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

NCT ID: NCT04723537

Last Updated: 2024-06-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-16
• Study Completion Date: 2021-12-28

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A: Upamostat 200 mg

Each day participants will receive a single 200 mg dose of upamostat along with a single matching placebo, for a total of 14 days.

Group Type: EXPERIMENTAL

Part A: Upamostat 200 mg

Intervention Type: DRUG

1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.

Part A: Upamostat 400 mg

Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days.

Group Type: EXPERIMENTAL

Part A: Upamostat 400 mg

Intervention Type: DRUG

2 capsules, each capsule comprising 200 mg of upamostat

Part A: Placebo

Each day participants will receive two matching placebos, for a total of 14 days.

Group Type: PLACEBO_COMPARATOR

Part A and B: Placebo

Intervention Type: DRUG

1 or 2 capsules, each capsule a matching placebo

Part B: Upamostat

Based on dose selected from Part A, each day participants will receive EITHER a single 200 mg dose of upamostat OR two 200 mg doses of upamostat, for a total of 14 days.

Group Type: EXPERIMENTAL

Part B: Upamostat 200 or 400 mg

Intervention Type: DRUG

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.

Part B: Placebo

Based on dose selected from Part A, each day participants will receive EITHER a single matching placebo OR two matching placebos, for a total of 14 days.

Group Type: PLACEBO_COMPARATOR

Part A and B: Placebo

Intervention Type: DRUG

1 or 2 capsules, each capsule a matching placebo

Interventions

Part A: Upamostat 200 mg

1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.

Intervention Type: DRUG

Part A: Upamostat 400 mg

2 capsules, each capsule comprising 200 mg of upamostat

Intervention Type: DRUG

Part A and B: Placebo

1 or 2 capsules, each capsule a matching placebo

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RedHill Biopharma Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Terry Plasse, MD

Role: STUDY_DIRECTOR

RedHill Biopharma Limited

Locations

Beautiful Minds Clinical Research

Cutler Bay, Florida, 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, United States

Great Lakes Research Group

Bay City, Michigan, United States

Henry Ford Hospital, emergency department

Detroit, Michigan, United States

Prime Global Research

The Bronx, New York, United States

Montefiore Medical Center

The 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, KwaZulu-Natal, South Africa

Global Clinical Trials PTY (LTD)

Arcadia, Pretoria, South Africa

WorthWhile Clinical Trials

Benoni, , South Africa

Countries

United States; South Africa

References

Plasse TF, Delgado B, Potts J, Abramson D, Fehrmann C, Fathi R, McComsey GA. A randomized, placebo-controlled pilot study of upamostat, a host-directed serine protease inhibitor, for outpatient treatment of COVID-19. Int J Infect Dis. 2023 Mar;128:148-156. doi: 10.1016/j.ijid.2022.12.003. Epub 2022 Dec 19.

Reference Type: RESULT

PMID: 36549549 (View on PubMed)

Plasse TF, Fathi R, Fehrmann C, McComsey GA. Upamostat: a serine protease inhibitor for antiviral, gastrointestinal, and anticancer indications. Expert Opin Investig Drugs. 2023 Jul-Dec;32(12):1095-1103. doi: 10.1080/13543784.2023.2284385. Epub 2023 Dec 28.

Reference Type: RESULT

PMID: 37970658 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RHB-107-01

Identifier Type: -

Identifier Source: org_study_id