<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04467840</url>
  </required_header>
  <id_info>
    <org_study_id>ABC-201</org_study_id>
    <nct_id>NCT04467840</nct_id>
  </id_info>
  <brief_title>Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RedHill Biopharma Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RedHill Biopharma Limited</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study in&#xD;
      Adult Subjects Hospitalized with Severe SARS-CoV-2 Positive Pneumonia to determine the&#xD;
      potential of opaganib to improve and/or stabilize the clinical status of the patient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled&#xD;
      study with an adaptive design that will utilize a futility assessment. The study is planned&#xD;
      be performed worldwide in up to approximately 80 clinical sites.&#xD;
&#xD;
      After informed consent is obtained, patients will enter a screening phase for no more than 3&#xD;
      days, to determine eligibility. Approximately 464 eligible patients will be randomized and&#xD;
      receive either opaganib added to standard of care, or matching placebo added to standard of&#xD;
      care, in a randomization ratio of 1:1. Treatment assignments will remain blinded to the&#xD;
      patient, investigator and hospital staff, as well as the sponsor. As the approval and/or&#xD;
      guidance for treating COVID-19 are evolving, for this protocol, standard of care will be&#xD;
      defined by the recommended schemes of treatment according to the severity of the disease,&#xD;
      taking into consideration regulatory approvals in one or more regions.&#xD;
&#xD;
      Study participants will receive either opaganib 2 x 250 mg capsules (500 mg) every 12 hours,&#xD;
      or matching placebo, in addition to standard of care (pharmacological as defined above and/or&#xD;
      supportive) at any given institution. Study drug will be administered every day for 14 days&#xD;
      (Day 1 to Day 14). All participants will be followed up for 28 days after their last dose of&#xD;
      study drug, which may occur at Day 14 or after premature study drug discontinuation, based&#xD;
      upon patient or physician determination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 21, 2020</start_date>
  <completion_date type="Actual">July 18, 2021</completion_date>
  <primary_completion_date type="Actual">July 18, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Supplemental oxygen requirement</measure>
    <time_frame>14 days</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0</measure>
    <time_frame>14 days</time_frame>
    <description>Compare ≥2 category improvement on the WHO Ordinal Scale for subjects taking opaganib and those on placebo, lower scores indicate improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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 8 down to 0</measure>
    <time_frame>14 days</time_frame>
    <description>Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to low oxygen flow via nasal cannula</measure>
    <time_frame>14 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to discharge from hospital</measure>
    <time_frame>14 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Requiring intubation and mechanical ventilation by Day 42</measure>
    <time_frame>42 days</time_frame>
    <description>To compare the proportion of patients requiring intubation and mechanical ventilation between subjects taking opaganib and those on placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to two consecutive negative swabs for SARS-CoV-2 at day 14</measure>
    <time_frame>14 days</time_frame>
    <description>To compare the the time to two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Negative swabs for SARS-CoV-2 at day 14</measure>
    <time_frame>14 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fever</measure>
    <time_frame>14 days</time_frame>
    <description>To compare the proportion of patients, with at least one measurement of fever at baseline (defined as temperature &gt;38.0 C [100.4 F]), who are afebrile (defined as temperature &lt;37.2C [99 F]) at Day 14 between subjects taking opaganib and those on placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>28 and 42 days</time_frame>
    <description>To compare mortality 28 and 42 days post-baseline between subjects taking opaganib and those taking placebo</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse events</measure>
    <time_frame>Up to 14 days and at the end of the 4 weeks follow-up after the end of treatment</time_frame>
    <description>To compare the number of adverse events in patients with severe COVID-19 pneumonia between subjects taking opaganib and subjects taking placebo</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">475</enrollment>
  <condition>COVID-19</condition>
  <condition>Lung Infection</condition>
  <arm_group>
    <arm_group_label>Opaganib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Opaganib</intervention_name>
    <description>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).</description>
    <arm_group_label>Opaganib</arm_group_label>
    <other_name>Yeliva</other_name>
    <other_name>ABC294640</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>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).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult male or female ≥18 to ≤80 years of age&#xD;
&#xD;
          2. Proven COVID-19 infection per RT-PCR assay of a pharyngeal sample (nasopharyngeal or&#xD;
             oropharyngeal) AND pneumonia defined as radiographic opacities on chest X-ray or CT&#xD;
             scan. that diagnosed COVID-19 pneumonia. Pharyngeal samples collected either at&#xD;
             screening or within 7-days prior to screening for the same ongoing COVID-19 pneumonia&#xD;
             illness are acceptable&#xD;
&#xD;
          3. The patient requires, at baseline, high flow supplemental oxygen or positive pressure&#xD;
             ventilation or is receiving oxygen via face mask, such as a non-rebreather or&#xD;
             reservoir mask, capable of delivering high concentrations of oxygen&#xD;
&#xD;
          4. Patient agrees to use appropriate methods of contraception during the study and 3&#xD;
             months after the last dose of study drug&#xD;
&#xD;
          5. The patient or legal representative has signed a written informed consent approved by&#xD;
             the IRB/Ethics Committee&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any co-morbidity that may add risk to the treatment in the judgment of the&#xD;
             investigator, particularly patients with known cardiac conditions, and serious&#xD;
             neuropsychiatric conditions such as psychosis or major depression&#xD;
&#xD;
          2. Requiring intubation and mechanical ventilation at baseline&#xD;
&#xD;
          3. Patient has a 'Do Not Intubate' and/or 'Do Not Resuscitate' order in place&#xD;
&#xD;
          4. Oxygen saturation &gt;95% on room air&#xD;
&#xD;
          5. Any preexisting respiratory condition that requires intermittent or continuous&#xD;
             ambulatory oxygen prior to hospitalization&#xD;
&#xD;
          6. Patient is, in the investigator's clinical judgement, unlikely to survive &gt;72 hours&#xD;
&#xD;
          7. Pregnant (positive serum or urine test within 3 days prior to randomization) or&#xD;
             nursing women .&#xD;
&#xD;
          8. Unwillingness or inability to comply with procedures required in this protocol.&#xD;
&#xD;
          9. Corrected QT (QTc) interval on electrocardiogram (ECG) &gt;470 ms for females or &gt;450 ms&#xD;
             for males, calculated using Friedericia's formula (QTcF)&#xD;
&#xD;
         10. AST (SGOT) or ALT (SGPT) &gt; 2.0 x upper limit of normal (ULN)&#xD;
&#xD;
         11. Total bilirubin &gt;1.5x ULN (except where bilirubin increase is due to Gilbert's&#xD;
             Syndrome)&#xD;
&#xD;
         12. Serum creatinine &gt;2.0 X ULN&#xD;
&#xD;
         13. Absolute neutrophil count &lt;1000 cells/mm3&#xD;
&#xD;
         14. Platelet count &lt;75,000/mm3&#xD;
&#xD;
         15. Hemoglobin &lt;8.0 g/dL&#xD;
&#xD;
         16. Medications that are sensitive substrates, or substrates with a narrow therapeutic&#xD;
             range, for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 CYP2D6 , CYP3A4, P-gP, BCRP and&#xD;
             OATP1B1 should be avoided with opaganib&#xD;
&#xD;
         17. Moderate or strong inhibitors of CYP1A2, CYP3A4, CYP2D6 or P-gP or moderate to strong&#xD;
             inducers of CYP3A4 and CYP1A2 are prohibited&#xD;
&#xD;
         18. Currently taking warfarin, apixaban, argatroban or rivaroxaban due to drug-drug&#xD;
             interaction based on CYP450 metabolism&#xD;
&#xD;
         19. Current drug or alcohol abuse&#xD;
&#xD;
         20. Currently participating in a clinical study assessing pharmacological treatments,&#xD;
             including anti-viral studies&#xD;
&#xD;
         21. Treatment with any medication that causes QT prolongation within seven days, or 5&#xD;
             half-lives, whichever is longest, prior to initiation of study drug, or intention to&#xD;
             use them throughout the study, including but not limited to: amiodarone,&#xD;
             amitriptyline, citalopram dose greater than 20 mg/day, dihydroergotamine,&#xD;
             disopyramide, dofetilide, dronedarone, ergotamine, ibutilde, ondansetron or other&#xD;
             5-HT3 receptor antagonists, pimozide, procainamide, quinidine, quinine, quinolone,&#xD;
             ranolazine, risperidone, sotaloland tolteridine. Investigators are directed to the&#xD;
             following up-to-date web site listing QT prolonging drugs:&#xD;
             https://www.crediblemeds.org/index.php/drugsearch&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark L Levitt, MD</last_name>
    <role>Study Director</role>
    <affiliation>RedHill Biopharma Limited</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ABC-201 Site 901</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>00000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 408</name>
      <address>
        <city>Belo Horizonte</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 411</name>
      <address>
        <city>Belo Horizonte</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 405</name>
      <address>
        <city>Joinville</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 404</name>
      <address>
        <city>Paraná</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 410</name>
      <address>
        <city>Passo Fundo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 409</name>
      <address>
        <city>Porto Alegre</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 401</name>
      <address>
        <city>Sao Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 402</name>
      <address>
        <city>São Bernardo Do Campo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 403</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 407</name>
      <address>
        <city>Tubarão</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 604</name>
      <address>
        <city>Medellín</city>
        <state>Antioquia</state>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 603</name>
      <address>
        <city>Bogotá</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 605</name>
      <address>
        <city>Cundinamarca</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 602</name>
      <address>
        <city>Medellín</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 601</name>
      <address>
        <city>Santiago de Cali</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 708</name>
      <address>
        <city>Ashkelon</city>
        <state>Ashketon</state>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 702</name>
      <address>
        <city>Ashdod</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 704</name>
      <address>
        <city>Holon</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 701</name>
      <address>
        <city>Jerusalem</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201,Site 709</name>
      <address>
        <city>Kfar Saba</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 705</name>
      <address>
        <city>Nahariya</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 706</name>
      <address>
        <city>Nazareth</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 703</name>
      <address>
        <city>Safed</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 203</name>
      <address>
        <city>Alessandria</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 201</name>
      <address>
        <city>Lecco</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 202</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 204</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 501</name>
      <address>
        <city>Mexico City</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 503</name>
