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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| opaganib | Active Comparator | Study participants will receive opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours |
|
| placebo | Placebo Comparator | Study participants will receive placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Opaganib | Drug | Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 14 days |
| The Percentage of Subjects no Longer Receiving Supplemental Oxygen for at Least 24 Hours by Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Safety TEAEs | The number of subjects with treatment-emergent adverse events in each arm of all treatment-emergent adverse events (TEAEs). | 6 weeks |
| Safety SAEs | The number of subjects with serious adverse events (SAEs) in each arm. |
Inclusion Criteria:
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:
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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark L Levitt, MD, PhD | RedHill Biopharma Limited | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HonorHealth Research Institute | Scottsdale | Arizona | 85258 | United States | ||
| Miami Cancer Institute |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | 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). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Opaganib | Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). |
| BG001 | Placebo | Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Modified ITT (mITT) population (randomized and treated with at least one dose of study medication). | Posted | Median | 95% Confidence Interval | L/min*day | 14 days |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vered Katz Ben-Yair | RedHill Biopharma Ltd. | +13474144462 | vered@redhillbio.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 30, 2020 | Jan 21, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 13, 2020 | Jan 21, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D018352 | Coronavirus Infections |
| ID | Term |
|---|---|
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
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| ID | Term |
|---|---|
| C548780 | 3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide |
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|
| Placebo | Drug | 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 in each arm no longer requiring supplemental oxygen for at least 24 hours by Day 14. |
| 14 days |
| 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. | 6 weeks |
| 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. | 14 days |
| Intubation and Mechanical Ventilation Requirements | The percentage of patients in each arm who require intubation and mechanical ventilation by Day 14 | From screening phase and every day from day 1 to day 14 of treatment |
| Evaluation of the Time to Intubation and Mechanical Ventilation | The time in each arm for the patient to require mechanical ventilation. | From screening phase and every day from day 1 to day 14 of treatment |
| 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 | From screening phase and every day from day 1 to day 14 of treatment |
| Evaluation of Mortality 30 Days Post-baseline | The mortality in each arm 30 days post-baseline. | 30 days after day 1 of treatment |
| 6 weeks |
| Miami |
| Florida |
| 33176 |
| United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Ascension St. John Hospital | Detroit | Michigan | 48236 | United States |
| Albany Medical Center | Albany | New York | 12208 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| Memorial Herman Southeast Hospital | Houston | Texas | 77089 | United States |
| Memorial Hermann, Memorial City Medical Center | Houston | Texas | 77204 | United States |
| Ziv Medical Center | Safed | Israel |
| Lost to Follow-up |
|
| Physician Decision |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Placebo |
Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive). |
|
|
| Secondary | 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. | 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. | Posted | Median | 95% Confidence Interval | Days | 14 days |
|
|
|
| Secondary | 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. | Modified ITT (mITT) population (randomized and treated with at least one dose of study medication). | Posted | Count of Participants | Participants | 14 days |
|
|
|
| Secondary | 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. | 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. | Posted | Median | 95% Confidence Interval | Days | 6 weeks |
|
|
|
| Secondary | 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. | 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. | Posted | Count of Participants | Participants | 14 days |
|
|
|
| Secondary | Intubation and Mechanical Ventilation Requirements | The percentage of patients in each arm who require intubation and mechanical ventilation by Day 14 | Modified ITT (mITT) population (randomized and treated with at least one dose of study medication). | Posted | Count of Participants | Participants | From screening phase and every day from day 1 to day 14 of treatment |
|
|
|
| Secondary | Evaluation of the Time to Intubation and Mechanical Ventilation | The time in each arm for the patient to require mechanical ventilation. | Modified ITT (mITT) population (randomized and treated with at least one dose of study medication). | Posted | Median | 95% Confidence Interval | Days | From screening phase and every day from day 1 to day 14 of treatment |
|
|
|
| Secondary | 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 | 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. | Posted | Count of Participants | Participants | From screening phase and every day from day 1 to day 14 of treatment |
|
|
|
| Secondary | Evaluation of Mortality 30 Days Post-baseline | The mortality in each arm 30 days post-baseline. | Modified ITT (mITT) population (randomized and treated with at least one dose of study medication). | Posted | Count of Participants | Participants | 30 days after day 1 of treatment |
|
|
|
| Other Pre-specified | Safety TEAEs | The number of subjects with treatment-emergent adverse events in each arm of all treatment-emergent adverse events (TEAEs). | 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. | Posted | Count of Participants | Participants | 6 weeks |
|
|
|
| Other Pre-specified | Safety SAEs | The number of subjects with serious adverse events (SAEs) in each arm. | 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. | Posted | Count of Participants | Participants | 6 weeks |
|
|
|
| Post-Hoc | Percent Change in Measurement of the Daily Oxygen Requirement | 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. | 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. | Posted | Median | 95% Confidence Interval | Percentage of change from baseline*day | 14 days |
|
|
|
| Post-Hoc | Measurement of the Relative Benefit for Each Treatment Are as Derived From Oxygen Requirements | 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. | 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. | Posted | Number | Percentage of relative benefit | 14 days |
|
|
|
| 3 |
| 23 |
| 3 |
| 23 |
| 11 |
| 23 |
| EG001 | 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). | 3 | 18 | 5 | 18 | 9 | 18 |
| COVID-19 pneumonia | Infections and infestations | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sepsis | Infections and infestations | Systematic Assessment |
|
| Septic shock | Infections and infestations | Systematic Assessment |
|
| Abdominal wall wound | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | Systematic Assessment |
|
| Blood calcium decreased | Investigations | Systematic Assessment |
|
| Candida infection | Infections and infestations | Systematic Assessment |
|
| Cellulitis | Infections and infestations | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Fibrin D dimer increased | Investigations | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
|
| Glucose tolerance impaired | Metabolism and nutrition disorders | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | Systematic Assessment |
|
| Hepatic enzyme increased | Investigations | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypertension | Vascular disorders | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| International normalised ratio increased | Investigations | Systematic Assessment |
|
| Megacolon | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | Systematic Assessment |
|
| Palpitations | Cardiac disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Shock | Vascular disorders | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Traumatic chest injury NOS | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Troponin I increased | Investigations | Systematic Assessment |
|
| Urinary tract infection bacterial | Infections and infestations | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| White blood cell count increased | Investigations | Systematic Assessment |
|
| Wound complication | Injury, poisoning and procedural complications | Systematic Assessment |
|
There are disclosure agreements between the Sponsor and each of the participating clinical sites and PI that slightly differ.
| D007239 |
| Infections |