Clinical trial NCT04723537: Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease
Official title: Phase 2/3 Study of Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Covid19
Lead sponsor: RedHill Biopharma Limited
Sponsor class: INDUSTRY
First posted: 2021-01-25
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Part A - Determination of the Safety and Tolerability of Two Dose Levels and Selection of an Upamostat Dose for Part B
timeFrame: 57 days
Secondary outcomes:
measure: Hospitalization or Death From Any Cause by End of Study
timeFrame: 57 days
measure: Hospitalization or Death For COVID With Presence of Concerning Conditions
timeFrame: 57 days
measure: Time to Sustained Recovery From Symptomatic Illness for Part A (Protocol Definition)
timeFrame: 57 days
measure: Time to Sustained Recovery From Symptomatic Illness - Part A (SAP Definition)
timeFrame: 57 days
measure: Development of New Disease-related Symptoms and/or Pneumonia on Study
timeFrame: 57 days
measure: Proportion of Patients Who Are PCR-negative at Day 8 From the Start of Treatment
timeFrame: 8 days
measure: Proportion of Patients Who Are PCR-negative at Day 57 From the Start of Treatment
timeFrame: 57 days
measure: Changes in D-dimer Levels, From Baseline to Day 57
timeFrame: 57 days
Other outcomes:
Locations:
city: Cutler Bay
country: United States
facility: Beautiful Minds Clinical Research
state: Florida
city: Hialeah
country: United States
facility: Research in Miami Inc.
state: Florida
city: Miami Springs
country: United States
facility: South Florida Research Phase I-IV, Inc.
state: Florida
city: Miami
country: United States
facility: Angels Clinical Research Institute
state: Florida
city: Bay City
country: United States
facility: Great Lakes Research Group
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital, emergency department
state: Michigan
city: Bronx
country: United States
facility: Prime Global Research
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Charlotte
country: United States
facility: On-Site Clinical Solutions
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland
state: Ohio
city: Dallas
country: United States
facility: Southwest Family Medicine Research
state: Texas
city: Kraaifontein
country: South Africa
facility: Langeberg Medical Centre - Clinical Trials
state: Cape Town
city: Roodepoort
country: South Africa
facility: Roodepoort Medicross Clinical Trial Research Centre
state: Gauteng
city: Vereeniging
country: South Africa
facility: FCRN Clinical Trial Centre
state: Gauteng
city: KwaZulu
country: South Africa
facility: PJ Sebastian
state: Natal
city: Arcadia
country: South Africa
facility: Global Clinical Trials PTY (LTD)
state: Pretoria
city: Benoni
country: South Africa
facility: WorthWhile Clinical Trials
Study officials:
affiliation: RedHill Biopharma Limited
name: Terry Plasse, MD
role: STUDY_DIRECTOR
References:
citation: 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.
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 28.