Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease

Covid19 Clinical Trial

Official title:

Phase 2/3 Study of Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04723537
• Other study ID #: RHB-107-01
• Status: Suspended
• Phase: Phase 2/Phase 3
• Start date: February 16, 2021
• Est. completion date: December 2023

Study information

• Verified date: August 2022
• Source: RedHill Biopharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Suspended
• Enrollment: 310
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Drug:
• Part A: Upamostat 200 mg
1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.
• Part A: Upamostat 400 mg
2 capsules, each capsule comprising 200 mg of upamostat
• Part A and B: Placebo
1 or 2 capsules, each capsule a matching placebo
• 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.

Locations

Country	Name	City	State
South Africa	Global Clinical Trials PTY (LTD)	Arcadia	Pretoria
South Africa	WorthWhile Clinical Trials	Benoni
South Africa	Langeberg Medical Centre - Clinical Trials	Kraaifontein	Cape Town
South Africa	PJ Sebastian	KwaZulu	Natal
South Africa	Roodepoort Medicross Clinical Trial Research Centre	Roodepoort	Gauteng
South Africa	FCRN Clinical Trial Centre	Vereeniging	Gauteng
United States	Great Lakes Research Group	Bay City	Michigan
United States	Montefiore Medical Center	Bronx	New York
United States	Prime Global Research	Bronx	New York
United States	On-Site Clinical Solutions	Charlotte	North Carolina
United States	University Hospitals Cleveland	Cleveland	Ohio
United States	Beautiful Minds Clinical Research	Cutler Bay	Florida
United States	Southwest Family Medicine Research	Dallas	Texas
United States	Henry Ford Hospital, emergency department	Detroit	Michigan
United States	Research in Miami Inc.	Hialeah	Florida
United States	Angels Clinical Research Institute	Miami	Florida
United States	South Florida Research Phase I-IV, Inc.	Miami Springs	Florida

Sponsors (1)

Lead Sponsor	Collaborator
RedHill Biopharma Limited

Countries where clinical trial is conducted

United States,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A - Determination of the safety and tolerability of two dose levels and selection of an upamostat dose for part B	Safety and tolerability will be determined 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.	57 days
Primary	Part B - Comparison between upamostat and placebo in time to sustained recovery from symptomatic illness.	Sustained recovery: recovery maintained for at least 14 or 28 days or through EOS, whichever comes first (assessed in part A and a decision reached as to which period to use for definition of sustained recovery in part B). A patient will be considered to have recovered after meeting the following criteria: 1) is afebrile for at least 48 hours without use of antipyretics; 2) all symptoms have resolved or returned to pre- illness levels, except for: a. fatigue, anosmia, ageusia or dysgeusia, which may be persistent at level similar to that during the acute illness; b. 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).	57 days
Secondary	Part B - Hospitalization or death from any cause by end of study	Hospitalization or death from any cause within 8 weeks after the first dose of study medication	57 days
Secondary	Part A and at Interim Analysis in Part B - assessment of risk of hospitilization or death	Assessment of risk of hospitilization or death as a function of the presence, number and severity of concerning conditions will be undertaken. This information may be used to develop a definition of very high risk for calculation of the incidence of hospitilization or death in the high risk/very high risk population in part B	57 days
Secondary	Part B - Proportion of patients who are PCR-negative at various time points during the study.	Proportion of patients who are PCR-negative at days 8, 15, 29 and 57 from the start of treatment (landmark analyses)	57 days
Secondary	Part B - Time to resolution of individual disease-related symptoms present at baseline	Time to resolution of individual disease-related symptoms present at baseline	57 days
Secondary	Part B - Development of new disease-related symptoms on study	Development of new disease-related symptoms on study will be captured using the same questionnaire as is being used to capture resolution of symptoms.	57 days
Secondary	Part B - Development of pneumonia on study	Incidence of pneumonia during study among patients without baseline pneumonia	57 days
Secondary	Part B - Changes in laboratory markers of disease severity	Changes in oxygen saturation from baseline to time points at which these are measured on study	57 days
Secondary	Part B - Changes in laboratory markers of disease severity	Changes in CRP from baseline to time points at which these are measured on study	57 days
Secondary	Part B - Changes in laboratory markers of disease severity	Changes in lymphocyte count from baseline to time points at which these are measured on study	57 days
Secondary	Part B - Changes in laboratory markers of disease severity	Changes in cardiac troponin from baseline to time points at which these are measured on study	57 days
Secondary	Part B - Changes in laboratory markers of disease severity	Changes in D-dimer levels from baseline to time points at which these are measured on study	57 days
Secondary	Part B - Adverse events	Adverse events	57 days