Clinical trial NCT05077332: LEAP-CT for Treatment of COVID-19 Patients (Master Protocol)
Official title: Leidos-Enabled Adaptive Protocol for Clinical Trials (LEAP-CT) to Evaluate the Safety and Efficacy of Drug Combinations in COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: 2019 Novel Coronavirus Disease
2019 Novel Coronavirus Infection
2019-nCoV Disease
2019-nCoV Infection
COVID-19 Pandemic
COVID-19 Virus Disease
COVID-19 Virus Infection
Covid19
Coronavirus Disease 2019
SARS-CoV-2 Infection
SARS-CoV-2 Acute Respiratory Disease
COVID-19
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: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects randomized 1:1, study drug:placebo
Primary purpose: TREATMENT

Brief summary: This master protocol serves as a common reference for the inpatient and outpatient clinical studies that share common elements.

Detailed description: There are currently two addenda to this master protocol:

Addendum 1, Study LDOS-21-001-01, is 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.

Addendum 2, Study LDOS-21-001-02, is a 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.

Eligibility criteria: * For eligibility criteria specific to the protocol, see:
* Addendum #1 (LDOS-21-001-01) or
* Addendum #2 (LDOS-21-001-02)

Primary outcomes:
measure: (LDOS-21-001-01) Time-to-event to achieve WHO level ≤3
timeFrame: 30 days
measure: (LDOS-21-001-01) All-Cause Mortality rate
timeFrame: 30 days
measure: (LDOS-21-001-02) Number of patients with at least one COVID-19-related medically attended contact due to increased COVID-19 symptom severity
timeFrame: 30 days
measure: (LDOS-21-001-02) Number of patients with at least one COVID-19-related medically attended contact due to death (all-cause mortality)
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: US02-04: Integrated Health Solutions
state: Florida
Study officials:
affiliation: Leidos, Inc.
name: Brian A Roberts, MS, PMP
role: STUDY_DIRECTOR
References:
citation: Malone RW, Tisdall P, Fremont-Smith P, Liu Y, Huang XP, White KM, Miorin L, Moreno E, Alon A, Delaforge E, Hennecker CD, Wang G, Pottel J, Blair RV, Roy CJ, Smith N, Hall JM, Tomera KM, Shapiro G, Mittermaier A, Kruse AC, Garcia-Sastre A, Roth BL, Glasspool-Malone J, Ricke DO. COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms. Front Pharmacol. 2021 Mar 23;12:633680. doi: 10.3389/fphar.2021.633680. eCollection 2021.
citation: Janowitz T, Gablenz E, Pattinson D, Wang TC, Conigliaro J, Tracey K, Tuveson D. Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series. Gut. 2020 Sep;69(9):1592-1597. doi: 10.1136/gutjnl-2020-321852. Epub 2020 Jun 4.
citation: Hogan Ii RB, Hogan Iii RB, Cannon T, Rappai M, Studdard J, Paul D, Dooley TP. Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients. Pulm Pharmacol Ther. 2020 Aug;63:101942. doi: 10.1016/j.pupt.2020.101942. Epub 2020 Aug 29.
citation: Tomera K, Malone R, Kittah J. Hospitalized COVID-19 Patients Treated with Celecoxib and High Dose Famotidine Adjuvant Therapy Sow Significant Clinical Responses. Frontiers in Pharmacology. 2021.
citation: Sun C, Chen Y, Hu L, Wu Y, Liang M, Ayaz Ahmed M, Bhan C, Guo Z, Yang H, Zuo Y, Yan Y, Zhou Q. Does Famotidine Reduce the Risk of Progression to Severe Disease, Death, and Intubation for COVID-19 Patients? A Systemic Review and Meta-Analysis. Dig Dis Sci. 2021 Nov;66(11):3929-3937. doi: 10.1007/s10620-021-06872-z. Epub 2021 Feb 24.
citation: Shoaibi A, Fortin SP, Weinstein R, Berlin JA, Ryan P. Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients. Am J Gastroenterol. 2021 Apr;116(4):692-699. doi: 10.14309/ajg.0000000000001153.
citation: Sander WJ, O'Neill HG, Pohl CH. Prostaglandin E2 As a Modulator of Viral Infections. Front Physiol. 2017 Feb 14;8:89. doi: 10.3389/fphys.2017.00089. eCollection 2017.
citation: Morimoto K, Shirata N, Taketomi Y, Tsuchiya S, Segi-Nishida E, Inazumi T, Kabashima K, Tanaka S, Murakami M, Narumiya S, Sugimoto Y. Prostaglandin E2-EP3 signaling induces inflammatory swelling by mast cell activation. J Immunol. 2014 Feb 1;192(3):1130-7. doi: 10.4049/jimmunol.1300290. Epub 2013 Dec 16.
citation: Hong W, Chen Y, You K, Tan S, Wu F, Tao J, Chen X, Zhang J, Xiong Y, Yuan F, Yang Z, Chen T, Chen X, Peng P, Tai Q, Wang J, Zhang F, Li YX. Celebrex Adjuvant Therapy on Coronavirus Disease 2019: An Experimental Study. Front Pharmacol. 2020 Nov 6;11:561674. doi: 10.3389/fphar.2020.561674. eCollection 2020.
citation: Chen JS, Alfajaro MM, Chow RD, Wei J, Filler RB, Eisenbarth SC, Wilen CB. Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection. J Virol. 2021 Mar 10;95(7):e00014-21. doi: 10.1128/JVI.00014-21. Epub 2021 Jan 13.