense the remainder of the 10-day supply of blinded study drug (LAM-002A or placebo) to the subject with instructions for self-administration at home. 


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Table 1: 
Schedule of Activities  
p. Study subjects will be given the blinded study drug (LAM-002A or placebo) after randomization and will self-administer continuously thereafter until the evening of Day 10 or the 
morning of Day 11 (20 total doses) depending on if the first dose is taken in the AM or PM on Day 1. On Day 1, subjects should ingest the study drug (LAM-002A or placebo) 
while fasting (defined as no food with the exception of clear liquids for ≥2 hours before and ≥1 hour after dosing). With other doses, subjects may take the study drug without 
regard to fed or fasting status, However, subjects should be advised to avoid ingestion of grapefruit, grapefruit juice, or Seville oranges, and should not use St. John’s wort. 
Subjects should take the study drug at approximately the same time each day, ideally at ~12-hour intervals (e.g. ~8AM and ~8PM every day).  At each dose administration, 5 
capsules of blinded study drug (equivalent to 125 mg of LAM-002A or placebo) should be taken. If a subject requires a dose modification for drug-related toxicity, 4 capsules of 
blinded study drug (equivalent to 100 mg of LAM-002A or placebo) should be taken. At each dose administration, all capsules should be swallowed whole with 100 to 200 mL (~4 
to 8 ounces) of water. Subjects who have a delay in administration of <6 hours should take the planned dose as soon as possible after the intended time of administration. For 
subjects who have a delay in administration of ≥6 hours, the dose should not be taken. The planned timing of subsequent drug administration should not be altered. For subjects 
who vomit shortly after taking the study drugs, the vomited dose should not be replaced. The planned timing of subsequent drug administration should not be altered. 
q. Empty, partially used, or full bottles of blinded study drug (LAM-002A or placebo) will be retrieved from the subject and drug compliance will be assessed throughout the dosing 
period. In addition, the subject’s dosing diary will be reviewed, any incomplete or inconsistent entries will be addressed, and the dosing diary will be photocopied. 
r. COVID-19 symptoms will be documented by the patient on the applicable diary every day and reviewed by the study staff on Day 1, Day 4, Day 6, Day 8, Day 11, Day 22, Day 
28. Patients should be instructed to collect this data on their patient diary every day, at the same time they take their study drug, until study completion. Patients should be 
instructed to return the paper diary to each clinic visit for review by study personnel. A copy of the paper diary will be collected as part of the source documentation and the 
original returned to the subject until the next visit. The original diary will be collected at the day 28 visit. Sites should schedule all visits, including phone visits, as close as possible 
to the drug dosing time on Day 1 to ensure consistency when reviewing patient symptoms. 
s. Serum or urine pregnancy testing will be performed in women of childbearing potential only. Pregnancy testing should be performed at Screening. 
t. Blood for genomic DNA and RNA will be used to assess for polymorphisms in the patient and the virus that may affect safety or efficacy; to be collected at Screening. 
u. Nasopharyngeal swabs collection to determine SARS-CoV-2 viral load and possibly sequence, expression biomarkers of target engagement and infectious disease diagnostic  
(Biofire or equivalent) to be collected on Day 1 (immediately prior to the first dose) and then on Day 4. The Day 4 swab should be obtained as close to 72 hours ( ± 4 hours) after 
the Day 1 dose as possible. 
v. Saliva collection to determine SARS-CoV-2 viral load, and possibly sequence and expression biomarkers of target engagement to be collected on Day 1 (immediately prior to the 
first dose) and then on Day 4, Day 11, and Day 28.  NOTE: The Day 4 sample should be obtained as close to 72 hours ( ± 4 hours) after the Day 1 dose as possible. 
w. Hematology to include hemoglobin, hematocrit, erythrocyte count, absolute counts of leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils; platelet count.  
Hematology testing should be performed on Day 1 (predose), and Day 11.  NOTE: Hematology results obtained within 30 days prior to the Screening visit are acceptable for the 
Day 1 sampling requirement. 
x. Serum chemistry to include sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium phosphorus, magnesium, total protein, albumin, ALT/SGPT, AST/SGOT, 
ALP, CK, LDH, total bilirubin, uric acid to be collected on Day 1 (predose) and Day 11. NOTE: Serum chemistry results obtained within 30 days prior to the Screening visit are 
acceptable for the Day 1 requirement.   
y. Blood to be split for plasma samples for cytokine analysis and cell pellet/PBMC for target engagement will be collected on Day 1 (predose), Day 4 and Day 11. PBMC collection 
is optional. 
z. Only a few sites will collect pharmacokinetic data. Blood for LAM-002A pharmacokinetics will be collected predose on Day 1 and at 1 hr. (± 15 min.) and 2 hr.(± 15 min.) 
postdose, and on Day 11 (12 hours post the last dose on Day 10) to be performed in a subset of subjects as defined in the laboratory manual. Patients participating in 
pharmacokinetics will take study drug on Day 1 while fasting (defined as no food with the exception of clear liquids for ≥2 hours before and ≥1 hour after dosing). 
aa. Documentation of whether the subject has died or become hospitalized due to COVID-19 disease; documentation of whether the subject is symptom-free on Day 28. 
 


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2. 
INTRODUCTION 
In December 2019, the Wuhan Municipal Health Committee identified an outbreak of viral 
pneumonia cases of unknown cause. Coronavirus RNA was quickly identified in some of these 
subjects. This novel coronavirus has been designated SARS-CoV-2, and the disease caused by 
this virus has been designated COVID-19. Following exposure to SARS-CoV-2, a window of 
treatment opportunity to prevent progression of disease exists. After exposure, there is a ~5-day 
incubation period (range 1-14 days), after which most individuals (~80%) develop mild disease. 
However, in high-risk individuals, including those ≥65 years of age, or those with pre-existing 
medical conditions (e.g. chronic lung disease, heart disease, or vascular disease), there is 
significantly increased risk of development of severe COVID-19 requiring intensive supportive 
care and often resulting in death.  
No vaccine prophylaxis exists for COVID-19 and only one antiviral agent, remdesivir, has been 
approved under emergency-use provisions for therapy of COVID-19.  Remdesivir has modest 
activity and must be given intravenously (IV), thus limiting its utility for outpatient care of 
subjects with mild COVID-19 symptoms. Development of a well-tolerated, easy-to-administer 
oral therapy for treatment of subjects with COVID-19 could prevent disease progression and 
consequent morbidity, need for intensive care, and mortality.  
2.1. 
Study Rationale 
The enzyme phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is known to be responsible for 
viral entry into cells. LAM-002A is a clinically tested, orally bioavailable, specific PIKfyve 
kinase inhibitor with in vitro antiviral activity against Ebola (EBV), Marburg (MARV), and the 
coronaviruses MERS-CoV, SARS-CoV, and SARS-CoV-2 (Ou et. al, 2020, Nelson et al, 2017; 
Qiu et al 2018; Riva et al., 2020; Kang et al, 2020). 
AI Therapeutics plans to conduct a Phase II randomized, double-blind, placebo-controlled, study 
of LAM-002A to test if LAM-002A can prevent the progression of COVID-19 in subjects with 
mild COVID-19.  
The study will enroll men and women within 8 days of symptom onset, who are ≥18 years of 
age, have documented SARS-CoV-2 infection as confirmed by a positive validated test, and have 
mild disease appropriate for initial outpatient care. 
The appropriate dose and safety of LAM-002A administration has been established through data 
from several clinical studies that enrolled more than 700 combined healthy subjects and subjects 
with inflammatory and malignant conditions (see LAM-002A IB V5). A dose-range-finding 
study of LAM-002A in subjects with hematological cancers indicated that LAM-002A was not 
well tolerated at doses of 150 mg BID due to the rapid onset of nausea, vomiting, and/or diarrhea 
that preclude compliance with therapy. However, when administered at 125 mg BID, the drug 
demonstrated anticancer efficacy, and was well tolerated with excellent compliance, over a 
period of 2 years. Toxicities at this dose level were infrequent nausea, vomiting, and/or diarrhea, 
requiring dose reduction to 100 mg BID in <10% of subjects. Accordingly, this same dosing 
regimen is proposed for evaluation in this study in subjects with COVID-19. 


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2.2. 
Background 
2.2.1. 
LAM-002A Mechanism of Action 
Viral entry into cells has been shown to occur through components of the endosomal network, 
including Rab9 GTPase, the endo/lysosomal cholesterol transporter Niemann-Pick C1 (NPC1) 
(Murray et.al; 2005; Carette et. al., 2011), and phosphatidylinositol-3-phosphate 5-kinase 
(PIKfyve) (Murray et.al; 2005; Carette et. al., 2011; Nelson et.al., 2017; Qiu et.al., 2018).  
PIKfyve, is a 240-kDa endosomal phosphatidylinositol (PI) 5 lipid kinase that catalyzes the 
phosphorylation of phosphatidylinositol 3-phosphate (PI(3)P) to phosphatidylinositol 3,5-
bisphosphate (PI(3,5)P2). PIKfyve regulates endosome and lysosome biogenesis and intracellular 
trafficking, facilitating late-endosome-to-trans-Golgi vesicular transport. This vesicular transport 
is part of the endosomal network that viruses use to enter the cell and replicate, suggesting 
PIKfyve inhibition can inhibit viral entry into cells and decrease viral replication.  
LAM-002A is a first-in-class inhibitor of PIKfyve with an IC50 of 14nM, and Kd of 
approximately 75 pM (range 69-81 pM). The potential of LAM-002A to inhibit coronavirus viral 
entry has been tested in vitro. Apilimod potently blocked the entry of severe acute respiratory 
syndrome (SARS) and Middle East respiratory syndrome (MERS) pseudotyped virus at all 
concentrations tested (62.5-250 nM) which has been independently replicated by Ou et.al., 2020. 
Importantly apilimod also blocked the entry of lentiviral pseudovirions expressing the 
SARS-CoV-2 S glycoprotein and displayed activity against several independent clinical isolates 
of SARS-CoV-2 (Ou et. al., 2020; Riva et al, 2020; Kang et al, 2020). Furthermore, 
combinatorial activity was observed with remdesivir suggesting that greater antiviral efficacy 
may be achieved with apilimod in combination with other anti-viral agents. Taken together, the 
effect on endolysosomal trafficking and in vitro anti-viral activity indicate that LAM-002A, the 
dimesylate salt of apilimod, has promising therapeutic potential for treating SARS-CoV-2 
infections.  
LAM-002A has also been found to potently inhibit the production of T-helper lymphocyte type 1 
(Th1) cytokines IL-12 and IL-23 in PBMCs when treated with multiple toll-like receptor (TLR) 
stimuli (LAM-002A IB V4). In addition, LAM-002A inhibits IL-6 in response to IFN-γ/SAC 
(Wada et.al, 2007). Significant reduction of IL-12 and IL-23 transcripts, with a simultaneous 
increase in IL-10 was also observed in the skin lesions of psoriatic subjects treated with apilimod 
at 70 mg of apilimod free base QD (Wada et.al, 2012). While the stimuli and role of specific 
cytokines in COVID-19 are not known, these data suggest that LAM-002A has the potential to 
repress pro-inflammatory cytokines (e.g. IL-12, IL-23) and induce anti-inflammatory cytokines 
(e.g. IL-10). 
2.2.2. 
Human Experience with LAM-002A 
In addition to its anti-viral mechanism of action, the study rationale for LAM-002A in subjects 
infected with SARS-CoV-2 is based on the well-established safety and tolerability profile of the 
molecule in human trials.  
 
Safety and Tolerability 
LAM-002A has a well-established clinical record supporting its safety and tolerability, including 
published literature (LAM-002A IB V5). Under IND 125,763, AI Therapeutics sponsored a 


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Phase 1 dose-ranging and expansion study evaluating the safety, pharmacokinetics, 
pharmacodynamics, and anticancer activity of LAM-002A in subjects with recurrent, previously 
treated non-Hodgkin lymphoma (NHL). Study results indicate that LAM-002A is very well 
tolerated and has a favorable safety profile at doses of ≤ 125 mg BID (250 mg total daily dose). 
To date, >700 study subjects have received apilimod dimesylate or apilimod, including 186 
healthy subjects participating in clinical pharmacology studies, 468 subjects with nonmalignant 
inflammatory conditions (psoriasis, rheumatoid arthritis, Crohn’s disease), and 62 subjects with 
B-cell hematological cancers. 
Most observed adverse events or laboratory abnormalities have been low-grade, infrequent, and 
largely attributable to the underlying disease, prior therapy, concomitant medications, or other 
conditions. Continuous oral administration of LAM-002A has been well tolerated in humans 
with dosing regimens of ≤125 mg BID (≤250 mg total daily dose). In subjects with cancer, 
dosing regimens of 150 mg BID (300 mg QD) or 75 mg TID (225 mg QD) were not well 
tolerated due to symptoms of nausea, vomiting, and diarrhea that effectively precluded drug 
compliance in most subjects.  
 
LAM-002A Pharmacokinetics in Humans 
The pharmacokinetics of LAM-002A was studied in healthy subjects and in subjects with 
hematological cancers as a monotherapy and in combination with rituximab, or atezolizumab. 
LAM-002A (apilimod free base of LAM-002A) was rapidly bioavailable following oral dosing 
with an approximate Tmax of 1 hour. The Cmax and AUC0-8 generally increased with increasing 
dose; the Day 8 AUC0-8 showed the closest relationship to dose proportionality. As steady-state 
exposures were achieved, mean Day 8/Day 1 accumulation indices (AI) for Cmax and AUC0-8 
across all dose levels were 1.3 and 1.7, respectively. Mean terminal t1/2 values ranged from 2.7 to 
3.9 hours on Day 1 and from 5.4 to 7.0 hours on Day 8 and did not show dose dependency. On 
the first day of administration, ~90% of the drug was cleared within 10 hours after which the 
remaining drug was eliminated with a terminal t1/2 of 5 to 10 hours. The terminal t½ increased to 
12 to 21 hours on Day 14 in healthy subjects. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of LAM-002A may be found in the LAM-002A IB V5. 
There have been no subjects with COVID-19 or SARS-CoV-2 exposures evaluated to date, and 
the risk/benefit of LAM-002A in COVID-19 is not understood. The safety and tolerability of 
LAM-002A has been established, with >800 subjects treated with the drug as of March 20, 2020. 
Overall, product administrations were well tolerated. Gastrointestinal TEAEs of nausea, 
vomiting, and diarrhea were commonly observed, and showed dose dependency, with most 
TEAEs being of Grade 1 or 2. At 125 mg BID, LAM-002A was found to be safe and tolerable. 
No vaccine prophylaxis exists for SARS-CoV-2 infection and only one antiviral agent, 
remdesivir, has been approved under an emergency-use authorization for therapy for COVID-19.  
Remdesivir has modest activity and must be given intravenously (IV), thus limiting its utility for 
outpatient care of subjects with mild COVID-19 symptoms. While anti-viral efficacy of 
LAM-002A has not been established in humans or in animal models, the in vitro anti-viral 
activity suggests it may have potential efficacy in humans. Development of a well-tolerated, 


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easy-to-administer oral therapy for treatment of subjects with COVID-19 could prevent disease 
progression and consequent morbidity, the need for intensive care, and mortality.  
A planned interim analysis with DSMB review early in the trial after 15 subjects in each 
treatment arm have completed treatment ensures the mitigation of any unanticipated safety risk 
in this COVID-19 population.  


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3. 
STUDY OBJECTIVES 
3.1. 
Primary Objective 
 To evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 with a baseline 
viral load >105 copies/mL as measured by SARS-CoV-2 clearance as determined by a 
qRT-PCR test from nasopharyngeal samples at Day 4 (72 hours ± 4 hours post the first drug 
dose) 
3.2. 
Secondary Objectives 
• To evaluate the safety and tolerability of LAM-002A administration in the treatment of 
subjects with mild COVID-19. 
• To evaluate the efficacy of LAM-002A in preventing COVID-19 disease progression in 
subjects who have proven infection with the SARS-CoV-2 virus as determined by a validated 
test; disease progression is defined as the occurrence of any of the following:  
o Death at Day 28 
o Hospitalization at Day 28 
• To evaluate change in COVID-19 clinical status, as defined by the ordinal scale, of subjects 
treated with LAM-002A compared to placebo at Day 28, in subjects who become 
hospitalized and continue LAM-002A/placebo treatment. 
• To compare the proportion of subjects at or above 95% oxygen saturation (O2 sat) between 
LAM-002A versus placebo treatment groups as measured on Days 1, 4, and 11.  
3.2.1. 
Safety and Tolerability 
 To evaluate the safety and tolerability of LAM-002A administration in the treatment of 
subjects with COVID-19. 
3.2.2. 
Clinical Efficacy 
 To evaluate the efficacy of LAM-002A in preventing COVID-19 progression in subjects who 
have proven infection with the SARS-CoV-2 virus as determined by a validated test; disease 
progression is defined as the occurrence of any of the following: 
o Death at Day 28 
o Hospitalization at Day 28 
3.2.3. 
Clinical Status 
 To evaluate change in COVID-19 clinical status as defined by the ordinal scale of subjects 
treated with LAM-002A compared to placebo at Day 28, including the subjects who become 
hospitalized and continue LAM-002A/placebo treatment.  
3.2.4. 
Oxygen Saturation 
 To compare the proportion of subjects at or above 95% oxygen saturation (O2 sat) between 
LAM-002A versus placebo treatment groups as measured on Days 1, 4 and 11.  


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3.3. 
Exploratory Objectives 
3.3.1. 
Pharmacokinetic  
 To potentially evaluate the pharmacokinetics of LAM-002A in subjects with mild 
COVID-19. 
3.3.2. 
Viral Clearance 
 To potentially evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 with 
a baseline viral load >105 copies/mL as measured by SARS-CoV-2 clearance as determined 
by a qRT-PCR test from saliva samples at Day 4. 
 To potentially evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 with 
a baseline viral load >105 copies/mL as measured by SARS-CoV-2 clearance as determined 
by a qRT-PCR test from saliva samples at Day 11. 
 To potentially evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 with 
a baseline viral load >105 copies/mL as measured by SARS-CoV-2 clearance as determined 
by a qRT-PCR test from saliva samples at Day 28.  
 To potentially evaluate the antiviral efficacy of LAM-002A in subjects with COVID-19 with 
a baseline viral load >105 copies/mL as measured by SARS-CoV-2 clearance as determined 
by a qRT-PCR from saliva samples at all available days based on AUC analysis. 
 To potentially evaluate the difference in proportion of subjects with a SARS-CoV-2 viral 
load <LLOQ between the LAM-002A and the placebo arm as measured by a qRT-PCR test 
from nasopharyngeal samples at Day 4. 
3.3.3. 
Pharmacodynamic Objectives 
 To potentially evaluate the effect of LAM-002A on target engagement biomarkers. 
 To potentially evaluate the effect of LAM-002A on pro- and anti-inflammatory cytokine 
levels in plasma of COVID-19 subjects. 
3.3.4. 
Genetic Evaluation Objectives 
 To potentially evaluate viral resistance by comparing genomic sequence of SARS-CoV-2 
before and after LAM-002A treatment. 
 To potentially evaluate the effect of SARS-CoV-2 genetic variants on LAM-002A efficacy. 
 To potentially evaluate the effect of germline DNA sequence polymorphisms on LAM-002A 
safety and efficacy. 


