2019-nCoV Disease, 2019-nCoV Infection, 2019 Novel Coronavirus Disease, 2019 Novel Coronavirus Infection, Coronavirus Disease 2019, Covid19, COVID-19, COVID-19 Pandemic, COVID-19 Virus Disease, COVID-19 Virus Infection, SARS-CoV-2 Acute Respiratory Disease, SARS-CoV2 Infection
Conditions
Keywords
COVID-19, COVID, COVID19, SARS-CoV-2
Brief 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.
Detailed 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.
Interventions
DRUGFamotidine
80 mg tablet, QID for 14 days
DRUGCelecoxib
400 mg (initial dose), then 200 mg capsule, BID for 5 days
DRUGPlacebo
tablet, QID for 14 days; capsule, BID for 5 days
Sponsors
United States Department of Defense
Leidos Life Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind
Intervention model description
Participants randomized 1:1, study drug:placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Increased COVID-19 Symptom Severity | Through Day 30 | Medically attended contact will be measured in whole numbers and reported as 1 medically attended contact each time, in the electronic data capture system for all study participants. |
| Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Death (All-cause Mortality). | Through Day 30 | Medically attended contact will be measured in whole numbers and reported as 1 medically attended contact in the electronic data capture system for all study participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Serious Adverse Events (SAE) as Assessed by Participant Withdrawal | 90 days | Study discontinuation will be measured in whole units, by number of participants who are removed with the reason of SAE and captured by the electronic data capture system. |
| Incidence of Death | 90 days | Deaths will be captured by whole numbers, by number of participants who are removed from the study with reason as death in the electronic data capture system. |
Countries
United States
Participant flow
Pre-assignment details
While 9 patients were randomized into the study only 4 patients received study drug due to early termination of the study.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Study Product) 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.
Famotidine: 80 mg tablet, QID for 14 days
Celecoxib: 400 mg (initial dose), then 200 mg capsule, BID for 5 days | 2 |
| 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.
Placebo: tablet, QID for 14 days; capsule, BID for 5 days | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Group 1 (Study Product) | Group 2 (Reference Therapy) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Continuous | 42.5 years | 27 years | 34.75 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 1 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Death (All-cause Mortality).
Medically attended contact will be measured in whole numbers and reported as 1 medically attended contact in the electronic data capture system for all study participants.
Time frame: Through Day 30
Population: Participants were all white (non-Hispanic) females between 18 and 65 years of age.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Study Product) | Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Death (All-cause Mortality). | 0 Participants |
| Group 2 (Reference Therapy) | Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Death (All-cause Mortality). | 0 Participants |
Primary
Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Increased COVID-19 Symptom Severity
Medically attended contact will be measured in whole numbers and reported as 1 medically attended contact each time, in the electronic data capture system for all study participants.
Time frame: Through Day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Study Product) | Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Increased COVID-19 Symptom Severity | 1 Participants |
| Group 2 (Reference Therapy) | Number of Patients With at Least One COVID-19-related Medically Attended Contact Due to Increased COVID-19 Symptom Severity | 2 Participants |
Secondary
Incidence of Death
Deaths will be captured by whole numbers, by number of participants who are removed from the study with reason as death in the electronic data capture system.
Time frame: 90 days
Population: Participants were all white (non-Hispanic) females between 18 and 65 years of age.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Study Product) | Incidence of Death | 0 Participants |
| Group 2 (Reference Therapy) | Incidence of Death | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Serious Adverse Events (SAE) as Assessed by Participant Withdrawal
Study discontinuation will be measured in whole units, by number of participants who are removed with the reason of SAE and captured by the electronic data capture system.
Time frame: 90 days
Population: Participants were all white (non-Hispanic) females between 18 and 65 years of age.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Study Product) | Number of Participants With Treatment-Emergent Serious Adverse Events (SAE) as Assessed by Participant Withdrawal | 0 participants |
| Group 2 (Reference Therapy) | Number of Participants With Treatment-Emergent Serious Adverse Events (SAE) as Assessed by Participant Withdrawal | 0 participants |