Back to resultsUpamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease
Primary Purpose
Covid19
Status
Suspended
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Part A: Upamostat 200 mg
Part A: Upamostat 400 mg
Part A and B: Placebo
Part B: Upamostat 200 or 400 mg
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- Beautiful Minds Clinical Research
- Research in Miami Inc.
- South Florida Research Phase I-IV, Inc.
- Angels Clinical Research Institute
- Great Lakes Research Group
- Henry Ford Hospital, emergency department
- Prime Global Research
- Montefiore Medical Center
- On-Site Clinical Solutions
- University Hospitals Cleveland
- Southwest Family Medicine Research
- Langeberg Medical Centre - Clinical Trials
- Roodepoort Medicross Clinical Trial Research Centre
- FCRN Clinical Trial Centre
- PJ Sebastian
- Global Clinical Trials PTY (LTD)
- WorthWhile Clinical Trials
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Part A: Upamostat 200 mg
Part A: Upamostat 400 mg
Part A: Placebo
Part B: Upamostat
Part B: Placebo
Arm 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.
Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days.
Each day participants will receive two matching placebos, for a total of 14 days.
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.
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.
Outcomes
Primary Outcome Measures
Part A - Determination of the safety and tolerability of two dose levels and selection of an upamostat dose for part B
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.
Part B - Comparison between upamostat and placebo in time to sustained recovery from symptomatic illness.
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
Part B - Hospitalization or death from any cause by end of study
Hospitalization or death from any cause within 8 weeks after the first dose of study medication
Part A and at Interim Analysis in Part B - assessment of risk of hospitilization or death
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
Part B - Proportion of patients who are PCR-negative at various time points during the study.
Proportion of patients who are PCR-negative at days 8, 15, 29 and 57 from the start of treatment (landmark analyses)
Part B - Time to resolution of individual disease-related symptoms present at baseline
Time to resolution of individual disease-related symptoms present at baseline
Part B - Development of new disease-related symptoms on study
Development of new disease-related symptoms on study will be captured using the same questionnaire as is being used to capture resolution of symptoms.
Part B - Development of pneumonia on study
Incidence of pneumonia during study among patients without baseline pneumonia
Part B - Changes in laboratory markers of disease severity
Changes in oxygen saturation from baseline to time points at which these are measured on study
Part B - Changes in laboratory markers of disease severity
Changes in CRP from baseline to time points at which these are measured on study
Part B - Changes in laboratory markers of disease severity
Changes in lymphocyte count from baseline to time points at which these are measured on study
Part B - Changes in laboratory markers of disease severity
Changes in cardiac troponin from baseline to time points at which these are measured on study
Part B - Changes in laboratory markers of disease severity
Changes in D-dimer levels from baseline to time points at which these are measured on study
Part B - Adverse events
Adverse events
Full Information
NCT ID
NCT04723537
First Posted
January 18, 2021
Last Updated
August 2, 2022
Sponsor
RedHill Biopharma Limited
1. Study Identification
Unique Protocol Identification Number
NCT04723537
Brief Title
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
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Suspended
Why Stopped
Part A complete
Study Start Date
February 16, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RedHill Biopharma Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
310 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part A: Upamostat 200 mg
Arm Type
Experimental
Arm 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.
Arm Title
Part A: Upamostat 400 mg
Arm Type
Experimental
Arm Description
Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days.
Arm Title
Part A: Placebo
Arm Type
Placebo Comparator
Arm Description
Each day participants will receive two matching placebos, for a total of 14 days.
Arm Title
Part B: Upamostat
Arm Type
Experimental
Arm 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.
Arm Title
Part B: Placebo
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Part A: Upamostat 200 mg
Intervention Description
1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.
Intervention Type
Drug
Intervention Name(s)
Part A: Upamostat 400 mg
Intervention Description
2 capsules, each capsule comprising 200 mg of upamostat
Intervention Type
Drug
Intervention Name(s)
Part A and B: Placebo
Intervention Description
1 or 2 capsules, each capsule a matching placebo
Intervention Type
Drug
Intervention Name(s)
Part B: Upamostat 200 or 400 mg
Intervention Description
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.
Primary Outcome Measure Information:
Title
Part A - Determination of the safety and tolerability of two dose levels and selection of an upamostat dose for part B
Description
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.
Time Frame
57 days
Title
Part B - Comparison between upamostat and placebo in time to sustained recovery from symptomatic illness.
Description
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).
Time Frame
57 days
Secondary Outcome Measure Information:
Title
Part B - Hospitalization or death from any cause by end of study
Description
Hospitalization or death from any cause within 8 weeks after the first dose of study medication
Time Frame
57 days
Title
Part A and at Interim Analysis in Part B - assessment of risk of hospitilization or death
Description
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
Time Frame
57 days
Title
Part B - Proportion of patients who are PCR-negative at various time points during the study.
Description
Proportion of patients who are PCR-negative at days 8, 15, 29 and 57 from the start of treatment (landmark analyses)
Time Frame
57 days
Title
Part B - Time to resolution of individual disease-related symptoms present at baseline
Description
Time to resolution of individual disease-related symptoms present at baseline
Time Frame
57 days
Title
Part B - Development of new disease-related symptoms on study
Description
Development of new disease-related symptoms on study will be captured using the same questionnaire as is being used to capture resolution of symptoms.
Time Frame
57 days
Title
Part B - Development of pneumonia on study
Description
Incidence of pneumonia during study among patients without baseline pneumonia
Time Frame
57 days
Title
Part B - Changes in laboratory markers of disease severity
Description
Changes in oxygen saturation from baseline to time points at which these are measured on study
Time Frame
57 days
Title
Part B - Changes in laboratory markers of disease severity
Description
Changes in CRP from baseline to time points at which these are measured on study
Time Frame
57 days
Title
Part B - Changes in laboratory markers of disease severity
Description
Changes in lymphocyte count from baseline to time points at which these are measured on study
Time Frame
57 days
Title
Part B - Changes in laboratory markers of disease severity
Description
Changes in cardiac troponin from baseline to time points at which these are measured on study
Time Frame
57 days
Title
Part B - Changes in laboratory markers of disease severity
Description
Changes in D-dimer levels from baseline to time points at which these are measured on study
Time Frame
57 days
Title
Part B - Adverse events
Description
Adverse events
Time Frame
57 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terry Plasse, MD
Organizational Affiliation
RedHill Biopharma Limited
Official's Role
Study Director
Facility Information:
Facility Name
Beautiful Minds Clinical Research
City
Cutler Bay
State/Province
Florida
ZIP/Postal Code
33157
Country
United States
Facility Name
Research in Miami Inc.
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33013
Country
United States
Facility Name
South Florida Research Phase I-IV, Inc.
City
Miami Springs
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Facility Name
Angels Clinical Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33122
Country
United States
Facility Name
Great Lakes Research Group
City
Bay City
State/Province
Michigan
ZIP/Postal Code
48706
Country
United States
Facility Name
Henry Ford Hospital, emergency department
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Prime Global Research
City
Bronx
State/Province
New York
ZIP/Postal Code
10456
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
On-Site Clinical Solutions
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28277
Country
United States
Facility Name
University Hospitals Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Southwest Family Medicine Research
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Langeberg Medical Centre - Clinical Trials
City
Kraaifontein
State/Province
Cape Town
ZIP/Postal Code
7570
Country
South Africa
Facility Name
Roodepoort Medicross Clinical Trial Research Centre
City
Roodepoort
State/Province
Gauteng
ZIP/Postal Code
1724
Country
South Africa
Facility Name
FCRN Clinical Trial Centre
City
Vereeniging
State/Province
Gauteng
ZIP/Postal Code
1935
Country
South Africa
Facility Name
PJ Sebastian
City
KwaZulu
State/Province
Natal
ZIP/Postal Code
4092
Country
South Africa
Facility Name
Global Clinical Trials PTY (LTD)
City
Arcadia
State/Province
Pretoria
ZIP/Postal Code
0001
Country
South Africa
Facility Name
WorthWhile Clinical Trials
City
Benoni
ZIP/Postal Code
1500
Country
South Africa
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease
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