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: Terminated

Administrative data

• NCT number: NCT04723537
• Other study ID #: RHB-107-01
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: February 16, 2021
• Est. completion date: December 28, 2021

Study information

• Verified date: March 2024
• 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: Terminated
• Enrollment: 61
• Est. completion date: December 28, 2021
• Est. primary completion date: December 28, 2021
• 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, 

References & 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 — View Citation

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 2 — View Citation

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	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	Hospitalization or Death From Any Cause by End of Study		57 days
Secondary	Hospitalization or Death For COVID With Presence of Concerning Conditions		57 days
Secondary	Time to Sustained Recovery From Symptomatic Illness for Part A (Protocol Definition)	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: is afebrile (<38.0°C core temperature/37.5°C oral temperature) for at least 48 hours without use of antipyretics; 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: 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; 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	Time to Sustained Recovery From Symptomatic Illness - Part A (SAP Definition)	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.	57 days
Secondary	Development of New Disease-related Symptoms and/or Pneumonia on Study		57 days
Secondary	Proportion of Patients Who Are PCR-negative at Day 8 From the Start of Treatment		8 days
Secondary	Proportion of Patients Who Are PCR-negative at Day 57 From the Start of Treatment		57 days
Secondary	Changes in D-dimer Levels, From Baseline to Day 57		57 days