A Study of Opaganib in Coronavirus Disease 2019 Pneumonia (COVID-19)

• ClinicalTrials.gov Identifier: NCT04414618
• Recruitment Status: Completed
• First Posted: June 4, 2020
• Last Update Posted: March 10, 2021
• Sponsor: RedHill Biopharma Limited
• Information provided by (Responsible Party): RedHill Biopharma Limited

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Coronavirus Infections	Drug: Opaganib; Drug: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 42 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 2a Study, in Adult Subjects Hospitalized With SARS-CoV-2 Positive Pneumonia
• Actual Study Start Date: July 2, 2020
• Actual Primary Completion Date: November 26, 2020
• Actual Study Completion Date: December 23, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: opaganib; Study participants will receive opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours	Drug: 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).; Other Names: Yeliva; ABC294640
Placebo Comparator: placebo; Study participants will receive placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours	Drug: 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).

Outcome Measures

Primary Outcome Measures :

1. Measurement of the oxygen requirement [ Time Frame: 14 days ]
   To compare the total oxygen requirement (area under the curve) for each arm using daily supplemental oxygen flow (L/min) over 14 days

Secondary Outcome Measures :

1. Measurement of the reduction in oxygen requirement. [ Time Frame: 14 days ]
   To comparing the time required between arms to achieve 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min
2. Eliminating supplemental oxygen [ Time Frame: 14 days ]
   To comparing the proportion of patients in each arm no longer requiring supplemental oxygen for at least 24 hours by Day 14
3. Elimination of fever [ Time Frame: 14 days ]
   To compare the proportion of afebrile patients in each arm at Day 14 via measurement of temperature.
4. Time to negative swabs for SARS-CoV-2 by PCR post treatment [ Time Frame: 6 weeks ]
   To compare the time in each arm to negative swabs for SARS-CoV-2 by PCR nasopharyngeal or oropharyngeal swab for SARS-CoV-2
5. Time to negative swabs for SARS-CoV-2 by PCR at Day 14 [ Time Frame: 14 days ]
   To comparing the time in each arm to achieve negative swabs for SARS-CoV-2 by PCR nasopharyngeal or oropharyngeal swab for SARS-CoV-2 during treatment
6. Intubation and mechanical ventilation requirements [ Time Frame: From screening phase and every day from day 1 to day 14 of treatment ]
   To compare the percentage of patients in each arm who require intubation and mechanical ventilation by Day 14
7. Evaluation of the time to mechanical ventilation [ Time Frame: From screening phase and every day from day 1 to day 14 of treatment ]
   To compare the time in each arm for the patient to require mechanical ventilation.
8. Evaluation the proportion of patients, with at least one measurement of fever at baseline who are afebrile at Day 14 [ Time Frame: From screening phase and every day from day 1 to day 14 of treatment ]
   To compare 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
9. Evaluation of mortality 30 days post-baseline [ Time Frame: 30 days after day 1 of treatment ]
   To compare the mortality in each arm 30 days post-baseline.

Other Outcome Measures:

1. Safety TEAEs [ Time Frame: 6 weeks ]
   To compare the number of all treatment-emergent adverse events in each arm of all treatment-emergent adverse events (TEAEs).
2. Safety SAEs [ Time Frame: 6 weeks ]
   To measure all serious adverse events (SAEs) in each arm.

Eligibility Criteria

• 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
3. The patient requires supplemental oxygen at baseline
4. The patient, guardian or legal representative has signed a written IRB-approved informed consent.

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:

• Abstinence from penile-vaginal intercourse and agree to remain abstinent.
• Male condom, with female partner using a highly effective contraceptive method. (For further details regarding highly effective contraceptive methods please see section 9.3.)

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:

1. not pregnant
2. not breastfeeding
3. not a woman of child-bearing potential (WOCBP, as defined in Section 9.3)
4. a WOCBP who agrees to use a highly effective method of contraception consistently and correctly during the treatment period and for at least 1 months after the last dose of study drug (please see further details on Section 9.3).

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
3. Patient having a do not intubate or do not resuscitate order
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 judgment, unlikely to survive >72 hours
7. Pregnant 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) > 2.5 x upper limit of normal (ULN)
11. Bilirubin >2.0 x 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. Currently taking medications that are sensitive CYP3A4, CYP1A2, CYP2C9, or CYP2C19 or CYP2D6 substrates and have a narrow therapeutic index. These should be decided in discussion with the Medical Monitor on a case-by-case basis.
17. Currently taking medications that are strong inducers or inhibitors of CYP2D6 and CYP3A4. These should be decided in discussion with the Medical Monitor on a case-by-case basis.
18. Currently taking warfarin, apixaban, argatroban or rivaroxaban.
19. Current drug or alcohol abuse.
20. Currently participating in a clinical study assessing pharmacological treatments, including anti-viral studies.

Contacts and Locations

Locations

United States, Arizona

HonorHealth Research Institute

Scottsdale, Arizona, United States, 85258

United States, Florida

Miami Cancer Institute

Miami, Florida, United States, 33176

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States, 48202

Ascension St. John Hospital

Detroit, Michigan, United States, 48236

United States, New York

Albany Medical Center

Albany, New York, United States, 12208

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Texas

Memorial Herman Southeast Hospital

Houston, Texas, United States, 77089

Memorial Hermann, Memorial City Medical Center

Houston, Texas, United States, 77204

Israel

Ziv Medical Center

Safed, Israel

Sponsors and Collaborators

RedHill Biopharma Limited

Investigators

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

More Information

• Responsible Party: RedHill Biopharma Limited
• ClinicalTrials.gov Identifier: NCT04414618
• Other Study ID Numbers: ABC-110
• First Posted: June 4, 2020
• Last Update Posted: March 10, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pneumonia; Coronavirus Infections; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases