Covid19Phase 2/3NCT04723537
Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease
A Phase 2/3 study testing Part A: Upamostat 200 mg, Part A: Upamostat 400 mg and Part B: Upamostat 200 or 400 mg in people with Covid19, run by RedHill Biopharma Limited at 17 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Part A: Upamostat 200 mg, Part A: Upamostat 400 mg and Part B: Upamostat 200 or 400 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 17 sitesin 2 countries
- Study dates
- 16 Feb 2021to 28 Dec 2021
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 9Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
United States11 sites
Great Lakes Research Group
Bay City, Michigan, 48706
On-Site Clinical Solutions
Charlotte, North Carolina, 28277
University Hospitals Cleveland
Cleveland, Ohio, 44106
Beautiful Minds Clinical Research
Cutler Bay, Florida, 33157
Southwest Family Medicine Research
Dallas, Texas, 75235
Henry Ford Hospital, emergency department
Detroit, Michigan, 48202
Research in Miami Inc.
Hialeah, Florida, 33013
Angels Clinical Research Institute
Miami, Florida, 33122
South Florida Research Phase I-IV, Inc.
Miami Springs, Florida, 33166
Prime Global Research
The Bronx, New York, 10456
Montefiore Medical Center
The Bronx, New York, 10467
South Africa6 sites
Global Clinical Trials PTY (LTD)
Arcadia, Pretoria, 0001
WorthWhile Clinical Trials
Benoni, 1500
Langeberg Medical Centre - Clinical Trials
Kraaifontein, Cape Town, 7570
PJ Sebastian
KwaZulu, KwaZulu-Natal, 4092
Roodepoort Medicross Clinical Trial Research Centre
Roodepoort, Gauteng, 1724
FCRN Clinical Trial Centre
Vereeniging, Gauteng, 1935
About this study
Official title: Phase 2/3 Study of Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease
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.
Read the 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.
- Conditions
- Covid19
- Being tested
- Part A: Upamostat 200 mg, Part A: Upamostat 400 mg, Part A and B: Placebo, Part B: Upamostat 200 or 400 mg
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part A: Upamostat 200 mgDrug
1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.
Part A: Upamostat 400 mgDrug
2 capsules, each capsule comprising 200 mg of upamostat
Part A and B: PlaceboDrug
1 or 2 capsules, each capsule a matching placebo
Part B: Upamostat 200 or 400 mgDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Upamostat 200 mg | Experimental | Each day participants will receive a single 200 mg dose of upamostat along with a single matching placebo, for a total of 14 days. Receives: Drug: Part A: Upamostat 200 mg |
| Part A: Upamostat 400 mg | Experimental | Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Receives: Drug: Part A: Upamostat 400 mg |
| Part A: Placebo | Placebo comparator | Each day participants will receive two matching placebos, for a total of 14 days. Receives: Drug: Part A and B: Placebo |
| Part B: Upamostat | Experimental | 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. Receives: Drug: Part B: Upamostat 200 or 400 mg |
| Part B: Placebo | Placebo comparator | 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. Receives: Drug: Part A and B: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A - Determination of the Safety and Tolerability of Two Dose Levels and Selection of an Upamostat Dose for Part B
This is a qualitative measure that takes into account safety and tolerability 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.
Measured: 57 days
Secondary outcomes (8)
Hospitalization or Death From Any Cause by End of Study
Measured: 57 days
Hospitalization or Death For COVID With Presence of Concerning Conditions
Measured: 57 days
Time to Sustained Recovery From Symptomatic Illness for Part A (Protocol Definition)
Sustained recovery was defined as recovery maintained for at least 14 or 28 days (two analyses), or through end of study, whichever comes first. A patient was considered to have recovered once he or she met the following criteria:
- is afebrile (<38.0°C core temperature/37.5°C oral temperature) for at least 48 hours without use of antipyretics;
- all symptoms have resolved or returned to pre-illness levels (e.g., if patient had respiratory compromise prior to the onset of COVID), except for:
- 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;
- 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).
Measured: 57 days
Time to Sustained Recovery From Symptomatic Illness - Part A (SAP Definition)
First day at which there are no symptoms, and no occurrence of any symptoms for at least 14 days or until end of study, whichever came first. Mild symptoms which were noted as preexisting conditions were excluded from this calculation. For example, if a patient noted preexisting shortness of breath, mild shortness of breath was excluded from the calculation of no symptoms.
Measured: 57 days
Development of New Disease-related Symptoms and/or Pneumonia on Study
Measured: 57 days
Proportion of Patients Who Are PCR-negative at Day 8 From the Start of Treatment
Measured: 8 days
Proportion of Patients Who Are PCR-negative at Day 57 From the Start of Treatment
Measured: 57 days
Changes in D-dimer Levels, From Baseline to Day 57
Measured: 57 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2021
- Study start16 Feb 2021
- Primary completion28 Dec 2021
- Study completion28 Dec 2021
Why it stopped: Part A complete; corporate decision made to cancel Part B.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- RedHill Biopharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Terry Plasse, MD, Study director, RedHill Biopharma Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04723537
- Sponsor's protocol ID
- RHB-107-01
- Status last verified
- Mar 2024
- First submitted
- 18 Jan 2021
- Last updated
- 6 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36549549Plasse 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.
PubMed 37970658
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2/3 Study of Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease
- ClinicalTrials.gov ID
- NCT04723537
- Acronym / sponsor ID
- RHB-107-01
- Conditions
- Covid19
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Part A complete; corporate decision made to cancel Part B.
- Enrolment
- 61 participants (actual)
- Lead sponsor
- RedHill Biopharma LimitedIndustry (pharma, biotech, devices)
- Study start
- 16 Feb 2021 (actual)
- Primary completion
- 28 Dec 2021 (actual)
- Study completion
- 28 Dec 2021 (actual)
- First posted
- 25 Jan 2021 (actual)
- Results
- Posted 6 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A: Upamostat 200 mg | Experimental | Drug: Part A: Upamostat 200 mgEach day participants will receive a single 200 mg dose of upamostat along with a single matching placebo, for a total of 14 days. |
| Part A: Upamostat 400 mg | Experimental | Drug: Part A: Upamostat 400 mgEach day participants will receive two 200 mg doses of upamostat, for a total of 14 days. |
| Part A: Placebo | Placebo comparator | Drug: Part A and B: PlaceboEach day participants will receive two matching placebos, for a total of 14 days. |
| Part B: Upamostat | Experimental | Drug: Part B: Upamostat 200 or 400 mgBased 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. |
| Part B: Placebo | Placebo comparator | Drug: Part A and B: PlaceboBased 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Part A: Upamostat 200 mg1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo. | Drug | Part A: Upamostat 200 mg |
| Part A: Upamostat 400 mg2 capsules, each capsule comprising 200 mg of upamostat | Drug | Part A: Upamostat 400 mg |
| Part A and B: Placebo1 or 2 capsules, each capsule a matching placebo | Drug | Part A: Placebo, Part B: Placebo |
| Part B: Upamostat 200 or 400 mgBased 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. | Drug | Part B: Upamostat |
Primary outcome
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
This is a qualitative measure that takes into account safety and tolerability 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.
8 secondary outcomes
Hospitalization or Death From Any Cause by End of Study
Time frame: 57 days
Hospitalization or Death For COVID With Presence of Concerning Conditions
Time frame: 57 days
Time to Sustained Recovery From Symptomatic Illness for Part A (Protocol Definition)
Time frame: 57 days
Time to Sustained Recovery From Symptomatic Illness - Part A (SAP Definition)
Time frame: 57 days
Development of New Disease-related Symptoms and/or Pneumonia on Study
Time frame: 57 days
Proportion of Patients Who Are PCR-negative at Day 8 From the Start of Treatment
Time frame: 8 days
Proportion of Patients Who Are PCR-negative at Day 57 From the Start of Treatment
Time frame: 57 days
Changes in D-dimer Levels, From Baseline to Day 57
Time frame: 57 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36549549Plasse 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.
- Results publication: PubMed 37970658Plasse 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Terry Plasse, MD study director
RedHill Biopharma Limited
17 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Part A: Upamostat 200 mg, Part A: Upamostat 400 mg and Part B: Upamostat 200 or 400 mg in people with Covid19, run by RedHill Biopharma Limited at 17 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04723537, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2024; AzTrials last refreshed its copy on 8 Nov 2026.