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4. 
STUDY ENDPOINTS 
4.1. 
Primary Endpoint 
 The primary efficacy outcome measure evaluates change in SARS-CoV-2 viral load at Day 4 
from Day 1, of LAM-002A or placebo-treated subjects. SARS-CoV-2 viral load will be 
measured by a qRT-PCR test of nasopharyngeal samples. Analysis will focus on log10 viral 
load on Day 4 compared to baseline viral load at Day 1 in subjects with baseline viral load 
>105 copies/mL. 
4.2. 
Secondary Endpoints 
4.2.1. 
Safety and Tolerability 
 The proportion of LAM-002A-treated subjects who develop TEAEs compared to placebo. 
4.2.2. 
Clinical Efficacy 
 The proportion of subjects treated with LAM-002A compared to placebo, who have disease 
progression by Day 28 as defined by the occurrence of: 
o Hospitalization 
o Death 
4.2.3. 
Clinical Status 
• Change in COVID-19 clinical status as defined by the ordinal scale, of subjects treated with 
LAM-002A compared to placebo at Day 28, in subjects who become hospitalized and 
continue LAM-002A/placebo treatment, based on the following scores: 
1. Not in the hospital 
2. Hospitalized, requiring low flow supplemental oxygen (such as nasal cannula)  
3. Hospitalized, not on invasive ventilation (such as 100% non-rebreather, BIPAP), (pre-
ICU) 
4. Hospitalized, in the ICU, on invasive ventilation or ECMO 
5. Dead 
4.2.4. 
Oxygen Saturation 
• Proportion of subjects at or above 95% oxygen saturation (O2 sat) between LAM-002A 
versus placebo as measured on Days 1, 4, and 11. 


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4.3. 
Exploratory Endpoints 
4.3.1. 
Pharmacokinetics 
 Plasma concentration time profile of LAM-002A, on Day 1 pre-dose, at 1 (± 15 min) and 
2 (± 15 min.) hr, and at trough on Day 11 will potentially be determined in a subset of 
subjects (target 20 subjects) to evaluate the deviation of pharmacokinetic parameters from 
expected exposure, and correlation of pharmacokinetic parameters with safety and efficacy. 
 Maximum observed concentrations within the bounds of the sampling time points and trough 
concentration on Day 11. 
4.3.2. 
Viral Clearance 
 Change from baseline (Day 1, Pre-dose) of SARS-CoV-2 viral load as measured by a 
qRT-PCR test from saliva samples on Day 4, compared between the LAM-002A arm and the 
placebo arm in subjects with a baseline viral load >105 copies/mL. 
 Change from baseline (Day 1, Pre-dose) of SARS-CoV-2 viral load as measured by a 
qRT-PCR test from saliva samples on Day 11, compared between the LAM-002A arm and 
the placebo arm in subjects with a baseline viral load >105 copies/mL. 
 Change from baseline (Day 1, Pre-dose) of SARS-CoV-2 viral load as measured by a 
qRT-PCR test from saliva samples on Day 28, compared between the LAM-002A arm and 
the placebo arm in subjects with a baseline viral load >105 copies/mL. 
 Difference in SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples 
based on AUC(Day1-Day11), between the LAM-002A arm and the placebo arm in subjects with 
a baseline viral load >105 copies/mL. 
 Difference in SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples 
based on AUC(Day1-Day28), between the LAM-002A arm and the placebo arm in subjects with 
a baseline viral load >105 copies/mL. 
 Difference in proportion of subjects with a SARS-CoV-2 viral load <LLOQ as measured by a 
qRT-PCR test from nasopharyngeal samples between the LAM-002A and the placebo arm at 
Day 4. 
4.3.3. 
Pharmacodynamics 
• Changes in the expression of target engagement biomarkers in the nasal epithelium, PBMCs, 
and plasma. 
4.3.4. 
Immunogenicity Endpoints 
• Changes in plasma levels of IL-12, IL-23, and IL-6, IFN-γ, IL-10 and GM-CSF (additional 
cytokines may be analyzed in parallel). 
4.3.5. 
Genetic Endpoints 
• Changes in viral genome sequence before and after LAM-002A treatment. 


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• Effect of SARS-CoV-2 genetic variants on efficacy (% of subjects that progress per variant), 
as determined by viral genome sequencing.  
• Effect of genetic polymorphisms on LAM-002A safety and efficacy. 


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5. 
STUDY DESIGN AND CONDUCT 
5.1. 
Study Design 
This is a double-blind, randomized, placebo-controlled Phase II study for the treatment of 
SARS-CoV-2 positive outpatient individuals with LAM-002A. The study will compare the 
active arm of LAM-002A plus standard of care, with the control placebo arm plus standard of 
care. This study will be conducted in approximately 142 adult subjects ages ≥ 18, with < 8 days 
of symptom onset, who are SARS-CoV-2 positive as determined by a validated test. The study 
will enroll subjects who have at least one of the following COVID-19-related symptoms 
indicating mild disease: fever (temperature ≥100.4), anosmia (loss of taste or smell), cough, sore 
throat, gastrointestinal complaints (e.g. nausea, vomiting or diarrhea), chills, congestion or runny 
nose, headaches, muscle or body aches, fatigue, without shortness of breath or dyspnea (RR<20, 
SpO2 >93% on room air), or  asymptomatic patients who have tested positive for COVID-19 via 
a validated test within the past 4 days. Subjects will be treated with 125 mg LAM-002A PO, 
BID, or with placebo PO, BID for 10 days (20 doses). The treatment schedule is outlined in the 
Schedule of Activities (SoA), Table 1. Subjects will be followed at 4, 6, 8, 11, 22 and 28 days 
after the treatment start.  
Subjects will be randomized using a permuted block scheme (with variable block size) in a 1:1 
ratio to one of the two groups: (1) LAM-002A, or (2) placebo. To assure at least 71 placebo 
participants have a viral load ≥2 ×103 copies/mL (the lower limit of detection of the assay) at 
Day 4, 142 participants with baseline viral load >105 copies/mL will be enrolled to achieve the 
primary objective; thus, an expected 142 subjects will be randomized (71 to receive LAM-002A 
and 71 to receive placebo). Because the existing longitudinal data on viral load in subjects are 
preliminary, this baseline viral load and number of participants randomized may be adjusted to 
allow for 71 placebo participants above the lower limit of detection of the assay (≥ 2 × 103 
copies/mL) at Day 4 so that a difference in viral clearance between the groups can be assessed.  
5.2. 
Study Conduct 
The study will be performed in accordance with the principles as set forth under the requirements 
of 21 Code of Federal Regulations (CFR) 50 and the ICH E6 GCP guideline. The research will 
be overseen by an institutional review board/independent ethics committee (IRB/IEC). The study 
protocol, any protocol amendments, informed consent documents, and any material used to 
describe the trial to potential subjects will be reviewed and approved by the IRB/IEC prior to the 
performance of any study-related procedures. 
AI Therapeutics, Inc. will serve as the regulatory sponsor for the study and will maintain an 
investigational new drug (IND) application with the FDA. The protocol will be submitted to an 
IND for LAM-002A (IND#148521) and the trial design and results will be subject to review by 
the FDA. 
A designated clinical research organization (CRO) will serve as the operational coordinator of 
the study and will oversee conduct of the study at participating study centers. The CRO will 
perform activities relating to pharmacovigilance; site monitoring; data management and study 
reporting; and sample handling. 


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The study will employ an independent Data Safety Monitoring Board (DSMB) for safety and 
clinical efficacy and analysis of viral clearance efficacy data. AEs and serious adverse events 
(SAEs) will be reviewed by the DSMB on an ongoing basis to identify any safety concerns. 
Conference calls among the members of the DSMB will be conducted periodically to discuss 
study progress, exchange study information, and review safety events (in particular, DLTs; 
SAEs; adverse events of special interest; and AEs leading to dose interruption, dose reduction, or 
therapy discontinuation), and discuss potential amendments to the protocol. 
The DSMB will be responsible for reviewing the interim safety and efficacy analyses and 
recommending study continuation, termination, or adaptation. An interim safety analysis of study 
data will be performed after the first 30 subjects (15 on LAM-002A and 15 on placebo) have 
completed treatment and have been followed up for 11 days post-first dose. During the analysis, 
study enrollment will not be halted. Recommendations from the DSMB will be used for decision 
of early termination, continuation, or study design adaptations.  
5.3. 
Rationale for Study Design 
The study is a randomized, placebo controlled, multi-center study in approximately 142 adults 
ages ≥18, randomized to LAM-002A or placebo in a 1:1 ratio. The study has been designed to 
provide data on the efficacy, safety, pharmacokinetics, and pharmacodynamics of LAM-002A in 
subjects with mild COVID-19 symptoms. After exposure with SARS-CoV-2, there is 
approximately a 5-day incubation period (range 1-14 days) (Guan et. Al., 2020; Li et.al., 2020; 
Lauer et. Al., 2020), after which most individuals (~80%) develop a mild disease. The study has 
been designed to treat individuals with antiviral LAM-002A early in the infection period, to 
reduce the viral load of SARS-CoV-2 and prevent COVID-19 progression.  
In order to mitigate unanticipated safety issues in this COVID-19 population, an early interim 
safety analysis after 30 subjects (15 on LAM-002A and 15 on placebo) have been treated and 
followed for 11 days, will be performed, and reviewed by a DSMB for decision on study 
continuation, termination or study adaptation.  
The primary outcome measure is reduction in SARS-CoV-2 viral load measured in 
nasopharyngeal samples at Day 4 in LAM-002A treated subjects compared to those on placebo. 
Exploratory outcome measures of SARS-CoV-2 viral load from saliva samples at Days 1, 4, 11, 
and 28 are included to further inform on the rate of viral clearance. For the primary and 
secondary objectives examining antiviral efficacy, the analysis will focus on the subgroup of 
randomized subjects with baseline viral load > 105 copies/mL. This subgroup was chosen 
because subjects in this group are predicted to have sufficient viral load at baseline for the study 
drug to show benefit when compared to placebo. Because the existing longitudinal data on viral 
load in participants are preliminary, this baseline viral load and number of participants 
randomized may be adjusted to allow for 71 placebo participants above the lower limit of 
detection of the assay (≥2228 copies/mL; see Section 10.1) at Day 4 such that a difference in 
viral clearance between the groups can be adequately assessed. Nasopharyngeal swabs to 
evaluate baseline viral load will be performed prior to randomization; however, results on viral 
load will not be available prior to initiation of treatment. Supportive analyses for viral load 
outcomes will be performed in all randomized participants.  
Secondary outcome measures of hospitalization or death at Day 28, and clinical status 
determination using the Ordinal Scale will further inform on efficacy of the drug and provide 


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valuable information for Phase III trials. In addition, safety and tolerability analyses are planned 
as secondary outcome measures. Exploratory pharmacokinetic and pharmacodynamic outcome 
measures of target engagement and biomarkers (pro- and anti-inflammatory cytokine analysis) 
have been included to inform on the mechanism of action. Additional viral clearance measures, 
as determined from SARS-CoV-2 viral load in saliva samples are included as exploratory 
endpoints.  Additional exploratory outcome measures are designed to explore resistance of 
SARS-CoV-2 genome variants to treatment with LAM-002A and how the subject’s germline 
DNA may impact safety or efficacy of LAM-002A in this disease.  
5.4. 
Justification for Dose 
The dose of 125 mg BID LAM-002A (apilimod dimesylate) chosen for the COVID-19 trial is 
based on safety, exposure and efficacy data from a clinical trial in patients with B-cell 
lymphomas and from in vitro measurements of potency in SARS-CoV-2 viral infection assays.  
The recommended dose of 125 mg BID was established in a Phase 1 population of 62 patients 
with previously treated, advanced, B-cell lymphomas. The study population median (range) of 
ages was 69 (46-89) years and patients were equally divided among males (n=32) and females 
(n=30). Patients typically had cancer-related symptoms and often had additional comorbidities 
(eg, diabetes mellitus, chronic obstructive lung disease, cardiovascular disease). Thus, the 
population evaluated was highly relevant to the population to be studied in the LAM-002A 
COVID-19 trial. 
Among these 62 patients, 39 received the recommended LAM-002A oral, continuous dosing 
regimen of 125 mg BID, either alone or in combination with the anti-CD20 antibody, rituximab, 
or the anti-PD-L1 antibody, atezolizumab (neither of which had overlapping toxicities with 
LAM-002A). Durations of therapy extended to >600 days and therapy is still ongoing in several 
patients. Of importance, the only evident drug-related adverse events (AEs) observed with this 
LAM-002A dosing regimen were gastrointestinal in nature. When they occurred, such events 
were seen in a minority of patients, were typically low-grade, and were readily managed with 
dose modification. Over the entire course of chronic treatment lasting many months, incidences 
of Grade 1-4 gastrointestinal AEs of any cause were nausea in 14/39 (35.9%) patients, vomiting 
in 10/39 (25.6%) patients, and/or diarrhea in 10/39 (25.6%) patients. The incidences of Grade 3-
4 gastrointestinal AEs of any cause were low: nausea in 2/39 (5.1%), vomiting in 1/39 (2.6%), 
and diarrhea in 0/39 (0%); in these patients, other reasons for such events were documented (eg, 
central nervous system tumor, gastrointestinal lymphoma, or viral gastroenteritis). As a 
consequence of this excellent safety profile, median compliance with therapy was >97% in the 
39 subjects. Symptoms leading to LAM-002A dose modification were primarily nausea or 
diarrhea and appeared to be LAM-002A-related in 4 (10.2%) subjects; gastrointestinal symptoms 
in these subjects lessened or resolve upon dose reduction and LAM-002A could be continued. It 
should be further emphasized that LAM-002A did not cause any disabling or life-threatening 
toxicities and did not cause cardiac or respiratory events that might worsen symptoms of 
COVID-19 or confound interpretation of COVID-19 manifestations. 
Furthermore, clinical efficacy was observed in patients with follicular lymphoma at the 
recommended dose of 125 mg BID. Among the 17 patients with follicular lymphoma, 9 with 
follicular lymphoma were treated with LAM-002A monotherapy or LAM-002A-based 
combination therapy at this dose level and had substantial tumor regressions meeting established 


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criteria for objective response [Cheson 2014]. Objective responses have been long-lasting, with 
durations exceeding 12 months among several subjects and are ongoing in 3 subjects who are 
still on therapy. When taken together with the safety and exposure data, these efficacy findings 
document that administration 125 mg BID of LAM-002A is pharmacologically active in 
producing a desired clinical effect with a well-tolerated dosing regimen.  
LAM-002 (apilimod), the active form of LAM-002A, has potent nanomolar in vitro activity 
against several independent clinical isolates of SARS-CoV-2 in Vero E6 cells [Riva 2020; 
Kang 2020]. Based on these data (Table 2), the EC50 is between 10 and 23 nM and the EC90 is 
estimated to be between 10 and 400 nM in Vero E6 cells.  
 
 


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Table 2. 
Summary of LAM-002A In Vitro Activity Against SARS CoV-2 
Reference 
SARS-CoV-2 Isolate 
Cell Line 
EC50 
EC90 
AI Therapeutics 
Hangzhou, China 
Vero E6 
<1.25 µM 
<1.25 µM 
Riva 2020 
USA-WA1/2020 
Vero E6 
23 nM 
>100 nM to <400 nM 
Kang 2020 
USA-WA1/2020 
Vero E6 
10 nM 
>10 nM to <50 nM 
These LAM-002 concentrations are similar to those active against B-cell non-Hodgkin 
lymphoma cell lines in vitro [Gayle 2017a]. Given the clinical responses observed in B-cell 
lymphoma patients at 125 mg BID and evidence of target inhibition in patient plasma samples, it 
would therefore be predicted that this dose would also provide efficacious drug levels in 
COVID-19 patients. Indeed, at 125 mg BID the plasma concentrations of active drug, which 
includes LAM-002 and its active metabolites (STA-5908, STA-5944, and STA-6048) weighted 
by their relative cell based activity and exposure, exceed the average in vitro anti-viral EC90 
(205 nM) in Vero E6 cells by 1.5 times at trough and by 7.4 times at Cmax. Furthermore, a rat 
distribution study of oral administration of [14C]-apilimod suggests that lung exposures are 1.1 to 
1.5 times higher than in blood, providing further rationale that 125 mg BID would provide 
sufficient drug levels for anti-viral activity in lung tissues.  
Consequently, it is the AI Therapeutics position that the LAM-002A dosing regimen of 
125 mg BID maximizes the potential for antiviral benefit in patients with COVID-19 and will be 
safe and well tolerated over the planned treatment course.  


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6. 
STUDY POPULATION 
This clinical trial can fulfill its objectives only if appropriate participants are enrolled. The 
protocol-specified eligibility criteria are designed to select subjects for whom study participation 
is considered appropriate. All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a study candidate. Eligibility 
criteria may not be waived by the investigator and conformance to the eligibility criteria will be 
reviewed in the case of a GCP or a regulatory authority audit. Any questions regarding a study 
candidate’s eligibility should be discussed with the medical monitor before enrollment. 
Reference is made to the National Early Warning Score (NEWS) for grading of illness intensity 
and the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 for severity of 
adverse events. 
6.1. 
Inclusion Criteria 
Study candidates must meet all of the following inclusion criteria to be eligible for participation 
in this study: 
1. Men and women of age ≥18 years. 
2. Written documentation of SARS-CoV-2 infection confirmed by a validated test. 
3. Presence of ≥1 of the following COVID 19-related symptoms indicating mild disease: fever 
(temperature ≥100.4), anosmia (loss of taste or smell), cough, sore throat, gastrointestinal 
complaints (e.g. nausea, vomiting or diarrhea), chills, congestion or runny nose, headaches, 
muscle or body aches, fatigue, or asymptomatic patients who have tested positive for 
COVID-19 via a validated test within the past 4 days.  
4. If symptomatic, symptom onset ≤8 days. 
5. For female subjects of childbearing potential, a negative urine (or serum) pregnancy test. 
6. For female subjects of childbearing potential, willingness to use a protocol-recommended 
method of contraception from the start of the screening period until ≥30 days after the final 
dose of study therapy. Note: A female subject is considered to be of childbearing potential 
unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has 
medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone 
[FSH] levels within the institutional laboratory postmenopausal range and a negative serum 
or urine beta human chorionic gonadotropin [βHCG]); or is menopausal (age ≥50 years 
with amenorrhea for ≥6 months). 
7. For male subjects who can father a child and are having intercourse with females of 
childbearing potential who are not using adequate contraception, willingness to use a 
protocol-recommended method of contraception from the start of study therapy until 
≥30 days after the final dose of study therapy and to refrain from sperm donation from the 
start of study therapy until ≥90 days after administration of the final dose of study therapy. 
Note: A male subject is considered able to father a child unless he has had a bilateral 
vasectomy with documented aspermia or a bilateral orchiectomy. 
8. Willingness and ability of the subject to ingest study drug capsules. 
9. Willingness of the subject to comply with scheduled visits, drug administration plan, 
protocol-specified laboratory tests, study procedures, and study restrictions.  


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10. Evidence of a personally signed informed consent indicating that the subject is aware of the 
nature of the disease and has been informed of the procedures to be followed, the 
experimental nature of the therapy, alternatives, potential risks and discomforts, potential 
benefits, and other pertinent aspects of study participation. 
6.2. 
Exclusion Criteria 
Study candidates who meet any of the following criteria will not be eligible for participation in 
this study: 
1. Respiratory rate ≥20 breaths per minute. 
2. Oxygen saturation by pulse oximetry ≤93% on room air or requirement for supplemental 
oxygen to maintain oxygen saturation >93%. 
3. Total NEWS score ≥6 or presence of a score of 3 on any of the individual NEWS parameters. 
4. Radiographic evidence of pulmonary infiltrates (clinical X-ray within 2 days of referral) 
5. Hepatic profile showing any of the following: 
• Serum alanine aminotransferase (ALT) >5 × upper limit of normal (ULN) (CTCAE 
Grade ≥3).  
• Serum aspartate aminotransferase (AST) >5 × ULN (CTCAE Grade ≥3). 
• Serum bilirubin >1.5 × ULN (CTCAE Grade ≥2). 
6. Renal profile showing an estimated creatinine clearance (eClCR) <30 mL/minute (with 
eClCR to be calculated by the method at the laboratory performing the serum creatinine test). 
7. Presence of a cancer with disease manifestations or therapy that could adversely affect 
subject safety or longevity, create the potential for drug-drug interactions, or compromise the 
interpretation of study results. 
8. Significant cardiovascular disease (e.g. myocardial infarction, arterial thromboembolism, 
cerebrovascular thromboembolism) within 1 month prior to start of study therapy; unstable 
angina; symptomatic peripheral vascular disease; CTCAE Grade ≥2 congestive heart failure; 
or uncontrolled CTCAE Grade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or 
systolic blood pressure ≥160 mmHg) despite antihypertensive therapy. 
9. Significant screening ECG abnormalities, including atrial fibrillation/flutter, 2nd degree 
atrioventricular (AV) block type II, 3rd-degree AV block, Grade ≥2 bradycardia, or corrected 
QT (QTc by Fridericia [QTcF]) >480 msec (Grade >1). 
10. Gastrointestinal disease (e.g. gastric or intestinal bypass surgery, pancreatic enzyme 
insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic 
diarrheal illness, bowel obstruction) that might interfere with drug absorption or with 
interpretation of gastrointestinal AEs. 
11. Pregnancy or breastfeeding. 
12. Prior solid organ transplantation. 
13. Use within 5 days prior to randomization of an approved or investigational therapy intended 
to treat COVID-19 (e.g. remdesivir, anti-interleukin [IL]-6 antibodies, therapeutic anti-
SARS-COV-2 antibodies or post-convalescent plasma, anti-SARS-COV-2 vaccine, Bruton 


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tyrosine kinase [BTK] inhibitor), use within 3 months of chloroquine or hydroxychloroquine. 
Note: Subjects are not precluded from undergoing evaluations involving observation, 
noninvasive diagnostic procedures or sampling, or questionnaires as follow-up to a prior 
study or as components of a concurrent noninterventional study. 
14. Use within 5 days prior to randomization of a strong inhibitor or inducer of cytochrome P450 
(CYP) 3A4 or expected requirement for chronic use of a strong inhibitor or inducer of 
CYP3A4 during study therapy (see Appendix 15.1 for a list of drugs known to be strong 
inhibitors or inducers of CYP3A4).  
15. Use within 5 days prior to randomization of drug that is a moderate-to-strong substrate of 
CYP2C9 (including warfarin, tolbutamide, phenytoin, glimepiride) or expected requirement 
for chronic use of such drugs during study therapy.  
16. Use within 5 days prior to randomization of a drug known to prolong the QT interval (see 
Appendix 15.2 for a list of drugs that are considered to have a known propensity to prolong 
the QT interval). 
17. Ongoing immunosuppressive therapy including systemic or enteric corticosteroids. (Note: At 
study entry, subjects may be using intraarticular, inhaled, or topical corticosteroids. During 
study therapy, subjects may use systemic, enteric, intraarticular, inhaled, or topical 
corticosteroids as required for intercurrent conditions.) 
18. Any illness, medical condition, organ system dysfunction, or social situation, including 
mental illness or substance abuse, deemed by the investigator to be likely to interfere with a 
subject’s ability to provide informed consent, adversely affect the subject’s ability to 
cooperate and participate in the study, or compromise the interpretation of study results. 
 


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7. 
STUDY DRUG ALLOCATION 
7.1. 
Randomization 
After a subject has completed the necessary screening assessments and has been confirmed to be 
eligible, the subject can be randomized into the study. In order to obtain a treatment arm 
assignment for a subject, a site representative will submit the appropriate information for 
randomization, and the system will make an assignment of a study drug bottle number. Subjects 
will be randomized in a 1:1 ratio (Arm A:Arm B) to either of the following treatment 
assignments: 
• Arm A: LAM-002A 
• Arm B: Placebo 
In order to balance treatment allocation, a permuted block centralized randomization will 
allocate subjects. 
It is anticipated that subjects will usually begin study drug immediately after randomization Day 
1 of the study. In case of administrative delays, every attempt should be made to initiate study 
drug treatment by Day 2. 
7.2. 
Blinding 
The identity of the treatments will be concealed by central blinding of study drug assignments. 
Blinding will be accomplished through use of a placebo that is well-matched to the active drug in 
appearance, packaging, labeling, and schedule of administration. During the study, subjects, 
caregivers, investigational site personnel, study sponsor study team members, and all other study 
personnel will remain blinded to the identity of the treatment assignments; these assignments 
will be available only to the unblinded randomization team, and the DSMB for the study, an 
independent bioanalytical group, and drug safety personnel who are not part of the study team. 
Unblinding during the study will only occur in the case of subject emergencies (see Section 8.3) 
or as requested by the DSMB. Where required by local regulation, expedited reporting of serious 
adverse events to specific regulatory authorities will include information regarding the study 
drug treatment assignment (LAM-002A or placebo); this will be done in such a way that 
subjects, investigational site personnel, institutional review board/independent ethics committees 
(IRB/IEC), and study team members remain blinded as to the treatment assignment for the 
subject described in the adverse event report. 
The final unblinded analysis of the study will only be performed when the database is completed 
and locked. While bioanalytical assays to determine LAM-002A concentrations may be 
performed prior to unblinding, pharmacokinetic data that would allow identification of treatment 
assignments for individual subjects will not be available to the study team until after the blind is 
broken and the primary analysis has occurred. Except for emergency unblinding, individual 
subjects, caregivers, and site personnel will not be informed of the randomized treatment 
assignments until the implications of revealing such data for the overall LAM-002A study 
program have been determined by the project leader for the LAM-002A development program. 


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8. 
STUDY DRUG INFORMATION, ADMINISTRATION, AND 
SUPPORT 
8.1. 
Blinded Study Drug (LAM-002A and Placebo) 
8.1.1. 
Description 
LAM-002A is formulated in capsules containing 25 mg of apilimod dimesylate (equivalent to 
17.1 mg of apilimod free base, respectively). The capsule is Swedish orange, Size 0 and has a 
total fill weight of 175 mg. Inactive components in active capsules are microcrystalline cellulose, 
silicified microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, colloidal silicon 
dioxide, and magnesium stearate.   
Placebo is formulated in capsules with identical appearance to the capsules containing active 
drug.  The inactive component in placebo capsules is microcrystalline cellulose. 
8.1.2. 
Source 
Study drug (LAM-002A and placebo) will be provided by the study sponsor. 
8.1.3. 
Packaging and Labelling 
Study drug (LAM-002A and placebo) is supplied in high density polyethylene (HDPE) bottles, 
induction sealed with child resistant closures. Each bottle contains 100 capsules. 
Labels for LAM-002A bottles meet all applicable FDA requirements. 
Concurrent stability studies are ongoing for lots used in current clinical trials. Additionally, there 
is ICH stability data supporting 36 months of stability for drug product.  
8.1.4. 
Shipping, Storage, and Stability 
The LAM‑002A and placebo capsules must be stored in a secure storage area, with limited 
access, at 2o C to 8oC. 
 Study centers will be provided with initial and updated product stability data, when available. 
8.1.5. 
Dispensing  
A pharmacist or other qualified staff member will dispense bottles containing study drug 
(LAM-002A or placebo). Sufficient bottles will be dispensed to the subject to provide an 
adequate drug supply for the duration of the planned treatment course.  
8.1.6. 
Return and Compliance Assessment 
After the completion of the treatment course, empty, partially used, or full bottles of study drug 
(LAM-002A or placebo) will be retrieved from the subject. The quantities of unused study drug 
and the date when these study supplies are returned by the subject should be recorded in the 
study drug accountability records. In addition, the subject’s dosing diary should be reviewed, any 
incomplete or inconsistent entries should be addressed, and the dosing diary should be copied. 
Returned capsules and bottles may be destroyed according to the site’s standard operating 
procedures (see Section 13.11).  


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8.1.7. 
Accountability 
See Section 13.11 for information regarding study drug (LAM-002A or placebo) accountability. 
8.1.8. 
Overdose Precautions 
An overdose is defined as a dose taken (accidentally or intentionally) exceeding the overdose 
limit. In the case of a discrepancy in drug accountability, an overdose will be established only 
when it is clear that the subject has received an excess dose, or the investigator has reason to 
suspect that the subject has received an excess dose. 
There are limited data on the effects of LAM-002A overdose. LAM-002A doses as high as 
150 mg BID (300 mg QD) were administered in a prior Phase 1 study. The adverse effects were 
primarily nausea, vomiting, and/or diarrhea that occurred acutely and tended to be treatment-
limiting. 
For this protocol, an overdose of study drug is defined as ingestion of a total daily dose >300 mg 
QD (total daily dose) of LAM-002A (or the placebo equivalent). In a subject who experiences an 
overdose, consideration should be given as to whether study drug administration should be 
temporarily interrupted. If the overdose is recent and substantial, use of gastric lavage or 
induction of emesis may be considered but may not be necessary given the emetogenic nature of 
the drug at high doses. Observation for any symptomatic side effects should be instituted, and 
safety laboratory parameters should be followed closely (consistent with the protocol or more 
frequently, as needed). Appropriate supportive management should be instituted to mitigate 
adverse effects. The subject should remain under observation until adverse effects have 
recovered to baseline. There is no specific antidote for LAM-002A. 
The medical monitor should be contacted if a study drug overdose occurs. The occurrence of an 
overdose does not preclude further protocol therapy if the subject appears to be safely benefiting 
from treatment and the circumstances that led to the initial overdose are unlikely to recur. 
8.1.9. 
Inadvertent Exposure Precautions 
Based on available data, LAM-002A is not expected to be acutely toxic, irritating, or genotoxic 
at levels that are likely to result from inadvertent exposure. However, personnel handling the 
drug should use reasonable precautions to avoid eye contact, skin contact, inhalation, or 
ingestion of study drug (LAM-002A or placebo). Subjects should be instructed to keep the drug 
secured such that it is out of the reach of children and is not inadvertently taken by others. The 
LAM-002A investigator brochure can be consulted for further information regarding exposure 
and spill precautions. 
8.2. 
Study Drug Administration 
8.2.1. 
Drug Administration 
Study participants will be randomized in a 1:1 ratio to receive study therapy, comprising either 
LAM-002A, 125 mg (five 25-mg capsules/dose) orally BID or placebo (five capsules/dose) 
orally BID for 10 days. 
Subjects are to self-administer study drug (LAM-002A or placebo) starting on Day 1 and then 
continuously thereafter for the planned treatment course. Subjects should take the study drug at 


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approximately the same time each day, ideally at ~12-hour intervals (e.g. ~8AM and ~8PM 
every day).  
On Day 1, subjects should take the drug at the study center under the supervision of study 
personnel and the timing of study drug administration must be documented in the clinic notes 
and/or in the subject diary. While variations in dosing schedule may occur in the outpatient 
setting, the prescribed regimen should be followed as closely as possible. 
At each dose administration, the number of study drug (LAM-002A or placebo) capsules 
corresponding to the appropriate dose of each drug should be swallowed whole with 100 to 
200 mL (~4 to 8 ounces) of water. Subjects should be instructed not to bite or chew the capsules. 
In case of breakage of the capsules in the oral cavity, additional water should be taken as a rinse. 
8.2.2. 
Fed/Fasting Status 
On Day 1, subjects should ingest the study drug (LAM-002A or placebo) while fasting (defined 
as no food with the exception of clear liquids for ≥2 hours before and ≥1 hour after dosing). With 
other doses, subjects may take the study drug without regard to fed or fasting status. 
8.2.3. 
Dose Schedule Interruptions and Vomited Doses 
Subjects who have a delay in administration of <6 hours should take the planned dose as soon as 
possible after the intended time of administration. For subjects who have a delay in 
administration of ≥6 hours, the dose should not be taken. The planned timing of subsequent drug 
administration should not be altered.  
Of note, the first (on-site) dose might occur at a time in the afternoon that would mean that the 
next scheduled (at home) dose is after midnight. In such a subject, the second dose may be taken 
in the morning of Day 2. Subsequent doses may then be adjusted to reflect 12-hour intervals 
following the time of administration of this second dose. For example, if the second dose is taken 
at 8AM, subsequent doses should follow an 8AM-8PM dosing schedule.  
For subjects who vomit shortly after taking the study drugs, the vomited dose should not be 
replaced. The planned timing of subsequent drug administration should not be altered. 
8.2.4. 
Dose Modification Recommendations 
If a subject experiences an AE that is suspected to be related to the study drug, appropriate 
monitoring and supportive care (e.g. antiemetics, antidiarrheals) should be instituted consistent 
with the nature of the event.  
If a subject experiences an intolerance to study drug that the investigator believes warrants dose 
modification. The study drug administration should be interrupted until the toxicity recovers to 
Grade ≤1 or baseline.  Subjects may then resume drug administration at the original dose level or 
at a reduced dose level of LAM-002A, 100 mg (four 25-mg capsules/dose) orally BID or placebo 
(four capsules/dose) orally BID. One further adjustments dose adjustment is permitted, to a 
reduced dose level of LAM-002A, 75 mg (three 25-mg capsules/dose) orally BID or placebo 
(three capsules/dose) orally BID.  If the subject cannot tolerate study drug after a decrease in 
dose by 2 dose levels, then the subject should be discontinued from study drug therapy.  
After the study drug dose is reduced, the dose should not be re-escalated, even if there is minimal 
or no toxicity with the reduced dose.  


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Investigators may discuss modifications in the dosing regimen with the medical monitor.  
8.3. 
Emergency Unblinding 
Every attempt should be made to preserve the integrity of study drug (LAM-002A/placebo) 
blinding. Unblinding in individual subjects who experience adverse events is rarely required to 
provide effective intervention and support. For subjects having adverse events or laboratory 
abnormalities that require drug cessation or medical intervention, the investigational staff should 
strive to provide necessary support to the subject without breaking the blind. In the exceptional 
circumstances that knowledge of the study drug assignment appears essential for providing 
appropriate medical management, the investigator should contact the medical monitor to discuss 
the rationale for breaking the blind and the adverse consequences of the unblinding for the 
subject’s continued participation in the study. If the investigator still believes that unblinding is 
warranted, the investigator will be able to access the randomization system in order to obtain the 
treatment assignment for that subject. No randomization lists or other unblinding information 
will be provided to the site. After breaking the blind, the investigational site staff should record 
details regarding the reasons for breaking the blind and any adverse events leading to the 
breaking of the blind in the source documents and in the appropriate eCRF. 
If the site breaks the blind, that subject will be discontinued from study therapy (LAM-002A or 
placebo).  
8.4. 
Supportive Care 
8.4.1. 
General Recommendations 
Consistent with subject safety and comfort, administration of any prescription or over-the-
counter drug products other than study medication will be minimized during the study period. 
Subjects should be discouraged from use of herbal remedies, self-prescribed drugs, tobacco 
products, or street drugs during their participation in the clinical study and should be counseled 
to minimize use of alcohol or nonmedical marijuana. 
If considered necessary for the subject’s well-being, drugs for concomitant medical conditions or 
for symptom management may be given at the discretion of the investigator. The investigator’s 
decision to authorize the use of any drug other than study drug should take into account subject 
safety, the medical need, the potential for drug interactions, the possibility for masking 
symptoms of a more significant underlying event, and whether use of the drug will compromise 
interpretation of study endpoints. 
Subjects will be instructed about the importance of the need to inform the clinic staff of the use 
of any drugs or remedies (whether prescribed or over the counter) before and during the study.  
Recommendations regarding specific types of concomitant therapies, supportive care, diet, and 
other interventions are provided below. To minimize variations in supportive care, the 
recommended supportive care agents should be considered unless there is a medical rationale in 
a specific subject for use of an alternative product. 
8.4.2. 
Antibiotics, Antifungals, and Antivirals 
Local practices or guidelines regarding infection prophylaxis may be followed. Subjects 
developing an intercurrent infection other than with SARS-CoV-2 during study drug treatment 


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may receive therapeutic antibacterial, antiviral, or antifungal drugs as needed. However, care 
should be taken to avoid or minimize concomitant administration of prophylactic or therapeutic 
antibacterial, antifungal, or antiviral, agents that are strong CYP3A4 inhibitors or inducers (see 
Section 8.4.9 and Section 15.1. Continuation of study therapy during treatment for an 
intercurrent infection is at the discretion of the investigator.  
8.4.3. 
Anti-SARS-CoV-2 Therapies 
At baseline and during study participation, study subjects may not receive chloroquine, 
hydroxychloroquine, BTK inhibitors, anti-SARS-CoV-2 vaccines, or other investigational anti-
SARS-CoV-2 drugs as long as they remain investigational. Subjects may not be receiving 
remdesivir, anti-IL-6 antibodies, therapeutic anti-SARS-CoV-2 antibodies, or post-convalescent 
plasma at baseline but may have such drug introduced as appropriate if they develop respiratory 
failure, cardiac failure, or other serious manifestations of COVID-19.  Continued study therapy 
together with these additional therapies is permitted at the discretion of the investigator. Subjects 
are not allowed to participate concurrently in any other therapeutic clinical study. 
8.4.4. 
Anticoagulants 
Use of local anticoagulation or antithrombotic agents to maintain a venous access catheter is 
permitted. In addition, subjects who develop conditions that require anticoagulant therapy are 
permitted to receive such drugs and are not required to discontinue study participation. 
8.4.5. 
Antidiarrheals 
Subjects experiencing diarrhea (and/or abdominal cramping) may take loperamide at the earliest 
sign of a loose stool, an increase in bowel movements by 1 to 2 episodes compared to baseline, 
or an increase in stool volume or liquidity. The recommended regimen is 4 mg at the first onset 
of diarrhea, then 2 mg with each succeeding diarrheal stool until the subject is diarrhea-free for 
at least 12 hours.  
Additional antidiarrheal measures may be implemented at the discretion of the investigator. 
Subjects should also be instructed to maintain oral fluid intake to help sustain fluid and 
electrolyte balance during episodes of diarrhea. 
8.4.6. 
Antiemetics 
If antiemetics are needed, it is recommended that subjects be offered granisetron (Kytril®, 
Granisol®), as an oral tablet or solution every 6 to 8 hours as needed. If subjects have persistent 
nausea or vomiting, consideration can be given to a 10-mg subcutaneous injection of the 
extended release form of granisetron (Sustol®). Alternatively, application of a 31.3-mg 
granisetron transdermal patch (Sancuso®) every 3 to 7 days can be considered. For transdermal 
prophylaxis, 24 to 48 hours may be necessary to allow a sufficient period to achieve effective 
granisetron systemic concentrations. Use of the serotonin antagonists, ondansetron (Zofran®, 
Zuplenz®) or dolasetron (Anzemet®) is also permitted.  
Aprepitant (Emend®) or netupitant+palonosetron (Akynzeo®) should be avoided because these 
drugs may inhibit CYP3A4 activity.  
Benzodiazepines may be considered.  


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Corticosteroids can be introduced if other types of antiemetic agents are not sufficiently 
effective. 
8.4.7. 
Antihistamine, Antiinflammatory, or Antipyretic, Drugs 
Antihistamines (e.g. cetirizine, diphenhydramine), and antiinflammatory/antipyretic drugs (e.g. 
acetaminophen [paracetamol], nonsteroidal anti-inflammatory drugs [NSAIDs]), may be used 
during the study, as medically warranted. 
8.4.8. 
Corticosteroids 
At study entry, subjects may be using systemic, intraarticular, inhaled, or topical corticosteroids. 
During study therapy, subjects may use systemic, intraarticular, enteric, inhaled, or topical 
corticosteroids as required for intercurrent conditions.  
8.4.9. 
Drugs with Drug-Drug Interaction Potential 
While clinical data are not yet available, in vitro data suggest that LAM-002A is metabolized by 
CYP3A. Based on these findings, protocol candidates who require therapy with the strong 
CYP3A4 inhibitors or inducers listed in Section 15.1 should not be enrolled into the study.  
During study participation, coadministration of study drug (LAM-002A or placebo) with the 
strong CYP3A4 inhibitors or inducers listed in Section 15.1 should be avoided, if possible. 
However, a subject who develops a condition that may require use of such drugs is not required 
to permanently discontinue study drug. If medically appropriate, investigators may wish to use a 
therapeutic alternative that would not be expected to affect these enzymes.  
For subjects who require temporary use of a drug that does affect these enzymes (e.g. treatment 
with a systemic antifungal agent), study drug therapy can be temporarily interrupted and then 
resumed after completion of the CYP3A4 inhibitor. For subjects who require initiation of chronic 
therapy with a drug that strongly affects these enzymes, investigators must consult with the 
medical monitor to consider the best course of action. If subjects do receive a CYP3A4 inhibitor 
concomitantly with study drug, they should be monitored closely for signs of LAM-002A 
toxicity.  
8.4.10. 
Drugs Known to Prolong the QT Interval 
Available nonclinical and clinical data do not suggest a high risk that LAM-002A will alter the 
QT interval at doses of ≤125 mg BID.  There is no specific restriction on use of drugs (e.g. 
antiemetics) that might prolong the QT interval. Drugs that are known to prolong QT Interval or 
cause Torsades De Pointes are listed in Section 15.2. 
8.4.11. 
Hematopoietic Support 
Red blood cell or platelet transfusions may be administered as medically indicated. 
8.4.12. 
Cardiopulmonary Support 
Study subjects should not be requiring supplemental oxygen or other cardiopulmonary support at 
baseline.  Subjects may be offered any medically necessary cardiopulmonary support during 
study participation. Study drug (LAM-002A or placebo) may be continued at investigator 
discretion as long as the subject is able to be administered the study drug via the enteral route. 


