A Phase 2 Randomized, Single-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of the Combination of Famotidine and Celecoxib as a Treatment in Moderate-to-severe Patients Hospitalized for COVID-19
Overview
- Phase
- Phase 2
- Intervention
- Famotidine
- Conditions
- 2019 Novel Coronavirus Disease
- Sponsor
- Leidos Life Sciences
- Primary Endpoint
- Time-to-event to achieve WHO level ≤3
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
Brief Summary
This study is designed to test the efficacy and safety of combinations of two well-understood agents - famotidine and celecoxib in patients hospitalized with moderate-to-severe COVID-19 (based on World Health Organization [WHO] Ordinal Scale for Clinical Improvement). Both famotidine and celecoxib separately demonstrate clinical activity in mitigating COVID-19 disease symptoms or severity, and appear to have separate and complementary mechanisms of action.
Detailed Description
Participants will be randomly assigned, in a 1:1 ratio, to one of two regimens, with 202 subjects per group as follows: Group 1 (study product) subjects 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, subjects will continue their famotidine treatment for an additional 9 days. Group 2 (reference therapy) subjects will receive matching placebos QID and BID, for 5 days. Following this 5-day period, subjects will continue to receive matching famotidine placebo, QID, for an additional 9 days. Safety, efficacy and pharmacokinetics of famotidine and celecoxib will be evaluated. All participants will receive the standard of care (SOC), which typically consists of remdesivir, decadron (dexamethasone), lovenox, tociluzimab, and convalescent plasma. At the discretion of the investigator, study treatment can be stopped and dexamethasone initiated in study participants who require supplemental oxygen (WHO 5) as outlined in the NIH COVID-19 Treatment Guidelines. Investigators are required to stop study treatment and initiate dexamethasone, as indicated in participants who require high-flow oxygen (WHO 6), non-invasive ventilation (NIV; WHO 6), invasive mechanical ventilation (WHO 7-8) or extracorporeal membrane oxygenation (ECMO; WHO 9), in accordance with the NIH COVID-19 Treatment Guidelines. The NIH COVID-19 Treatment Guidelines recommend against the use of dexamethasone only in hospitalized patients not requiring supplemental oxygen (WHO 4).
Investigators
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 COVID-19 or symptom onset within 7 days of hospitalization, as shown by medical history, physical exam, and laboratory tests (PCR), and who have been hospitalized for COVID-19 at WHO Grade 4-
- •Contraceptive use by men or women should be consistent with Appendix 4 of the Master Protocol (LDOS-21-001).
- •Capable of understanding and providing a signed informed consent form.
- •Reliable access to the internet.
Exclusion Criteria
- •Participants are excluded from the study if any of the following criteria apply:
- •Pregnant or breastfeeding
- •History of HIV
- •Ongoing treatment that cannot be temporarily discontinued during the study: anti-inflammatory treatment (nonsteroidal anti-inflammatory drugs \[NSAIDS\]);corticosteroids; antimalarials; antiarrhythmics; tricyclic antidepressants; natalizumab; quinolones; macrolides; and agalsidase alfa and beta
- •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;
- •Ongoing famotidine, celecoxib, or other COVID-19 clinical investigational treatment(s) within the past 30 days or current participation in another investigational clinical trial
- •History of immunosuppression
Arms & Interventions
Group 1 (Study Product)
Subjects 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, subjects will continue their famotidine treatment for an additional 9 days.
Intervention: Famotidine
Group 1 (Study Product)
Subjects 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, subjects will continue their famotidine treatment for an additional 9 days.
Intervention: Celecoxib
Group 2 (Reference Therapy)
Subjects will receive matching placebos QID and BID, for 5 days. Following this 5-day period, subjects will continue to receive matching famotidine placebo, QID, for an additional 9 days.
Intervention: Placebo
Outcomes
Primary Outcomes
Time-to-event to achieve WHO level ≤3
Time Frame: 30 days
Evaluation of the time-to-event to achieve a WHO level score ≤3
Death rate
Time Frame: 30 days
Evaluation of the time-to-event where all-cause mortality occurs
Secondary Outcomes
- Hospital discharge to chronic palliative care(30 days)
- Study discontinuation due to related AEs or SAEs(90 days)
- Hospital discharge with no additional medical care(30 days)
- Related adverse events (AEs) and serious adverse events (SAEs)(90 days)