A 2-part, multicenter, Phase 2/3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of upamostat in adult patients with COVID-19 disease who do not require inpatient care.
Patients will be seen in a medical facility (ER or COVID-19 clinic) for initial evaluation.
Consenting, diagnostically-confirmed COVID-19 patients not in need of hospitalization per
investigator assessment and who meet all other inclusion and exclusion criteria will be
randomized to treatment and provided with medication and home monitoring devices, and
instructed in drug administration and use of the devices. They will take medication daily for
two weeks, complete a smartphone-based questionnaire, provide additional monitoring
information via devices provided periodically over an 8-week period. Patients will be seen at
home by a study nurse or return to the clinic after 2, 4 and 8 weeks on study ("follow up"
visits); additional televisits will also be conducted. At the follow up visits nasal swab
specimens for COVID-19 PCR and blood specimens for safety labs and disease markers will be
collected.
In part A of the study, patients will be randomized 1:1:1 to one of two doses of upamostat or
placebo. Based on safety results of part A, a dose for part B will be selected, and patients
will be randomized 3:2 to active vs placebo.
Drug: Part A: Upamostat 200 mg
1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.
Drug: Part A: Upamostat 400 mg
2 capsules, each capsule comprising 200 mg of upamostat
Drug: Part A and B: Placebo
1 or 2 capsules, each capsule a matching placebo
Drug: Part B: Upamostat 200 or 400 mg
Based on dose selection from Part A, "Part B Upamostat" will be EITHER a single 200 mg dose of upamostat OR two 200 mg doses of upamostat, for a total of 14 days.
Inclusion Criteria:
1. Patients with symptomatic, diagnostically confirmed COVID-19, per RT-PCR or antigen
assay of respiratory tract sample.
2. Patient must have either become symptomatic or found positive by RT-PCR or antigen
assay within 5 days, whichever is greater, of randomization.
3. Patients must fill out a baseline questionnaire which is reviewed by study personnel
to determine eligibility.
4. Males and females ≥age 18 years.
5. Oxygen saturation by pulse oximeter ≥92% on room air
6. Negative urine or serum pregnancy test (if woman of childbearing potential).
7. Females of childbearing potential and males with female partners of childbearing
potential must agree to use acceptable contraceptive methods during the study and for
at least two months after the last dose of study medication.
8. Ability to complete the daily diary independently.
9. The patient must give informed consent
Exclusion Criteria:
1. Patient is in need of acute hospitalization per clinician assessment.
2. Pregnant or nursing women.
3. Unwillingness or inability to comply with procedures required in this protocol.
4. Patient requires supplemental oxygen.
5. Patient is currently receiving, has received within the past 7 days or is expected to
receive during the course of the study remdesivir, or other specific antiviral or
anticytokine therapy for COVID-19, other than therapeutic monoclonal antibodies
allowed or approved in the region in which the patient lives, or systemic
corticosteroid equivalent to ≥20 mg daily prednisone/3 mg dexamethasone daily.
6. Patient is currently receiving or has received within 30 days prior to screening any
other investigational agent for any indication, including approved agents given for
investigational indications (e.g., anti-cytokine treatments).
7. Patient is currently taking or is expected to start taking warfarin, apixaban
(Eliquis), or rivaroxaban (Xarelto). Patients may be taking or start on study
dabigatran (Pradaxa), standard or low molecular weight heparin.
Beautiful Minds Clinical Research
Cutler Bay, Florida, United States
Research in Miami Inc.
Hialeah, Florida, United States
South Florida Research Phase I-IV, Inc.
Miami Springs, Florida, United States
Angels Clinical Research Institute
Miami, Florida, United States
Great Lakes Research Group
Bay City, Michigan, United States
Henry Ford Hospital, emergency department
Detroit, Michigan, United States
Prime Global Research
Bronx, New York, United States
Montefiore Medical Center
Bronx, New York, United States
On-Site Clinical Solutions
Charlotte, North Carolina, United States
University Hospitals Cleveland
Cleveland, Ohio, United States
Southwest Family Medicine Research
Dallas, Texas, United States
Langeberg Medical Centre - Clinical Trials
Kraaifontein, Cape Town, South Africa
Roodepoort Medicross Clinical Trial Research Centre
Roodepoort, Gauteng, South Africa
FCRN Clinical Trial Centre
Vereeniging, Gauteng, South Africa
PJ Sebastian
KwaZulu, Natal, South Africa
Global Clinical Trials PTY (LTD)
Arcadia, Pretoria, South Africa
WorthWhile Clinical Trials
Benoni, South Africa
Terry Plasse, MD, Study Director
RedHill Biopharma Limited