Trial Outcomes & Findings for A Study of Opaganib in Coronavirus Disease 2019 Pneumonia (NCT NCT04414618)

Last Updated: 2022-03-21

Results Overview

Maximal oxygen flow (L/min) was recorded daily for the 14 days of treatment for each participant. Participant individual area under the curve (AUC) was calculated based on the trapezoidal rule, after subtracting the baseline oxygen requirement at each day. The median AUC absolute change from baseline (L/min) for each treatment arm is presented.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

14 days

Results posted on

2022-03-21

Participant Flow

Participant milestones

Participant milestones
Measure	Opaganib Study participants will receive opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, in addition to standard of care (pharmacological and/or supportive).	Placebo Study participants will receive placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours Placebo: Study participants will receive placebo 2 x 250 mg capsules (500 mg) every 12 hours, in addition to standard of care (pharmacological and/or supportive).
Overall Study STARTED	23	19
Overall Study COMPLETED	15	12
Overall Study NOT COMPLETED	8	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Opaganib Study participants will receive opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, in addition to standard of care (pharmacological and/or supportive).	Placebo Study participants will receive placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours Placebo: Study participants will receive placebo 2 x 250 mg capsules (500 mg) every 12 hours, in addition to standard of care (pharmacological and/or supportive).
Overall Study Death	3	3
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	2	3
Overall Study Physician Decision	1	0

Baseline Characteristics

A Study of Opaganib in Coronavirus Disease 2019 Pneumonia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Opaganib n=23 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=19 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Total n=42 Participants Total of all reporting groups
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	19 participants n=7 Participants	42 participants n=5 Participants
Age, Customized <70 years	20 Participants n=5 Participants	15 Participants n=7 Participants	35 Participants n=5 Participants
Age, Customized >=70 years	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	11 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 14 days

Population: Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).

Outcome measures

Outcome measures
Measure	Opaganib n=22 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Measurement of the Change in Oxygen Requirement From Baseline	-38.8 L/min*day Interval -56.5 to 0.0	-33.0 L/min*day Interval -149.5 to -12.5

SECONDARY outcome

Timeframe: 14 days

Population: Modified ITT (mITT) population (randomized and treated with at least one dose of study medication). However, one subject who did not have supplemental oxygen requirement at randomization was excluded from this analysis.

The time required between arms to achieve 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min.

Outcome measures

Outcome measures
Measure	Opaganib n=21 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Measurement of Time to the Reduction in Oxygen Requirement.	5.00 Days Interval 4.0 to 12.0	8.00 Days Interval 4.0 to Some subjects didn't reach 50% reduction in oxygen requirement.

SECONDARY outcome

Timeframe: 14 days

Population: Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).

The percentage of subjects in each arm no longer requiring supplemental oxygen for at least 24 hours by Day 14.

Outcome measures

Outcome measures
Measure	Opaganib n=22 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
The Percentage of Subjects no Longer Receiving Supplemental Oxygen for at Least 24 Hours by Day 14	11 Participants	4 Participants

SECONDARY outcome

Timeframe: 6 weeks

Population: Modified ITT (mITT) population (randomized and treated with at least one dose of study medication). However, as most subjects had been discharged by Day 7 and as the study was not designed to be performed on an outpatient basis, data was not available from enough subjects to perform these analyses.

The time in each arm to two consecutive negative swabs for SARS-CoV-2 by PCR nasopharyngeal or oropharyngeal swab, at least 24 hrs. apart.

Outcome measures

Outcome measures
Measure	Opaganib n=22 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Time to Negative Swabs for SARS-CoV-2 by PCR Post Treatment	NA Days As most subjects had been discharged by Day 7 and as the study was not designed to be performed on an outpatient basis, data was not available from enough subjects to perform these analyses.	NA Days As most subjects had been discharged by Day 7 and as the study was not designed to be performed on an outpatient basis, data was not available from enough subjects to perform these analyses.

SECONDARY outcome

Timeframe: 14 days

The percentage of subjects in each arm to achieve two consecutive negative PCR nasopharyngeal or oropharyngeal swabs for SARS-CoV-2 at Day 14, at least 24 hrs. apart.

Outcome measures

Outcome measures
Measure	Opaganib n=22 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
The Percentage of Subjects With at Least Two Consecutive Negative Swabs for SARS-CoV-2 by PCR at Day 14	NA Participants As most subjects had been discharged by Day 7 and as the study was not designed to be performed on an outpatient basis, data was not available from enough subjects to perform these analyses.	NA Participants As most subjects had been discharged by Day 7 and as the study was not designed to be performed on an outpatient basis, data was not available from enough subjects to perform these analyses.

SECONDARY outcome

Timeframe: From screening phase and every day from day 1 to day 14 of treatment

Population: Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).

The percentage of patients in each arm who require intubation and mechanical ventilation by Day 14

Outcome measures

Outcome measures
Measure	Opaganib n=22 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Intubation and Mechanical Ventilation Requirements	2 Participants	2 Participants

SECONDARY outcome

Timeframe: From screening phase and every day from day 1 to day 14 of treatment

Population: Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).

The time in each arm for the patient to require mechanical ventilation.

Outcome measures

Outcome measures
Measure	Opaganib n=22 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Evaluation of the Time to Intubation and Mechanical Ventilation	NA Days The median time to intubation and mechanical ventilation was not reached in either group.	NA Days The median time to intubation and mechanical intubation was not reached in either group.

SECONDARY outcome

Timeframe: From screening phase and every day from day 1 to day 14 of treatment

Population: Patients in the Modified ITT (mITT) population (randomized and treated with at least one dose of study medication) with at least one measurement of fever at baseline.

The proportion of patients in each arm, with at least one measurement of fever at baseline (defined as temperature \>38.0 C\[100.4 F\]), who are afebrile (defined as temperature \<37.2C \[99 F\]) at Day 14

Outcome measures

Outcome measures
Measure	Opaganib n=4 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=1 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Evaluation the Proportion of Patients, With at Least One Measurement of Fever at Baseline Who Are Afebrile at Day 14	3 Participants	0 Participants

SECONDARY outcome

Timeframe: 30 days after day 1 of treatment

Population: Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).

The mortality in each arm 30 days post-baseline.

Outcome measures

Outcome measures
Measure	Opaganib n=22 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Evaluation of Mortality 30 Days Post-baseline	3 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

Population: Safety population includes all subjects randomized and treated with at least one dose of study medication. One subject randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice.

The number of subjects with treatment-emergent adverse events in each arm of all treatment-emergent adverse events (TEAEs).

Outcome measures

Outcome measures
Measure	Opaganib n=23 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Safety TEAEs	11 Participants	9 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

The number of subjects with serious adverse events (SAEs) in each arm.

Outcome measures

Outcome measures
Measure	Opaganib n=23 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Safety SAEs	3 Participants	5 Participants

POST_HOC outcome

Timeframe: 14 days

The changes in supplemental oxygen requirement \[oxygen flow (L/min)\] were calculated as percent change from baseline to account for the variability of baseline values, up to Day 14. Percentage from baseline area under the (AUC) is calculated by dividing the baseline adjusted AUC with the baseline. The median AUC absolute change from baseline (L/min) for each treatment arm is presented.

Outcome measures

Outcome measures
Measure	Opaganib n=21 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Percent Change in Measurement of the Daily Oxygen Requirement	-770.0 Percentage of change from baseline*day Interval -1044.3 to 0.0	-583.6 Percentage of change from baseline*day Interval -916.7 to -223.3

POST_HOC outcome

Timeframe: 14 days

The relative benefit for each treatment group derived from total oxygen requirement \[area under the curve (AUC)\] for each arm using daily supplemental oxygen flow (L/min) over 14 days based on the daily percent change (reduction or increase) from baseline adjusted for each subject. As the maximal possible AUC benefit of -1250% is achieved if reduction to zero (100% reduction) occurred the day after baseline and was maintained through Day 14, the relative benefit derived for each group was calculated.

Outcome measures

Outcome measures
Measure	Opaganib n=21 Participants Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).	Placebo n=18 Participants Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Measurement of the Relative Benefit for Each Treatment Are as Derived From Oxygen Requirements	61.6 Percentage of relative benefit	46.7 Percentage of relative benefit

Adverse Events

Opaganib

Serious events: 3 serious events

Other events: 11 other events

Deaths: 3 deaths

Placebo

Serious events: 5 serious events

Other events: 9 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Opaganib n=23 participants at risk Study participants will receive opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours Opaganib: Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, in addition to standard of care (pharmacological and/or supportive).	Placebo n=18 participants at risk Study participants will receive placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours Placebo: Study participants will receive placebo 2 x 250 mg capsules (500 mg) every 12 hours, in addition to standard of care (pharmacological and/or supportive).
Renal and urinary disorders Acute kidney injury	4.3% 1/23 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.	11.1% 2/18 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.
Infections and infestations COVID-19 pneumonia	4.3% 1/23 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.	5.6% 1/18 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/23 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.	5.6% 1/18 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.
Respiratory, thoracic and mediastinal disorders Respiratory failure	8.7% 2/23 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.	11.1% 2/18 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.
Infections and infestations Sepsis	4.3% 1/23 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.	0.00% 0/18 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.
Infections and infestations Septic shock	0.00% 0/23 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.	5.6% 1/18 • 6 weeks One participant in the placebo arm was not dosed and therefore was removed from the safety population. One participant was randomized to receive placebo, was mistakenly given 2 doses of opaganib and is therefore included twice, once in each arm.

Other adverse events

Additional Information

Vered Katz Ben-Yair

RedHill Biopharma Ltd.

Phone: +13474144462

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