leidos-enabled adaptive protocol (leap-ct) for evaluation of post-exposure prophylaxis for newly-infected covid-19 patients

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

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.

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

Keywords: covid-19 covid covid19 sars-cov-2