Clincosm LogoSign in Get a demo

Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia

Sponsor
RedHill Biopharma Limited (Industry)
Overall Status
Completed
CT.gov ID
NCT04467840
Collaborator
(none)
475
Enrollment
57
Locations
2
Arms
10.9
Actual Duration (Months)
8.3
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

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
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, taking into consideration regulatory approvals in one or more regions.

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

Study Type:
Interventional
Actual Enrollment :
475 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 :
Aug 21, 2020
Actual Primary Completion Date :
Jul 18, 2021
Actual Study Completion Date :
Jul 18, 2021

Arms and Interventions

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

    Primary Outcome Measures

    1. Supplemental oxygen requirement [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 [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 [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 [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 [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 by Day 42 [42 days]

      To compare the proportion of patients requiring intubation and mechanical ventilation between subjects taking opaganib and those on placebo.

    6. Time to two consecutive negative swabs for SARS-CoV-2 at day 14 [14 days]

      To compare the the time to two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.

    7. Negative swabs for SARS-CoV-2 at day 14 [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 [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 [28 and 42 days]

      To compare mortality 28 and 42 days post-baseline between subjects taking opaganib and those taking placebo

    Other Outcome Measures

    1. Adverse events [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

    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 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, such as a non-rebreather or reservoir mask, capable of delivering high concentrations of oxygen

    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 judgment of the investigator, particularly patients with known cardiac conditions, and serious neuropsychiatric conditions such as psychosis or major depression

    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) > 2.0 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 should be avoided with opaganib

    17. Moderate or strong inhibitors of CYP1A2, CYP3A4, CYP2D6 or P-gP or moderate to strong inducers of CYP3A4 and CYP1A2 are prohibited

    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

    21. Treatment with any medication that causes QT prolongation within seven days, or 5 half-lives, whichever is longest, prior to initiation of study drug, or intention to use them throughout the study, including but not limited to: amiodarone, amitriptyline, citalopram dose greater than 20 mg/day, dihydroergotamine, disopyramide, dofetilide, dronedarone, ergotamine, ibutilde, ondansetron or other 5-HT3 receptor antagonists, pimozide, procainamide, quinidine, quinine, quinolone, ranolazine, risperidone, sotaloland tolteridine. Investigators are directed to the following up-to-date web site listing QT prolonging drugs: https://www.crediblemeds.org/index.php/drugsearch

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 ABC-201 Site 901 Detroit Michigan United States 00000
    2 ABC-201 Site 408 Belo Horizonte Brazil
    3 ABC-201 Site 411 Belo Horizonte Brazil
    4 ABC-201 Site 405 Joinville Brazil
    5 ABC-201 Site 404 Paraná Brazil
    6 ABC-201 Site 410 Passo Fundo Brazil
    7 ABC-201 Site 409 Porto Alegre Brazil
    8 ABC-201 Site 401 Sao Paulo Brazil
    9 ABC-201 Site 402 São Bernardo Do Campo Brazil
    10 ABC-201 Site 403 São Paulo Brazil
    11 ABC-201 Site 407 Tubarão Brazil
    12 ABC-201 Site 604 Medellín Antioquia Colombia
    13 ABC-201 Site 603 Bogotá Colombia
    14 ABC-201 Site 605 Cundinamarca Colombia
    15 ABC-201 Site 602 Medellín Colombia
    16 ABC-201 Site 601 Santiago de Cali Colombia
    17 ABC-201 Site 708 Ashkelon Ashketon Israel
    18 ABC-201 Site 702 Ashdod Israel
    19 ABC-201 Site 704 Holon Israel
    20 ABC-201 Site 701 Jerusalem Israel
    21 ABC-201,Site 709 Kfar Saba Israel
    22 ABC-201 Site 705 Nahariya Israel
    23 ABC-201 Site 706 Nazareth Israel
    24 ABC-201 Site 703 Safed Israel
    25 ABC-201 Site 203 Alessandria Italy
    26 ABC-201 Site 201 Lecco Italy
    27 ABC-201 Site 202 Milano Italy
    28 ABC-201 Site 204 Torino Italy
    29 ABC-201 Site 501 Mexico City Mexico
    30 ABC-201 Site 503 Sinaloa Mexico
    31 ABC-201 Site 655 Lima Peru
    32 ABC-201 Site 303 Bolesławiec Poland
    33 ABC-201 Site 306 Katowice Poland
    34 ABC-201 Site 304 Koszalin Poland
    35 ABC-201 Site 307 Lublin Poland
    36 ABC-201 Site 302 Ostróda Poland
    37 ABC-201 Site 301 Racibórz Poland
    38 ABC-201 Site 305 Wrocław Poland
    39 ABC-201 Site 308 Łódź Poland
    40 ABC-201 Site 110 Barnaul Russian Federation
    41 ABC-201 Site 122 Kirovsk Russian Federation
    42 ABC-201 Site 101 Moscow Russian Federation
    43 ABC-201 Site 132 Moscow Russian Federation
    44 ABC-201 Site 120 Murmansk Russian Federation
    45 ABC-201 Site 103 Ryazan Russian Federation
    46 ABC-201 Site 114 Ryazan Russian Federation
    47 ABC-201 Site 129 Saint Petersburg Russian Federation
    48 ABC-201 Site 108 Saratov Russian Federation
    49 ABC-201 Site 102 Smolensk Russian Federation
    50 ABC-201 Site 109 St Petersburg Russian Federation
    51 ABC-201 Site 111 St Petersburg Russian Federation
    52 ABC-201 Site 104 Tver Russian Federation
    53 ABC-201 Site 118 Volgograd Russian Federation
    54 ABC-201 Site 112 Yaroslavl Russian Federation
    55 ABC-201 Site 253 Antrim United Kingdom
    56 ABC-201 Site 251 Gillingham United Kingdom
    57 ABC-201 Site 252 Taunton United Kingdom

    Sponsors and Collaborators

    • RedHill Biopharma Limited

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    RedHill Biopharma Limited
    ClinicalTrials.gov Identifier:
    NCT04467840
    Other Study ID Numbers:
    • ABC-201
    First Posted:
    Jul 13, 2020
    Last Update Posted:
    Jul 20, 2021
    Last Verified:
    Jul 1, 2021
    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
    Keywords provided by RedHill Biopharma Limited
    Therapeutic Use
    Additional relevant MeSH terms:
    COVID-19
    Pneumonia

    Study Results

    No Results Posted as of Jul 20, 2021