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

Sponsor

Leidos Life Sciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT05077969

Collaborator

United States Department of Defense (U.S. Fed)

Enrollment

Locations

Arms

6.3

Actual Duration (Months)

0.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Famotidine Drug: Celecoxib Drug: Placebo	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants randomized 1:1, study drug:placeboParticipants randomized 1:1, study drug:placebo

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Double-blind

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 29, 2021

Actual Primary Completion Date :

Jun 28, 2022

Actual Study Completion Date :

Jul 8, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 (Study Product) 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 80 mg tablet, QID for 14 days Other Names: Pepcid Drug: Celecoxib 400 mg (initial dose), then 200 mg capsule, BID for 5 days Other Names: Celebrex
Placebo Comparator: 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.	Drug: Placebo tablet, QID for 14 days; capsule, BID for 5 days

Arm

Intervention/Treatment

Experimental: Group 1 (Study Product)

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

80 mg tablet, QID for 14 days

Other Names:

Pepcid

Drug: Celecoxib

400 mg (initial dose), then 200 mg capsule, BID for 5 days

Other Names:

Celebrex

Placebo Comparator: 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.

Drug: Placebo

tablet, QID for 14 days; capsule, BID for 5 days

Outcome Measures

Primary Outcome Measures

Number of patients with at least one COVID-19-related medically attended contact due to increased COVID-19 symptom severity [Through Day 30]
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.
Number of patients with at least one COVID-19-related medically attended contact due to death (all-cause mortality). [Through Day 30]
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.

Secondary Outcome Measures

Incidence of Treatment-Emergent Serious Adverse Events (SAE) as assessed by participant withdrawal [90 days]
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.
Incidence of death [90 days]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Integrated Therapeutic Solutions USA, Inc.	Newport Beach	California	United States	92603
2	Integrated Therapeutic Solutions USA, Inc.	Miami	Florida	United States	33126
3	Integrated Health Solutions USA, Inc.	Atlanta	Georgia	United States	30363
4	Integrated Therapeutic Solutions USA, Inc	Hazlehurst	Georgia	United States	31539
5	Integrated Therapeutic Solutions USA, Inc.	Chicago	Illinois	United States	60611
6	Integrated Therapeutic Solutions USA, Inc	Prospect	Kentucky	United States	40059
7	Integrated Therapeutic Solutions USA, Inc	Frederick	Maryland	United States	21702
8	Integrated Therapeutic Solutions USA, Inc	Gaithersburg	Maryland	United States	20878
9	Integrated Therapeutic Solutions USA, Inc	Rockville	Maryland	United States	20850
10	Integrated Therapeutic Solutions USA, Inc	Dearborn	Michigan	United States	48120
11	Integrated Therapeutic Solutions USA, Inc.	Newark	New Jersey	United States	07102
12	Integrated Therapeutic Solutions USA, Inc.	New York	New York	United States	10005
13	Integrated Therapeutic Solutions USA, Inc.	Huntingdon	Pennsylvania	United States	16652
14	Integrated Therapeutic Solutions USA, Inc.	Charleston	South Carolina	United States	29414
15	Integrated Therapeutic Solutions USA, Inc.	Dallas	Texas	United States	75219