      <address>
        <city>Sinaloa</city>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 655</name>
      <address>
        <city>Lima</city>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 303</name>
      <address>
        <city>Bolesławiec</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 306</name>
      <address>
        <city>Katowice</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 304</name>
      <address>
        <city>Koszalin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 307</name>
      <address>
        <city>Lublin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 302</name>
      <address>
        <city>Ostróda</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 301</name>
      <address>
        <city>Racibórz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 305</name>
      <address>
        <city>Wrocław</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 308</name>
      <address>
        <city>Łódź</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 110</name>
      <address>
        <city>Barnaul</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 122</name>
      <address>
        <city>Kirovsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 101</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 132</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 120</name>
      <address>
        <city>Murmansk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 103</name>
      <address>
        <city>Ryazan</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 114</name>
      <address>
        <city>Ryazan</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 129</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 108</name>
      <address>
        <city>Saratov</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 102</name>
      <address>
        <city>Smolensk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 109</name>
      <address>
        <city>St Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 111</name>
      <address>
        <city>St Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 104</name>
      <address>
        <city>Tver</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 118</name>
      <address>
        <city>Volgograd</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 112</name>
      <address>
        <city>Yaroslavl</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 253</name>
      <address>
        <city>Antrim</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 251</name>
      <address>
        <city>Gillingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ABC-201 Site 252</name>
      <address>
        <city>Taunton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Colombia</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Mexico</country>
    <country>Peru</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 9, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>July 19, 2021</last_update_submitted>
  <last_update_submitted_qc>July 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Therapeutic Use</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>January 28, 2023</submitted>
    <returned>February 24, 2023</returned>
    <submitted>March 26, 2023</submitted>
    <returned>April 18, 2023</returned>
    <submitted>July 24, 2023</submitted>
    <returned>August 21, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04467840
org study id: ABC-201
nct id: NCT04467840
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Supplemental oxygen requirement
time frame: 14 days
description: 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.
measure: WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0
time frame: 14 days
description: Compare ≥2 category improvement on the WHO Ordinal Scale for subjects taking opaganib and those on placebo, lower scores indicate improvement.
measure: 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 8 down to 0
time frame: 14 days
description: Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement.
measure: Time to low oxygen flow via nasal cannula
time frame: 14 days
description: 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.
measure: Time to discharge from hospital
time frame: 14 days
description: 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.
measure: Requiring intubation and mechanical ventilation by Day 42
time frame: 42 days
description: To compare the proportion of patients requiring intubation and mechanical ventilation between subjects taking opaganib and those on placebo.
measure: Time to two consecutive negative swabs for SARS-CoV-2 at day 14
time frame: 14 days
description: To compare the the time to two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.
measure: Negative swabs for SARS-CoV-2 at day 14
time frame: 14 days
description: 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.
measure: Fever
time frame: 14 days
description: To compare the proportion of patients, 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 between subjects taking opaganib and those on placebo.
measure: Mortality
time frame: 28 and 42 days
description: To compare mortality 28 and 42 days post-baseline between subjects taking opaganib and those taking placebo
measure: Adverse events
time frame: Up to 14 days and at the end of the 4 weeks follow-up after the end of treatment
description: To compare the number of adverse events in patients with severe COVID-19 pneumonia between subjects taking opaganib and subjects taking placebo
arm group label: Opaganib
arm group type: Experimental
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: 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.
intervention type: Drug
intervention name: Opaganib
description: 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).
arm group label: Opaganib
other name: Yeliva
other name: ABC294640
intervention type: Drug
intervention name: Placebo
description: 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).
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Mark L Levitt, MD
role: Study Director
affiliation: RedHill Biopharma Limited
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country: Brazil
country: Colombia
country: Israel
country: Italy
country: Mexico
country: Peru
country: Poland
country: Russian Federation
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pneumonia
sharing ipd: No
submitted: January 28, 2023
returned: February 24, 2023
submitted: March 26, 2023
returned: April 18, 2023
submitted: July 24, 2023
returned: August 21, 2023