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8.5. 
Study Restrictions 
8.5.1. 
Breast Feeding 
There is no information regarding the presence of LAM-002A or its metabolites in human milk, 
the potential effects of the drug or its metabolites on the breastfed infant, or the potential effects 
of the drug or its metabolites on milk production. For these reasons, women who are nursing are 
not eligible to participate in this study. Lactating women who do participate in this clinical trial 
must discontinue nursing during study therapy. 
8.5.2. 
Contraception/Reproduction 
In general toxicology studies, LAM-002A administration was not associated with adverse 
histopathological effects on organs of reproduction at exposures that are likely to be achieved 
clinically. However, no studies evaluating drug effects on reproductive function in animals or 
humans are available. Thus, subjects should be advised that the risks of LAM-002A for future 
reproduction are unknown. 
No nonclinical data or clinical data are available regarding LAM-002A effects during embryo-
fetal development. Accordingly, female subjects cannot be pregnant at the time of study entry 
and must be removed from study therapy if they do become pregnant. 
Sexually active females of childbearing potential must agree to use a protocol-recommended 
method of contraception during heterosexual intercourse from the start of the screening period 
until ≥30 days after the final dose of study therapy. In the context of this protocol, a female 
subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral 
tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum 
estradiol and follicle-stimulating hormone [FSH] levels within the institutional laboratory 
postmenopausal range and a negative serum or urine beta human chorionic gonadotropin 
[βHCG]); or is menopausal (age ≥50 years with amenorrhea for ≥6 months).  
Sexually active male subjects who can father a child and are having intercourse with females of 
childbearing potential who are not using adequate contraception must agree to use a protocol-
recommended method of contraception from the start of study therapy until ≥30 days after the 
final dose of the study therapy and to refrain from sperm donation from the start of study therapy 
until ≥90 days after administration of the final dose of study therapy. In the context of this 
protocol, a male subject is considered able to father a child unless he has had a bilateral 
vasectomy with documented aspermia or a bilateral orchiectomy. 
Protocol-recommended contraceptive methods are those that are considered highly effective (ie, 
can achieve a failure rate of <1% per year when used consistently and correctly) [CTFG 2014]. 
Such methods include:  
• Oral, intravaginal, or transdermal hormonal contraception that contains both estrogen and 
progestogen and is associated with inhibition of ovulation 
• Oral, injectable, or implantable progestogen-only hormonal contraception that is associated 
with inhibition of ovulation 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 


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• Bilateral tubal occlusion 
• Vasectomy or vasectomized partner with documented aspermia 
• Sexual abstinence (i.e., refraining from heterosexual intercourse during the entire period of 
risk associated with the study drug administration considering that the reliability of sexual 
abstinence may be influenced by such factors as the duration of the clinical trial and the 
preferred and usual lifestyle of the subject) 
It is advised that male subjects having heterosexual intercourse with a female partner of 
childbearing potential should use condoms plus an additional contraceptive method that together 
result in a failure rate of <1% per year. To avoid any potential study drug exposure to a partner, 
it is recommended that vasectomized men also wear condoms during sexual intercourse. 
8.5.3. 
Diet 
Because LAM-002A is a substrate of CYP3A4, subjects should be advised to avoid ingestion of 
grapefruit, grapefruit juice, or Seville oranges (which contains a potent CYP3A4 inhibitor) and 
should not use St. John’s wort, which is a potent CYP3A4 inducer. No other specific dietary 
restrictions are required. 
8.6. 
Duration of Study Drug Administration and Study Participation 
Subjects may receive study therapy (LAM-002A or placebo) for as long as 10 days. However, 
the occurrence of any of the following events requires treatment discontinuation: 
• Subject request to withdraw from study treatment  
• Intolerable study drug toxicity despite appropriate supportive care and/or dose modification 
• The development of intercurrent illness or other substantial change in the subject’s condition 
or circumstances that would place the subject at unacceptable risk as determined by the study 
investigator in consultation with the medical monitor 
• Pregnancy or breastfeeding 
• Substantial noncompliance with study drug administration, study procedures, or study 
requirements in circumstances that increase risk or substantially compromise the 
interpretation of study results 
• Discontinuation of the study by the study center, the study sponsor, relevant regulatory 
agencies, or the IRB/IEC 
Subjects who discontinue study therapy will continue on study for acquisition of safety 
information through at least Day 28. Study follow-up will continue through Day 28 unless any of 
the following circumstances occurs: 
• Subject request to withdraw from follow-up 
• Subject lost to follow-up 
• Subject death 
• Termination of the study by the study center, the study sponsor, relevant regulatory agencies, 
or the IRB/IEC 


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9. 
SAFETY ASSESSMENT 
9.1. 
Definitions 
9.1.1. 
Adverse Event 
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
medicinal product; the event does not necessarily have a causal relationship with study drug 
administration or usage. An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product. 
In this study, any of the following events will be considered an AE: 
• Any complication that occurs as a result of a protocol-mandated procedure (e.g. 
venipuncture, ECG). 
• Any preexisting condition that increases in severity or changes in nature during or as a 
consequence of study drug administration. Worsening manifestations of the underlying 
infection (e.g. increase in COVID-19 manifestations) may be considered AEs in this study.  
• Any injury or accident. If a medical condition is known to have caused the injury or accident 
(e.g. a fall secondary to dizziness), the medical condition (dizziness) and the accident (fall) 
should be reported as 2 separate AEs.  
• Any abnormality in physiological testing or a physical examination finding that requires 
clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test). 
• Any laboratory (e.g. clinical chemistry, hematology, urinalysis) or investigational 
abnormality (e.g. ECG, X-ray) independent of the underlying medical condition that requires 
clinical intervention, results in further investigation (beyond ordering a repeat [confirmatory] 
test), or leads to investigational medicinal product interruption or discontinuation unless it is 
associated with an already reported clinical event. If the laboratory abnormality is part of a 
syndrome, the syndrome or diagnosis (e.g. anemia) not the laboratory result (e.g. decreased 
hemoglobin) should be recorded.  
• A complication related to pregnancy or termination of a pregnancy (see Section 9.7.2 for 
additional information). 
None of the following events is considered an AE: 
• Laboratory abnormalities not requiring clinical intervention or further investigation. Such 
abnormalities will be captured as part of laboratory monitoring. 
• A diagnostic, medical, or surgical procedure (e.g. surgery, endoscopy, tooth extraction, 
transfusion). However, the medical condition for which the procedure was performed should 
be reported if it meets the definition of an AE. For example, an acute appendicitis that begins 
during the AE reporting period should be reported as the AE and the resulting appendectomy 
should be recorded in the source documents.  
• A preexisting disease or condition or laboratory abnormality present or detected before the 
initial screening visit and that does not worsen. 
• An intervention not associated with an untoward medical occurrence (e.g. hospitalization for 
elective surgery or for social and/or convenience reasons). 
• An overdose without clinical sequelae. 


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9.1.2. 
Serious Adverse Event 
An SAE is defined as an untoward medical occurrence that results in any of the following 
outcomes: 
• Death (ie, all deaths occurring between signing of the consent form to within 30 days after 
last study drug administration), including deaths due to COVID-19 if no other event more 
satisfactorily explains the reason for death. Deaths that occur as a result of an AE that started 
during the study period should be reported. Death is not an SAE term; the reported AE 
should be the event that caused the death. Death is the outcome of this SAE. 
• Life-threatening situation (ie, with an immediate risk of death from the event as it occurred 
but not including an event that, had it occurred in a more serious form, might have caused 
death). 
• In-patient hospitalization or prolongation of existing hospitalization. Of note, an untoward 
medical occurrence that occurs during hospitalization is an AE but a complication that 
prolongs hospitalization is an SAE. In-subject hospitalization comprises formal admission to 
a hospital for medical reasons, for any length of time, whether or not hospitalization extends 
overnight. However, hospital admissions or prolongations of hospitalization for 
administration of the study drug or procedures required by the study protocol, diagnostic 
observations or procedures, administration of concomitant or subsequent therapy for the 
cancer, logistical issues (e.g. lengthy travel), or the convenience of the subject or clinical 
personnel are not considered serious.  
• Persistent or significant disability/incapacity. 
• Congenital anomaly/birth defect in the offspring of a subject who received the investigational 
medicinal product. 
• Other medically significant event. Such events may not be immediately life-threatening or 
result in death or hospitalization, but based upon appropriate medical and scientific 
judgment, may jeopardize the subject, or may require medical or surgical intervention to 
prevent one of the outcomes listed above. Examples of such events might include: 
o Allergic bronchospasm requiring intensive treatment in an emergency room or at home 
o New cancers or blood dyscrasias 
o Convulsions that do not result in hospitalization 
o Development of drug dependency or drug abuse 
9.1.3. 
Unexpected Adverse Event 
An unexpected AE is defined as an event that has a nature, severity, or specificity that is not 
consistent with the applicable investigator brochure, or that is symptomatically and 
pathophysiologically related to a known toxicity but differs because of greater severity or 
specificity. For example, under this definition, hepatic necrosis would be unexpected (by virtue 
of greater severity) if the investigator brochure only referred to elevated hepatic enzymes or 
hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis would be unexpected (by 
virtue of greater specificity) if the investigator brochure only listed cerebral vascular accidents. 
“Unexpected,” as used in this definition, refers to an adverse drug experience that has not been 


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previously observed and reported rather than an experience that has not been anticipated based 
on the pharmacological properties of the study drug. 
9.1.4. 
Treatment-Emergent Adverse Event  
A TEAE is defined as an AE that occurs or worsens in the period from the first dose of study 
drug administration to Day 28 of the study. 
9.1.5. 
Adverse Events of Special Interest 
There are no adverse events of special interest in this protocol. 
9.2. 
Eliciting Adverse Event Information 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by the 
study subject. In addition, each study subject should be questioned about AEs at each scheduled 
study center visit or during any telephone contact with the subject. The type of question asked 
should typically be open-ended, e.g. “Have you had any new health problems?” or a similar type 
of query.  
9.3. 
Recording Adverse Events 
All AEs will be assessed by the investigator or qualified designee and recorded in the electronic 
case report forms (eCRFs). The following considerations apply in collecting AE information: 
• Recognized medical terms (not colloquialisms, abbreviations, or jargon) should be used 
when recording AEs. Ideally the description should be consistent with MedDRA 
nomenclature. 
• The medical diagnosis (ie, disease or syndrome) should be recorded instead of signs and 
symptoms (e.g. pneumonia instead of shortness of breath, coughing, and fever). 
• Any sign or symptom considered as unrelated to an encountered disease or syndrome should 
be recorded as an individual AE (e.g. if nausea and severe headache are observed at the same 
time, each event should be recorded as a separate AE). 
• If an AE resolves and reoccurs at a later date, a new AE must be documented and reported, as 
appropriate. 
The following information should be recorded: 
• Description as to whether the AE is serious, if applicable (see Section  9.1.2) 
• The start date (date of AE onset) 
• The stop date (date of AE resolution) 
• The severity of the AE (see Section 9.4) 
• A description of the relatedness of the AE to the study drug or to a study procedure (see 
Section 9.5)  
• The action taken due to the AE 
• The outcome of the AE 


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9.4. 
Grading of the Severity of an Adverse Event 
The severity of AEs will be graded and reported using the CTCAE, Version 5.0.  
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: Grade 1 
(mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal) to 
describe the maximum intensity of the AE. For purposes of consistency with the CTCAE, these 
intensity grades are defined in Table 3. 
Table 3. 
Grading of Adverse Event Severity 
Grade 
Adjective 
Description 
Grade 1 
Mild 
Sign or symptom is present, but it is easily tolerated, is not expected to 
have a clinically significant effect on the subject’s overall health and 
well-being, does not interfere with the subject’s usual function, and is 
not likely to require medical attention. 
Grade 2 
Moderate 
Sign or symptom causes interference with usual activity or affects 
clinical status and may require medical intervention. 
Grade 3 
Severe 
Sign or symptom is incapacitating or significantly affects clinical status 
and likely requires medical intervention and/or close follow-up. 
Grade 4 
Life-threatening 
Sign or symptom results in a potential threat to life. 
Grade 5 
Fatal 
Sign or symptom results in death. 
The distinction between the seriousness and the severity of an AE should be noted. Severity is a 
measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For example, a 
headache may be severe in intensity, but would not be classified as serious unless it met one of 
the criteria for serious events (as listed in Section 9.1.2). 
9.5. 
Describing Adverse Event Relationship to Study Drug and Study Procedures 
The investigator will evaluate the causal relationship of each AE to a study drug and/or to a 
study procedure (e.g. venipuncture or ECG evaluation) and record that relationship on the 
appropriate CRFs. Causality will be assessed considering whether the AE is reasonably related to 
the study drug or procedure or whether the AE is not reasonably related to the study drug or 
procedure considering the definitions in Table 4. 
It should be emphasized that the determination of the relationship of an adverse event to study 
drug (LAM-002A or placebo) should be based on the presumption that the study subject is 
receiving active LAM-002A even though the blind remains unbroken. As noted in Section 8.3, 
unblinding should be avoided unless absolutely necessary for a subject’s well-being; breaking 
the blind should not be performed merely to obtain enhanced certainty regarding the relationship 
of an adverse event to study drug.  
 
 


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Table 4.  
Relationship of Study Drug to Adverse Event 
Relationship 
Description 
Definite 
A clinical event in which a relationship to the use of the study drug seems definite because 
of such factors as consistency with known effects of the drug; a clear temporal association 
with the use of the drug; lack of alternative explanations for the event; improvement upon 
withdrawal of the drug (de-challenge); and recurrence upon resumption of the drug 
(rechallenge).  
Probable 
A clinical event in which a relationship to the study drug seems probable because of such 
factors as consistency with known effects of the drug; a reasonable temporal association 
with the use of the drug; lack of alternative explanations for the event; and improvement 
upon withdrawal of the drug (de-challenge). 
Possible 
A clinical event with a reasonable temporal association with administration of the study 
drug, and that is not likely to be explained by concurrent disease or other drugs or 
chemicals. Information on drug withdrawal may be lacking. 
Unlikely 
A clinical event with a temporal relationship to study drug administration that makes a 
causal relationship improbable and for which other factors suggesting an alternative etiology 
exist. Such factors might include a known relationship of the clinical event to a concomitant 
drug, past medical history of a similar event, the subject’s disease state, intercurrent illness, 
or environmental factors. 
Unrelated 
A clinical event in which a relationship to the study drug seems improbable because of 
factors such as inconsistency with known effects of the study drug; lack of a temporal 
association with study drug administration; lack of association of the event with study drug 
withdrawal or rechallenge; and/or presence of alternative explanations for the event. 
Alternative explanations might include a known relationship of the clinical event to a 
concomitant drug, past medical history of a similar event, the subject’s disease state, 
intercurrent illness, or environmental factors. 
9.6. 
Adverse Event Reporting Period 
The start of the AE reporting for a study subject will coincide with the first administration of 
study drug for this study. After the first administration of study drug, all AEs (serious and 
nonserious, related and unrelated) should be reported. Unless a subject withdraws consent for 
follow-up, each subject must be followed until the end of the AE reporting period at Day 28 or 
when any ongoing drug-related AEs and/or SAEs have resolved or become stable. The 
investigator should use appropriate judgment in ordering additional tests as necessary to monitor 
the resolution of events. The medical monitor or the sponsor may request that certain AEs be 
followed longer.  
Investigators are not obligated to actively seek information regarding the occurrence of new 
SAEs beginning after Day 28. However, if the investigator learns of such an SAE and that event 
is deemed relevant to the use of LAM-002A, he/she should promptly document and report the 
event. A longer reporting period applies in the case of pregnancy (see Section 9.7.2). 
9.7. 
Study Center Reporting Requirements 
9.7.1. 
Adverse Event Reporting Requirements 
Classification of an event as serious or nonserious (see Section 9.1) determines the reporting 
procedures to be followed by the study center. Study center reporting requirements for AEs are 
summarized in Table 5. 


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Table 5.  
Study Center Reporting Requirements for Adverse Events 
Classification 
Reporting Time 
Reporting Action 
Serious 
Within 24 hours of becoming aware 
of the event 
E-mail report on designated SAE report form to 
the sponsor or designee [a] and to the study center 
IRB, as per local IRB/IEC requirements 
Within 10 working days 
E-mail copies of relevant source documents (e.g. 
progress notes, laboratory and diagnostic test 
results, discharge summaries) [b] to the sponsor or 
designee [a].  
Per eCRF submission procedure 
Record and submit information on appropriate 
eCRFs. 
Nonserious 
Per eCRF submission procedure 
Record and submit information on appropriate 
eCRFs. 
a. 
See contact information provided. 
b. Subject name, address, and other personal identifiers should be obscured but without losing the traceability 
of a document to the study subject identifiers. 
Abbreviations: eCRF=case report form; IRB/IEC= institutional review board/independent ethics committee; 
SAE=serious adverse event 
For SAEs, in addition to completing the AE portion of the eCRF, an SAE report form must also 
be completed and emailed within 24 hours of first awareness of the event to the sponsor (or 
designee).  
Investigators must also submit written safety reports as required by the IRB/IEC within timelines 
set by local and regional regulations. The study site should retain documentation of the 
submission of expedited safety reports to the IRB/IEC, and their receipt. Study site personnel 
should not wait to receive complete information or the investigator’s signature before notifying 
the sponsor (or designee) and the IRB/IEC of an SAE. 
The following minimum information is required: 
• Subject identification (i.e. subject number, sex, age) 
• Description of the SAE (diagnosis preferred, symptoms, etc.) 
• Study drug and causal relationship of the SAE to the study drugs or study procedures 
• Investigator name 
Collection of complete information concerning SAEs is extremely important. The information in 
the AE portion of the eCRF and the SAE report form must match or be reconciled. Where the 
same data are collected, the forms must be completed in a consistent manner. For example, the 
same AE term should be used on both forms.  
All available and relevant supporting documentation (e.g. progress notes, pertinent laboratory 
and diagnostic test results, discharge summaries) should also be provided. The subject’s name, 
address, and other personal identity information should be obscured on any source documents 
(e.g. progress notes, nurses’ notes, laboratory and diagnostic test results, discharge summaries). 
The subject’s unique study number should be included on each page of any document provided.  
The sponsor (or designee) will review SAE reports for missing information and send queries to 
the site for resolution as indicated. The study site is responsible for obtaining pertinent follow-up 
information missing from initial reports and forwarding the information within 24 hours of 


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receipt to the sponsor (or designee). Follow-up information to the SAE should be clearly 
documented as “follow-up” in the SAE report form.  
The original SAE form and any follow-up forms must be kept on file at the study site. An SAE is 
followed until it is considered resolved, it returns to baseline, is chronically ongoing, or 
explained otherwise by the principal investigator. 
9.7.2. 
Pregnancy  
Each female subject should be instructed to inform the investigator immediately if she becomes 
pregnant at any time between the start of study screening until 30 days after the last 
administration of study drug.  Similarly, a male subject should also be instructed to inform the 
investigator immediately if his female partner becomes pregnant during the same study period. 
The investigator should counsel the subject regarding the possible effects of study drug exposure 
on the fetus and the need to inform the study center, the medical monitor, and the sponsor (or 
designee) of the outcome of the pregnancy. 
Neither the pregnancy itself nor an induced elective abortion to terminate the pregnancy without 
medical reasons is considered an AE; such occurrences should be reported on the appropriate 
pregnancy report forms. However, if the outcome of the pregnancy meets the criteria for 
classification as an SAE (ie, spontaneous abortion, induced abortion due to complications, 
stillbirth, neonatal death, or congenital anomaly [including that in an aborted fetus]), the 
investigator should follow the procedures for reporting SAEs (ie, report the event to the sponsor 
[or designee] and follow up by submission of the appropriate AE eCRFs (see Section 9.7.1).  
Additional information about pregnancy outcomes that are classified as SAEs includes:  
• Any spontaneous abortion, including miscarriage and missed abortion, will be reported as an 
SAE. 
• An induced therapeutic abortion to terminate any pregnancy due to complications or other 
medical reasons will be recorded as an SAE. The underlying medical reason for this 
procedure should be recorded as the AE term. 
• All neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 1 month that the investigator assesses 
as possibly related to the in-utero exposure to the study drug should also be reported. 
• In the case of a live birth, the “normality” of the newborn can be assessed at the time of birth 
(ie, there is no required minimum follow-up of a presumably normal infant before the 
pregnancy outcome report eCRF can be completed). 
• The “normality” of an aborted fetus can be assessed by gross visual inspection unless there 
are pre-abortion laboratory findings suggestive of a congenital anomaly, in which case 
pathologic examination should be requested.  
Information regarding any pregnancy in a study subject or the female partner of a male subject 
must be documented on a pregnancy report form and forwarded to the sponsor (or designee) for 
contact list) within 24 hours of becoming aware of the pregnancy. Monitoring of the pregnancy 
in both female study subjects and female partners of male study subjects should continue until 
the conclusion of the pregnancy. For female partners of male study subjects, such monitoring 


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applies if the pregnancy occurs in the period from the subject’s start of study drug until 30 days 
after the subject’s last dose of study drug. The outcome of the pregnancy should be reported on 
the pregnancy outcome report form within 5 days of the conclusion of the pregnancy. If the end 
of the pregnancy occurs after the study has been completed, the outcome should be reported to 
the sponsor (or designee). 
9.7.3. 
Contact Information for Reporting an SAE or Pregnancy 
Contact information for reporting an SAE or Pregnancy will be managed by the CRO. 
9.8. 
Sponsor Reporting Requirements 
Each SAE or special situation report received from the investigator will be evaluated by the 
sponsor (or designee). The sponsor (or designee) will assess the seriousness of the event (see 
Section 9.1.2), the expectedness of the event (see Section 9.1.3), and the relationship to 
participation in the study (see Section 9.5). The sponsor (or designee) will also indicate whether 
there is concurrence with the details of the report provided by the investigator.  
The sponsor (or designee) will provide information for reporting of suspected, unexpected, 
serious adverse reactions (SUSARs) to regulatory authorities worldwide consistent with relevant 
legislation or regulations, including the applicable US FDA CFR, the European Commission 
Clinical Trials Directive (2001/20/EC, and revisions), and other country specific legislation or 
regulations. SUSARs will be reported to regulatory authorities within 7 calendar days for life 
threatening and fatal events, or 15 calendar days for all others. These timeframes begin with the 
first notification of the event from the reporting investigator to the sponsor (or designee), which 
represents the start of the regulatory clock (Day 0).  
The sponsor (or designee) will also provide all investigators with a safety letter describing the 
SUSAR. The information will be provided by e-mail, fax, or overnight mail within 15 calendar 
days from Day 0. Investigators will be requested to provide written notification of the event to 
the relevant IRB/IEC as soon as is practical and consistent with local regulatory requirements 
and local institutional policy.  


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10. 
LABORATORY AND OTHER ASSESSMENTS  
10.1. 
Methods and Analytes 
Samples to be obtained and parameters to be analyzed are indicated in Table 6. 
General safety laboratory assays (serum pregnancy test, serum chemistry, hematology,) will be 
performed using standard clinical pathology methods at Clinical Laboratory Improvement 
Amendments (CLIA)-certified laboratories associated with the study centers.  
For pharmacokinetic analyses, evaluation of LAM-002A blood concentrations will be performed 
using a validated assay at a contract laboratory designated by the sponsor.  
Viral load measurements from nasopharyngeal swabs at Days 1, and 4 will be conducted at 
Covance using the Quantification of COVID-19 Viral Load using the 2019-nCoV Real-Time 
RT-PCR Viral Load assay on Applied Biosystems QuantStudio 7/12K Flex Real-Time PCR 
system (v2) assay.   The method has been validated to CAP/CLIA standards by Covance.  The 
quantitative assay does not have EUA, but the non-qualitative version of the assay developed by 
Covance does have EUA.  The limit of detection of the assay is set to the lower limit of 
quantification (LLOQ) of the quantitative 2019-nCoV CDC EUA assay using respiratory 
specimens which was determined using a synthetic RNA panel prepared at different target input 
levels at the lower end of the AMR. The panel was tested 5 times in triplicate in at least one run.  
The LLOQ for 2019-nCoV CDC EUA assay for respiratory swabs is 3.348 Log10 copies/mL 
(2228 copies/mL). For values below the LLOQ that are still detected, a value of “detected” will 
be reported.  When no virus is detected a value of “undetected” will be reported.  
The method for saliva samples is currently completing similar CAP/CLIA validation at Covance. 
Details for both methods will be included in the Laboratory Manual. 
Pharmacodynamic and biomarker assessments will be conducted at contract laboratories 
designated by the sponsor. 
Clinical assessments (body weight and height, vital signs, oxygen saturation) will be obtained 
using standard clinical equipment available at each study center.  
ECGs will be performed at the clinical sites using equipment provided by the sites and will be 
interpreted by the sites. 


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Table 6.  
Laboratory and Other Parameters to Be Assessed 
Test/Procedure 
Parameters 
Laboratory – Safety  
Urine (or serum) 
pregnancy test 
Urine or serum β-HCG  
Serum chemistry 
Sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium, 
phosphorus, magnesium, total protein, albumin, ALT, AST, ALP, CK, LDH, total 
bilirubin, uric acid.  
Hematology 
Hematocrit, hemoglobin, erythrocyte count, absolute counts of leukocytes, 
neutrophils, lymphocytes, monocytes, eosinophils, basophils 
Platelet count 
Laboratory – Pharmacokinetic1 
Plasma pharmacokinetics 
Plasma LAM-002A concentrations (as assessed by validated bioassays) (Worldwide 
Clinical Trials Early Phase Services/Bioanalytical Sciences, LLC., 8609 Cross Park 
Dr., Austin, TX 78754.) 
Retention of plasma for potential metabolite analyses 
Laboratory – Pharmacodynamic1 
Peripheral blood and 
nasopharyngeal swabs for 
cellular 
pharmacodynamics 
Plasma cytokines might be analyzed for levels of IL-12, IL-23, IL-6, IFN-γ, IL-10 
and GM-CSF (additional cytokines may be analyzed in parallel) 
Target engagement biomarkers might be assessed via RNA-seq or qRT-PCR from 
RNA isolated from nasopharyngeal swabs and PBMC, or in plasma via established 
Luminex and or ELISA assays 
Laboratory – Disease-related 
SARS-CoV-2 
assessments 
Nasopharyngeal swab and saliva to determine SARS-COV-2 viral load using a 
qRT-PCR method. 
SARS-CoV-2 mutational 
analysis 
Mutational profiling of SARS-CoV-2 viral genome might be analyzed by RNA-seq 
or comparable technology1 
Genetic Polymorphism in 
COVID-19 subjects 
Analysis of germline DNA sequence polymorphisms in genomic DNA isolated from 
blood or Nasopharyngeal swabs1   
Other 
Body weight/height 
Weight in kilograms, height in centimeters  
Body temperature  
Temperature in degrees Celsius 
Blood pressure  
Diastolic and systolic blood pressure in mm Hg 
Oxygen saturation  
% saturation 
12-lead ECG  
Heart rate, cardiac intervals, wave form abnormalities, ectopy 
Abbreviations: ALP=alkaline phosphatase, ALT=alanine aminotransferase, AST=aspartate aminotransferase, 
BUN=blood urea nitrogen, CK=creatine kinase, DNA=deoxyribonucleic acid, ECG=electrocardiogram, 
LDH=lactate dehydrogenase, PCR=polymerase chain reaction, RNA=ribonucleic acid. 
1Samples will be collected for pharmacokinetic, immunogenicity, and genetic exploratory end points. The 
analysis for these exploratory endpoints is optional 
10.2. 
Sample Shipping, Storage, and Retention 
Routine clinical safety samples (for pregnancy test, serum chemistry, and hematology) will be 
analyzed at the clinical laboratory at the study center and will not be shipped. These samples will 
not be stored and will be discarded promptly after analysis.  


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Other samples (viral nasopharyngeal swab samples; saliva; plasma for pharmacokinetics; blood 
and plasma for pharmacodynamics) will be prepared following the instructions outlined in a 
detailed clinical study laboratory manual.  
These samples will be shipped to the sponsor or the contract analytical laboratories using a 
shipping service designated by the sponsor and as specified in the clinical study laboratory 
manual. For the duration of the sample analysis campaign, samples will be stored at these 
contract laboratory facilities or sent for long-term storage at a storage facility designated by the 
sponsor. Samples will be retained as described for study records (see Section 13.7). 
As described for other study records (see Section 13.7), copies of data relating to body weight 
and height, vital signs, oxygen saturation, etc. will be retained on file at the study centers. The 
sponsor may request copies of primary ECGs or radiography images (redacted of subject 
personal identifying information) for storage at the company. 


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11. 
EFFICACY ASSESSMENTS 
11.1. 
Primary Efficacy Endpoint: Viral Clearance at Day 4 
The primary efficacy outcome measure evaluates SARS-CoV-2 viral load at Day 4 for 
LAM-002A or placebo-treated subjects. SARS-CoV-2 viral load will be measured in 
nasopharyngeal specimens by a qRT-PCR method. Analysis will focus on log10 viral load on 
Day 4 adjusted for baseline viral load at Day 1 in subjects with baseline viral load >105 
copies/mL.  
11.2. 
Secondary Efficacy Endpoint 
11.2.1. 
Clinical Efficacy 
An additional secondary efficacy endpoint measures the proportion of subjects treated with 
LAM-002A who progressed to hospitalization or who died at Day 28 of randomization compared 
to those in the placebo arm.  
The need for referral for consideration for hospitalization will be assessed based on the CDC 
guidelines for presentation of mild/moderate, severe, and critical disease 
• Mild to moderate: mild symptoms (fever [temperature ≥100.4], cough, sore throat, anosmia, 
malaise, headache, or muscle pain, gastrointestinal symptoms) up to mild pneumonia   
• Severe: dyspnea, hypoxia, or >50% lung involvement on imaging 
• Critical: respiratory failure, shock, or multiorgan system dysfunction 
Severe and critical disease require hospitalization. 
The National Early Warning Score (NEWS) has demonstrated an ability to discriminate patients 
who are at risk of poor outcomes (Smith et.al., 2015), and has been recommended by the World 
Health Organization (WHO, 2020). This score is based on 7 clinical parameters. The vital sign 
scores as measured by the NEWS (Table 1) provides measures of dyspnea, hypoxia as well as 
other vital signs important to COVID-19 symptoms such as temperature and blood pressure.  
Vital signs related to COVID-19 illness will be monitored as specified in Table 7.  A composite 
score of vital sign parameters is calculated at baseline and at each visit. Change of NEWS from 
baseline will be used to assess resolution or progression of disease and decision for 
hospitalization. 
The following criteria will be used to determine need for hospitalization:  
• A composite NEWS >6, or  
• One NEWS parameter score of 3 (e.g. RR≥25, Oxygen saturation <91), or 
• Respiratory failure, or  
• Severe presentations of other COVID-19 symptoms, or 
• ECOG Status (see table in Section 15.3) 


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If the NEWS score increases during the follow-up visits, the subject will be followed more 
closely with subsequent day tele-health visits until the NEWS score improves or subject further 
declines, requiring hospitalization. 
 
 


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Table 7 
National Early Warning Score (NEWS)  
 
Level of consciousness = alert (A), and arousable only to voice (V) or pain (P), and unresponsive (U). 
NEWS Composite Score 
NEWS = 0-4 Low score: Assessment by a competent registered nurse who should decide if a 
change to frequency of clinical monitoring or an escalation of clinical care is 
required. 
NEWS = 5-7 Medium Score: Urgent review by a clinician skilled with competencies in the 
assessment of acute illness. 
NEWS ≥ 7 
High Score: Emergency assessment by a clinical/critical care outreach team with 
critical-care competencies and usually transfer of the patient to a higher 
dependency care area. 
11.2.2. 
Hospitalization: Clinical Status 
The secondary efficacy endpoint evaluates COVID-19 clinical status including subjects who 
become hospitalized and continue LAM-002A/placebo treatment. Clinical status is defined by 
the ordinal scale.  For subjects (who have the same ordinal score), control versus experimental 
arms will be compared based on percentage of subjects at each score on Day 28. 


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COVID-19 Severity Ordinal Scale scores in LAM-002A-treated and placebo-treated subjects 
will be determined at Day 28 based on the following scores: 
1. Not in the hospital 
2. Hospitalized, requiring low flow supplemental oxygen (such as nasal cannula)  
3. Hospitalized, not on invasive ventilation (such as 100% non-rebreather, BIPAP), (pre-ICU) 
4. Hospitalized, in the ICU, on invasive ventilation or ECMO 
5. Dead 


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12. 
STATISTICAL CONSIDERATIONS 
This is a double-blind placebo-controlled trial to determine the superiority of LAM-002A 
compared to placebo in reducing viral load during a 10-day course of therapy.  
COVID-19 patients that fulfill all enrollment criteria and provide informed consent to study 
participation will have their baseline assessments performed and will be randomized using a 
permuted block scheme (with variable block size) in a 1:1 ratio to one of the two groups: (1) 
LAM-002A, or (2) placebo.  
The study will include an early evaluation of safety, and an interim analysis. Full details of the 
statistical methods will be developed and outlined in the statistical analysis plan (SAP) and filed 
with the study sponsor prior to database lock. 
12.1. 
Statistical Hypotheses 
All tests performed will be tests of superiority. 
For the primary efficacy endpoint, the hypothesis that LAM-002A results in a reduction in viral 
load compared to placebo in the subgroup of participants with baseline nasopharyngeal viral load 
> 105 copies/mL will be tested. 
12.2. 
Sample Size Determination 
The study is designed to have high power at a moderate significance level to detect a signal of 
benefit for the viral load outcome. The sample size calculation is based on the primary endpoint 
of interest: log10 respiratory (nasopharyngeal swab) viral load at Day 4 post-randomization. 
Given the limited data on the variability of the change in log10 viral load, the study is powered 
based on detecting a moderate standardized effect size of 0.3 using an analysis of covariance 
(ANCOVA), adjusting for baseline log10 viral load. (NOTE: For ANCOVA, the effect size is the 
standard deviation of the treatment means divided by the pooled standard deviations of the 
observations. An ANCOVA standardized effect size of 0.3 is equivalent to a Cohen’s d of 0.60). 
To be conservative, a R-squared of 0 between the log10 viral RNA at 4-days and baseline log10 
viral RNA was assumed.  With a power of 90%, and a type I error rate of 20% (2-sided), it will 
be possible to detect the hypothesized 0.3 standardized effect size with 74 total patients – 37 
patients per group with a 1:1 randomization.  We will enroll a sample size of 142 to assure that a 
sufficient number of participants with baseline viral load >105 copies/ml. The table below shows 
the power to detect an effect size of 0.3 given 10% loss to follow-up and various proportions 
enrolled with baseline viral load >105 copies ml. 
 
Proportion of Enrolled Participants with >105 copies/ml 
 
0.40 
0.50 
0.60 
0.70 
0.80 
0.90 
1.00 
Power to Detect 
Effect Size of 0.3 
0.79 
0.86 
0.91 
0.94 
0.96 
0.97 
0.98 
 


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Based on available data regarding the distribution of viral load, it is conservatively estimated that 
≥50% of randomized participants will have a baseline viral load >105 copies/mL. The table 
above demonstrates that enrolling 142 will provide sufficient power even if the proportion with 
baseline viral load >105 copies/ml is as low as 40%.  The prevalence of this subgroup will be 
monitored and adjustments to overall sample size may be made if necessary. 
12.3. 
Analysis Sets 
12.3.1. 
Intention to Treat (ITT) Population 
The intention-to-treat (ITT) population includes all participants randomized according to their 
initial randomized assignment regardless of the treatment actually received.  
12.3.2. 
Antiviral Efficacy Analysis Population 
The antiviral efficacy analysis population will consist of all randomized participants with a 
baseline viral load >105 copies/mL. 
12.3.3. 
Per Protocol (PP) Population 
The per-protocol (PP) population includes all ITT participants who did not have any major 
protocol deviations. The final determination of the exclusion of subjects from the PP population 
will be made prior to the database lock.  
12.3.4. 
Safety Population 
The safety population will include all randomized subjects who received at least one dose of the 
study drug.  
12.4. 
Statistical Analyses 
12.4.1. 
General Considerations 
This is a double-blind placebo controlled randomized trial testing the superiority of LAM-002A 
compared to placebo for Day 4 viral load at the two-sided overall type I error rate of 0.20. 
Secondary hypotheses will be described according to the appropriate summary statistics (e.g., 
proportions for categorical data, means with 95% confidence intervals for continuous data, 
median for time-to-event data). Diagnostic tests and sensitivity analyses will be performed. 
Parametric distributional assumptions will be checked. If assumptions fail, other distributions 
will be considered prior to transformations and non-parametric methods for sensitivity analysis. 
A statistical analysis plan (SAP) will be developed and filed with the study sponsor prior to 
database lock. 
12.4.2. 
Comparability of Baseline Characteristics.  
Distributions of baseline demographic and clinical characteristics will be summarized by 
intervention group. Comparability for continuous variables will be examined graphically and by 
summary statistics (means, medians, quartiles, etc.). Categorical variables will be examined by 
calculating frequency distributions. No inferential statistics will be calculated. 


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12.4.3. 
Analysis of Primary Outcome: Viral Load in Nasopharyngeal Samples at Day 4 
The primary analysis will test whether the viral load in nasopharyngeal samples is lower at Day 4 
in those receiving LAM-002A compared to placebo. All participants in the antiviral efficacy 
analysis set (i.e. the subgroup with baseline viral load >105 copies/mL) will be included in the 
primary analysis. Viral load will be measured by a qRT-PCR test at Days 1 and 4. The analysis 
for the primary endpoint will focus on the log10 viral RNA on Day 4. A repeated measures mixed 
model will be used to compare the two treatment groups. The mixed model will jointly model 
day 1 and day 4 viral load and will allow for the inclusion of all participants with at least one 
viral load assessment [Carpenter 2007]. The model will include fixed effects for treatment and 
age. Random effects will be included for subject and site. Linear contrasts will be used to 
compare the difference between groups for Day 4. This difference will be conditional on baseline 
viral load and is equivalent to an analysis adjusted for baseline [Carpenter 2007]. 95% CIs will 
be estimated for treatment differences at Day 4. A supportive analysis will be conducted using 
the ITT population, stratified by baseline viral load >105 copies/mL vs. viral load ≤105 
copies/mL.  
12.4.4. 
Analysis of Secondary Outcomes 
The statistical and analytical methods that will be used to evaluate the secondary endpoints are 
described in this section. 
 
Secondary Outcome: Hospitalization or Death Within 28 Days 
The proportion of those progressing to hospitalization or death within 28 days of randomization 
will be compared between treatment groups using logistic regression (Ge 2011). All participants 
in the ITT population will be included in this analysis. Covariates in the analysis will include 
age. Site will be included as a random effect. The risk difference and 95% confidence interval 
will be estimated. Supportive analysis of this outcome will use the antiviral efficacy analysis 
population and the PP population.  
 
Clinical Status (Disease Progression) 
The distribution of ordinal scale severity results will be summarized by treatment arm as 
percentages in the ITT population. A proportional odds model will be used to compare groups on 
this ordinal scale. The common odds ratio measures the effect size and is valid under the 
proportional odds assumption that will be verified via a goodness of fit likelihood ratio test. The 
model will include fixed effects for treatment, and age. Hypothesis tests for the model are nearly 
identical to the Wilcoxon Rank Sum test. Supportive analysis of this outcome will use the 
antiviral efficacy analysis population and the PP population. 
 
Secondary Outcome: Oxygen Saturation (O2 sat)  
A logistic regression using generalized estimating equations will be used compare the proportion 
of subjects at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo as 
measured on Days 1, 4 and 11 in participants in the ITT population. Individuals requiring 
respiratory assistance, hospitalized or who died will be considered as having O2 sat <93%. Those 
who require baseline O2 will be excluded from the analysis. Supportive analysis of this outcome 
will use the antiviral efficacy analysis population and the PP population. 


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12.4.5. 
Exploratory Endpoints 
Analysis for exploratory endpoints will be defined in the study SAP or separate reports, as 
appropriate. 
12.4.6. 
Subgroup Analyses 
Heterogeneity of treatment effect (HTE) for the primary and secondary progression to 
hospitalization or death outcome will be examined for the following subgroup variables:  days 
from onset of symptoms to randomization, NEWS score at randomization and sex (male vs. 
female). HTE will be evaluated within a mixed model for the primary outcome and a logistic 
regression for the secondary progression outcome. The models will include treatment, site, the 
subgroup variable, and the interaction of the subgroup variable with time. Differences in means 
or risk with 95% confidence intervals will be estimated for the treatment difference within each 
level of the subgroup variable. The significance test of the interaction will be used to formally 
test HTE at the two-sided 0.05 significance level. 
12.4.7. 
Plan for Missing Data 
Several strategies will be imposed to minimize the impact of missing data on conclusions. 
Prevention is the most obvious and effective manner to control bias and loss of power from 
missing data (NRC 2010). This protocol will follow the intent to treat principle, requiring follow-
up of all subjects randomized regardless of the actual treatment received (Lachin, 2000). The 
only reasons for not considering a subject in analyses will be withdrawal of consent, a false 
positive test for SARS-CoV-2, or lost to follow-up. The informed consent and protocol will 
distinguish between treatment discontinuation and study withdrawal and the consent will also 
include a statement about the importance of continuing data collection despite treatment 
discontinuation. Alternative contact information will be identified on entry into the study to 
minimize loss-to follow-up. Timely data entry combined with weekly missing data reports will 
trigger protocols for tracking and obtaining missing data items or outcome assessments. Despite 
these prevention efforts it is reasonable to assume missing data will occur. The primary analysis 
is valid under the assumption that missing data is missing at random (MAR). The plausibility of 
this assumption will be evaluated by determining the extent of missing data and using logistic 
regression to identify factors associated with dropout. While differential rates of dropout 
between groups or high loss to follow-up are not expected, sensitivity analysis using pattern-
mixture and selection models under missing not at random (MNAR) assumptions will be 
performed to examine the robustness of conclusions of the primary analysis to missing data. 
12.4.8. 
Safety and Tolerability Analyses 
Adverse events (AEs) and serious adverse events (SAEs) will be categorized by severity and 
relation to study drug using the Safety population. AEs will be classified according to the 
National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.  
Safety endpoints including SAEs, Grade 3 and 4 adverse events and signs compatible with 
cardiac arrhythmias, allergic reactions, gastrointestinal, hepatobiliary, eye and ear, blood and 
lymphatic system disorders and acute exacerbation of lung disorders will be described by 
treatment group.  Each AE will be counted once for a given participant and graded by severity 
and relationship to COVID-19 or study intervention. AEs will be presented by system organ 


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class, duration (in days), start- and stop-date. Adverse events leading to premature 
discontinuation from the study intervention and serious treatment-emergent AEs will be 
presented in tables and listings. 
Differences between treatment groups for safety outcomes will be tested at the 0.05 (2-sided 
level of significance) without correction for multiple testing. 
 
Adverse Events 
Treatment-emergent AEs and non-TEAEs (those occurring prior to administration of study 
medication or that first occurred prior to study drug administration and did not worsen in 
frequency or severity) will be listed. TEAEs will be defined as AEs that occur on or after the 
date and time of study drug administration, or those that first occur pre-dose but worsen in 
frequency or severity after study drug administration. AEs will be followed-up until complete 
resolution, or until the PI or Sub-Investigator judges safe to discontinue follow-up.  
The incidence of TEAEs will be summarized using the safety population. The MedDRA® 
dictionary Version 23 will be used to classify all AEs reported during the study by system organ 
class (SOC) and preferred term (PT). Incidence of subjects who experienced TEAEs will be 
presented by treatment and overall, SOC, PT, by Investigator-assessed relationship and also by 
severity. Each subject may only contribute once to each of the incidence rates, for a TEAE 
following a given treatment, regardless of the number of occurrences; the highest severity or 
highest relationship will be presented, as appropriate. In each table, SOC will be presented in 
descending order of overall incidence rate in terms of frequency of subjects and then in 
frequency of events (alphabetical order will be used in case of equal rates). For each SOC, PT 
will be presented the same way. 
Incidence of TEAEs (number of events) will also be presented by treatment and overall, by SOC, 
and PT, by Investigator-assessed relationship and severity. 
Severity of AEs will be rated according to CTCAE criteria as outlined in Section 9.4 and defined 
in Table 3 as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening) 
and Grade 5 (fatal). 
 
Laboratory Parameters 
Clinical laboratory tests including biochemistry, hematology, and other screening tests, will be 
performed as listed in Table 6, and at time points specified in the SoA (Table 1). Microscopic 
examination will be performed on abnormal findings. Listings of all clinical laboratory results 
will be provided with the abnormal values flagged with "L" (Below normal range) and "H" 
(Above normal range) for continuous parameters, and “N” (Normal Range) for categorical 
parameters. 
Descriptive statistics (mean, median, SD, Min, Max, and sample size) for each clinical laboratory 
test (continuous variables) will be presented. Change from baseline to study exit will also be 
presented. For a given laboratory test, any value (scheduled or unscheduled), prior to the first 
dosing will replace any missing screening value (if scheduled value is missing). However, 
unscheduled results will not be included in the summary tables. For categorical variable, the 
number of subjects (frequency and percentage) will be tabulated by results (e.g., negative, 
positive, trace, etc.). A summary table of shifts from screening to study exit will be provided. 


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Results from repeat tests will not be included in the summary statistics unless the repeat was 
required (and documented as such) due to technical reasons or an invalid initial result. 
12.4.9. 
Other Safety Analyses 
Any other safety analysis will be made on the safety population. 
12.5. 
Interim Analyses  
The study will incorporate an interim analysis for safety after the first 30 subjects (15 on 
LAM-002A and 15 on placebo) have completed treatment and have been followed up to Day 11. 
Recommendations from an independent Data Safety Monitoring Board (DSMB) will be used for 
decision of early termination or design adaptations (see table of Death Trigger Study 
Termination below). No formal assessment of futility or efficacy will be performed at this first 
interim report.  
Subsequent interim DSMB reports will be reviewed with no more than 6 months between 
reviews. In addition to safety, at 50% enrollment the DSMB will review the proportion of 
participants that have a baseline viral load of >105 copies/ml. Based on this proportion the 
DSMB may recommend an increase in sample size to assure a sufficient number of participants 
in the subgroup for primary analysis. If a recommendation for a sample size increase is being 
considered, futility will be examined via conditional power to assist in this determination. Details 
will be provided in the SAP. 
The first interim analysis for safety will be conducted and presented to the DSMB when 
15 participants in each treatment arm have reached 11 days following randomization. At this 
review, it is proposed that the study be stopped if mortality is significantly higher in the 
LAM-002A arm compared to placebo arm based on a Fisher’s exact test. Table 8 shows the 
differences in deaths between the LAM-002A and placebo arm that will prompt discontinuation 
of the study.  
Table 8.  
Death Boundary for Study Termination 
Placebo Deaths, n 
LAM-002A Deaths, n 
Difference  
(LAM-002A – Placebo) 
Fisher’s Exact P-Value 
0 
5 
5 
0.042 
1 
7 
6 
0.035 
2 
8 
6 
0.05 
3 
10 
7 
0.025 
4 
11 
7 
0.027 
5 
12 
7 
0.025 
6 
13 
7 
0.021 
7 
13 
6 
0.050 


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13. 
STUDY ADMINISTRATION AND RESPONSIBILTIES  
13.1. 
General Investigator Responsibilities 
The principal investigator must ensure that: 
• He or she will personally conduct or supervise the study. 
• His or her staff and all persons who assist in the conduct of the study clearly understand their 
responsibilities and have their names included in the relevant Study Personnel documents. 
• The study is conducted according to the protocol and all applicable regulations. 
• The protection of each subject’s rights and welfare is maintained. 
• Signed and dated informed consent and, when applicable, permission to use protected health 
information are obtained from each subject before conducting study procedures. If a subject 
withdraws permission to use protected health information, the investigator will obtain a 
written request from the subject and will ensure that no further data be collected from the 
subject. 
• The consent process is conducted in compliance with all applicable regulations and privacy 
acts. 
• The IRB/IEC complies with applicable regulations and conducts initial and ongoing reviews 
and approvals of the study. 
• Any amendment to the protocol is submitted promptly to the IRB/IEC. 
• Any significant protocol deviations are reported to the medical monitor, the sponsor, and the 
IRB/IEC according to the guidelines at each study center. 
• eCRF pages are completed in a timely fashion. 
• All SAEs are reported to the sponsor (or designee) within 24 hours of knowledge and to the 
IRB/IEC per IRB/IEC requirements. 
• All safety reports are submitted promptly to the IRB/IEC. 
13.2. 
Protocol Compliance 
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol. 
13.3. 
Compliance with Ethical and Regulatory Guidelines 
The investigator will ensure that this study is conducted in accordance with ICH guidelines, or 
with the laws and regulations of the country in which the research is conducted, whichever 
affords the greater protection to the study subject. For studies conducted under a US IND, the 
investigator will ensure adherence to the basic principles of GCP as outlined in 21 CFR 312, 
subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, Part 50, 1998, and 21 CFR, 
Part 56, 1998. 
This study is also subject to and will be conducted in accordance with 21 CFR, Part 320, 1993, 
“Retention of Bioavailability and Bioequivalence Testing Samples.” 


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Because this is a “covered” clinical trial, the investigator will ensure adherence to 21 CFR, 
Part 54, 1998; a covered clinical trial is any “study of a drug or device in humans submitted in a 
marketing application or reclassification petition subject to this part that the applicant or FDA 
relies on to establish that the product is effective (including studies that show equivalence to an 
effective product) or that make a significant contribution to the demonstration of safety.” This 
requires that investigators and all sub-investigators must provide documentation of their financial 
interest or arrangements with the sponsor, or proprietary interests in the drug being studied. This 
documentation must be provided before participation of the investigator and any sub-investigator 
in the trial. The investigator or sub-investigator agrees to notify the sponsor of any change in 
reportable financial interests during the study and for 1 year following completion of the study. 
Study completion is defined as the date that the last subject has completed the protocol-defined 
activities. 
13.4. 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) 
This protocol and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain informed 
consent) will be submitted by the investigator to an IRB/IEC. Approval from the IRB/IEC must 
be obtained before starting the study and should be documented in a letter from the IRB/IEC to 
the investigator specifying the protocol number, protocol version, protocol date, documents 
reviewed, and date on which the committee met and granted the approval. A signed protocol 
approval page, a letter confirming IRB/IEC approval of the protocol and informed consent, and a 
statement that the IRB/IEC is organized and operates according to GCP and the applicable laws 
and regulations must be forwarded to the sponsor before screening subjects for the study. 
Additionally, study centers must forward a signed Form FDA 1572 (Investigator Obligation 
Form) to the sponsor before screening subjects for study enrollment. 
Any modifications or amendments made to the protocol or informed consent document after 
receipt of the initial IRB/IEC approval must also be submitted to the IRB/IEC for approval 
before implementation. Only changes necessary to eliminate apparent immediate hazards to the 
subjects may be initiated prior to IRB/IEC approval. In that event, the investigator must notify 
the IRB/IEC, the medical monitor, and the sponsor in writing within 5 working days after 
implementation. If a change to the protocol in any way increases the risk to the subject or 
changes the scope of the study, then written documentation of IRB/IEC approval must be 
received by the sponsor before the amendment may take effect. Additionally, under this 
circumstance, information on the increased risk and/or change in scope must be provided to 
subjects already actively participating in the study, and they must read, understand, and sign any 
revised informed consent document confirming willingness to remain in the trial. 
The investigator shall submit a progress report at least once yearly to the IRB/IEC and must 
provide a copy to the sponsor. As soon as possible after completion or termination of the study, 
the investigator will submit a final report to the IRB/IEC and to the sponsor. This report should 
include the dates of initiation and completion of the trial, a description of any changes in study 
procedures or amendments to the protocol, any deviations from the protocol, the number and 
type of subjects evaluated, the number of subjects who discontinued (and the reasons for 
discontinuation), the number of subjects who completed the trial, and the results of the trial, 
including a description of any AEs. The sponsor will assist the investigator in the preparation of 
this report, as needed. 


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13.5. 
Informed Consent 
The investigator, or a designee (designee must be listed in the relevant in the relevant study 
personnel documents), must explain to each subject the purpose and nature of the study, the 
study procedures, the possible adverse effects, and all other elements of consent as defined in 
21 CFR Part 50 and other applicable national and local regulations governing informed consent. 
Each subject must provide a signed and dated informed consent before enrollment into this 
study. Signed consent forms must remain in each subject’s study file and be available for 
verification by study monitors at any time. 
A copy of the IRB/IEC-approved informed consent must be forwarded to the sponsor or designee 
for regulatory purposes.  
13.6. 
Confidentiality 
Every effort will be made to maintain the anonymity and confidentiality of all subjects during 
this clinical study. However, because of the experimental nature of this study drug, the 
investigator agrees to allow the IRB/IEC, representatives of the sponsor and its designated 
agents, and authorized employees of appropriate regulatory agencies to inspect the facilities used 
in this study and, for purposes of verification, allow direct access to the study center records of 
all subjects enrolled into this study. This includes providing by fax, email, or regular mail 
de-identified copies of clinical, laboratory, ECG, radiology, pathology, and/or other test results 
when requested by the sponsor. A statement to this effect will be included in the informed 
consent and a permission form authorizing the use of protected health information will also be 
included. 
In accordance with local and national subject privacy regulations, the investigator or designee 
must explain to each subject that in order to evaluate study results, the subject’s protected health 
information obtained during the study may be shared with IRB/IECs, the sponsor and its 
designees, and regulatory agencies. It is the investigator’s or designee’s responsibility to obtain 
written permission to use protected health information from each subject. If a subject withdraws 
permission to use protected health information, it is the investigator’s responsibility to obtain the 
withdrawal request in writing from the subject and to ensure that no further data will be collected 
from the subject. Any data collected on the subject before withdrawal will be used in the analysis 
of study results. The sponsor will only use or disclose the subject’s protected health information 
as defined in the informed consent document. 
The investigator must assure that each subject’s anonymity will be strictly maintained, and that 
each subject’s identity is protected from unauthorized parties. Only subject initials, date of birth, 
and an identification code (but no subject names) should be recorded on any form or biological 
sample submitted to the IRB/IEC, to the sponsor or its designees (e.g. laboratories), or to 
regulatory authorities. However, sufficient information must be retained at the study center to 
permit sample data and data in the database to be connected with the unique subject number 
assigned to each study participant. 
The investigator agrees that all information received from the sponsor, including but not limited 
to the study drug, the investigator brochure, this protocol, the eCRFs, and any other study 
information remain the sole and exclusive property of the sponsor during the conduct of the 
study and thereafter. This information is not to be disclosed to any third party (except employees 
or agents directly involved in the conduct of the study or as required by law) without prior 


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written consent from the sponsor. The investigator further agrees to take all reasonable 
precautions to prevent the disclosure by any employee or agent of the study center to any third 
party or otherwise into the public domain. 
13.7. 
Study Files and Retention of Records and Biological Samples 
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified by the IRB/IEC, 
representatives of the sponsor and its designated agents, and authorized employees of appropriate 
regulatory agencies. These documents should be classified into at least the following 
2 categories: (1) investigator’s study file, and (2) subject clinical source documents.  
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, the 
IRB/IEC and governmental approval with correspondence, signed informed consent documents, 
drug accountability records, staff curriculum vitae and authorization forms (e.g. Form 
FDA 1572), and other appropriate documents and correspondence pertaining to the conduct of 
the study.  
The required source data referenced in the monitoring plan for the study should include 
sequential notes containing at least the following information for each subject: 
• Subject identification (name, date of birth, gender) 
• Documentation that the subject meets eligibility criteria, e.g. history, physical examination, 
and confirmation of diagnosis (to support inclusion and exclusion criteria) 
• Participation in trial (including trial number) 
• Trial discussed and date of informed consent 
• Dates of all visits 
• Documentation that protocol-specific procedures were performed 
• Results of efficacy parameters, as required by the protocol 
• Start and end date (including dose regimen) of study drug (including relevant drug 
dispensing information) 
• Record of all AEs and other safety parameters (including start and end date, causality and 
intensity) 
• Concomitant medications (including start and end date and dose if relevant dose changes 
occur) 
• Date of trial completion and reason for discontinuation, if applicable 
All clinical study documents must be retained by the investigator until at least 2 years after the 
last approval of a marketing application in an ICH region (i.e. the United States, Europe, or 
Japan) and until there are no pending or contemplated marketing applications in an ICH region; 
or, if no application is filed or if the application is not approved for such indication, until 2 years 
after the investigation is discontinued and regulatory authorities have been notified or for 
15 years, whichever is longer. Investigators may be required to retain documents longer if 
required by applicable regulatory requirements, by local regulations, or by an agreement with the 


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sponsor. The investigator must notify the sponsor and obtain written approval from the sponsor 
before destroying any clinical study records. The investigator will promptly notify the sponsor in 
the event of accidental loss or destruction of any study records. The sponsor will inform the 
investigator of the date that study records may be destroyed or returned to the sponsor. 
The sponsor must be notified in advance and must provide express written approval of any 
change in the maintenance of the foregoing documents if the investigator wishes to move study 
records to another location or assign responsibility for record retention to another party.  
If the investigator cannot guarantee this archiving requirement at the study center for any of the 
documents, special arrangements must be made between the investigator and the sponsor to store 
these in sealed containers outside of the study center so that they can be returned sealed to the 
investigator in case of a regulatory audit. When source documents are required for the continued 
care of the subject, appropriate copies should be made for storage outside of the study center. 
Biological samples retained by the investigator will be stored and maintained by the investigator 
until notification is received from the sponsor that the retained samples and records no longer 
need to be retained. The investigator must obtain written permission from the sponsor before 
disposing of any retained samples. The investigator should promptly notify the sponsor in the 
event of accidental loss or destruction of any study samples. With the permission of the sponsor, 
the retained samples may be transferred to an acceptable designee, such as another investigator, 
another institution, a contract laboratory, a contract storage site, or to the sponsor. 
13.8. 
Subject Screening Log 
The investigator must keep a record that lists all subjects who signed the informed consent 
(including those who did not undergo screening). For those subjects who declined to participate 
or were subsequently excluded from enrollment, the reasons for not enrolling in the study must 
be described. 
13.9. 
Modifications of the Protocol or Informed Consent Documents 
Protocol modifications, except those intended to reduce immediate risk to study participants, will 
be made only by the sponsor. All protocol modifications must be submitted to the IRB/IEC in 
accordance with local requirements. Except as noted in Section 13.4, IRB/IEC approval must be 
obtained before changes can be implemented.  
Informed consent documents cannot be changed without prior approval by the sponsor and the 
study center IRB/IEC. 
13.10. 
Case Report Forms 
Authorized study center personnel will complete eCRFs designed for this study according to the 
completion guidelines that will be provided. An eCRF is required and must be completed for 
each enrolled subject, with all required study data accurately recorded such that the information 
matches the data contained in medical records (e.g. physicians’ notes, nurses’ notes, study center 
charts, or other study-specific source documents). The investigator will ensure that the eCRFs 
are accurate, complete, legible, and completed in a timely fashion after each subject’s visit. The 
investigator will ensure that source documents that are required to verify the validity and 
completeness of data transcribed on the eCRFs are never obliterated or destroyed. As required by 
the protocol, eCRFs should also be completed for those subjects who fail to complete the study 


