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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04467840
• Other study ID #: ABC-201
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 21, 2020
• Est. completion date: July 18, 2021

Study information

• Verified date: September 2023
• Source: RedHill Biopharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 475
• Est. completion date: July 18, 2021
• Est. primary completion date: July 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Lung Infection
• Pneumonia

Intervention

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).
• 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).

Locations

Country	Name	City	State
Brazil	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	Sao Paulo
Brazil	ABC-201 Site 403	São Paulo
Brazil	ABC-201 Site 407	Tubarão
Colombia	ABC-201 Site 603	Bogotá
Colombia	ABC-201 Site 605	Cundinamarca
Colombia	ABC-201 Site 602	Medellín
Colombia	ABC-201 Site 604	Medellín	Antioquia
Colombia	ABC-201 Site 601	Santiago de Cali
Israel	ABC-201 Site 702	Ashdod
Israel	ABC-201 Site 708	Ashkelon	Ashketon
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
Italy	ABC-201 Site 203	Alessandria
Italy	ABC-201 Site 201	Lecco
Italy	ABC-201 Site 202	Milano
Italy	ABC-201 Site 204	Torino
Mexico	ABC-201 Site 501	Mexico City
Mexico	ABC-201 Site 503	Sinaloa
Peru	ABC-201 Site 655	Lima
Poland	ABC-201 Site 303	Boleslawiec
Poland	ABC-201 Site 306	Katowice
Poland	ABC-201 Site 304	Koszalin
Poland	ABC-201 Site 308	Lódz
Poland	ABC-201 Site 307	Lublin
Poland	ABC-201 Site 302	Ostróda
Poland	ABC-201 Site 301	Racibórz
Poland	ABC-201 Site 305	Wroclaw
Russian Federation	ABC-201 Site 110	Barnaul
Russian Federation	ABC-201 Site 122	Kirovsk
Russian Federation	ABC-201 Site 101	Moscow
Russian Federation	ABC-201 Site 132	Moscow
Russian Federation	ABC-201 Site 120	Murmansk
Russian Federation	ABC-201 Site 103	Ryazan
Russian Federation	ABC-201 Site 114	Ryazan
Russian Federation	ABC-201 Site 129	Saint Petersburg
Russian Federation	ABC-201 Site 108	Saratov
Russian Federation	ABC-201 Site 102	Smolensk
Russian Federation	ABC-201 Site 109	St Petersburg
Russian Federation	ABC-201 Site 111	St Petersburg
Russian Federation	ABC-201 Site 104	Tver
Russian Federation	ABC-201 Site 118	Volgograd
Russian Federation	ABC-201 Site 112	Yaroslavl
United Kingdom	ABC-201 Site 253	Antrim
United Kingdom	ABC-201 Site 251	Gillingham
United Kingdom	ABC-201 Site 252	Taunton
United States	ABC-201 Site 901	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
RedHill Biopharma Limited

Countries where clinical trial is conducted

United States,  Brazil,  Colombia,  Israel,  Italy,  Mexico,  Peru,  Poland,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	To compare the number of participants with treatment emergent adverse events (TEAEs) in patients with severe COVID-19 pneumonia between participants taking opaganib and participants taking placebo	From first dose until 4 weeks follow-up after the end of treatment
Primary	Supplemental Oxygen Requirement	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.	14 days maintained up to 42 days
Secondary	Percentage of Subjects With = 2 Category Improvement on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement by Day 14 Maintained to Day 42	Compare =2 category improvement on the WHO Ordinal Scale for Clinical Improvement from 0(uninfected) to 8(death) for subjects taking opaganib and those on placebo, lower scores indicate improvement. Success was defined as subject who reached improvement of at least two points on the WHO Ordinal Scale by Day 14, maintained by the end of study visit, and failure otherwise.	14 days maintained up to 42 days
Secondary	Number of Subjects With 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	Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement to determine 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 0 (uninfected) to 8 (death)	14 days maintained up to 42 days
Secondary	Number of Participants With Low Oxygen Flow Via Nasal Cannula	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.	14 days maintained up to 42 days
Secondary	Time to Discharge From Hospital Measured at 14 Days	Time to subject discharge from hospital	14 days
Secondary	Patients Requiring Intubation and Mechanical Ventilation by Day 42	To compare the proportion of patients requiring intubation and mechanical ventilation between subjects taking opaganib and those on placebo.	42 days
Secondary	Number of Patients With Two Consecutive Negative Swabs for SARS-CoV-2 at Day 14	To compare the number of patients with two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.	14 days
Secondary	Patients With Negative Swabs for SARS-CoV-2 at Day 14	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.	14 days
Secondary	Mortality Due to Any Cause	To compare mortality 28 days post-baseline between subjects taking opaganib and those taking placebo	28 days
Secondary	Mortality Due to Any Cause	To compare mortality 42 days post-baseline between subjects taking opaganib and those taking placebo	42 days