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.
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.
Drug: Opaganib
Study participants received opaganib 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
Other Name: Array
Drug: Placebo
Study participants received placebo 2 x 250 mg capsules (500 mg) plus standard of care every 12 hours (pharmacological and/or supportive).
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.
HonorHealth Research Institute
Scottsdale, Arizona, United States
Miami Cancer Institute
Miami, Florida, United States
Henry Ford Hospital
Detroit, Michigan, United States
Ascension St. John Hospital
Detroit, Michigan, United States
Albany Medical Center
Albany, New York, United States
Oregon Health & Science University
Portland, Oregon, United States
Memorial Herman Southeast Hospital
Houston, Texas, United States
Memorial Hermann, Memorial City Medical Center
Houston, Texas, United States
Ziv Medical Center
Safed, Israel
Mark L Levitt, MD, PhD, Study Director
RedHill Biopharma Limited