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(even during the screening period). If a subject withdraws from the study, the reason must be 
noted on the eCRF and thorough efforts should be made to clearly document outcome.  
The eCRFs for this study will exist within a web-based electronic data capture (EDC) system. 
After the investigator or the investigator’s designees (e.g. research coordinators) have been 
appropriately trained, they will be given access to the EDC system and will enter the data 
required by the protocol into the EDC system. Any change of data will be made via the EDC 
system, with all changes tracked by the system to provide an audit trail. 
The eCRF must be completed and signed by the principal investigator or sub-investigator (as 
appropriate) within a reasonable time period after data collection. This signature serves to attest 
that the information contained in the eCRF is true. 
13.11. 
Study Drug Accountability  
The disposition of all study drug (LAM-002A and placebo) should be documented from the time 
of receipt at the study center through subject administration. An investigational drug 
accountability log must be maintained for drug accountability. It is acceptable to use a protocol-
specific form or a study center form that captures the relevant information. Within the drug 
accountability log, the responsible study center personnel must maintain accurate records of the 
receipt of all study drug (LAM-002A and placebo) shipped by the sponsor (or its designee), 
including, but not limited to, the date received, bottle number, amount received, pertinent details 
about the condition of the study drug upon receipt based on visual inspection, and the disposition 
of the drug (e.g. to storage). If a study drug shipment arrives damaged, or if there are any other 
complaints relating specifically to the drug, a product complaint should be emailed to the 
sponsor or the sponsor’s representative. Study drug accountability records must also be 
maintained that include the subject number to whom the study drug is administered, and the date, 
quantity and bottle number of the study drug administered. 
Study personnel must ensure that study drug is kept in a secure locked area with access limited to 
authorized personnel. The study drug must not be used outside the context of this protocol. 
Under no circumstances should the investigator or study center personnel supply study drug to 
other investigators, subjects, or clinics, or allow the study drug to be used other than as directed 
by this protocol without the prior authorization from the sponsor.  
Depending upon the decision of the sponsor, remaining unused study drug supply will be 
returned to the sponsor or its designee after the study is completed or will be discarded or 
destroyed at the study center. After investigational product accountability has been performed, 
study drug disposal can occur per instructions provided by the sponsor. If the study drug is 
discarded or destroyed at the study center, standard institutional policy should be followed. At 
study initiation, the monitor will evaluate the study center’s standard operating procedure for 
study drug disposal/destruction in order to ensure that it complies with sponsor requirements. At 
the end of the study, following final drug inventory reconciliation by the monitor, the study 
center will dispose of and/or destroy all unused study drug supplies, including empty containers, 
per instructions provided by the sponsor. If the study center cannot meet sponsor requirements 
for disposal, arrangements will be made between the study center and the sponsor or its 
representative for destruction or return of unused study drug supplies. 
All study drug supplies and associated documentation will be periodically reviewed and verified 
by the study monitor over the course of the study. Study drug accountability records must be 


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readily available for inspection by the study monitor or other representatives of the sponsor or by 
regulatory authorities. 
13.12. 
Monitoring 
Representatives of the sponsor or its designee will monitor this study until completion. 
Monitoring may be conducted through telephonic, web-based, or personal visits with the 
investigator and study center staff as well as any appropriate communications by email, regular 
mail, or fax. The monitor is responsible for routine review of the eCRFs at regular intervals 
throughout the study to verify adherence to the protocol and the completeness, consistency, and 
accuracy of the data being entered on them. The purpose of monitoring is to ensure compliance 
with the protocol and the quality and integrity of the data.  
In accordance with GCP, the study monitor must have direct access to the investigator’s source 
documentation in order to verify the data recorded in the eCRFs for consistency. The investigator 
agrees to cooperate with the monitor to ensure that any problems detected in the course of these 
monitoring visits are resolved. 
13.13. 
Inspections 
The source documents for this trial must be made available to appropriately qualified personnel 
from the sponsor or its representatives, to IRB/IECs, and to regulatory authority or health 
authority inspectors as a part of their responsibility to protect human subjects in research. The 
investigator agrees to provide access to records, facilities, and personnel for the effective conduct 
of any inspection or audit to representatives of the sponsor and regulatory agencies. It is 
important that the investigator and relevant institutional personnel are available during 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. If the investigator is notified of an inspection by a regulatory authority the investigator 
agrees to notify the sponsor immediately.  
13.14. 
Data Management 
Electronic data capture will be used to enter study data into eCRFs and to transfer the data into a 
study-specific electronic database. During the data collection process, automated quality 
assurance programs will be used to identify missing data, out-of-range data, and other data 
inconsistencies. Requests for data clarification or correction will be forwarded to the 
investigative study center for resolution. As appropriate, eCRFs, listings, tables, and SAS 
datasets will be provided to the study centers for review. 
Quality assurance and quality control systems will be implemented and maintained according to 
written standard operating procedures to ensure that the data are generated, recorded, and 
reported in compliance with the protocol, GCP, and applicable regulatory requirements. Data 
collection and storage systems will provide audit trail, security mechanisms, and electronic 
signature capabilities that meet the requirements of FDA Title 21 of CFR Part 11 regarding 
electronic records and electronic signatures.  
Data security will be controlled through appropriate and specific restriction of access only to data 
and systems required by individual users to accomplish their roles in the data management 
process. Individual login and password protections will be employed at study centers and at the 
sponsor or its designee. The database will exist on physically secured servers. Data backups will 


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be done regularly and will be stored in separate facilities. Printed documents relating to the study 
will be secured when not under review.  
13.15. 
Clinical Trial Insurance 
The sponsor will secure clinical trial insurance. An insurance certificate will be made available 
to the participating study centers before study initiation. 
13.16. 
Communications with Regulatory Authorities 
The sponsor (or its designee) will assume responsibility for interactions with the FDA and any 
other relevant regulatory authorities. The sponsor will maintain an IND for LAM-002A in 
support of the study in the US and will maintain similar regulatory applications with other 
regulatory authorities as required for conduct of the study. In fulfilling these responsibilities, the 
sponsor (or a designee) will collect and assemble all required regulatory documents (e.g. Form 
FDA 1572, investigator financial disclosure forms, protocol and protocol amendments, 
investigator brochures, informed consent documents, annual reports) as required by regulation. 
The sponsor (or a designee) will also assume responsibility for AE reporting to regulatory 
authorities (as described in Section 9.8). 
13.17. 
Public Notification of Study Conduct 
Consistent with Section 113 of the Food and Drug Modernization Act of 1997 (FDAMA) and to 
ensure meeting the requirement of the International Committee of Medical Journal Editors 
(ICMJE) as a condition of consideration for publication of study results, the sponsor will register 
this protocol at the ClinicalTrials.gov website (or equivalent). If the protocol is registered at 
ClinicalTrials.gov, the sponsor will appropriately update the information at the website relating 
to study design and conduct during the course of the study. In order to facilitate this process, 
investigators will need to supply the sponsor with appropriate contact information for study 
center personnel. 
13.18. 
Study Reporting and Publication 
The sponsor may make information obtained during this study available in order to further the 
scientific or business needs of the company or as required by law or regulation. In this regard, 
the sponsor may provide study information to private or public organizations (e.g. business 
partners, collaborators, consultants, CROs, investors, other physicians who are conducting 
similar studies, funding organizations, regulatory authorities, or other government authorities). 
The results may also be used for papers, abstracts, posters or other material presented at 
scientific meetings or published in professional journals or as part of an academic thesis. 
The sponsor will prepare a clinical study report for submission to relevant regulatory agencies. 
The sponsor will ensure that the report meets the standards set out in the ICH Guideline for 
Structure and Content of Clinical Study Reports (ICH E3). An abbreviated report may be 
prepared in certain cases, as appropriate. 
The sponsor intends that the data from this study will be presented and published. Because the 
data will ultimately be part of a multicenter clinical trial, data from all study centers will be 
pooled and analyzed for a primary publication of the study results. The sponsor will coordinate 
and prepare this primary publication. The investigator agrees that the primary publication, which 


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will be coordinated by the sponsor, will be the first publication to present the pooled study 
results. Other ancillary publications or presentations relating to the pooled data from this study 
may be suggested by the investigator but can only be published with the express consent of the 
sponsor and the other investigators; such ancillary publications will also be coordinated by the 
sponsor.  
After the primary publication, or if the primary publication is not published within 2 years of 
termination of the study, the investigator may freely publish or present the results of his or her 
work conducted under the clinical trial agreement, subject to providing the sponsor with the 
opportunity to review the contents of any proposed presentation, abstract, or publication about 
such work, including any results of this study, in advance of any presentation or submission for 
publication. Within that advance notice period, the sponsor may review the proposed publication 
to identify patentable subject matter and/or any inadvertent disclosure of its confidential 
information, which must be redacted from any final publication or presentation. If necessary, to 
permit the preparation and filing of patent applications, the sponsor may elect an additional 
review period. The durations of the review periods will be specified in contractual agreements 
between each study center and the sponsor. 
In most cases, the principal investigators at the study centers with the highest accruals of eligible 
subjects and/or who have provided significant intellectual input into the study design, shall be 
listed as lead or senior authors on publications and presentations of study results. Sponsor 
clinical personnel, lead statistician, scientific personnel, or other staff members meeting the 
requirements for authorship may also be included in the list of authors. This custom can be 
adjusted upon mutual agreement of the authors and the sponsor. 
13.19. 
Study Discontinuation 
Both the investigator and the sponsor reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures. The investigator will be 
responsible for notifying the relevant study center IRB/IEC. The sponsor will be responsible for 
notifying the appropriate regulatory authorities. In terminating the study, the investigator and the 
sponsor will assure that adequate consideration is given to the protection of the subjects’ 
interests. As directed by the sponsor, all study materials must be collected and all eCRFs 
completed to the greatest extent possible.  


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14. 
BIBLIOGRAPHY 
Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, 
Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, 
Brummelkamp TR. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. 
Nature. 2011 Aug 24;477(7364):340-3. doi: 10.1038/nature10348. PMID: 21866103. 
Carpenter, JR; Kenward, MG; (2007) Missing data in randomised controlled trials: a practical 
guide. Health Technology Assessment Methodology Programme, Birmingham, p. 199. 
https://researchonline.lshtm.ac.uk/id/eprint/4018500.   
Clinical Trials Facilitation Group (CTFG). Recommendations related to contraception and 
pregnancy testing in clinical trials. 2014 Sep 15. Available at: 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf (accessed . 
2019 Dec 17). 
Food and Drug Administration (FDA). Drug development and drug interactions: Table of 
substrates, inhibitors and inducers. 2020 Mar 10. Available at: 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractio
nsLabeling/ucm093664.htm#4  
Ge M, Durham L.K., Meyer R.D., Xie W, Thomas N. “Covariate Adjusted Difference in 
Proportions from Clinical Trials Using Logistic Regression and Weighted Risk Difference” Drug 
Information Journal 2011 45: 481-493. https://doi.org/10.1177/009286151104500409 
Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. 
The New England journal of medicine. 2020 82:1708-1720. DOI: 10.1056/NEJMoa2002032 
Kang YL, Chou YY, Rothlauf PW, Liu Z, Piccinotti S, Soh TK, Cureton D, Case JB, Chen RE, 
Diamond MS, Whelan SPJ, Kirchhausen T. Inhibition of PIKfyve kinase prevents infection by 
EBOV and SARS-CoV-2. bioRxiv. doi: https://doi.org/10.1101/2020.04.21.053058. 2020 Apr 
Preprint 
Lachin JM.  Statistical considerations in the intent-to-treat principle. Controlled Clinical Trials. 
2000 21:167-89. 
Lan, K.K.G. and DeMets, D.L. 'Discrete sequential boundaries for clinical trials.' Biometrika, 
1983 70, pages. 659-663. 
Lauer SA, Grantz KH, Bi Q, et al. The Incubation Period of Coronavirus Disease 2019 
(COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Annals of 
internal medicine. 2020. 
Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel 
Coronavirus-Infected Pneumonia. The New England journal of medicine. 2020. 
Murray JL, Mavrakis M, McDonald NJ, Yilla M, Sheng J, Bellini WJ, Zhao L, Le Doux JM, 
Shaw MW, Luo CC, Lippincott-Schwartz J, Sanchez A, Rubin DH, Hodge TW. Rab9 GTPase is 
required for replication of human immunodeficiency virus type 1, filoviruses, and measles virus. 
J Virol. 2005 Sep;79(18):11742-51. PMID: 16140752 


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National Research Council. “The Prevention and Treatment of Missing Data in Clinical Trials.  
Panel on Handling Missing Data in Clinical Trials”.  Committee on National Statistics, Division 
of Behavioral and Social Sciences and Education.  Washington, DC: The National Academies 
Press, 2010. 
Nelson EA, Dyall J, Hoenen T, Barnes AB, Zhou H, Liang JY, Michelotti J, Dewey WH, 
DeWald LE, Bennett RS, Morris PJ, Guha R, Klumpp-Thomas C, McKnight C, Chen YC, Xu X, 
Wang A, Hughes E, Martin S, Thomas C, Jahrling PB, Hensley LE, Olinger  GG Jr, White JM. 
The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and 
infection. PLoS Negl Trop Dis. 2017 Apr 12;11(4):e0005540. PMID: 28403145 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, et al. Toxicity and response criteria of 
the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. 
Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J, Xiang Z, Mu Z, Chen X, 
Chen J, Hu K, Jin Q, Wang J, Qian Z. Characterization of spike glycoprotein of 2019-nCoV on 
virus entry and its immune cross-reactivity with spike glycoprotein of SARS-CoV. Nat 
Communications. 2020 Feb. Under Review 
Qiu, S., Leung, A., Bo, Y. et.al. Ebola virus requires phosphatidylinositol (3,5) bisphosphate 
production for efficient viral entry Virology, 2018, 513 17-28 
Riva L, Yuan S, Yin X, Martin-Sancho L, Matsunaga N, Burgstaller-Muehlbacher S, Pache L, 
De Jesus PP, Hull MV, Chang M, Chan JFW, Cao J, Poon VKM, Herbert K, Nguyen TT, Pu Y, 
Nguyen C, Rubanov A, Martinez-Sobrido L, Liu WC, Miorin L, White KM, Johnson JR, Benner 
C, Sun R, Schultz PG, Su A, Garcia-Sastre A, Chatterjee AK, Yuen K-Y, Chanda SK. A Large-
scale Drug Repositioning Survey for SARS-CoV-2 Antivirals. bioRxiv. doi: 
https://doi.org/10.1101/2020.04.16.044016. 2020 Apr Preprint 
Smith GB, Prytherch DR, Meredith P, Schmidt PE. Early warning scores: unravelling detection 
and escalation. Int J Health Care Qual Assur 2015;28:872–5. 
Wada Y, Lu R, Zhou D, Chu J, Przewloka T, Zhang S, Li L, Wu Y, Qin J, Balasubramanyam V, 
Barsoum J, Ono M. Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 
inhibitor. Blood. 2007 Feb 1;109(3):1156-1164. 
Wada Y, Cardinale I, Khatcherian A, Chu J, Kantor AB, Gottlieb AB, Tatsuta N, Jacobson E, 
Barsoum J, Krueger JG. Apilimod inhibits the production of IL-12 and IL-23 and reduces 
dendritic cell infiltration in psoriasis. PLoS One. 2012;7(4):e35069. PMID: 22493730 
WHO Master Protocol, 2020. “A Multi-center, Adaptive, Randomized, Double-Blind, Placebo-
Controlled Clinical Trial of the Safety and Efficacy of Investigational Therapeutics for the 
Treatment of COVID-19 in Hospitalized Subjects.” 
Woosley RL, Romero KA. Qtdrugs List, 2015 Jul 3, AZCERT, Inc., Available at: 
www.Crediblemeds.orgwww.Crediblemeds.org (accessed 27 Dec 2018). 


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15. 
APPENDICES 
15.1. 
Strong CYP3A Inhibitors and Inducers 
Effect on CYP3A  
Drug 
Strong CYP3A Inhibitors 
boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, 
grapefruit juice, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and 
ritonavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), 
posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and 
ritonavir), telithromycin, troleandomycin, voriconazole 
Strong CYP3A Inducers 
apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, 
St. John’s wort 
Reference: [FDA 2020] 
Abbreviation: CYP=cytochrome P450 enzyme 
 
 


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15.2. 
Drugs Known to Prolong the QT Interval and/or Cause Torsades De Pointes  
Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Amiodarone 
Cordarone®, Pacerone®, 
Nexterone® 
Antiarrhythmic 
Abnormal heart rhythm 
Anagrelide 
Agrylin®, Xagrid® 
Phosphodiesterase 3 
inhibitor 
Thrombocythemia 
Arsenic trioxide 
Trisenox® 
Anticancer 
Cancer (leukemia) 
Astemizole (removed 
from market) 
Hismanal® 
Antihistamine 
Allergic rhinitis 
Azithromycin 
Zithromax®, Zmax® 
Antibiotic 
Bacterial infection 
Bepridil (removed 
from market) 
Vascor® 
Antianginal 
Angina Pectoris (heart pain) 
Chloroquine 
Aralen® 
Antimalarial 
Malaria 
Chlorpromazine 
Thorazine®, Largactil®, 
Megaphen® 
Antipsychotic / 
Antiemetic 
Schizophrenia, nausea, many 
others 
Cilostazol 
Pletal® 
Phosphodiesterase 3 
inhibitor 
Intermittent claudication 
Ciprofloxacin 
Cipro®, Cipro-XR®, 
Neofloxin® 
Antibiotic 
Bacterial infection 
Cisapride (removed 
from market) 
Propulsid® 
Gastrointestinal 
stimulant 
Increase gastrointestinal 
motility 
Citalopram 
Celexa®, Cipramil® 
Antidepressant, 
selective serotonin 
reuptake inhibitor 
Depression 
Clarithromycin 
Biaxin®, Prevpac® 
Antibiotic 
Bacterial infection 
Cocaine 
Cocaine 
Local anesthetic 
Anesthesia (topical) 
Disopyramide 
Norpace® 
Antiarrhythmic 
Abnormal heart rhythm 
Dofetilide 
Tikosyn® 
Antiarrhythmic 
Abnormal heart rhythm 
Domperidone (only 
on non-US market) 
Motilium®, Motillium®, 
Motinorm Costi®, 
Nomit® 
Antinausea 
Nausea, vomiting 
Donepezil 
Aricept® 
Cholinesterase 
inhibitor 
Dementia (Alzheimer’s 
Disease) 
Dronedarone 
Multaq® 
Antiarrhythmic 
Abnormal heart rhythm 
Droperidol 
Inapsine®, Droleptan®, 
Dridol®, Xomolix® 
Antipsychotic / 
Antiemetic 
Anesthesia (adjunct), nausea 
Erythromycin 
E.E.S.®, Robimycin®, 
Emycin®, Erymax®, Ery-
Tab®, Eryc Ranbaxy®, 
Erypar®, Eryped®, 
Erythrocin Stearate 
Filmtab®, Erythrocot®, 
E-Base®, Erythroped®, 
Ilosone®, MY-E®, 
Pediamycin®, Zineryt®, 
Abboticin®, Abboticin-
ES®, Erycin®, PCE 
Dispertab®, Stiemycine®, 
Acnasol®, Tiloryth® 
Antibiotic 
Bacterial infection, increase 
gastrointestinal motility 


