Clinical trial NCT04880642: A Trial to Investigate Recovery From COVID-19 With C21 in Adult Subjects
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Phase 3, Multicenter Trial Investigating the Efficacy and Safety of C21 as add-on to Standard of Care in Adult Subjects With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Vicore Pharma AB
Sponsor class: INDUSTRY
First posted: 2021-05-11
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: The trial consists of 3 consecutive periods: a screening period of up to 48 hours, a 2-week investigational medicinal product (IMP) treatment period and a follow-up period of up to 7 weeks after last IMP intake.

All subjects went through a series of efficacy, safety, and laboratory assessments. Safety laboratory tests and samples for future exploratory analysis were obtained at the screening visit.

The trial duration for an individual subject was not exceeded 9 weeks.

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

Primary outcomes:
measure: All-cause Mortality up to Day 60
timeFrame: Day 1 to Day 60
Secondary outcomes:
measure: Time to Sustained Hospital Discharge up to Day 60
timeFrame: Day 1 to Day 60
measure: Supplemental Oxygen-free Days up to Day 29
timeFrame: Day 1 to Day 29, maximum 28 Days
measure: Proportion of Subjects Free of Respiratory Failure, Defined as an 8-point Ordinal Scale Score ≤5, at Day 15
timeFrame: Day 15
measure: Proportion of Subjects Discharged From Hospital and Free of Supplemental Oxygen at Day 15
timeFrame: Day 15
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Winfield
country: United States
facility: Northwestern Medicine Central DuPage Hospital
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Physicians Group - Infectious Diseases
state: Indiana
city: Minot
country: United States
facility: Trinity Health
state: North Dakota
city: Allentown
country: United States
facility: Lehigh Valley Hospital - 17th Street
state: Pennsylvania
city: Roanoke
country: United States
facility: Carilion Roanoke Memorial Hospital
state: Virginia
city: Río Cuarto
country: Argentina
facility: Instituto Médico Río Cuarto
state: Córdoba
city: Rosario
country: Argentina
facility: Hospital Italiano Rosario - Centro
state: Santa Fe
city: Rosario
country: Argentina
facility: Hospital Italiano Rosario
state: Santa Fe
city: Córdoba
country: Argentina
facility: Nuevo Hospital San Roque
city: Natal
country: Brazil
facility: Instituto Atena de Pesquisa Clínica
state: Rio Grande Do Norte
city: Botucatu
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Botucatu
city: Brasília
country: Brazil
facility: Hospital Brasília
city: Caxias Do Sul
country: Brazil
facility: Fundação Universidade de Caxias do Sul
city: Natal
country: Brazil
facility: Centro de Pesquisas Clínicas de Natal
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: São Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz - Paulista
city: Rionegro
country: Colombia
facility: Clinica Somer
state: Antioquia
city: Bogotá
country: Colombia
facility: Fundación Santa Fe de Bogotá
state: Cundinamarca
city: Bogotá
country: Colombia
facility: Hospital Universitario San Ignacio
state: Cundinamarca
city: Brno
country: Czechia
facility: Fakultní Nemocnice u sv. Anny v Brně II. Interní Klinika kardiologická JIP,
state: South Moravian
city: Brno
country: Czechia
facility: Fakultní Nemocnice u sv. Anny v Brne Number 1
city: Slaný
country: Czechia
facility: Nemocnice Slaný
city: Ústí Nad Labem
country: Czechia
facility: Masarykova nemocnice v Ústí nad Labem
city: Mahabalipuram
country: India
facility: Chettinad Hospital and Research Institute
state: Chennai
city: Ahmedabad
country: India
facility: Civil Hospital and B J Medical College
state: Gujarat
city: Pune
country: India
facility: Smt. Kashibai Navale Medical College and General Hospital
state: Gujarat
city: Vadodara
country: India
facility: Rhythm Heart Institute
state: Gujarat
city: Kozhikode
country: India
facility: Malabar Medical College Hospital and Research Centre
state: Kerala
city: Thrissur
country: India
facility: Elite Mission Hospital
state: Kerala
city: Bhopal
country: India
facility: Chirayu Medical College and Hospital
state: Madhya Pradesh
city: Nagpur
country: India
facility: Government Medical College and Hospital
state: Maharashtra
city: Nagpur
country: India
facility: Meditrina Institute of Medical Sciences
state: Maharashtra
city: Pune
country: India
facility: Noble Hospital
state: Maharashtra
city: Pune
country: India
facility: Ruby Hall Clinic
state: Maharashtra
city: Thāne
country: India
facility: Rajiv Gandhi Medical College
state: Maharashtra
city: Imphal
country: India
facility: Jawaharlal Nehru Institute of Medical Sciences
state: Manipur
city: Iloilo City
country: Philippines
facility: The Medical City
state: Iloilo
city: Davao City
country: Philippines
facility: Southern Philippines Medical Center
city: Iloilo City
country: Philippines
facility: West Visayas State University Medical Center
city: Makati
country: Philippines
facility: Makati Medical Center
city: Quezon City
country: Philippines
facility: Lung Center of the Philippines
city: Quezon City
country: Philippines
facility: Quirino Memorial Medical Center
city: Taguig
country: Philippines
facility: St. Luke's Medical Center - Global City
city: Moscow
country: Russian Federation
facility: Clinical Infectious Disease Hospital 1 of the Moscow Department of Health
city: Saint Petersburg
country: Russian Federation
facility: Alexandrovskaya State Hospital
city: Saint Petersburg
country: Russian Federation
facility: Nikolaevskaya State Hospital
city: Saint Petersburg
country: Russian Federation
facility: Pokrovskaya City Hospital
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg State Budgetary Healthcare Institution City Hospital Number 40 of the Kurortny District
city: Tongaat
country: South Africa
facility: Mediclinic Southern Africa
state: KwaZulu-Natal
city: George
country: South Africa
facility: TASK Eden
state: Western Cape
city: Tygerberg Hills
country: South Africa
facility: Tygerberg Hospital
state: Western Cape
city: Zaporizhia
country: Ukraine
facility: Zaporizhzhia Regional Clinical Hospital
state: Zaporizhzhia
city: Dnipropetrovs'k
country: Ukraine
facility: City Clinical Hospital №6 of the Dnipro City Council
city: Kharkiv
country: Ukraine
facility: City Clinical Hospital №13" Of Kharkiv City Council
city: Kharkiv
country: Ukraine
facility: Regional Clinical Hospital of Infectious Diseases
city: Kiev
country: Ukraine
facility: Kyiv city clinical hospital number 12
city: Kyiv
country: Ukraine
facility: Oleksandrivska Kyiv City Clinical Hospital
city: Vinnytsia
country: Ukraine
facility: Vinnytsia City Clinical Hospital №1
city: Zhytomyr
country: Ukraine
facility: Hospital №1 of Zhytomyr City Council
Study officials:
affiliation: Johns Hopkins University School of Medicine, Baltimore, USA
name: Maureen Horton, MD
role: PRINCIPAL_INVESTIGATOR
References: