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Trial record 1 of 1 for:    NCT04467840
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Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia

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ClinicalTrials.gov Identifier: NCT04467840
Recruitment Status : Recruiting
First Posted : July 13, 2020
Last Update Posted : March 5, 2021
Sponsor:
Information provided by (Responsible Party):
RedHill Biopharma Limited

Study Description
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Brief Summary:
A phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study in Adult Subjects Hospitalized with Severe SARS-CoV-2 Positive Pneumonia to determine the potential of opaganib to improve and/or stabilize the clinical status of the patient.

Condition or disease Intervention/treatment Phase
COVID-19 Lung Infection Drug: Opaganib Drug: Placebo Phase 2 Phase 3

Detailed Description:

This is a phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study with an adaptive design that will utilize a futility assessment. The study is planned be performed worldwide in up to approximately 80 clinical sites.

After informed consent is obtained, patients will enter a screening phase for no more than 3 days, to determine eligibility. Approximately 464 eligible patients will be randomized and receive either opaganib added to standard of care, or matching placebo added to standard of care, in a randomization ratio of 1:1. Treatment assignments will remain blinded to the patient, investigator and hospital staff, as well as the sponsor. As the approval and/or guidance for treating COVID-19 are evolving, for this protocol, standard of care will be defined by the recommended schemes of treatment according to the severity of the disease based on local diagnostic and guideline documents such as the Temporary Methodic Recommendations: Prophylactic, Diagnostics and Treatment of New Corona Virus Infection (COVID-19) (Appendix 10); the EU Commission, the European Medicines Agency (EMA), the Heads of Medicines Agency (HMA) and FDA, and as updated to the most current version of the recommendations.

Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14). All participants will be followed up for 28 days after their last dose of study drug, which may occur at Day 14 or after premature study drug discontinuation, based upon patient or physician determination.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 464 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 2/3 Study, in Adult Subjects Hospitalized With Severe SARS-CoV-2 Positive Pneumonia
Actual Study Start Date : August 21, 2020
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arms and Interventions
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Arm Intervention/treatment
Experimental: Opaganib
In addition to standard of care, opaganib will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. When required this may be made into a suspension form and may be administered by nasogastric tube.
 Drug: Opaganib
Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).
Other Names:
  • Yeliva
  • ABC294640
Placebo Comparator: Placebo
In addition to standard of care, a matching placebo will be administered orally with 2 x 250 mg capsules (500 mg) every 12 hours. Where required this may be made into a suspension form and may be administered by nasogastric tube.
 Drug: Placebo
Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours, or matching placebo, in addition to standard of care (pharmacological as defined above and/or supportive) at any given institution. Study drug will be administered every day for 14 days (Day 1 to Day 14).


Outcome Measures
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Primary Outcome Measures :
  1. Supplemental oxygen requirement [ Time Frame: 14 days ]
    To compare the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 between subjects taking opaganib and those on placebo.


Secondary Outcome Measures :
  1. WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0 [ Time Frame: 14 days ]
    Compare ≥2 category improvement on the WHO Ordinal Scale for subjects taking opaganib and those on placebo, lower scores indicate improvement.

  2. Time to recovery as defined by improvement to a score of 3 or less on the WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0 [ Time Frame: 14 days ]
    Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement.

  3. Time to low oxygen flow via nasal cannula [ Time Frame: 14 days ]
    To compare the time to low oxygen flow via nasal cannula e.g. from high oxygen flow via nasal cannula or CPAP, if high oxygen flow is not an available option between subjects taking opaganib and those on placebo.

  4. Time to discharge from hospital [ Time Frame: 14 days ]
    To compare the time to low oxygen flow via nasal cannula e.g. from high oxygen flow via nasal cannula or CPAP, if high oxygen flow is not an available option between subjects taking opaganib and those on placebo.

  5. Requiring intubation and mechanical ventilation [ Time Frame: 14 days ]
    To compare the time to intubation and mechanical ventilation between subjects taking opaganib and those on placebo.

  6. Time to negative swabs for SARS-CoV-2 [ Time Frame: 14 days ]
    To compare the time to two consecutive negative swabs for SARS-CoV-2 by PCR between subjects taking opaganib and those on placebo.

  7. Negative swabs for SARS-CoV-2 at day 14 [ Time Frame: 14 days ]
    To compare the proportion of patients with two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.

  8. Fever [ Time Frame: 14 days ]
    To compare the proportion of patients, 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 between subjects taking opaganib and those on placebo.

  9. Mortality [ Time Frame: 30 days post baseline ]
    To compare mortality 30 days post-baseline between subjects taking opaganib and those taking placebo


Other Outcome Measures:
  1. Adverse events [ Time Frame: Up to 14 days and at the end of the 4 weeks follow-up after the end of treatment ]
    To compare the number of adverse events in patients with severe COVID-19 pneumonia between subjects taking opaganib and subjects taking placebo

  2. Inflammatory markers - D-dimer [ Time Frame: 14 days ]
    To compare the change in the systemic marker of inflammation, D-dimer, over the treatment period between subjects taking opaganib and those on placebo.

  3. Inflammatory markers - cardiac troponin [ Time Frame: 14 days ]
    To compare the change in the systemic marker of inflammation, cardiac troponin, over the treatment period between subjects taking opaganib and those on placebo.

  4. Inflammatory markers - C-reactive protein [ Time Frame: 14 days ]
    To compare the change in the systemic marker of inflammation, C-reactive protein [CRP], over the treatment period between subjects taking opaganib and those on placebo.

  5. Inflammatory markers - lactate dehydrogenase [ Time Frame: 14 days ]
    To compare the change in the systemic marker of inflammation lactate dehydrogenase [LDH] over the treatment period between subjects taking opaganib and those on placebo.

  6. Inflammatory markers - ferritin [ Time Frame: 14 days ]
    To compare the change in the systemic marker of inflammation ferritin over the treatment period between subjects taking opaganib and those on placebo.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 or CT scan. that diagnosed COVID-19 pneumonia. Pharyngeal samples collected either at screening or within 7-days prior to screening for the same ongoing COVID-19 pneumonia illness are acceptable
  3. The patient requires, at baseline, high flow supplemental oxygen or positive pressure ventilation or is receiving oxygen via face mask, with an oxygen flow of >5L/min.
  4. Patient agrees to use appropriate methods of contraception during the study and 3 months after the last dose of study drug
  5. The patient or legal representative has signed a written informed consent approved by the IRB/Ethics Committee

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 at baseline
  3. Patient has a 'Do Not Intubate' and/or 'Do Not Resuscitate' order in place
  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 judgement, unlikely to survive >72 hours
  7. Pregnant (positive serum or urine test within 3 days prior to randomization) 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) > 5.0 x upper limit of normal (ULN)
  11. Total bilirubin >1.5x 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. Medications that are sensitive substrates, or substrates with a narrow therapeutic range, for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 CYP2D6 , CYP3A4, P-gP, BCRP and OATP1B1. These should be decided in discussion with the Medical Monitor on a case-by-case basis.
  17. Moderate or strong inhibitors of CYP1A2, CYP3A4, CYP2D6 or P-gP or moderate to strong inducers of CYP3A4 and CYP1A2. These should be decided in discussion with the Medical Monitor on a case-by-case basis.
  18. Currently taking warfarin, apixaban, argatroban or rivaroxaban due to drug-drug interaction based on CYP450 metabolism
  19. Current drug or alcohol abuse
  20. Currently participating in a clinical study assessing pharmacological treatments, including anti-viral studies
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04467840


Contacts
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Contact: Mark Levitt, MD +972-3-541-3131 info@redhillbio.com
Contact: Vered Katz Ben-Yair, MSc +972-3-541-3131 vered@redhillbio.com

Locations
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Sponsors and Collaborators
RedHill Biopharma Limited
Investigators
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Study Director: Mark L Levitt, MD RedHill Biopharma Limited
More Information
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Responsible Party: RedHill Biopharma Limited
ClinicalTrials.gov Identifier: NCT04467840    
Other Study ID Numbers: ABC-201
First Posted: July 13, 2020    Key Record Dates
Last Update Posted: March 5, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by RedHill Biopharma Limited:
Therapeutic Use
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections