Condition

• Post-Acute COVID-19 Syndrome

Eligibility

Eligible Ages

Over 18 Years

Eligible Genders

All

Accepts Healthy Volunteers

No

Criteria

In order to be eligible to participate in this study, an individual must meet all of the
following criteria:

1. Obtain a signed and dated informed consent form from participant

2. State their willingness to comply with all study procedures and availability for the
duration of the study

3. Male or female, aged ≥18 years old

4. Meet the following criteria for "Post-COVID Condition" or Long COVID:

1. 6-months prior, documented SARS-CoV-2 infection

2. Cognitive impairment as defined by having at least 20% positive (worse or much
worse) items on the ECOG assessment

3. Neurocognitive symptoms must have been present for at least 60 days prior to
screening. Symptoms that wax and wane must have been initially present at least
60 days prior to screening.

5. Ability to take oral medication and be willing to adhere to the baricitinib regimen

6. Females of childbearing potential must agree to either abstinence or use at least
one acceptable method of contraception from the time of screening though at least 28
days after the end of the study intervention period. Note: Acceptable methods
include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine
devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical
sterilization.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation
in this study:

1. Pre-existing cognitive impairment not exacerbated by acute COVID as determined by
study physicians after thorough review of participant's history and medical records

2. Current use of baricitinib or other disease-modifying antirheumatic drug (DMARDs)

3. Known allergic reactions to components of the baricitinib

4. Have ever been randomized in this study or any other study investigating baricitinib

5. Positive SARS-CoV-2 PCR or rapid Antigen test in the past 14 days

6. Pregnancy or breastfeeding

7. Any history of venous thromboembolism ever

8. History of malignancy or lymphoproliferative disorder

9. Renal dysfunction with estimated glomerular filtration rate of < 30 mL/min/1.73m2

10. Absolute Neutrophil Count (ANC) <1200 cells/mm3

11. History or evidence of severe or end-stage liver disease (e.g. bilirubin ≥1.5x or
AST/ALT >2x normal).

12. Positive Hepatitis B surface antibody, antigen or core antibody, or Positive
Hepatitis C RNR or antigen

13. Positive HIV 4th generation (antibody/antigen) ELISA test

14. Have had symptomatic herpes zoster infection within 3 months prior to study entry or
have a history of disseminated/complicated herpes zoster or herpes simplex infection

15. History of latent (diagnosed with Quantiferon testing) or active tuberculosis

16. History of a current or recent (< 30 days from screening) clinically significant
viral, bacterial, fungal, or parasitic infection

17. History of chronic alcohol abuse, Intravenous (IV) drug abuse, or other illicit drug
abuse within the 2 years prior to study entry

18. Are immunocompromised and, in the opinion of the investigator, are at an
unacceptable risk for participating in the study

19. Treatment with another investigational drug or other intervention < 30 days of study
enrollment

20. Are unable or unwilling to make themselves available for the duration of the study
and/or are unwilling to follow study restrictions/procedures

21. Severe cognitive, physical, or psychological disability that would prevent
participation in the study

Detailed Description

This is a multi-site randomized, placebo-controlled, double-blind, parallel-design REVERSE-LC phase 3 study. Individuals meeting inclusion criteria will be randomized to one of two arms: the intervention arm of baricitinib 4 mg daily for 24 weeks (dose adjusted to 2 mg or 1 mg for baseline renal dysfunction) versus the placebo arm for 24 weeks. In addition to safety, a variety of clinical and biological outcome measures will be assessed.