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

Sponsor
RedHill Biopharma Limited (Industry)
Overall Status
Suspended
CT.gov ID
NCT04723537
Collaborator
(none)
310
17
5
33.4
18.2
0.5

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Part A: Upamostat 200 mg
  • Drug: Part A: Upamostat 400 mg
  • Drug: Part A and B: Placebo
  • Drug: Part B: Upamostat 200 or 400 mg
Phase 2/Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
310 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Phase 2/3 Study of Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease
Actual Study Start Date :
Feb 16, 2021
Anticipated Primary Completion Date :
Dec 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Part A: Upamostat 200 mg
1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.

Experimental: Part A: Upamostat 400 mg

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

Drug: Part A: Upamostat 400 mg
2 capsules, each capsule comprising 200 mg of upamostat

Placebo Comparator: Part A: Placebo

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

Drug: Part A and B: Placebo
1 or 2 capsules, each capsule a matching placebo

Experimental: 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.

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.

Placebo Comparator: 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.

Drug: Part A and B: Placebo
1 or 2 capsules, each capsule a matching placebo

Outcome Measures

Primary Outcome Measures

  1. Part A - Determination of the safety and tolerability of two dose levels and selection of an upamostat dose for part B [57 days]

    Safety and tolerability will be determined 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.

  2. Part B - Comparison between upamostat and placebo in time to sustained recovery from symptomatic illness. [57 days]

    Sustained recovery: recovery maintained for at least 14 or 28 days or through EOS, whichever comes first (assessed in part A and a decision reached as to which period to use for definition of sustained recovery in part B). A patient will be considered to have recovered after meeting the following criteria: 1) is afebrile for at least 48 hours without use of antipyretics; 2) all symptoms have resolved or returned to pre- illness levels, except for: a. fatigue, anosmia, ageusia or dysgeusia, which may be persistent at level similar to that during the acute illness; b. 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).

Secondary Outcome Measures

  1. Part B - Hospitalization or death from any cause by end of study [57 days]

    Hospitalization or death from any cause within 8 weeks after the first dose of study medication

  2. Part A and at Interim Analysis in Part B - assessment of risk of hospitilization or death [57 days]

    Assessment of risk of hospitilization or death as a function of the presence, number and severity of concerning conditions will be undertaken. This information may be used to develop a definition of very high risk for calculation of the incidence of hospitilization or death in the high risk/very high risk population in part B

  3. Part B - Proportion of patients who are PCR-negative at various time points during the study. [57 days]

    Proportion of patients who are PCR-negative at days 8, 15, 29 and 57 from the start of treatment (landmark analyses)

  4. Part B - Time to resolution of individual disease-related symptoms present at baseline [57 days]

    Time to resolution of individual disease-related symptoms present at baseline

  5. Part B - Development of new disease-related symptoms on study [57 days]

    Development of new disease-related symptoms on study will be captured using the same questionnaire as is being used to capture resolution of symptoms.

  6. Part B - Development of pneumonia on study [57 days]

    Incidence of pneumonia during study among patients without baseline pneumonia

  7. Part B - Changes in laboratory markers of disease severity [57 days]

    Changes in oxygen saturation from baseline to time points at which these are measured on study

  8. Part B - Changes in laboratory markers of disease severity [57 days]

    Changes in CRP from baseline to time points at which these are measured on study

  9. Part B - Changes in laboratory markers of disease severity [57 days]

    Changes in lymphocyte count from baseline to time points at which these are measured on study

  10. Part B - Changes in laboratory markers of disease severity [57 days]

    Changes in cardiac troponin from baseline to time points at which these are measured on study

  11. Part B - Changes in laboratory markers of disease severity [57 days]

    Changes in D-dimer levels from baseline to time points at which these are measured on study

  12. Part B - Adverse events [57 days]

    Adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Beautiful Minds Clinical Research Cutler Bay Florida United States 33157
2 Research in Miami Inc. Hialeah Florida United States 33013
3 South Florida Research Phase I-IV, Inc. Miami Springs Florida United States 33166
4 Angels Clinical Research Institute Miami Florida United States 33122
5 Great Lakes Research Group Bay City Michigan United States 48706
6 Henry Ford Hospital, emergency department Detroit Michigan United States 48202
7 Prime Global Research Bronx New York United States 10456
8 Montefiore Medical Center Bronx New York United States 10467
9 On-Site Clinical Solutions Charlotte North Carolina United States 28277
10 University Hospitals Cleveland Cleveland Ohio United States 44106
11 Southwest Family Medicine Research Dallas Texas United States 75235
12 Langeberg Medical Centre - Clinical Trials Kraaifontein Cape Town South Africa 7570
13 Roodepoort Medicross Clinical Trial Research Centre Roodepoort Gauteng South Africa 1724
14 FCRN Clinical Trial Centre Vereeniging Gauteng South Africa 1935
15 PJ Sebastian KwaZulu Natal South Africa 4092
16 Global Clinical Trials PTY (LTD) Arcadia Pretoria South Africa 0001
17 WorthWhile Clinical Trials Benoni South Africa 1500

Sponsors and Collaborators

  • RedHill Biopharma Limited

Investigators

  • Study Director: Terry Plasse, MD, RedHill Biopharma Limited

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
RedHill Biopharma Limited
ClinicalTrials.gov Identifier:
NCT04723537
Other Study ID Numbers:
  • RHB-107-01
First Posted:
Jan 25, 2021
Last Update Posted:
Aug 5, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 5, 2022