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

Leidos

Status and phase: Terminated; Phase 2

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

Treatments: Drug: Famotidine; Drug: Celecoxib; Drug: Placebo

Study type: Interventional

Funder types: Industry; Other U.S. Federal agency

Identifiers

NCT05077969

LDOS-21-001-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 4 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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)

  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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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4 participants in 2 patient groups, including a placebo group

Group 1 (Study Product)

Experimental group

Description:

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.

Treatment:

Drug: Celecoxib

Drug: Famotidine

Group 2 (Reference Therapy)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo