Leidos-Enabled Adaptive Protocol for Clinical Trials (LEAP-CT) in Hospitalized Patients With COVID-19 (Addendum 1)

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05085574
• Other study ID #: LDOS-21-001-01
• Status: Withdrawn
• Phase: Phase 2
• Start date: February 7, 2023
• Est. completion date: February 7, 2023

Study information

• Verified date: October 2023
• Source: Leidos Life Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 7, 2023
• Est. primary completion date: February 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 4-5.
• 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

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 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
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
• Rejection of participation at the discretion of the Principal Investigator or Sponsor
• Any contraindication for famotidine or celecoxib treatment:

a. Famotidine or celecoxib hypersensitivity; b. Retinopathy, visual field or visual acuity disturbances; c. History of cardiovascular disease, such as congestive heart failure, QT prolongation, bradycardia (<50 bpm), ventricular tachycardia, other arrhythmias, as determined at screening electrocardiogram (ECG) or medical history; d. Potassium <3 mEq/L (milliequivalent/liter) as determined at Visit 1; e. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 upper normal limit, as determined at Visit 1; f. Previous myocardial infarction; e. Myasthenia gravis; h. Psoriasis or porphyria; i. Glomerular clearance, 60 mL/min; j. Previous history of severe hypoglycemia; k. 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; l. Moderate or severe hepatic impairment, e.g., Child-Pugh Class B or C.

Related Conditions & MeSH terms

• 2019 Novel Coronavirus Infection
• Communicable Diseases
• Coronavirus Disease 2019
• Coronavirus Infections
• COVID-19
• COVID-19 Pandemic
• COVID-19 Virus Disease
• COVID-19 Virus Infection
• Covid19
• Infections
• Respiration Disorders
• Respiratory Tract Diseases
• SARS-CoV-2 Acute Respiratory Disease
• SARS-CoV-2 Infection
• Virus Diseases

Intervention

Drug:
• Famotidine
80 mg tablet, QID for 14 days
• Celecoxib
400 mg (initial dose), then 200 mg capsule, BID for 5 days
• Placebo
tablet, QID for 14 days; capsule, BID for 5 days

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Leidos Life Sciences	United States Department of Defense

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetic (PK) endpoint-Assess area under the curve	Measure area under the curve (AUC) for famotidine and celecoxib combination in 10 patients per group	14 days
Other	Pharmacokinetic (PK) endpoint-Assess time to maximum plasma concentration	Measure time to maximum plasma concentration (tmax) for famotidine and celecoxib combination in 10 patients per group	14 days
Other	Pharmacokinetic (PK) endpoint-Assess maximum serum concentration	Measure maximum serum concentration (Cmax) for famotidine and celecoxib combination in 10 patients per group	14 days
Other	Exploratory endpoint-Incidence of symptom reduction	Cumulative incidence of clinically significant symptom reduction (severity and duration) using COVID-19 Symptom Score	14 days
Other	Exploratory endpoint-Incidence of clinical improvement	Cumulative incidence of clinically significant symptom reduction (severity and duration) using WHO Ordinal Scale for Clinical Improvement	14 days
Other	Special Assessment - High-resolution computed tomography (HRCT), 20 patients/group, change from baseline	HRCT scan of the chest	Study Day 1 (baseline), Day 16 (discharge), 30 days after first dose, and 90 days after first dose
Other	Special Assessment - Total lung capacity (TLC), 20 patients/group, change from baseline	TLC	Study Day 1 (baseline), 16 (discharge), 30 days after first dose, and 90 days after first dose
Other	Special Assessment - Prostaglandin E2 (PGE2), 20 patients/group, change from baseline	PGE2 testing	Study Day 1 (baseline), 16 (discharge), 30 days after first dose, and 90 days after first dose
Other	Special Assessments - Urinalysis, 20 patients/group, change from baseline	Urinalysis	Study Day 1 (baseline) and 16 (discharge)
Primary	Time-to-event to achieve WHO level =3	Evaluation of the time-to-event to achieve a WHO level score =3	30 days
Primary	Death rate	Evaluation of the time-to-event where all-cause mortality occurs	30 days
Secondary	Hospital discharge to chronic palliative care	Measured incidence of hospital discharge to chronic palliative care	30 days
Secondary	Hospital discharge with no additional medical care	Measured incidence of hospital discharge with no additional medical care required	30 days
Secondary	Related adverse events (AEs) and serious adverse events (SAEs)	Measured incidence of related AEs and SAEs	90 days
Secondary	Study discontinuation due to related AEs or SAEs	Measured incidence of study discontinuation due to related AEs or SAEs	90 days