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Trial record 3 of 57 for:    redhill

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

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ClinicalTrials.gov Identifier: NCT04723537
Recruitment Status : Recruiting
First Posted : January 25, 2021
Last Update Posted : April 15, 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, PCR-positive 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 after 2, 4 and 8 weeks on study; additional televisits will also be conducted. At the home 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.

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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 2021
Estimated Study Completion Date : September 2021

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. Sustained recovery is recovery, per below definition, maintained for at least 28 days or through end of study, whichever comes first. [ Time Frame: 57 days ]

    A patient will be considered to have recovered once he or she meets the following criteria:

    1. is afebrile (<38.0° C core temperature) for at least 48 hours without use of antipyretics;
    2. all symptoms have resolved or returned to pre- illness levels (e.g., if patient had respiratory compromise prior to the onset of COVID-19), except for:

      1. fatigue, anosmia, ageusia or dysgeusia, which may be persistent at level similar to that during the acute illness, i.e., the same level per symptom questionnaire;
      2. 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). A symptom questionnaire generally following the FDA guidance, Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subject in Clinical Trials of Drugs and Biological Products for COVID-19 Prevention or Treatment, September, 2020, for both the terms and severity grading, will be used to capture symptomology.


Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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.

  4. Part B - Incidence of pneumonia during study among patients without baseline pneumonia [ Time Frame: 57 days ]
    Incidence of pneumonia during study among patients without baseline pneumonia

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Part B - Hospitalization [ Time Frame: 57 days ]
    Hospitalization within 8 weeks after the first dose of study medication, overall and for COVID-19-related indications

  11. Part B - Mortality [ Time Frame: 57 days ]
    Mortality within 57 days of the start of study medication

  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.


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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 assay of respiratory tract sample.
  2. Patient must have either become symptomatic or found positive by RT-PCR 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. At baseline the laboratory parameters listed below are not worse than NCI CTCAE v5.0 grade 2, with exceptions noted below:

    • Bilirubin ≤ 1.5 times upper limit of normal (ULN; grade 1 only)
    • AST (SGOT), ALT (SGPT) ≤ 5.0 x ULN,
    • Serum creatinine ≤ 1.5 X ULN (grade 1)
    • Albumin ≥ 2.0 g/dL
  6. Acceptable hematologic status:

    • Absolute neutrophil count ≥1000 cells/mm3
    • Platelet count ≥50,000 plt/mm3
    • Hemoglobin ≥ 8.0 g/dL
  7. Clinically acceptable blood sugar control in the opinion of the investigator.
  8. INR and partial thromboplastin time (PTT) each ≤ 1.5 X ULN (i.e., grade 1), unless patient is taking dabigatran or heparin.
  9. Oxygen saturation by pulse oximeter ≥92% on room air
  10. Negative pregnancy test (if woman of childbearing potential).
  11. 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.
  12. Ability to complete the daily diary independently.
  13. 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, chloroquine, hydroxychloroquine, azithromycin or other specific antiviral therapy for COVID-19 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


Contacts
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Contact: Danielle Abramson, PhD 978-376-2156 danielle@redhillbio.com
Contact: Danielle Fisher, MHS, ACRP-CP dafisher@fhiclinical.com

Locations
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United States, Florida
RecioMed Clinical Research Network, Inc. Not yet recruiting
Boynton Beach, Florida, United States, 33472
Contact: Diana de la Torre    561-880-0170    diana@reciomed.com   
Principal Investigator: Luis Pena-Hernandez, MD         
South Florida Research Phase I-IV, Inc. Recruiting
Miami Springs, Florida, United States, 33166
Contact: Lisbelle Revoredo    305-418-0847    lrevoredo@southfloridatrials.com   
Principal Investigator: Belkis Delgado, MD, CPI         
Floridian Research Institute Not yet recruiting
Miami, Florida, United States, 33145
Contact: Milene Garcia    786-391-1137    mgarcia@floridianresearch.com   
Principal Investigator: Gretel Trullenque, MD         
United States, Michigan
Henry Ford Hospital, emergency department Recruiting
Detroit, Michigan, United States, 48202
Contact: Timothy Asmar    313-404-9110    TAsmar2@hfhs.org   
Principal Investigator: Joseph B Miller, MD         
United States, Ohio
University Hospitals Cleveland Recruiting
Cleveland, Ohio, United States, 44106
Contact: Melinda Caraballo, RN    833-788-7425    Melinda.Caraballo@UHhospitals.org   
Principal Investigator: Grace A McComsey, MD, FIDSA         
United States, Texas
DM Clinical Research Recruiting
Tomball, Texas, United States, 77375
Contact: Amar Syed       amar@apdcr.com   
Principal Investigator: Najmuddin Karimjee, MD         
Sponsors and Collaborators
RedHill Biopharma Limited
Investigators
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Study Director: Terry Plasse, MD RedHill Biopharma Limited
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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: April 15, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No