COVID-19: A Study of Opaganib in Coronavirus Disease 2019 Pneumonia

Sponsor
RedHill Biopharma Limited (Industry)
Overall Status
Completed
CT.gov ID
NCT04414618
Collaborator
(none)
42
9
2
5.7
4.7
0.8

Study Details

Study Description

Brief Summary

This proof of concept study will take place in the US and other countries in approximately 15 clinical sites and will enroll about 40 hospitalized patients diagnosed with COVID-19 infection who have developed pneumonia and require supplemental oxygen. 20 patients will receive opaganib in addition to standard of care twice each day for 14 days. 20 will receive matching placebo in addition to standard of care unless the patient has been discharged from the hospital without requiring supplemental oxygen, in which case study drug will only be administered for 10 days. All participants will be followed up for 4 weeks after their last dose of study drug.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Opaganib, a sphingosine kinase-2 (SphK2) inhibitor, has been broadly tested in Phase I/II studies. Extensive nonclinical data indicates both anti-viral and anti-inflammatory activity via selective SphK2 inhibition which may prove beneficial for treating COVID-19 infection and resulting pneumonia. This proof of concept study will take place in the US and other countries and will enroll about 40 hospitalized patients diagnosed with COVID-19 infection who have developed pneumonia and require supplemental oxygen. Half of the patients, i.e. 20 patients, will receive opaganib in addition to standard of care for 14 days. The other 20 will receive matching placebo (capsules that do not contain the medication) in addition to standard of care. Study drug will be administered every day for 14 days, twice each day, unless the patient has been discharged from the hospital without requiring supplemental oxygen, in which case study drug will only be administered for 10 days. All participants will be followed up for 4 weeks after their last dose of study drug.

Study Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2a Study, in Adult Subjects Hospitalized With SARS-CoV-2 Positive Pneumonia
Actual Study Start Date :
Jul 2, 2020
Actual Primary Completion Date :
Nov 26, 2020
Actual Study Completion Date :
Dec 23, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: opaganib

Study participants will receive opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours

Drug: Opaganib
Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Other Names:
  • Yeliva
  • ABC294640
  • Placebo Comparator: placebo

    Study participants will receive placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours

    Drug: Placebo
    Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).

    Outcome Measures

    Primary Outcome Measures

    1. Measurement of the Change in Oxygen Requirement From Baseline [14 days]

      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.

    Secondary Outcome Measures

    1. Measurement of Time to the Reduction in Oxygen Requirement. [14 days]

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

    2. The Percentage of Subjects no Longer Receiving Supplemental Oxygen for at Least 24 Hours by Day 14 [14 days]

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

    3. Time to Negative Swabs for SARS-CoV-2 by PCR Post Treatment [6 weeks]

      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.

    4. The Percentage of Subjects With at Least Two Consecutive Negative Swabs for SARS-CoV-2 by PCR at Day 14 [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.

    5. Intubation and Mechanical Ventilation Requirements [From screening phase and every day from day 1 to day 14 of treatment]

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

    6. Evaluation of the Time to Intubation and Mechanical Ventilation [From screening phase and every day from day 1 to day 14 of treatment]

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

    7. Evaluation the Proportion of Patients, With at Least One Measurement of Fever at Baseline Who Are Afebrile at Day 14 [From screening phase and every day from day 1 to day 14 of treatment]

      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

    8. Evaluation of Mortality 30 Days Post-baseline [30 days after day 1 of treatment]

      The mortality in each arm 30 days post-baseline.

    Other Outcome Measures

    1. Safety TEAEs [6 weeks]

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

    2. Safety SAEs [6 weeks]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Adult male or female ≥18 to ≤80 years of age

    2. Proven COVID-19 infection per RT-PCR assay of a pharyngeal sample (nasopharyngeal or oropharyngeal) AND pneumonia defined as radiographic opacities on chest X-ray

    3. The patient requires supplemental oxygen at baseline

    4. The patient, guardian or legal representative has signed a written IRB-approved informed consent.

    1. Male participants with female partners of child-bearing potential agree to one of the following methods of contraception during the treatment period and for at least 1 month after the last dose of study drug:
    • Abstinence from penile-vaginal intercourse and agree to remain abstinent.

    • Male condom, with female partner using a highly effective contraceptive method. (For further details regarding highly effective contraceptive methods please see section 9.3.)

    In addition, male participants must refrain from donating sperm for the duration of the study and for 1 months after last dose of study drug.

    Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration for at least 1 months after the last dose of study drug

    Female participants:
    A female participant is eligible to participate if she is:
    1. not pregnant

    2. not breastfeeding

    3. not a woman of child-bearing potential (WOCBP, as defined in Section 9.3)

    4. a WOCBP who agrees to use a highly effective method of contraception consistently and correctly during the treatment period and for at least 1 months after the last dose of study drug (please see further details on Section 9.3).

    Exclusion Criteria:
    1. Any co-morbidity that may add risk to the treatment in the judgement of the investigator.

    2. Requiring intubation and mechanical ventilation

    3. Patient having a do not intubate or do not resuscitate order

    4. Oxygen saturation >95% on room air

    5. Any preexisting respiratory condition that requires intermittent or continuous ambulatory oxygen prior to hospitalization

    6. Patient is, in the investigator's clinical judgment, unlikely to survive >72 hours

    7. Pregnant or nursing women

    8. Unwillingness or inability to comply with procedures required in this protocol.

    9. Corrected QT (QTc) interval on electrocardiogram (ECG) >470 ms for females or >450 ms for males, calculated using Friedericia's formula (QTcF)

    10. AST (SGOT) or ALT (SGPT) > 2.5 x upper limit of normal (ULN)

    11. Bilirubin >2.0 x ULN (except where bilirubin increase is due to Gilbert's Syndrome)

    12. Serum creatinine >2.0 X ULN

    13. Absolute neutrophil count <1000 cells/mm3

    14. Platelet count <75,000/mm3

    15. Hemoglobin <8.0 g/dL

    16. Currently taking medications that are sensitive CYP3A4, CYP1A2, CYP2C9, or CYP2C19 or CYP2D6 substrates and have a narrow therapeutic index. These should be decided in discussion with the Medical Monitor on a case-by-case basis.

    17. Currently taking medications that are strong inducers or inhibitors of CYP2D6 and CYP3A4. These should be decided in discussion with the Medical Monitor on a case-by-case basis.

    18. Currently taking warfarin, apixaban, argatroban or rivaroxaban.

    19. Current drug or alcohol abuse.

    20. Currently participating in a clinical study assessing pharmacological treatments, including anti-viral studies.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 HonorHealth Research Institute Scottsdale Arizona United States 85258
    2 Miami Cancer Institute Miami Florida United States 33176
    3 Henry Ford Hospital Detroit Michigan United States 48202
    4 Ascension St. John Hospital Detroit Michigan United States 48236
    5 Albany Medical Center Albany New York United States 12208
    6 Oregon Health & Science University Portland Oregon United States 97239
    7 Memorial Herman Southeast Hospital Houston Texas United States 77089
    8 Memorial Hermann, Memorial City Medical Center Houston Texas United States 77204
    9 Ziv Medical Center Safed Israel

    Sponsors and Collaborators

    • RedHill Biopharma Limited

    Investigators

    • Study Director: Mark L Levitt, MD, PhD, RedHill Biopharma Limited

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    RedHill Biopharma Limited
    ClinicalTrials.gov Identifier:
    NCT04414618
    Other Study ID Numbers:
    • ABC-110
    First Posted:
    Jun 4, 2020
    Last Update Posted:
    Mar 21, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Opaganib Placebo
    Arm/Group Description 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). 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).
    Period Title: Overall Study
    STARTED 23 19
    COMPLETED 15 12
    NOT COMPLETED 8 7

    Baseline Characteristics

    Arm/Group Title Opaganib Placebo Total
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Total of all reporting groups
    Overall Participants 23 19 42
    Age, Customized (Count of Participants)
    <70 years
    20
    87%
    15
    78.9%
    35
    83.3%
    >=70 years
    3
    13%
    4
    21.1%
    7
    16.7%
    Sex: Female, Male (Count of Participants)
    Female
    7
    30.4%
    8
    42.1%
    15
    35.7%
    Male
    16
    69.6%
    11
    57.9%
    27
    64.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    12
    52.2%
    8
    42.1%
    20
    47.6%
    Not Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    11
    47.8%
    11
    57.9%
    22
    52.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    4.3%
    1
    5.3%
    2
    4.8%
    Asian
    0
    0%
    1
    5.3%
    1
    2.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    3
    13%
    2
    10.5%
    5
    11.9%
    White
    18
    78.3%
    15
    78.9%
    33
    78.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    4.3%
    0
    0%
    1
    2.4%
    Region of Enrollment (participants) [Number]
    United States
    23
    100%
    19
    100%
    42
    100%

    Outcome Measures

    1. Primary Outcome
    Title Measurement of the Change in Oxygen Requirement From Baseline
    Description 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.
    Time Frame 14 days

    Outcome Measure Data

    Analysis Population Description
    Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 22 18
    Median (95% Confidence Interval) [L/min*day]
    -38.8
    -33.0
    2. Secondary Outcome
    Title Measurement of Time to the Reduction in Oxygen Requirement.
    Description The time required between arms to achieve 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min.
    Time Frame 14 days

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 21 18
    Median (95% Confidence Interval) [Days]
    5.00
    8.00
    3. Secondary Outcome
    Title The Percentage of Subjects no Longer Receiving Supplemental Oxygen for at Least 24 Hours by Day 14
    Description The percentage of subjects in each arm no longer requiring supplemental oxygen for at least 24 hours by Day 14.
    Time Frame 14 days

    Outcome Measure Data

    Analysis Population Description
    Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 22 18
    Count of Participants [Participants]
    11
    47.8%
    4
    21.1%
    4. Secondary Outcome
    Title Time to Negative Swabs for SARS-CoV-2 by PCR Post Treatment
    Description 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.
    Time Frame 6 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 22 18
    Median (95% Confidence Interval) [Days]
    NA
    NA
    5. Secondary Outcome
    Title The Percentage of Subjects With at Least Two Consecutive Negative Swabs for SARS-CoV-2 by PCR at Day 14
    Description 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.
    Time Frame 14 days

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 22 18
    Count of Participants [Participants]
    NA
    NaN
    NA
    NaN
    6. Secondary Outcome
    Title Intubation and Mechanical Ventilation Requirements
    Description The percentage of patients in each arm who require intubation and mechanical ventilation by Day 14
    Time Frame From screening phase and every day from day 1 to day 14 of treatment

    Outcome Measure Data

    Analysis Population Description
    Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 22 18
    Count of Participants [Participants]
    2
    8.7%
    2
    10.5%
    7. Secondary Outcome
    Title Evaluation of the Time to Intubation and Mechanical Ventilation
    Description The time in each arm for the patient to require mechanical ventilation.
    Time Frame From screening phase and every day from day 1 to day 14 of treatment

    Outcome Measure Data

    Analysis Population Description
    Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 22 18
    Median (95% Confidence Interval) [Days]
    NA
    NA
    8. Secondary Outcome
    Title Evaluation the Proportion of Patients, With at Least One Measurement of Fever at Baseline Who Are Afebrile at Day 14
    Description 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
    Time Frame From screening phase and every day from day 1 to day 14 of treatment

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 4 1
    Count of Participants [Participants]
    3
    13%
    0
    0%
    9. Secondary Outcome
    Title Evaluation of Mortality 30 Days Post-baseline
    Description The mortality in each arm 30 days post-baseline.
    Time Frame 30 days after day 1 of treatment

    Outcome Measure Data

    Analysis Population Description
    Modified ITT (mITT) population (randomized and treated with at least one dose of study medication).
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 22 18
    Count of Participants [Participants]
    3
    13%
    2
    10.5%
    10. Other Pre-specified Outcome
    Title Safety TEAEs
    Description The number of subjects with treatment-emergent adverse events in each arm of all treatment-emergent adverse events (TEAEs).
    Time Frame 6 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 23 18
    Count of Participants [Participants]
    11
    47.8%
    9
    47.4%
    11. Other Pre-specified Outcome
    Title Safety SAEs
    Description The number of subjects with serious adverse events (SAEs) in each arm.
    Time Frame 6 weeks

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 23 18
    Count of Participants [Participants]
    3
    13%
    5
    26.3%
    12. Post-Hoc Outcome
    Title Percent Change in Measurement of the Daily Oxygen Requirement
    Description 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.
    Time Frame 14 days

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 21 18
    Median (95% Confidence Interval) [Percentage of change from baseline*day]
    -770.0
    -583.6
    13. Post-Hoc Outcome
    Title Measurement of the Relative Benefit for Each Treatment Are as Derived From Oxygen Requirements
    Description 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.
    Time Frame 14 days

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Opaganib Placebo
    Arm/Group Description Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
    Measure Participants 21 18
    Number [Percentage of relative benefit]
    61.6
    46.7

