A Multicentre, Adaptive, Randomised, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalised Adults

Phase 1

• Conditions: COVID-19 (Coronavirus RNA); MedDRA version: 23.0Level: PTClassification code 10051905Term: Coronavirus infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Health Care [N] - Environment and Public Health [N06]

• Registration Number: EUCTR2020-001052-18-GR
• Lead Sponsor: Regents of the University of Minnesota

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-02
• Last Update Posted: 29 June 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1032

Inclusion Criteria

ACTT Stage 2:
1. Admitted to a hospital with symptoms suggestive of COVID-19.
2. Subject (or legally authorised representative) provides informed consent prior to initiation of any study procedures.
3. Subject (or legally authorised representative) understands and agrees to comply with planned study procedures.
4. Male or non-pregnant female adults = 18 years of age at time of enrolment.
5. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assayin any specimen, as documented by either of the following:PCR positive in sample collected < 72 hours prior to randomisation; ORPCR positive in sample collected = 72 hours prior to randomisation, documented inability to obtain a repeat sample(e.g. due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc) AND progressive diseasesuggestive of ongoing SARS-CoV-2 infection.
6. Illness of any duration, and at least one of the following:
Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), ORSpO2 = 94% on room air, OR
Requiring supplemental oxygen, ORRequiring mechanical ventilation or ECMO.
7. Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception
not including hormonal contraception from the time of screening through Day 29.
8. Agrees to not participate in another clinical trial for the treatment of COVID-19 through Day 29.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 33
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 33

Exclusion Criteria

ACTT Stage 2:
1. ALT or AST > 5 times the upper limit of normal.
2. Estimated glomerular filtration rate (eGFR) < 30 ml/min or patient is receiving hemodialysis or hemofiltration at timeof screening.
3. Neutropenia (absolute neutrophil count <1000 cells/µL) (<1.0 x 103/µL or <1.0 GI/L).
4. Lymphopenia (absolute lymphocyte count <200 cells/µL) (<0.20 x 103/µL or <0.20 GI/L)
5. Pregnancy or breast feeding.
6. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.
7. Allergy to any study medication.
8. Received three or more doses of remdesivir including the loading dose, outside of the study under the EUA (or
similar mechanism) for COVID-19.
9. Received convalescent plasma or intravenous immunoglobulin (IVIg) for COVID-19, the current illness for whichthey are being enrolled.
10. Received small molecule tyrosine kinase inhibitors (e.g., baricitinib, imatibib, genfinitib) in the 1 week prior to
screening.
11. Received monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6
[tocilizumab or sarilumab]) or cells (e.g., abatacept) in the 4 weeks prior to screening.
12. Received monoclonal antibodies targeting B-cell (e.g., rituximab, and including any targeting multiple cell lines
including B-cells) in the 3 months prior to screening.
13. Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator,
the risk of immunosuppression with baricitinib is larger than the risk of COVID-19.
14. Received =20 mg/day of prednisone or equivalent for =14 consecutive days in the 4 weeks prior to screening.
15. Use of probenecid that cannot be discontinued at study enrollment.
16. Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with
appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
17. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the
investigator could constitute a risk when taking investigational product.
18. Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a livevaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects.
19. Have a history of VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 12 weeks prior to
screening or have a history of recurrent (>1) VTE (DVT/PE).
20. Immunocompromised patients, patients with a chronic medical condition, or those taking a medication that cannot be discontinued at enrollment, who, in the judgment of PI, are at increased risk for serious infections or other safety concerns given the study products.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified