Back to resultsA Study of Opaganib in Coronavirus Disease 2019 Pneumonia (COVID-19)
Primary Purpose
Coronavirus Infections
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Opaganib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Coronavirus Infections
Eligibility Criteria
Inclusion Criteria:
- Adult male or female ≥18 to ≤80 years of age
- 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
- The patient requires supplemental oxygen at baseline
- The patient, guardian or legal representative has signed a written IRB-approved informed consent.
5) 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:
- not pregnant
- not breastfeeding
- not a woman of child-bearing potential (WOCBP, as defined in Section 9.3)
- 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:
- Any co-morbidity that may add risk to the treatment in the judgement of the investigator.
- Requiring intubation and mechanical ventilation
- Patient having a do not intubate or do not resuscitate order
- Oxygen saturation >95% on room air
- Any preexisting respiratory condition that requires intermittent or continuous ambulatory oxygen prior to hospitalization
- Patient is, in the investigator's clinical judgment, unlikely to survive >72 hours
- Pregnant or nursing women
- Unwillingness or inability to comply with procedures required in this protocol.
- Corrected QT (QTc) interval on electrocardiogram (ECG) >470 ms for females or >450 ms for males, calculated using Friedericia's formula (QTcF)
- AST (SGOT) or ALT (SGPT) > 2.5 x upper limit of normal (ULN)
- Bilirubin >2.0 x ULN (except where bilirubin increase is due to Gilbert's Syndrome)
- Serum creatinine >2.0 X ULN
- Absolute neutrophil count <1000 cells/mm3
- Platelet count <75,000/mm3
- Hemoglobin <8.0 g/dL
- 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.
- 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.
- Currently taking warfarin, apixaban, argatroban or rivaroxaban.
- Current drug or alcohol abuse.
- Currently participating in a clinical study assessing pharmacological treatments, including anti-viral studies.
Sites / Locations
- HonorHealth Research Institute
- Miami Cancer Institute
- Henry Ford Hospital
- Ascension St. John Hospital
- Albany Medical Center
- Oregon Health & Science University
- Memorial Herman Southeast Hospital
- Memorial Hermann, Memorial City Medical Center
- Ziv Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
opaganib
placebo
Arm Description
Study participants will receive opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours
Study participants will receive placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours
Outcomes
Primary Outcome Measures
Measurement of the Change in Oxygen Requirement From Baseline
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
Measurement of Time to the Reduction in Oxygen Requirement.
The time required between arms to achieve 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min.
The Percentage of Subjects no Longer Receiving Supplemental Oxygen for at Least 24 Hours by Day 14
The percentage of subjects in each arm no longer requiring supplemental oxygen for at least 24 hours by Day 14.
Time to Negative Swabs for SARS-CoV-2 by PCR Post Treatment
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.
The Percentage of Subjects With at Least Two Consecutive Negative Swabs for SARS-CoV-2 by PCR at Day 14
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.
Intubation and Mechanical Ventilation Requirements
The percentage of patients in each arm who require intubation and mechanical ventilation by Day 14
Evaluation of the Time to Intubation and Mechanical Ventilation
The time in each arm for the patient to require mechanical ventilation.
Evaluation the Proportion of Patients, With at Least One Measurement of Fever at Baseline Who Are Afebrile at Day 14
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
Evaluation of Mortality 30 Days Post-baseline
The mortality in each arm 30 days post-baseline.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04414618
Brief Title
A Study of Opaganib in Coronavirus Disease 2019 Pneumonia
Acronym
COVID-19
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
July 2, 2020 (Actual)
Primary Completion Date
November 26, 2020 (Actual)
Study Completion Date
December 23, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RedHill Biopharma Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
opaganib
Arm Type
Active Comparator
Arm Description
Study participants will receive opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Study participants will receive placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours
Intervention Type
Drug
Intervention Name(s)
Opaganib
Other Intervention Name(s)
Yeliva, ABC294640
Intervention Description
Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
Other Pre-specified Outcome Measures:
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
Title
Safety SAEs
Description
The number of subjects with serious adverse events (SAEs) in each arm.
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult male or female ≥18 to ≤80 years of age
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
The patient requires supplemental oxygen at baseline
The patient, guardian or legal representative has signed a written IRB-approved informed consent.
5) 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:
not pregnant
not breastfeeding
not a woman of child-bearing potential (WOCBP, as defined in Section 9.3)
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:
Any co-morbidity that may add risk to the treatment in the judgement of the investigator.
Requiring intubation and mechanical ventilation
Patient having a do not intubate or do not resuscitate order
Oxygen saturation >95% on room air
Any preexisting respiratory condition that requires intermittent or continuous ambulatory oxygen prior to hospitalization
Patient is, in the investigator's clinical judgment, unlikely to survive >72 hours
Pregnant or nursing women
Unwillingness or inability to comply with procedures required in this protocol.
Corrected QT (QTc) interval on electrocardiogram (ECG) >470 ms for females or >450 ms for males, calculated using Friedericia's formula (QTcF)
AST (SGOT) or ALT (SGPT) > 2.5 x upper limit of normal (ULN)
Bilirubin >2.0 x ULN (except where bilirubin increase is due to Gilbert's Syndrome)
Serum creatinine >2.0 X ULN
Absolute neutrophil count <1000 cells/mm3
Platelet count <75,000/mm3
Hemoglobin <8.0 g/dL
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.
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.
Currently taking warfarin, apixaban, argatroban or rivaroxaban.
Current drug or alcohol abuse.
Currently participating in a clinical study assessing pharmacological treatments, including anti-viral studies.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark L Levitt, MD, PhD
Organizational Affiliation
RedHill Biopharma Limited
Official's Role
Study Director
Facility Information:
Facility Name
HonorHealth Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Miami Cancer Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Ascension St. John Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48236
Country
United States
Facility Name
Albany Medical Center
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Memorial Herman Southeast Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77089
Country
United States
Facility Name
Memorial Hermann, Memorial City Medical Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77204
Country
United States
Facility Name
Ziv Medical Center
City
Safed
Country
Israel
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Opaganib in Coronavirus Disease 2019 Pneumonia
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