Trial Outcomes & Findings for Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease (NCT NCT04723537)

Last Updated: 2024-06-06

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

61 participants

Primary outcome timeframe

57 days

Results posted on

2024-06-06

Participant Flow

Participant milestones

Participant milestones
Measure	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. Part A: Upamostat 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Overall Study STARTED	20	21	20
Overall Study COMPLETED	16	20	18
Overall Study NOT COMPLETED	4	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Part A: Upamostat 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Overall Study Withdrawal by Subject	3	0	0
Overall Study Physician Decision	0	0	1
Overall Study Medical monitor decision, sponsor decision and other	1	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Upamostat 200 mg n=20 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=21 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=20 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo	Total n=61 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=93 Participants	19 Participants n=4 Participants	18 Participants n=27 Participants	55 Participants n=483 Participants
Age, Categorical >=65 years	2 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	6 Participants n=483 Participants
Age, Continuous	40.5 years n=93 Participants	50.0 years n=4 Participants	46.0 years n=27 Participants	47.0 years n=483 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	9 Participants n=4 Participants	11 Participants n=27 Participants	34 Participants n=483 Participants
Sex: Female, Male Male	6 Participants n=93 Participants	12 Participants n=4 Participants	9 Participants n=27 Participants	27 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	6 Participants n=483 Participants
Race (NIH/OMB) White	18 Participants n=93 Participants	17 Participants n=4 Participants	16 Participants n=27 Participants	51 Participants n=483 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race/Ethnicity, Customized Hispanic/Latino	10 participants n=93 Participants	10 participants n=4 Participants	7 participants n=27 Participants	27 participants n=483 Participants
Race/Ethnicity, Customized Non-Hispanic/Non-Latino	10 participants n=93 Participants	11 participants n=4 Participants	13 participants n=27 Participants	34 participants n=483 Participants
Region of Enrollment United States	19 participants n=93 Participants	21 participants n=4 Participants	20 participants n=27 Participants	61 participants n=483 Participants
Region of Enrollment South Africa	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants

PRIMARY outcome

Timeframe: 57 days

Population: All patients entered

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=20 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=21 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=20 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Part A - Determination of the Safety and Tolerability of Two Dose Levels and Selection of an Upamostat Dose for Part B Safe and well tolerated	20 Participants	21 Participants	20 Participants
Part A - Determination of the Safety and Tolerability of Two Dose Levels and Selection of an Upamostat Dose for Part B Dose reductions or discontinuation of therapy	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 57 days

Population: ITT

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=20 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=21 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=20 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Hospitalization or Death From Any Cause by End of Study	0 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 57 days

Population: Patient with concerning conditions per NIAID guideline

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=8 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=15 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=13 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Hospitalization or Death For COVID With Presence of Concerning Conditions	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 57 days

Population: ITT

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: 1. is afebrile (\<38.0°C core temperature/37.5°C oral 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), 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).

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=20 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=21 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=20 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Time to Sustained Recovery From Symptomatic Illness for Part A (Protocol Definition)	19.0 days Interval 13.0 to 57.0	27.0 days Interval 14.0 to 43.0	19 days Interval 12.5 to 38.0

SECONDARY outcome

Timeframe: 57 days

Population: ITT

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.

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=20 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=21 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=20 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Time to Sustained Recovery From Symptomatic Illness - Part A (SAP Definition)	29.5 days Interval 18.5 to 57.0	38.0 days Interval 16.0 to 57.0	38.0 days Interval 15.5 to 57.0

SECONDARY outcome

Timeframe: 57 days

Population: ITT

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=20 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=21 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=20 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Development of New Disease-related Symptoms and/or Pneumonia on Study	17 Participants	12 Participants	16 Participants

SECONDARY outcome

Timeframe: 8 days

Population: Patients with PCR results

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=19 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=19 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=17 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Proportion of Patients Who Are PCR-negative at Day 8 From the Start of Treatment	9 Participants	10 Participants	7 Participants

SECONDARY outcome

Timeframe: 57 days

Population: Patients with PCR results

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=16 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=13 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=18 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Proportion of Patients Who Are PCR-negative at Day 57 From the Start of Treatment	16 Participants	12 Participants	17 Participants

SECONDARY outcome

Timeframe: 57 days

Population: Patient with D dimer results at end of study

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=14 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=14 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=18 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Changes in D-dimer Levels, From Baseline to Day 57	-0.21 ug/ml Standard Deviation 0.27	-0.64 ug/ml Standard Deviation 0.81	0.01 ug/ml Standard Deviation 0.41

POST_HOC outcome

Timeframe: 57 days

Population: Patients with severe symptoms at baseline

Outcome measures

Outcome measures
Measure	Part A: Upamostat 200 mg n=8 Participants Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=11 Participants Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=10 Participants Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Time to Sustained Recovery From Severe Symptoms - Part A	4.0 days Interval 2.0 to 6.0	3.0 days Interval 2.0 to 6.0	8.0 days Interval 4.0 to 26.0

Adverse Events

Part A: Upamostat 200 mg

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Part A: Upamostat 400 mg

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Part A: Placebo

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: Upamostat 200 mg n=20 participants at risk Each 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 200 mg: 1 capsule comprising 200 mg of upamostat and 1 capsule comprising matching placebo.	Part A: Upamostat 400 mg n=21 participants at risk Each day participants will receive two 200 mg doses of upamostat, for a total of 14 days. Part A: Upamostat 400 mg: 2 capsules, each capsule comprising 200 mg of upamostat	Part A: Placebo n=20 participants at risk Each day participants will receive two matching placebos, for a total of 14 days. Part A and B: Placebo: 1 or 2 capsules, each capsule a matching placebo
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/20 • 57 days AEs assessed first dose through day 57. All new abnormal lab findings and those abnormal at baseline which change by at least one toxicity grade as defined in \[NCI CTCAE\] v5.0 were considered AEs. Laboratory values outside the normal range will not be considered AEs if they are generally not considered as indicating an abnormality in CTCAE. Exacerbation of COVID-19-related signs and symptoms were considered lack of efficacy and not adverse events. Hospitalization for COVID was not an SAE.	4.8% 1/21 • Number of events 1 • 57 days AEs assessed first dose through day 57. All new abnormal lab findings and those abnormal at baseline which change by at least one toxicity grade as defined in \[NCI CTCAE\] v5.0 were considered AEs. Laboratory values outside the normal range will not be considered AEs if they are generally not considered as indicating an abnormality in CTCAE. Exacerbation of COVID-19-related signs and symptoms were considered lack of efficacy and not adverse events. Hospitalization for COVID was not an SAE.	0.00% 0/20 • 57 days AEs assessed first dose through day 57. All new abnormal lab findings and those abnormal at baseline which change by at least one toxicity grade as defined in \[NCI CTCAE\] v5.0 were considered AEs. Laboratory values outside the normal range will not be considered AEs if they are generally not considered as indicating an abnormality in CTCAE. Exacerbation of COVID-19-related signs and symptoms were considered lack of efficacy and not adverse events. Hospitalization for COVID was not an SAE.

Other adverse events

Additional Information

Gilead Raday, COO

RedHill Biopharma Ltd.

Phone: +972-(0)3-541-3131

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee There are disclosure agreements between the Sponsor and each of the participating clinical sites and PI that slightly differ.
Publication restrictions are in place

Restriction type: OTHER