A Trial to Investigate Recovery From COVID-19 With C21 in Adult Subjects (ATTRACT-3)

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo; Drug: C21

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.

• Study Type: Interventional
• Enrollment (Actual): 272
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina
    • Nuevo Hospital San Roque
  • Córdoba
    • Río Cuarto, Córdoba, Argentina, X5800
      • Instituto Medico Rio Cuarto
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000
      • Hospital Italiano Rosario - Centro
    • Rosario, Santa Fe, Argentina, S2001
      • Hospital Italiano Rosario
• Brazil
  • Botucatu, Brazil
    • Hospital das Clínicas da Faculdade de Medicina de Botucatu
  • Brasília, Brazil, 71681-603
    • Hospital Brasilia
  • Caxias Do Sul, Brazil
    • Fundacao Universidade de Caxias do Sul
  • Natal, Brazil, 59025-050
    • Centro de Pesquisas Clínicas de Natal
  • Porto Alegre, Brazil
    • Hospital de Clínicas de Porto Alegre
  • São Paulo, Brazil, 01323-020
    • Hospital Alemão Oswaldo Cruz - Paulista
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil
      • Instituto Atena de Pesquisa Clinica
• Colombia
  • Antioquia
    • Rionegro, Antioquia, Colombia
      • Clinica Somer
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia
      • Hospital Universitario San Ignacio
    • Bogotá, Cundinamarca, Colombia
      • Fundacion Santa Fe de Bogota
• Czechia
  • Brno, Czechia
    • Fakultní Nemocnice u sv. Anny v Brne Number 1
  • Slaný, Czechia
    • Nemocnice Slany
  • Ústí Nad Labem, Czechia
    • Masarykova Nemocnice V Usti Nad Labem
  • South Moravian
    • Brno, South Moravian, Czechia
      • Fakultní Nemocnice u sv. Anny v Brně II. Interní Klinika kardiologická JIP,
• India
  • Chennai
    • Mahabalipuram, Chennai, India
      • Chettinad Hospital and Research Institute
  • Gujarat
    • Ahmedabad, Gujarat, India
      • Civil Hospital and B J Medical College
    • Pune, Gujarat, India
      • Smt. Kashibai Navale Medical College and General Hospital
    • Vadodara, Gujarat, India
      • Rhythm Heart Institute
  • Kerala
    • Kozhikode, Kerala, India
      • Malabar Medical College Hospital and Research Centre
    • Thrissur, Kerala, India
      • Elite Mission Hospital
  • Madhya Pradesh
    • Bhopal, Madhya Pradesh, India
      • Chirayu Medical College and Hospital
  • Maharashtra
    • Nagpur, Maharashtra, India
      • Meditrina Institute Of Medical Sciences
    • Nagpur, Maharashtra, India
      • Government Medical College and Hospital
    • Pune, Maharashtra, India
      • Noble Hospital
    • Pune, Maharashtra, India
      • Ruby Hall Clinic
    • Thāne, Maharashtra, India
      • Rajiv Gandhi Medical College
  • Manipur
    • Imphal, Manipur, India
      • Jawaharlal Nehru Institute of Medical Sciences
• Philippines
  • Davao City, Philippines
    • Southern Philippines Medical Center
  • Iloilo City, Philippines
    • West Visayas State University Medical Center
  • Makati, Philippines
    • Makati Medical Center
  • Quezon City, Philippines
    • Lung Center of the Philippines
  • Quezon City, Philippines
    • Quirino Memorial Medical Center
  • Taguig, Philippines
    • St. Luke's Medical Center - Global City
  • Iloilo
    • Iloilo City, Iloilo, Philippines
      • The Medical City
• Russian Federation
  • Moscow, Russian Federation
    • Clinical Infectious Disease Hospital 1 of the Moscow Department of Health
  • Saint Petersburg, Russian Federation
    • Pokrovskaya City Hospital
  • Saint Petersburg, Russian Federation
    • Alexandrovskaya State Hospital
  • Saint Petersburg, Russian Federation
    • Nikolaevskaya State Hospital
  • Saint Petersburg, Russian Federation
    • St. Petersburg State Budgetary Healthcare Institution City Hospital Number 40 of the Kurortny District
• South Africa
  • KwaZulu-Natal
    • Tongaat, KwaZulu-Natal, South Africa, 4400
      • Mediclinic Southern Africa
  • Western Cape
    • George, Western Cape, South Africa, 6530
      • TASK Eden
    • Tygerberg Hills, Western Cape, South Africa, 7505
      • Tygerberg hospital
• Ukraine
  • Dnipropetrovs'k, Ukraine
    • City Clinical Hospital №6 of the Dnipro City Council
  • Kharkiv, Ukraine
    • City Clinical Hospital №13" Of Kharkiv City Council
  • Kharkiv, Ukraine
    • Regional Clinical Hospital of Infectious Diseases
  • Kiev, Ukraine
    • Kyiv city clinical hospital number 12
  • Kyiv, Ukraine
    • Oleksandrivska Kyiv City Clinical Hospital
  • Vinnytsia, Ukraine
    • Vinnytsia City Clinical Hospital №1
  • Zhytomyr, Ukraine
    • Hospital №1 of Zhytomyr City Council
  • Zaporizhzhia
    • Zaporizhia, Zaporizhzhia, Ukraine
      • Zaporizhzhia Regional Clinical Hospital
• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
  • Illinois
    • Winfield, Illinois, United States, 60190
      • Northwestern Medicine Central DuPage Hospital
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Physicians Group - Infectious Diseases
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Trinity Health
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18102
      • Lehigh Valley Hospital - 17th Street
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Roanoke Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C21; 50 mg capsules, oral administration twice daily,for 14 days	Drug: C21; C21
Placebo Comparator: Placebo; placebo capsules, oral administration twice daily,for 14 days	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause Mortality up to Day 60	Proportion of subjects in the mITT (all randomised, including 5 subjects not treated) with death up to Day 60 follow-up	Day 1 to Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Sustained Hospital Discharge up to Day 60	Time to sustained hospital discharge from Day 1 to Day 60: Time to sustained hospital discharge was defined as the time to the date of discharge from the initial hospitalization or re-hospitalization due to COVID-19 after which the subject was not re-hospitalized for COVID-19 related reasons.	Day 1 to Day 60
Supplemental Oxygen-free Days up to Day 29	Supplemental oxygen-free days from Day 1 up to Day 29, observed range 0 to 28 days. Subjects with deaths imputed as -1 day according to SAP and FDA guidance. Outcome was identical in both groups for both median and range	Day 1 to Day 29, maximum 28 Days
Proportion of Subjects Free of Respiratory Failure, Defined as an 8-point Ordinal Scale Score ≤5, at Day 15	Proportion of subjects free of respiratory failure, defined as an 8-point ordinal scale score ≤5, at Day 15. Missing data imputed by MI, proportion given are average over the imputations.	Day 15
Proportion of Subjects Discharged From Hospital and Free of Supplemental Oxygen at Day 15	Proportion of subjects discharged from hospital and free of supplemental oxygen at Day 15. Missing data imputed by MI, proportion given are average over the imputations.	Day 15

Other Outcome Measures

Outcome Measure	Time Frame
Number of adverse events	Day 29
Number of serious adverse events	Day 60
Number of withdrawals due to Adverse events	Day 29
Proportion of subjects discharged from hospital and free of supplemental oxygen	Day 8
Proportion of subjects discharged from hospital and free of supplemental oxygen	Day 22
Proportion of subjects discharged from hospital and free of supplemental oxygen	Day 29
Proportion of hospitalized subjects on non-invasive, invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) or supplemental oxygen use	Day 8
Proportion of hospitalized subjects on non-invasive, invasive mechanical ventilation, ECMO or supplemental oxygen use	Day 15
Proportion of hospitalized subjects on non-invasive, invasive mechanical ventilation, ECMO or supplemental oxygen use	Day 22
Proportion of hospitalized subjects on non-invasive, invasive mechanical ventilation, ECMO or supplemental oxygen use	Day 29
Proportion of hospitalized subjects on non-invasive, invasive mechanical ventilation, ECMO or supplemental oxygen use	Day 60
Proportion of subjects in each category of the 8-point ordinal scale	Day 8
Proportion of subjects in each category of the 8-point ordinal scale	Day 15
Proportion of subjects in each category of the 8-point ordinal scale	Day 22
Proportion of subjects in each category of the 8-point ordinal scale	Day 29
Proportion of subjects in each category of the 8-point ordinal scale	Day 60
Duration of hospitalization, including re-hospitalization	Day 60
Proportion of subjects needing intensive care unit stay	Day 8
Proportion of subjects needing intensive care unit stay	Day 15
Proportion of subjects needing intensive care unit stay	Day 22
Proportion of subjects needing intensive care unit stay	Day 29
Proportion of subjects needing intensive care unit stay	Day 60
Duration of intensive care unit stay, including re-admission	Day 60
Proportion of subjects on invasive mechanical ventilation or ECMO	Day 8
Proportion of subjects on invasive mechanical ventilation or ECMO	Day 15
Proportion of subjects on invasive mechanical ventilation or ECMO	Day 22
Proportion of subjects on invasive mechanical ventilation or ECMO	Day 29
Proportion of subjects on invasive mechanical ventilation or ECMO	Day 60
Duration of use of invasive mechanical ventilation or ECMO up to Day 60	Day 60
All-cause mortality	Day 8
All-cause mortality	Day 15
All-cause mortality	Day 22
All-cause mortality	Day 29
Change from baseline in oxygen saturation/ fraction of inspired oxygen	Day 15
Change from baseline in C-reactive protein concentration	Day 15
Change from baseline in lactate dehydrogenase (LDH)	Day 15
Proportion of subjects free of respiratory failure	Day 8
Proportion of subjects free of respiratory failure	Day 22
Proportion of subjects free of respiratory failure	Day 29
Proportion of subjects free of respiratory failure	Day 60
Proportion of respiratory failure free days up to Day 60	Day 60

Collaborators and Investigators

• Sponsor: Vicore Pharma AB
• Investigators: Principal Investigator: Maureen Horton, MD, Johns Hopkins University School of Medicine, Baltimore, USA

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2021
• Primary Completion (Actual): April 25, 2022
• Study Completion (Actual): April 25, 2022

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: VP-C21-008; 2021-000264-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No