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

RedHill Biopharma

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Covid19

Treatments: Drug: Part A: Upamostat 200 mg; Drug: Part B: Upamostat 200 or 400 mg; Drug: Part A: Upamostat 400 mg; Drug: Part A and B: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04723537

RHB-107-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 61 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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61 participants in 5 patient groups, including a placebo group

Part A: Upamostat 200 mg

Experimental group

Description:

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

Treatment:

Drug: Part A: Upamostat 200 mg

Part A: Upamostat 400 mg

Experimental group

Description:

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

Treatment:

Drug: Part A: Upamostat 400 mg

Part A: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Part A and B: Placebo

Part B: Upamostat

Experimental group

Description:

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.

Treatment:

Drug: Part B: Upamostat 200 or 400 mg

Part B: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Part A and B: Placebo