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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Escitalopram 
Cipralex®, Lexapro®, 
Nexito®, Anxiset-E® 
(India), Exodus® (Brazil), 
Esto® (Israel), Seroplex®, 
Elicea®, Lexamil®, 
Lexam®, Entact® 
(Greece), Losita® 
(Bangladesh), Reposil® 
(Chile), Animaxen® 
(Colombia), Esitalo® 
(Australia), Lexamil® 
(South Africa) 
Antidepressant, 
selective serotonin 
reuptake inhibitor 
Depression (major), anxiety 
disorders 
Flecainide 
Tambocor®, Almarytm®, 
Apocard®, Ecrinal®, 
Flécaine® 
Antiarrhythmic 
Abnormal heart rhythm 
Fluconazole 
Diflucan®, Trican® 
Antifungal 
Fungal infection 
Gatifloxacin 
(removed from 
market) 
Tequin® 
Antibiotic 
Bacterial infection 
Grepafloxacin 
Raxar® 
Antibiotic 
Bacterial infection 
Halofantrine 
Halfan® 
Antimalarial 
Malaria 
Haloperidol 
Haldol® (US & UK), 
Aloperidin®, 
Bioperidolo®, Brotopon®, 
Dozic®, Duraperidol® 
(Germany), Einalon S®, 
Eukystol®, Halosten®, 
Keselan®, Linton®, 
Peluces®, Serenace®, 
Serenase®, Sigaperidol® 
Antipsychotic 
Schizophrenia, agitation 
Ibogaine (only on 
non-US market) 
None 
Psychedelic 
Narcotic addiction, unproven 
Ibutilide 
Corvert® 
Antiarrhythmic 
Abnormal heart rhythm 
Levofloxacin 
Levaquin®, Tavanic® 
Antibiotic 
Bacterial infection 
Levomepromazine 
(methotrimeprazine) 
only on non-US 
market) 
Nosinan®, Nozinan®, 
Levoprome® 
Antipsychotic 
Schizophrenia 
Levosulpiride (only 
on non-US market) 
Lesuride®, Levazeo®. 
Enliva® (with rabeprazole) 
Antipsychotic 
Schizophrenia 
Levomethadyl 
acetate (removed 
from market) 
Orlaam® 
Opioid agonist 
Narcotic dependence 
Mesoridazine 
(removed from 
market) 
Serentil® 
Antipsychotic 
Schizophrenia 
Methadone 
Dolophine®, Symoron®, 
Amidone®, Methadose®, 
Physeptone®, Heptadon® 
Opioid agonist 
Narcotic dependence, pain 


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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Moxifloxacin 
Avelox®, Avalox®, 
Avelon® 
Antibiotic 
Bacterial infection 
Ondansetron 
Zofran®, Anset®, 
Ondemet®, Zuplenz®, 
Emetron®, Ondavell®, 
Emeset®, Ondisolv®, 
Setronax® 
Antiemetic 
Nausea, vomiting 
Oxaliplatin 
Eloxatin® 
Antineoplastic 
Agent 
Cancer 
Papaverine HCl 
none 
Vasodilator, 
Coronary 
Diagnostic adjunct 
Pentamidine 
Pentam® 
Antifungal 
Fungal infection 
(Pneumocystis pneumonia) 
Pimozide 
Orap® 
Antipsychotic 
Tourette’s Disorder 
Probucol (removed 
from market) 
Lorelco® 
Antilipemic 
Hypercholesterolemia 
Procainamide 
Pronestyl®, Procan® 
Antiarrhythmic 
Abnormal heart rhythm 
Propofol 
Diprivan®, Propoven® 
Anesthetic, general 
Anesthesia 
Quinidine 
Quinaglute®, Duraquin®, 
Quinact®, Quinidex®, 
Cin-Quin®, Quinora® 
Antiarrhythmic 
Abnormal heart rhythm 
Roxithromycin (only 
on non-US market) 
Rulide®, Xthrocin®, 
Roxl-150®, Roxo®, 
Surlid®, Rulide®, 
Biaxsig®, Roxar®, 
Roximycinv®, 
Roxomycin®, Rulid®, 
Tirabicin®, Coroxin® 
Antibiotic 
Bacterial infection 
Sevoflurane 
Ulane®, Sojourn® 
Anesthetic, general 
Anesthesia 
Sotalol 
Betapace®, Sotalex®, 
Sotacor® 
Antiarrhythmic 
Abnormal heart rhythm 
Sparfloxacin 
(removed from 
market) 
Zagam® 
Antibiotic 
Bacterial infection 
Sulpiride (only on 
non-US market) 
Dogmatil®, Dolmatil®, 
Eglonyl®, Espiride®, 
Modal®, Sulpor® 
Antipsychotic, 
atypical 
Schizophrenia 
Sultopride (only on 
non-US market) 
Barnetil®, Barnotil®, 
Topral® 
Antipsychotic, 
atypical 
Schizophrenia 
Terfenadine 
(removed from 
market) 
Seldane® 
Antihistamine 
Allergic rhinitis 
Terlipressin (only on 
non-US market) 
Teripress®, Glypressin®, 
Terlipin®, Remestyp®, 
Tresil®, Teriss®, and 
others 
Vasoconstrictor 
Septic shock 
Terodiline (only on 
non-US market) 
Micturin®, Mictrol® (not 
bethanechol) 
Muscle relaxant 
Bladder spasm 


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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Thioridazine 
Mellaril®, Novoridazine®, 
Thioril® 
Antipsychotic 
Schizophrenia 
Vandetanib 
Caprelsa® 
Anticancer 
Cancer (thyroid) 
Note: Includes those drugs known to prolong the cardiac QT interval or cause TdP (Woosley 2018> 8 
days8). 
Abbreviation: QT: Time of start of Q wave until end of T wave in the heart’s electrical cycle; TdP: 
Torsades de Pointes; UK: United Kingdom; US: United States  
 
 
 


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15.3. 
ECOG Performance Status 
Grade 
Description 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g. light housework, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work 
activities. Up and about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or 
chair 
5 
Dead 
Reference: [Oken 1982] 
 
 


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15.4. 
Protocol Amendment History 
15.4.1. 
Summary of Changes: Version 2 (10 July 2020) 
 
Overall Rationale for the Amendment 
This amendment clarifies wording in the 22 June 2020 version of the clinical protocol and 
addresses requests received from the FDA following FDA review of the 22 June 2020 version of 
the clinical protocol. 
 
Description of Changes 
Section or Table Number 
Description of Change 
Brief Rationale 
Various sections 
• Changes to protocol versions and dates were 
made 
• Minor typographical, syntax, or formatting 
corrections were made  
To make appropriate 
editorial modifications 
Table 1: Schedule of Activities 
3.1 Primary Objective 
3.2 Secondary Objectives 
4.1 Primary Endpoint 
4.2 Secondary Endpoints 
4.3 Exploratory Endpoints 
5.1 Study Design 
5.4 Rationale for Study Design 
11 Efficacy Assessments 
12 Statistical Considerations 
• Timing of sampling were clarified or 
updated  
• Assessment of mRNA from nasopharyngeal 
swab and saliva on Day 28 was added 
• Cytokine analysis on Day 4 was added 
• Definition of clinical status endpoint was 
corrected 
• Definition of oxygen saturation endpoint 
was corrected 
• SARS-CoV-2 viral load endpoints relating 
to nasopharyngeal and salivary samples 
were added or clarified 
• Definition of cytokine endpoint was 
corrected 
• Definition of viral genome sequence 
endpoint was corrected  
To ensure consistency of 
assessment and to address 
FDA requests 
Table 1: Schedule of Activities 
• Instructions regarding timing of screening 
ECG, hematology testing, and serum 
chemistry testing were modified 
To define allowable 
screening window for these 
tests 
Table 1: Schedule of Activities 
• Requirements for fasting during 
pharmacokinetic assessments were included 
To ensure consistency of 
fed-fasting status during 
pharmacokinetic 
evaluations 
6.1 Inclusion Criteria 
• Modified definition of symptoms of mild 
COVID-19 disease 
To provide clarification 
Table 1: Schedule of Activities 
8.1. Supportive Care 
• Discussion of use of illicit drugs removed 
To delete unneeded text 
9.1.2 Serious Adverse Event 
• Text was modified to indicate that deaths 
due to COVID-19 (rather than cancer 
progression) may be defined as SAEs 
To correct SAE definition 


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Section or Table Number 
Description of Change 
Brief Rationale 
9.7.2 Pregnancy 
• Reporting requirements for pregnancy in 
female partners of male subjects were 
updated 
To ensure timely reporting 
of such occurrences 
12.4.5 Exploratory Endpoints 
• Erroneous reference to exploratory 
objectives was removed and analyses were 
referenced to the SAP or separate reports 
To clarify plan for analyses 
of exploratory endpoints 
12.4.10 Other Analyses 
• Section was removed 
To delete unneeded text 
13.11 Study Drug Accountability 
• Instructions for recording of bottle numbers 
were included 
• Instructions for disposition of study drug 
were updated 
To clarify appropriate 
procedures for study drug 
accountability 
 
 


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Version 4 (16 October 2020) 
15.4.2. 
Summary of Changes: Version 3 (31 August 2020) 
 
Overall Rationale for the Amendment 
This amendment incorporates the following changes to the protocol.  
 
Description of Changes 
Section or Table Number 
Description of Change 
Brief Rationale 
Various sections 
• Changes to protocol versions and dates were 
made 
• Minor typographical, syntax, or formatting 
corrections were made  
• Changes in the synopsis were made 
consistent with changes to the body of the 
protocol document 
To make appropriate 
editorial modifications 
Table 1: Schedule of Activities 
• Instructions were included to described 
activities to be performed in a subject 
terminating from the study prematurely 
• The timing of the LAM-002A compliance 
checks was clarified 
• Incorrect mention of urinalysis was removed 
from the table 
• It was indicated that screening and baseline 
visits could occur on the same day. 
• Instructions for drug dispensing were 
clarified 
• It was indicated that subjects taking only a 
single dose of study drug on Day 1 due to 
initiation late in the day should continue 
drug through Day 11 in order to ensure 
completion of a full 20 doses of study drug 
administration. 
• It was indicated that compliance would be 
assessed at each visit throughout the dosing 
period. 
• To enhance flexibility in study conduct, it 
was noted that obtaining nasopharyngeal 
swabs on Days 6 and 8 would be optional; 
saliva would still be collected at these time 
points, thus allowing an alternative and 
better tolerated evaluation of viral load 
To provide appropriate 
direction to investigational 
personnel 
2.1 Study Rationale 
5.1 Study Design 
6.1 Inclusion Criteria (Number 4) 
• The permissible duration of COVID-19 
symptoms before study enrollment was 
increased from 4 days to 8 days 
To permit greater 
flexibility in prestudy 
symptom duration to 
enhance ease of subject 
enrollment. 


Investigational Drug: LAM-002A 
 
Study Protocol: LAM-002A-CVD-CLN01 
AI Therapeutics, Inc. 
CONFIDENTIAL 
Page 88 of 91  
Version 4 (16 October 2020) 
Section or Table Number 
Description of Change 
Brief Rationale 
3 Study Objectives 
4 Study Endpoints 
5.Study Design 
11 Efficacy Assessments 
12 Statistical Considerations 
• Multiple sections of the protocol were 
modified to indicate that that the study 
would focus on analyzing subjects with a 
baseline viral load of >105 copies/mL; 
accordingly, the total sample size was 
increased to ~284 subjects to ensure accrual 
of the sample of  ~142 subjects with 
baseline viral load of >105 copies/mL 
required to perform the analysis consistent 
with the primary hypothesis of the study 
• An antiviral efficacy analysis population 
consisting of all randomized subjects with a 
baseline viral load >105 copies/mL was 
added 
• Clarifications were provided regarding the 
populations (ITT, Antiviral Efficacy, PP) to 
be analyzed for each endpoint 
To ensure that there would 
be sufficient subjects with 
an adequate viral load to 
allow evaluation of 
LAM-002A effects and to 
update and clarify the 
populations in which 
specific analyses would be 
performed 
6.1 Inclusion Criteria (Number 3) 
• The types and specificity of the descriptions 
of permissible symptoms of COVID-19 
necessary for study enrollment was 
enhanced 
To improve clarity and 
enhance enrollment 
potential 
8.2.3 Dose Schedule Interruptions 
and Vomited Doses 
• It was indicated that subjects taking only a 
single dose of study drug on Day 1 due to 
initiation late in the day could skip taking a 
2nd dose on that day, could resume study 
drug administration on the morning of Day 2 
and continue drug through Day 11 in order 
to ensure completion of a full 20 doses of 
study drug administration. 
To provide clarification to 
study center personnel and 
study subjects regarding 
permitted variations in the 
dosing schedule  
12.4.7 Plan for Missing Data 
• The reasons for not considering a subject for 
analysis were updated to include a false 
positive test for SARS-CoV-2 (in additional 
to withdrawal of consent or lost to follow-
up). 
To clarify the analysis plan 
14 Bibliography 
• An explanatory reference was added 
To document the approach 
to logistic regression 
analysis 
 
 


Investigational Drug: LAM-002A 
 
Study Protocol: LAM-002A-CVD-CLN01 
AI Therapeutics, Inc. 
CONFIDENTIAL 
Page 89 of 91  
Version 4 (16 October 2020) 
15.4.3. 
Summary of Changes: Version 4 (16 October 2020) 
 
Overall Rationale for the Amendment 
This amendment incorporates the following changes to the protocol.  
 
Description of Changes 
Section or Table Number 
Description of Change 
Brief Rationale 
Various sections 
• Changes to protocol versions and dates were 
made. 
• Minor typographical, syntax, or formatting 
corrections were made. 
• Changes in the synopsis were made 
consistent with changes to the body of the 
protocol document. 
To make appropriate 
editorial modifications 
Table 1: Schedule of Activities 
• Day 6 and 8 were changed to remote visits. 
• Footnote d of the Schedule of Activities was 
added to clarify an optional provision for a 
confirmatory viral test for those who do not 
have a documentation of a positive test. 
• Vital signs/oxygen saturation on Days 6 and 
Days 8 were removed in Footnote i. 
• Telehealth visits on Days, 6, 8 and 22 were 
noted in the Schedule of Activities table 
header.  
• Footnote j was clarified to indicate that the 
AE review on Days 6, 8 and 22 will be via 
telehealth/telephone. 
• Footnote k was changed to indicate that the 
concomitant medication review on Days, 6, 
8 and 22 will be via telehealth/telephone. 
•  Footnote r was added regarding subject 
COVID-19 symptoms diary . 
• Footnote v was added for saliva sample 
collection on Days 1, 4, 11, and 28. 
To provide appropriate 
direction to investigational 
personnel 
Section 1: Protocol synopsis 
• The secondary objective for antiviral 
assessment  from nasopharyngeal samples 
on Days 11 and 28 were removed. 
• The secondary objective for assessment of 
O2 saturation was changed from Days 1, 4, 
6, 8 and 11 to Days 1, 4, and 11. 
• The exploratory objective for antiviral 
assessment was hanged from 
nasopharyngeal samples on Day 6 to saliva 
samples on Day 4. 
• The exploratory objective for antiviral 
assessment using nasopharyngeal samples 
on Day 8 was changed to saliva samples on 
Day 11. 
To provide appropriate 
direction to investigational 
personnel. 
To clarifies timing of 
antiviral assessments and 
the type of sample 
(whether nasopharyngeal 
vs saliva). 
To add an alternative 
nasopharyngeal endpoint. 


Investigational Drug: LAM-002A 
 
Study Protocol: LAM-002A-CVD-CLN01 
AI Therapeutics, Inc. 
CONFIDENTIAL 
Page 90 of 91  
Version 4 (16 October 2020) 
Section or Table Number 
Description of Change 
Brief Rationale 
• A separate exploratory objective for saliva 
antiviral assessment was specified at 
Day  28. 
• An antiviral assessment in saliva samples 
based on AUC analysis added 
• An exploratory anti-viral assessment was 
added based on the difference in the 
proportion of subjects with SARS-CoV-2 
viral load <LLOQ between the LAM-002A 
and the placebo as measured by a qRT-PCR 
test from nasopharyngeal samples at Day 4. 
• A requirement was added for written 
documentation of SARS-CoV-2 infection 
via a validated test. 
Section 3: Study Objectives 
• Secondary and exploratory objectives were 
revised to align to objectives in synopsis 
(Section 1) 
To align study objectives 
with those in the synopsis 
Section 4: Study Endpoints 
• Primary endpoint: Added clarifying 
language around quantitation of viral load  
• Secondary Endpoint for antiviral assessment  
from nasopharyngeal samples on Days 11 
and 28, and by AUC analysis was removed 
• Secondary Endpoint for assessment of O2 
saturation was changed from Days 1, 4, 6, 8 
and 11 to Days 1, 4, and 11. 
• Exploratory endpoints for assessment of 
viral load from nasopharyngeal samples at 
Day 6 and Day 8 were removed. 
• The endpoint of difference in proportion of 
subjects with SARS-CoV-2 viral load 
<LLOQ between the LAM-002A and the 
placebo as measured by a qRT-PCR test 
from nasopharyngeal samples at Day 4 arm 
was added. 
To clarify changes in study 
endpoints and add an 
alternative exploratory 
endpoint  
Section 5.1 Study Design 
• Paragraph 1: Text was added regarding  
asymptomatic subjects with a positive test. 
• Paragraph 2: Information was added 
regarding randomization via a centralized 
randomization system. 
• Paragraph 2: Stratification by site was 
removed. 
To allow flexibility in 
randomization 
Section 5.2 Study Conduct 
• Paragraph 3: It was clarified that a CRO 
other than Yale University could become 
involved in conduct of the study. 
To permit alternatives 
approaches to operational 
coordination 
Section 6.1 Inclusion Criteria 
• The need for written documentation of a 
positive test was included. 
To include more 
outpatients and document 
positive infection. 


Investigational Drug: LAM-002A 
 
Study Protocol: LAM-002A-CVD-CLN01 
AI Therapeutics, Inc. 
CONFIDENTIAL 
Page 91 of 91  
Version 4 (16 October 2020) 
Section or Table Number 
Description of Change 
Brief Rationale 
• Text was added to allow for inclusion of 
asymptomatic patients. 
Section 7.1 Randomization 
• Text was added to accommodate more 
clinical sites. 
To provide additional 
operational flexibility 
Section 8.1.4 Shipping Storage 
and Stability 
• Paragraph 2: Reference to Yale University 
was replaced with more general language to 
add operational flexibility 
To clarify change in 
operational coordination 
Section 9.7.3 
• Management of contact information for 
SAEs and pregnancy was changed from 
Yale University to a CRO 
To clarify change in 
operational coordination 
Section 10.1 Laboratory and 
Other Parameters to be Assessed 
• A footnote was added to Table 6 
(Laboratory and Other Parameters to be 
Assessed), clarifying that samples for these 
exploratory endpoints will be collected but 
analysis of the samples is optional 
To provide clarity to 
investigation personnel 
Section 10.1 Methods and 
Analytes 
• Paragraphs were added to clarify method of 
viral load measurements and limits of 
detection (LLOQ), details of 
pharmacodynamic and biomarker 
measurements, and optional nature of some 
assays 
To provide clarity to 
investigation personnel 
Section 11.1 
• Additional text was added to define the 
analysis of primary endpoint 
To provide clarity on 
endpoint 
Section 12 Statistical 
Considerations 
• Paragraph 2: stratification by site was 
removed. 
• Changes in statistical parameters were 
incorporated. 
To clarify stratification and 
adjust statistical analysis 
Section 12.4.4 Analysis of 
Secondary Outcomes 
• The secondary endpoint for analysis of 
nasopharyngeal viral load analysis at Day 11 
and by AUCDay1-Day11 was removed. 
• It was specified that analyses of secondary 
endpoints will be in the antiviral efficacy 
analysis population (population with viral 
load >105 copies/mL). 
To provide clarity to 
investigation personnel 
To clarify the statistical 
analysis population for 
secondary endpoints 
Section 12.5 Interim Analyses 
• Potential DSMB decisions regarding 
interim analyses were updated. 
To clarify statistical 
analysis population for 
interim analysis. 
Section 14 Bibliography 
• The Carpenter et al. reference was added. 
To provide support for the 
statistical approach.