Clinical trial NCT05077969: Leidos-Enabled Adaptive Protocol (LEAP-CT) for Evaluation of Post-exposure Prophylaxis for Newly-infected COVID-19 Patients
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Keywords: COVID-19
COVID
COVID19
SARS-CoV-2
Lead sponsor: Leidos Life Sciences
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
First posted: 2021-10-14
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants randomized 1:1, study drug:placebo
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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)

  1. drugs dependent on gastric pH for absorption, e.g., dasatinib, delavirdine, mesylate, cefditoren, and fosamprenavir;
  2. tizanidine (CYP1A2) substrate;
  3. drugs that interfere with hemostasis (e.g., warfarin, aspirin, selective serotonin reuptake inhibitors \[SSRIs\]/serotonin norepinephrine reuptake inhibitors (SNRIs\]);
  4. angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), or beta-blockers;
  5. diuretics;
  6. 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:

  1. Famotidine or celecoxib hypersensitivity
  2. Retinopathy, visual field or visual acuity disturbances
  3. History of cardiovascular disease, such as congestive heart failure, QT prolongation, myocardial infarction, bradycardia (\<50 bpm), ventricular tachycardia, other arrhythmias
  4. Myasthenia gravis
  5. Psoriasis or porphyria
  6. History of renal failure/dialysis or a glomerular clearance \<60 mL/min
  7. History of severe hypoglycemia
  8. Moderate or severe hepatic impairment, e.g., Child-Pugh Class B or C
  9. 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

Primary outcomes:
measure: Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Increased COVID-19 Symptom Severity
timeFrame: Through Day 30
measure: Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Death (All-cause Mortality).
timeFrame: Through Day 30
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Serious Adverse Events (SAE) as Assessed by Participant Withdrawal
timeFrame: 90 days
measure: Incidence of Death
timeFrame: 90 days
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Integrated Therapeutic Solutions USA, Inc.
state: California
city: Miami
country: United States
facility: Integrated Therapeutic Solutions USA, Inc.
state: Florida
city: Atlanta
country: United States
facility: Integrated Health Solutions USA, Inc.
state: Georgia
city: Hazlehurst
country: United States
facility: Integrated Therapeutic Solutions USA, Inc
state: Georgia
city: Chicago
country: United States
facility: Integrated Therapeutic Solutions USA, Inc.
state: Illinois
city: Prospect
country: United States
facility: Integrated Therapeutic Solutions USA, Inc
state: Kentucky
city: Frederick
country: United States
facility: Integrated Therapeutic Solutions USA, Inc
state: Maryland
city: Gaithersburg
country: United States
facility: Integrated Therapeutic Solutions USA, Inc
state: Maryland
city: Rockville
country: United States
facility: Integrated Therapeutic Solutions USA, Inc
state: Maryland
city: Dearborn
country: United States
facility: Integrated Therapeutic Solutions USA, Inc
state: Michigan
city: Newark
country: United States
facility: Integrated Therapeutic Solutions USA, Inc.
state: New Jersey
city: New York
country: United States
facility: Integrated Therapeutic Solutions USA, Inc.
state: New York
city: Huntingdon
country: United States
facility: Integrated Therapeutic Solutions USA, Inc.
state: Pennsylvania
city: Charleston
country: United States
facility: Integrated Therapeutic Solutions USA, Inc.
state: South Carolina
city: Dallas
country: United States
facility: Integrated Therapeutic Solutions USA, Inc.
state: Texas
Study officials:
affiliation: Leidos, Inc.
name: Brian A Roberts, MS, PMP
role: STUDY_DIRECTOR
References: