Leidos-Enabled Adaptive Protocol (LEAP-CT) for Evaluation of Post-exposure Prophylaxis for Newly-infected COVID-19 Patients (Addendum 2)

Study Overview
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Brief Summary
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This study is designed to test the efficacy and safety of combinations of two well-understood agents - famotidine and celecoxib. Each of these agents separately demonstrate clinical activity in mitigating COVID-19 disease symptoms or severity, and each of which appear to have separate and complementary mechanisms of action.

Detailed Description
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Qualifying patients will have been confirmed positive for COVID-19 and have symptoms of World Health Organization (WHO) Ordinal Scale for Clinical Improvement with scores of ≤3 on the 11-point scale and will be randomly assigned, in a 1:1 ratio, to one of two regimens, with 659 participants per group, as follows: Group 1 (study product) participants will receive 80 mg famotidine by mouth (PO) 4 times per day (QID) + 400 mg celecoxib as a first dose, followed by 200 mg celecoxib (PO) 2 times per day (BID), for 5 days. Following this 5-day period, participants will continue their famotidine treatment for an additional 9 days. Group 2 (reference therapy) participants will receive matching placebos QID and BID, for 5 days. Following this 5-day period, participants will continue to receive matching famotidine placebo, QID, for an additional 9 days. Safety and efficacy of famotidine and celecoxib will be evaluated. This is a completely virtual trial and you can participate from your own home. Please call 1-888-370-9330 to speak to someone regarding study participation in your area.

Official Title
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A Virtual Phase 2 Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of the Combination of Famotidine and Celecoxib as a Post-exposure Prophylaxis (PEP) for Newly-infected COVID-19 Patients

Conditions
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2019 Novel Coronavirus Disease, 2019 Novel Coronavirus Infection, 2019-nCoV Disease, 2019-nCoV Infection, COVID-19, COVID-19 Pandemic, COVID-19 Virus Disease, COVID-19 Virus Infection, Covid19, Coronavirus Disease 2019, SARS-CoV2 Infection, SARS-CoV-2 Acute Respiratory Disease

Intervention / Treatment
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* Drug: Famotidine
* Drug: Celecoxib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants must be at least 18 years of age, inclusive, at the time of signing the informed consent form. Confirmed SARS-CoV-2 polymerase chain reaction (PCR) positive patient within 5 days of enrollment, as shown by medical history and reported PCR test result. Reports having one or more symptoms consistent with SARS-CoV-2, as defined in Master Protocol Appendix 3 Table 4. COVID-19 diagnosis must be WHO grade ≤3. Contraceptive use by men or women should be consistent with Appendix 4 of the Master protocol (LDOS-21-001). Reliable access to the Internet via a browser installed on personal device or computer. Capable of understanding and providing signed informed consent. Exclusion Criteria: Pregnancy or breastfeeding Ongoing antiviral or antiretroviral treatment Known history of HIV Ongoing anti-inflammatory treatment that cannot be temporarily discontinued during the study. This includes nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids - including Dexamethasone (dexamethasone administration restricted to recommended standard of care use per NIH COVID-19 Guidelines) drugs dependent on gastric pH for absorption, e.g., dasatinib, delavirdine, mesylate, cefditoren, and fosamprenavir; tizanidine (CYP1A2) substrate; drugs that interfere with hemostasis (e.g., warfarin, aspirin, selective serotonin reuptake inhibitors [SSRIs]/serotonin norepinephrine reuptake inhibitors (SNRIs]); angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), or beta-blockers; diuretics; digoxin Ongoing treatment that cannot be temporarily discontinued during the study, with: antimalarials, antiarrhythmics, tricyclic antidepressants, natalizumab, quinolones, macrolides, agalsidase alfa and beta Ongoing famotidine or celecoxib or other COVID-19 clinical investigational treatment(s) within the past 30 days, or current participation in another investigational clinical trial History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs History of immunosuppression Rejection of participation by Principal Investigator or Sponsor Any contraindication for famotidine or celecoxib treatment: Famotidine or celecoxib hypersensitivity Retinopathy, visual field or visual acuity disturbances History of cardiovascular disease, such as congestive heart failure, QT prolongation, myocardial infarction, bradycardia (<50 bpm), ventricular tachycardia, other arrhythmias Myasthenia gravis Psoriasis or porphyria History of renal failure/dialysis or a glomerular clearance <60 mL/min History of severe hypoglycemia Moderate or severe hepatic impairment, e.g., Child-Pugh Class B or C Known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history or experience with other CYP2C9 substrates, such as warfarin and phenytoin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants randomized 1:1, study drug:placebo
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (Study Product)<br>Participants will receive 80 mg famotidine (PO) QID and 400 mg celecoxib as a first dose, followed by 200 mg (PO) BID celecoxib, for 5 days. Following this 5-day period, participants will continue their famotidine treatment for an additional 9 days. | Drug: Famotidine<br>* 80 mg tablet, QID for 14 days<br>* Other names: Pepcid;Drug: Celecoxib<br>* 400 mg (initial dose), then 200 mg capsule, BID for 5 days<br>* Other names: Celebrex;|
| Placebo Comparator: Group 2 (Reference Therapy)<br>Participants will receive matching placebos QID and BID, for 5 days. Following this 5-day period, participants will continue to receive matching famotidine placebo, QID, for an additional 9 days. | Drug: Placebo<br>* tablet, QID for 14 days; capsule, BID for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with at least one COVID-19-related medically attended contact due to increased COVID-19 symptom severity | Medically attended contact will be measured in whole numbers and reported as 1 medically attended contact each time, in the electronic data capture system for all study participants. | Through Day 30 | 
| Number of patients with at least one COVID-19-related medically attended contact due to death (all-cause mortality). | Medically attended contact will be measured in whole numbers and reported as 1 medically attended contact in the electronic data capture system for all study participants. | Through Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Serious Adverse Events (SAE) as assessed by participant withdrawal | Study discontinuation will be measured in whole units, by number of participants who are removed with the reason of SAE and captured by the electronic data capture system. | 90 days | 
| Incidence of death | Deaths will be captured by whole numbers, by number of participants who are removed from the study with reason as death in the electronic data capture system. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, COVID, COVID19, SARS-CoV-2