SARS-CoV-2
Conditions
Keywords
COVID-19, Early Treatment, Post-Exposure Prophylaxis, Outpatient
Brief summary
This study is an adaptive, randomized, double blind, platform trial evaluating promising investigational products (IP) for safety and efficacy as early outpatient treatment and post-exposure prophylaxis for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
Detailed description
This multicenter trial will be conducted in both domestic and international sites. The study will compare IPs to control in standard and intermediate risk, non-hospitalized adult SARS-CoV-2 infected participants and uninfected adult contacts of SARS-CoV-2 confirmed cases. The master protocol will outline the core elements of the study. Investigational products may be included in either or both study indications: early treatment and post-exposure prophylaxis (PEP). The study includes a phase 2 evaluation for all IPs. The platform trial design will allow for multiple IPs to be incorporated into the protocol as product specific appendices (PSA) as products are identified and become available. Each PSA will detail the interventions, the endpoints, target treatment effect, intended statistical analysis, the relevant control arms, and the sample size range. The PSA may define additional adaptive design elements, such as early declaration rules.
Interventions
DRUGUpamostat
Upamostat is available as a hydrogen sulphate salt (also designated as WX-671.1). WX-671.1 is a white to yellowish powder which is freely soluble in dimethyl sulfoxide and soluble in ethanol. The drug substance is very slightly soluble in water or 0.1 M HCl.
DRUGPlacebo (PO)
Oral Capsules
Sponsors
Henry M. Jackson Foundation for the Advancement of Military Medicine
Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies
RedHill Biopharma Limited
FHI Clinical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
An adaptive, randomized, double-blind, platform trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Population A: Symptomatic adults seeking care or testing for COVID-19 Inclusion Criteria: 1. Age ≥ 18 years 2. Positive molecular or antigen diagnostic test for SARS-CoV-2 at study enrollment or within ≤ 5 days prior to enrollment 3. Presence of two or more Screening Symptoms listed in Supplement 3 with at least two symptoms classified as moderate to severe (and/or ≥ 2 on the frequency questions or loss of taste/smell questions) at the time of enrollment a. For participants who have preexisting conditions causing mild or moderate symptoms listed on the Screening Symptom Questionnaire, there must be an increase of at least one severity level for that symptom at enrollment (For example, prior to illness participant routinely experienced headaches rated as moderate severity, now rating headache as severe at enrollment) * Supplement 3 Screening Symptoms: stuffy or runny nose, hoarse voice, sore throat, difficulty breathing, cough, fatigue (low energy or tiredness), muscle or body aches, headache, fever (documented temperature \> 38° C \[100.4° F\]) or subjective fever, chills or shivering, feeling hot or feverish, nausea, vomiting, diarrhea, loss of smell, loss of taste 4. Symptom onset ≤ 5 days prior to enrollment
Exclusion criteria
1. Hospital admission at the time of enrollment 2. Hospitalization will be defined as requiring medical care not available in an outpatient setting for greater than 24 hours 3. Hospitalization for isolation or quarantine requirements or for social reasons will NOT constitute an exclusion criterion 4. Laboratory confirmed SARS-CoV-2 infection 6 to 90 days prior to enrollment 5. Oxygen saturation \< 92% on room air 6. Baseline use of supplemental oxygen at the time of enrollment 7. Presence of any of the following comorbidities that per the PI puts the patient at high risk of developing severe COVID-19 illness: a. Age ≥ 75 years b. Active treatment for solid tumor and hematologic malignancies c. Hematologic malignancy, myeloma, or related disorder (e.g., myelodysplastic syndrome, myelofibrosis) d. Receipt of solid-organ transplant or an islet transplant and taking immunosuppressive therapy e. Chemotherapy or radiotherapy for solid organ cancer in the last 12 months f. Receipt of chimeric antigen receptor (CAR)-T-cell therapy or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppressive therapy) g. Moderate or severe primary immunodeficiency (e.g., common variable immunodeficiency disease, severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome) h. Advanced or untreated HIV infection (people with HIV and CD4 cell counts less than 200/mm3, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV) i. Active treatment with high-dose corticosteroids (i.e., 20 or more mg of prednisone or equivalent per day when administered for 2 or more weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory j. Sickle cell disease k. Chronic liver disease (e.g., Child-Pugh Class A, B or C cirrhosis) l. Down syndrome m. Dementia or neurocognitive disability (e.g., Parkinson's disease) n. Participants with 3 or more of the following conditions: i) No prior COVID-19 infection OR has not completed a COVID-19 vaccine series within the last 6 months OR has not received a vaccine booster within the last 6 months ii) Age 65-74 years iii) BMI ≥35 (or \>95th percentile in adolescents) iv) Type 1 or type 2 diabetes mellitus v) Cardiovascular disease (including HTN if age \>55) vi) Chronic lung disease (including bronchiectasis, CF, COPD, ILD, PHTN, PE, moderate-to-severe asthma) vii) Chronic kidney disease (eGFR \<30) 8. Participants who are receiving or plan to receive anti-SARS-CoV-2 antivirals for treatment of their COVID-19 Population B: Uninfected adult contacts of symptomatic SARS-CoV-2 infected individuals Inclusion Criteria: 1. Age ≥ 18 years 2. Asymptomatic contact of an individual with laboratory confirmed SARS-CoV-2 infection defined as: a. Indoor exposure to the symptomatic case or cases within 6 feet (2 meters) for ≥ 15 minutes over a 24-hour period without the use of personal protective equipment 3. Negative screening SARS-CoV-2 molecular or antigen diagnostic test performed at screening or within less than or equal to 24 hours of enrollment 4. Exposure and enrollment within 6 days or less from when the symptomatic, confirmed SARS-CoV-2 positive case first had symptoms
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sustained Alleviation or Resolution of COVID-19 Symptoms | Day 0 to Day 28 | Defined as the number of days from randomization within a PSA to the first day the participant reports all symptoms as mild or none for at least 3 consecutive days. Symptoms will be assessed via completion of a Screening Symptom Questionnaire at Enrollment and then a Daily Follow Up Symptom Questionnaire. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Overall COVID-19 Symptom Severity Score | Day 0 to Day 28 | Participants complete a Daily Symptom Follow Up Questionnaire on Days 1 through 28 and then at follow up visits. Symptoms are reported on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). Symptoms assessed include nasal congestion, sore throat, hoarse voice, shortness of breath, cough, fatigue, myalgias, headache, chills, fever, nausea or vomiting, change in taste and change in smell. An additional question assesses overall symptom severity on the same 4 point scale |
| Time to Negative SARS-CoV-2 PCR | Day 0 to Week 12 | the time of the first of two consecutive readings below the lower limit of detection |
| Development of New Severe COVID-19 Symptoms | Day 0 to Week 12 | Proportion of participants in each treatment group developing new COVID-19 symptoms on the Daily Symptom Questionnaire rated as severe from Day 0 to Day 28 |
| Return to Usual State of Health | Day 0 to Week 12 | Proportion of participants who report a return to usual state of health at Days 7, 14, 28, Week 8, and Week 12 |
| Return to Usual Activities | Day 0 to Week 12 | Proportion of participants who report a return to usual activities at Days 7, 14, 28, Week 8, and Week 12. |
| All Cause Hospitalization | Day 0 to Week 12 | number of participants hospitalized for any reason |
| All Cause Deaths | Day 0 to Week 12 | Number of all cause deaths |
Countries
South Africa, Thailand, Uganda, United States
Participant flow
Pre-assignment details
Overall, 135 patients were screened for inclusion under the Master Protocol. Of these, 34 were screen failures and 2 participants were found to be eligible but declined to participate. The remaining 99 were screened for the upamostat PSA eligibility. Of these, 5 patients were screen failures and 2 participants were found to be eligible but declined to participate. 92 participants underwent the step 2 randomization to upamostat or control
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 37.5 years STANDARD_DEVIATION 11.52 |
| COVID vaccination history | 42 participants receiving COVID vaccination |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height (cm) | 167.2 cm STANDARD_DEVIATION 11.47 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 34 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment South Africa | 3 participants |
| Region of Enrollment Thailand | 67 participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 14 Participants |
| weight (kg) | 71.4 kg STANDARD_DEVIATION 16.45 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 46 |
| other Total, other adverse events | 4 / 46 | 0 / 46 |
| serious Total, serious adverse events | 0 / 46 | 0 / 46 |
Outcome results
None listed