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

NCT ID: NCT04467840

Last Updated: 2025-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 475 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-21
• Study Completion Date: 2021-07-18

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.

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.

Conditions

COVID-19; Lung Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Opaganib

Intervention Type: DRUG

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).

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Yeliva; ABC294640

Eligibility 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, 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RedHill Biopharma Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark L Levitt, MD

Role: STUDY_DIRECTOR

RedHill Biopharma Limited

Locations

ABC-201 Site 901

Detroit, Michigan, United States

ABC-201 Site 408

Belo Horizonte, , Brazil

ABC-201 Site 411

Belo Horizonte, , Brazil

ABC-201 Site 405

Joinville, , Brazil

ABC-201 Site 404

Paraná, , Brazil

ABC-201 Site 410

Passo Fundo, , Brazil

ABC-201 Site 409

Porto Alegre, , Brazil

ABC-201 Site 402

São Bernardo do Campo, , Brazil

ABC-201 Site 401

São Paulo, , Brazil

ABC-201 Site 403

São Paulo, , Brazil

ABC-201 Site 407

Tubarão, , Brazil

ABC-201 Site 604

Medellín, Antioquia, Colombia

ABC-201 Site 603

Bogotá, , Colombia

ABC-201 Site 605

Cundinamarca, , Colombia

ABC-201 Site 602

Medellín, , Colombia

ABC-201 Site 601

Santiago de Cali, , Colombia

ABC-201 Site 708

Ashkelon, Ashketon, Israel

ABC-201 Site 702

Ashdod, , Israel

ABC-201 Site 704

Holon, , Israel

ABC-201 Site 701

Jerusalem, , Israel

ABC-201,Site 709

Kfar Saba, , Israel

ABC-201 Site 705

Nahariya, , Israel

ABC-201 Site 706

Nazareth, , Israel

ABC-201 Site 703

Safed, , Israel

ABC-201 Site 203

Alessandria, , Italy

ABC-201 Site 201

Lecco, , Italy

ABC-201 Site 202

Milan, , Italy

ABC-201 Site 204

Torino, , Italy

ABC-201 Site 501

Mexico City, , Mexico

ABC-201 Site 503

Sinaloa, , Mexico

ABC-201 Site 655

Lima, , Peru

ABC-201 Site 303

Bolesławiec, , Poland

ABC-201 Site 306

Katowice, , Poland

ABC-201 Site 304

Koszalin, , Poland

ABC-201 Site 308

Lodz, , Poland

ABC-201 Site 307

Lublin, , Poland

ABC-201 Site 302

Ostróda, , Poland

ABC-201 Site 301

Racibórz, , Poland

ABC-201 Site 305

Wroclaw, , Poland

ABC-201 Site 110

Barnaul, , Russia

ABC-201 Site 122

Kirovsk, , Russia

ABC-201 Site 101

Moscow, , Russia

ABC-201 Site 132

Moscow, , Russia

ABC-201 Site 120

Murmansk, , Russia

ABC-201 Site 103

Ryazan, , Russia

ABC-201 Site 114

Ryazan, , Russia

ABC-201 Site 109

Saint Petersburg, , Russia

ABC-201 Site 111

Saint Petersburg, , Russia

ABC-201 Site 129

Saint Petersburg, , Russia

ABC-201 Site 108

Saratov, , Russia

ABC-201 Site 102

Smolensk, , Russia

ABC-201 Site 104

Tver', , Russia

ABC-201 Site 118

Volgograd, , Russia

ABC-201 Site 112

Yaroslavl, , Russia

ABC-201 Site 253

Antrim, , United Kingdom

ABC-201 Site 251

Gillingham, , United Kingdom

ABC-201 Site 252

Taunton, , United Kingdom

Countries

United States; Brazil; Colombia; Israel; Italy; Mexico; Peru; Poland; Russia; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ABC-201

Identifier Type: -

Identifier Source: org_study_id