Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    RHB-107
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04723537
Recruitment Status : Recruiting
First Posted : January 25, 2021
Last Update Posted : October 12, 2021
Sponsor:
Information provided by (Responsible Party):
RedHill Biopharma Limited

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
Covid19 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 16, 2021
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

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




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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 57 days ]
    Time to resolution of individual disease-related symptoms present at baseline

  5. Part B - Development of new disease-related symptoms on study [ Time Frame: 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 [ Time Frame: 57 days ]
    Incidence of pneumonia during study among patients without baseline pneumonia

  7. Part B - Changes in laboratory markers of disease severity [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 57 days ]
    Changes in D-dimer levels from baseline to time points at which these are measured on study

  12. Part B - Adverse events [ Time Frame: 57 days ]
    Adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04723537


Locations
Show Show 18 study locations
Sponsors and Collaborators
RedHill Biopharma Limited
Investigators
Layout table for investigator information
Study Director: Terry Plasse, MD RedHill Biopharma Limited
Layout table for additonal information
Responsible Party: RedHill Biopharma Limited
ClinicalTrials.gov Identifier: NCT04723537    
Other Study ID Numbers: RHB-107-01
First Posted: January 25, 2021    Key Record Dates
Last Update Posted: October 12, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases