Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease
- Conditions
- Covid19
- Registration Number
- NCT04723537
- Lead Sponsor
- RedHill Biopharma Limited
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 61
- Patients with symptomatic, diagnostically confirmed COVID-19, per RT-PCR or antigen assay of respiratory tract sample.
- Patient must have either become symptomatic or found positive by RT-PCR or antigen assay within 5 days, whichever is greater, of randomization.
- Patients must fill out a baseline questionnaire which is reviewed by study personnel to determine eligibility.
- Males and females ≥age 18 years.
- Oxygen saturation by pulse oximeter ≥92% on room air
- Negative urine or serum pregnancy test (if woman of childbearing potential).
- 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.
- Ability to complete the daily diary independently.
- The patient must give informed consent
- Patient is in need of acute hospitalization per clinician assessment.
- Pregnant or nursing women.
- Unwillingness or inability to comply with procedures required in this protocol.
- Patient requires supplemental oxygen.
- 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.
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Part A - Determination of the Safety and Tolerability of Two Dose Levels and Selection of an Upamostat Dose for Part B 57 days This is a qualitative measure that takes into account safety and tolerability based on the relative incidence and severity (CTCAE v 5.0 criteria) of adverse events, both clinical and laboratory (SOC=investigations) in each active treatment group as compared to placebo. In addition, toxicities (i.e., adverse events considered at lease possible related to study medication) resulting in dose reductions or discontinuation of therapy will be tabulated and compared among treatment groups.
- Secondary Outcome Measures
Name Time Method Development of New Disease-related Symptoms and/or Pneumonia on Study 57 days Hospitalization or Death From Any Cause by End of Study 57 days Time to Sustained Recovery From Symptomatic Illness for Part A (Protocol Definition) 57 days Sustained recovery was defined as recovery maintained for at least 14 or 28 days (two analyses), or through end of study, whichever comes first. A patient was considered to have recovered once he or she met the following criteria:
1. is afebrile (\<38.0°C core temperature/37.5°C oral temperature) for at least 48 hours without use of antipyretics;
2. all symptoms have resolved or returned to pre-illness levels (e.g., if patient had respiratory compromise prior to the onset of COVID), except for:
1. fatigue, anosmia, ageusia or dysgeusia, which may be persistent at level similar to that during the acute illness, i.e., the same level per symptom questionnaire;
2. chest pain, cough or dyspnea which if persistent must be at least one grade lower than at the start of treatment and no worse than grade 1 (mild).Hospitalization or Death For COVID With Presence of Concerning Conditions 57 days Time to Sustained Recovery From Symptomatic Illness - Part A (SAP Definition) 57 days First day at which there are no symptoms, and no occurrence of any symptoms for at least 14 days or until end of study, whichever came first. Mild symptoms which were noted as preexisting conditions were excluded from this calculation. For example, if a patient noted preexisting shortness of breath, mild shortness of breath was excluded from the calculation of no symptoms.
Proportion of Patients Who Are PCR-negative at Day 8 From the Start of Treatment 8 days Proportion of Patients Who Are PCR-negative at Day 57 From the Start of Treatment 57 days Changes in D-dimer Levels, From Baseline to Day 57 57 days
Trial Locations
- Locations (17)
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
PJ Sebastian
🇿🇦KwaZulu, Natal, South Africa
Beautiful Minds Clinical Research
🇺🇸Cutler Bay, Florida, United States
Henry Ford Hospital, emergency department
🇺🇸Detroit, Michigan, United States
Angels Clinical Research Institute
🇺🇸Miami, Florida, United States
Roodepoort Medicross Clinical Trial Research Centre
🇿🇦Roodepoort, Gauteng, South Africa
FCRN Clinical Trial Centre
🇿🇦Vereeniging, Gauteng, South Africa
Global Clinical Trials PTY (LTD)
🇿🇦Arcadia, Pretoria, South Africa
WorthWhile Clinical Trials
🇿🇦Benoni, South Africa
Research in Miami Inc.
🇺🇸Hialeah, Florida, United States
South Florida Research Phase I-IV, Inc.
🇺🇸Miami Springs, Florida, United States
On-Site Clinical Solutions
🇺🇸Charlotte, North Carolina, United States
Great Lakes Research Group
🇺🇸Bay City, Michigan, United States
Prime Global Research
🇺🇸Bronx, New York, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States