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.
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.
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 Name: Array
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).
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
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 401
Sao Paulo, Brazil
ABC-201 Site 402
São Bernardo Do Campo, 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
Milano, 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 307
Lublin, Poland
ABC-201 Site 302
Ostróda, Poland
ABC-201 Site 301
Racibórz, Poland
ABC-201 Site 305
Wrocław, Poland
ABC-201 Site 308
Łódź, Poland
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, Russian Federation
ABC-201 Site 253
Antrim, United Kingdom
ABC-201 Site 251
Gillingham, United Kingdom
ABC-201 Site 252
Taunton, United Kingdom
Mark L Levitt, MD, Study Director
RedHill Biopharma Limited