    Adverse Events

    Time Frame 6 weeks
    Adverse Event Reporting Description 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.
    Arm/Group Title Opaganib Placebo
    Arm/Group Description 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). 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).
    All Cause Mortality
    Opaganib Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/23 (13%) 3/18 (16.7%)
    Serious Adverse Events
    Opaganib Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/23 (13%) 5/18 (27.8%)
    Infections and infestations
    COVID-19 pneumonia 1/23 (4.3%) 1/18 (5.6%)
    Sepsis 1/23 (4.3%) 0/18 (0%)
    Septic shock 0/23 (0%) 1/18 (5.6%)
    Renal and urinary disorders
    Acute kidney injury 1/23 (4.3%) 2/18 (11.1%)
    Respiratory, thoracic and mediastinal disorders
    Pneumonia aspiration 0/23 (0%) 1/18 (5.6%)
    Respiratory failure 2/23 (8.7%) 2/18 (11.1%)
    Other (Not Including Serious) Adverse Events
    Opaganib Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/23 (47.8%) 9/18 (50%)
    Blood and lymphatic system disorders
    Anemia 1/23 (4.3%) 1/18 (5.6%)
    Cardiac disorders
    Palpitations 1/23 (4.3%) 0/18 (0%)
    Tachycardia 0/23 (0%) 1/18 (5.6%)
    Gastrointestinal disorders
    Abdominal distension 0/23 (0%) 1/18 (5.6%)
    Constipation 1/23 (4.3%) 0/18 (0%)
    Diarrhoea 2/23 (8.7%) 0/18 (0%)
    Gastrooesophageal reflux disease 1/23 (4.3%) 0/18 (0%)
    Haematochezia 1/23 (4.3%) 0/18 (0%)
    Megacolon 0/23 (0%) 1/18 (5.6%)
    Nausea 1/23 (4.3%) 0/18 (0%)
    Vomiting 0/23 (0%) 1/18 (5.6%)
    General disorders
    Pyrexia 0/23 (0%) 2/18 (11.1%)
    Infections and infestations
    Candida infection 0/23 (0%) 1/18 (5.6%)
    Cellulitis 1/23 (4.3%) 0/18 (0%)
    Oral candidiasis 1/23 (4.3%) 0/18 (0%)
    Urinary tract infection bacterial 0/23 (0%) 1/18 (5.6%)
    Injury, poisoning and procedural complications
    Abdominal wall wound 0/23 (0%) 1/18 (5.6%)
    Traumatic chest injury NOS 0/23 (0%) 1/18 (5.6%)
    Wound complication 0/23 (0%) 1/18 (5.6%)
    Investigations
    Blood calcium decreased 0/23 (0%) 1/18 (5.6%)
    Fibrin D dimer increased 1/23 (4.3%) 0/18 (0%)
    Hepatic enzyme increased 1/23 (4.3%) 1/18 (5.6%)
    International normalised ratio increased 1/23 (4.3%) 0/18 (0%)
    Troponin I increased 0/23 (0%) 1/18 (5.6%)
    White blood cell count increased 0/23 (0%) 1/18 (5.6%)
    Metabolism and nutrition disorders
    Glucose tolerance impaired 0/23 (0%) 1/18 (5.6%)
    Hyperglycaemia 0/23 (0%) 1/18 (5.6%)
    Hyperkalaemia 0/23 (0%) 1/18 (5.6%)
    Hypermagnesaemia 0/23 (0%) 2/18 (11.1%)
    Hypernatraemia 1/23 (4.3%) 0/18 (0%)
    Hypocalcaemia 1/23 (4.3%) 1/18 (5.6%)
    Hypokalaemia 2/23 (8.7%) 1/18 (5.6%)
    Hypomagnesaemia 0/23 (0%) 2/18 (11.1%)
    Nervous system disorders
    Dizziness 1/23 (4.3%) 0/18 (0%)
    Psychiatric disorders
    Anxiety 0/23 (0%) 1/18 (5.6%)
    Insomnia 1/23 (4.3%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 1/23 (4.3%) 0/18 (0%)
    Respiratory distress 0/23 (0%) 1/18 (5.6%)
    Skin and subcutaneous tissue disorders
    Rash 1/23 (4.3%) 1/18 (5.6%)
    Vascular disorders
    Deep vein thrombosis 0/23 (0%) 1/18 (5.6%)
    Hypertension 0/23 (0%) 1/18 (5.6%)
    Shock 0/23 (0%) 1/18 (5.6%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There are disclosure agreements between the Sponsor and each of the participating clinical sites and PI that slightly differ.

    Results Point of Contact

    Name/Title Vered Katz Ben-Yair
    Organization RedHill Biopharma Ltd.
    Phone +13474144462
    Email vered@redhillbio.com
    Responsible Party:
    RedHill Biopharma Limited
    ClinicalTrials.gov Identifier:
    NCT04414618
    Other Study ID Numbers:
    • ABC-110
    First Posted:
    Jun 4, 2020
    Last Update Posted:
    Mar 21, 2022
    Last Verified:
    Mar 1, 2022