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

NCT04723537 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: RHB-107-01
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 17

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.

Conditions

Covid19

Outcome Measures

Primary Outcomes (1)

• Part A - Determination of the Safety and Tolerability of Two Dose Levels and Selection of an Upamostat Dose for Part B

  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.

  57 days

Secondary Outcomes (8)

• Hospitalization or Death From Any Cause by End of Study

  57 days

• Hospitalization or Death For COVID With Presence of Concerning Conditions

  57 days

• Time to Sustained Recovery From Symptomatic Illness for Part A (Protocol Definition)

  57 days

• Time to Sustained Recovery From Symptomatic Illness - Part A (SAP Definition)

  57 days

• Development of New Disease-related Symptoms and/or Pneumonia on Study

  57 days

Study Arms (5)

Part A: Upamostat 200 mg

EXPERIMENTAL

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

Drug: Part A: Upamostat 200 mg

Part A: Upamostat 400 mg

EXPERIMENTAL

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

Drug: Part A: Upamostat 400 mg

Part A: Placebo

PLACEBO COMPARATOR

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

Drug: Part A and B: Placebo

Part B: Upamostat

EXPERIMENTAL

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.

Drug: Part B: Upamostat 200 or 400 mg

Part B: Placebo

PLACEBO COMPARATOR

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.

Drug: Part A and B: Placebo

Interventions

Part A: Upamostat 200 mg DRUG

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

Part A: Upamostat 200 mg

Part A: Upamostat 400 mg DRUG

2 capsules, each capsule comprising 200 mg of upamostat

Part A: Upamostat 400 mg

Part A and B: Placebo DRUG

1 or 2 capsules, each capsule a matching placebo

Part A: Placebo; Part B: Placebo

Part B: Upamostat 200 or 400 mg 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: Upamostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• RedHill Biopharma Limited: lead

Study Sites (17)

Beautiful Minds Clinical Research

Cutler Bay, Florida, 33157, United States

Location

Research in Miami Inc.

Hialeah, Florida, 33013, United States

Location

Angels Clinical Research Institute

Miami, Florida, 33122, United States

Location

South Florida Research Phase I-IV, Inc.

Miami Springs, Florida, 33166, United States

Location

Great Lakes Research Group

Bay City, Michigan, 48706, United States

Location

Henry Ford Hospital, emergency department

Detroit, Michigan, 48202, United States

Location

Prime Global Research

The Bronx, New York, 10456, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

On-Site Clinical Solutions

Charlotte, North Carolina, 28277, United States

Location

University Hospitals Cleveland

Cleveland, Ohio, 44106, United States

Location

Southwest Family Medicine Research

Dallas, Texas, 75235, United States

Location

Langeberg Medical Centre - Clinical Trials

Kraaifontein, Cape Town, 7570, South Africa

Location

Roodepoort Medicross Clinical Trial Research Centre

Roodepoort, Gauteng, 1724, South Africa

Location

FCRN Clinical Trial Centre

Vereeniging, Gauteng, 1935, South Africa

Location

PJ Sebastian

KwaZulu, KwaZulu-Natal, 4092, South Africa

Location

Global Clinical Trials PTY (LTD)

Arcadia, Pretoria, 0001, South Africa

Location

WorthWhile Clinical Trials

Benoni, 1500, South Africa

Location

Related Publications (2)

• 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.

  PMID: 36549549 RESULT

• 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.

  PMID: 37970658 RESULT

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Gilead Raday, COO
• Organization: RedHill Biopharma Ltd.

info@redhillbio.com

+972-(0)3-541-3131

Study Officials

• Terry Plasse, MD

  RedHill Biopharma Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: January 25, 2021
• Study Start: February 16, 2021
• Primary Completion: December 28, 2021
• Study Completion: December 28, 2021
• Last Updated: June 6, 2024
• Results First Posted: June 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); ZA (6)