A Trial to Investigate Recovery From COVID-19 With C21 in Adult Subjects
Condition: COVID-19
MeSH terms: COVID-19
Intervention: C21; Placebo
Intervention description: C21; Placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 272.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial is a randomized, double-blind, placebo-controlled, parallel-group, 2-arm,
      multicenter trial to evaluate the efficacy and safety of C21 versus placebo as add-on to
      standard of care (SoC) in adult subjects with COVID-19.

      The trial planned to enroll a total of maximum 300 randomized subjects, 150 per arm (oral C21
      100 mg twice a day (BID) or placebo for 14 days) according to the 1:1 randomization.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥18 years or the legal age of consent in the jurisdiction in which the trial was
             taking place at the time of signing the informed consent (Specific for India; Age ≥18
             to ≤65 years at the time of signing the informed consent)

          2. Hospitalized due to SARS-CoV-2 infection confirmed by a hospital-approved polymerase
             chain reaction (PCR) test, documented by either of the following:

               1. PCR positive in sample collected <72 hours prior to randomization (Visit 2); OR

               2. PCR positive in sample collected ≥72 hours and ≤7 days prior to randomization,
                  documented inability to obtain a repeat sample AND progressive disease suggestive
                  of ongoing SARS-CoV-2 infection

          3. A score of 5 or 6 on the 8-point ordinal scale:

               1. Score 5: Hospitalized, requiring supplemental oxygen

               2. Score 6: Hospitalized, on non-invasive ventilation or high-flow oxygen device

          4. Contraceptive use by men and women of childbearing potential consistent with local
             regulations regarding the methods of contraception for those participating in clinical
             studies and according to Appendix 3 in the Protocol (see Section 10.3)

          5. Written informed consent, consistent with International Council for Harmonization Good
             Clinical Practice Revision 2 and local laws, obtained before the initiation of any
             trial-related procedure

          6. Capable of giving signed informed consent as described in Appendix 1 in the Protocol
             (see Section 10.1.3) which includes compliance with the requirements and restrictions
             listed in the informed consent form and in this Protocol

             Country specific:

          7. Specific for India: For subjects with an ordinal scale score of 5, moderate to severe
             COVID-19 disease confirmed by at an SpO2≤93 % or a respiratory rate≥24/min on room
             air. Note: If a subject was on supplemental oxygen with SpO2>93% and respiratory
             rate<24/min, but desaturation to ≤93 % or increase of respiratory rate to ≥24/min on
             lower supplemental oxygen or room air is documented during screening, the inclusion
             criterion was considered to be met.

        Exclusion Criteria:

          1. Concurrent serious medical condition which in the opinion of the investigator
             constituted a risk or a contraindication for the participation in the trial or that
             could interfere with the trial objectives, conduct or evaluation

          2. Known, active tuberculosis, active hepatitis B, C, or human immunodeficiency virus
             (HIV) infection (i.e., HIV with a CD4 count<500 cells/mm³).

          3. Moderate or severe impairment of hepatic function (e.g., Child-Pugh class B or C where
             alterations in the score components were not due to another underlying disease (see
             Section 8.4.5 in the Protocol)).

          4. Severe renal impairment (i.e., estimated glomerular filtration rate (eGFR)≤30
             ml/min/1.73m2)

          5. COVID-19 symptom onset >21 days prior to screening (Visit 1).

          6. Hospitalized due to COVID-19 for >72 hours at screening (Visit 1).

          7. Invasive mechanical ventilation or ECMO within 72 hours of screening (Visit 1).

          8. Expected need for invasive mechanical ventilation or ECMO in <48 hours in the opinion
             of the investigator

          9. Moderate to severe ARDS (e.g., same-day PaO2/FiO2 ≤200 mmHg; or SpO2/FiO2 ≤232 if
             arterial blood gas test is not available), if on non-invasive mechanical ventilation
             or high-flow oxygen.

         10. Pregnant or breast-feeding female subjects

         11. Any previous and concurrent experimental treatment for COVID-19 that was not
             considered local SoC.

         12. Treatment with the medications listed below within 1 week prior to screening (Visit 1)
             or anticipated need for such medication during the participation in this trial:

               1. Strong Cytochrome P450 (CYP) 3A4 inducers.

               2. P-glycoprotein (P-gp) substrates with narrow therapeutic index.

               3. High dose Breast Cancer Resistance Protein (BCRP) sensitive substrates.

               4. Warfarin.

               5. Sulphasalazine or rosuvastatin.

         13. Current or previous participation in any other clinical trial where the subject had
             received a dose of IMP within 1 month or 5 half-lives of the IMP, whichever was
             longest, prior to screening (Visit 1).

         14. Positive pregnancy test (see Section 8.4.6 in the Protocol).

         15. Abnormal laboratory value at screening (Visit 1) indicating a potential risk for the
             subject if enrolled in the trial as evaluated by the investigator