Long Covid (LC)-REVITALIZE - A Long Covid Repurposed Drug Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dr. Douglas D. Fraser

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2026-02-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-522611-42-00

ClinicalTrials.gov

NCT06928272

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the efficacy of study drugs in improving symptom severity in participants with Long Covid.

Secondary objectives 10

1. To compare symptom burden of participants with Long Covid treated with study drugs versus placebo (e.g., overall well-being, anxiety, depression).
2. To assess whether symptom burden worsens in participants with Long Covid treated with study drugs versus placebo, specifically when symptoms are reported across multiple scales.
3. To compare the severity of post exertional malaise (PEM) in participants with Long Covid treated with study drugs versus placebo
4. To measure specific pathophysiological biomarkers of study drugs versus placebo.
5. To assess changes in exercise capacity over time of participants with Long Covid treated with study drugs versus placebo
6. To evaluate the safety and tolerability of the study drugs in participants with Long Covid
7. Analyze plasma proteomics to understand protein/pathway analyses and mechanisms of action for the study drugs
8. Analyze plasma metabolomics to understand metabolic changes and the final consequences of the study drugs
9. RNA sequencing to identify gene expression changes to understand response to study drugs
10. Exome/single nucleotide polymorphisms to identify genetic variants to understand the metabolism/efficacy of the study drugs

Conditions and MedDRA coding

Long Covid

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Adults ≥ 18 years of age and ≤ 65 years of age
2. Previous Covid-19 (SARS-CoV-2 infection) within the past four years, as determined by the site investigator using the following certainty scale (based on available clinical history and/or serologic data): 3 – Confirmed Infection (PCR or n-Capsid Test): Prior positive nasopharyngeal or salivary PCR test for Covid-19 (documented proof and/or verbal confirmation by participant) or has positive nucleocapsid antibodies results. 2 – Probable Infection (Antigen Test): Participant verbally confirms a prior positive rapid antigen test without PCR confirmation. 1 – Possible Infection (Viral Syndrome and Epidemiological Link): Participant verbally confirms experiencing symptoms consistent with Covid-19 infection and has an epidemiological link (i.e., exposure to a confirmed case) without any positive testing.
3. Persistent or new symptoms diagnosed as "Long Covid" as defined by the World Health Organization; "the continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection (Covid-19), with these symptoms lasting for at least 2 months with no other explanation". This diagnosis may come from a healthcare professional experienced in Long Covid diagnosis, or the site investigator. These symptoms must be present for more days than not and must not have been present prior to the onset of SARS-CoV-2 (Covid-19) infection.
4. At the time of screening, participants should be experiencing at least one of the following self-reported symptoms or symptom clusters. Participant has self-reported issues with: Fatigue Breathing Circulation Memory, thinking, and/or communication Muscles and/or joints These five symptoms or symptom clusters were selected based on unpublished data from the National Institutes for Health and Care Research (NIHR, United Kingdom) and their alignment with five validated SBQ scales. The selection was driven by their prevalence and their significant impact on quality of life as reported in symptom assessments.
5. Participant has the ability and is willing to follow study procedures throughout the study
6. Participant can provide informed consent

Exclusion criteria 40

1. Participants who do not meet the criteria outlined above
2. Participants who are unable to provide their informed consent
3. Participants who are pregnant, lactating, or plan to become pregnant during the time of the study
4. Persons of childbearing potential who are unwilling or unable to abstain from sex or to use at least one acceptable method of contraception from the time of screening through at least 30 days after the end of the study intervention period. Acceptable methods include barrier contraceptives (e.g., condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization. Participants unwilling to be counseled about the risks related to pregnancy or breastfeeding will also be excluded.
5. Male participants must take precautions to avoid impregnating a female while participating in this study. If a male participant's partner can become pregnant, she must use an effective and reliable form of birth control, as listed above, during the study and for 30 days after the male participant's last dose of the investigational product. Additionally, male participants must agree to use a latex condom during sexual activity with partners who could become pregnant.
6. eGFR <30 mL/min/1.73m2
7. Moderate to severe liver dysfunction, defined as Bilirubin > 1.5 x ULN or AST or ALT > 2 x ULN
8. Hemoglobin (Hbg) < 8.0 g/dL
9. Absolute neutrophil count (ANC) below 1,000 cells/mm³, confirmed with repeat testing
10. Absolute lymphocyte count (ALC) below 500 cells/mm³
11. Alkaline phosphatase (ALP) levels equal to or greater than three times the upper limit of normal (ULN)
12. Creatine phosphokinase (CPK) levels equal to or greater than three times the ULN
13. Platelet count below 100,000 cells/mm³, confirmed with repeat testing
14. Platelet count above 500,000 cells/mm³, confirmed with repeat testing
15. Total fasting cholesterol levels of 280 mg/dL or higher, confirmed with repeat testing
16. Fasting low-density lipoprotein (LDL) levels of 180 mg/dL or higher, confirmed with repeat testing
17. A personal or family history of long QT syndrome or an electrocardiogram (ECG) during screening showing a corrected QT interval (QTc) of 500 milliseconds or greater, calculated using Fridericia's formula
18. Participants with HIV diagnosis
19. Participants with active hepatitis B or C diagnosis. Note: treated or cleared hepatitis C is not exclusionary.
20. Active herpes zoster infection (visible skin lesions) within 3 months prior to screening, or any history of disseminated or complicated herpes zoster or herpes simplex infection (e.g., VZV encephalitis)
21. Participants with active or latent tuberculosis
22. Immunocompromised status, as determined by the investigator, that places the participant at an unacceptable risk for study participation
23. Active malignancy or lymphoproliferative disorder that has not been in remission for at least five years. Localized non-melanoma skin cancers that have been definitively treated are not exclusionary.
24. Positive SARS-CoV-2 test in the last 30 days or symptomatic with Covid-19 like illness
25. Previous admission to an intensive care unit (ICU) for the treatment of acute COVID-19 infection
26. Any history of deep venous thrombosis, pulmonary embolism, unstable angina, atrial fibrillation, ventricular fibrillation, or myocardial infarction or stroke
27. History of sepsis or a significant viral, bacterial, fungal, or parasitic infection within 30 days prior to enrollment, as determined by the investigator.
28. Use of one or more of the study drugs within 30 days prior to enrollment for the original indication or other purposes
29. Known allergic reactions to the components of the study drugs
30. Any prior exposure to JAK inhibitors
31. Taking any of the listed medications on the prohibited medications list in Appendix A
32. Intake or planned consumption of any of the following: Taurine, Curcumin, CoQ10, Creatine, Resveratrol, Fisetin, Nicotinamide mononucleotide (NMN), Nicotinamide adenine dinucleotide (NAD+), Quercetin, Glycine, Spermidine, Arginine alpha-ketoglutarate, Ergothioneine, Alpha Lipoic Acid, Carnitine, Benfotiamine, Carnosine, Crocin, N-acetylcysteine
33. Covid vaccinations are prohibited within 30 days prior to enrollment
34. Live vaccine within the 30 days before enrollment or plan to receive live vaccines during the study period
35. Other vaccines, including influenza vaccine, are prohibited within 14 days of enrollment
36. Major surgery within 30 days prior to enrollment or plans for major surgery during the study
37. Any other co-existing medical condition or concomitant medication/therapy that might in the judgment of the study investigators, potentially impact the participant's safety or ability to adhere to the study protocol or interfere with the meaning of the clinical and research measurements as judged by the study investigators
38. Participation in any clinical study within the last 30 days prior to enrollment
39. Participants who participated in Phase One of this study (LC-Revitalize) are not eligible to participate in Phase Two
40. Currently hospitalized and/or incarcerated

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The aim of this study is to evaluate the efficacy of two repurposed drugs in reducing symptom severity in participants with Long Covid. The change in symptom score (transformed scale of 0-100) from baseline to both the interim and final analyses will be compared across one of the five validate subscales, relative to the placebo. This study will utilize five validated subscales: 1) Fatigue, 2) Breathing, 3) Memory, Thinking, and Communication, 4) Muscles and Joints, and 5) Circulation.

Secondary endpoints 8

1. To compare symptom burden of participants with Long Covid treated with study drug versus placebo by measuring the change in total scores of the Patient Reported Outcome Measurement Information System (PROMIS)-29 questionnaire.
2. To compare symptom burden of participants with Long Covid treated with study drug versus placebo by measuring the change in total scores of the Generalized Anxiety Disorder (GAD)-7 questionnaire from baseline to the interim and final analyses.
3. To compare symptom burden of participants with Long Covid treated with study drug versus placebo by measuring the change in total scores of the Patient Health Questionnaire (PHQ)-9 from baseline to the interim and final analyses. The PHQ-9 questionnaire consists of 9 items related to the symptoms of depression. Each item is scored on a scale of 0-3 with higher scores indicating more severe symptoms.
4. To assess whether symptom burden worsens in participants with Long Covid treated with study drugs versus placebo, specifically when symptoms are reported across multiple scales indicated by the total number of participants with increased SBQ subscale scores. The following SBQ subscales will be used during this study: 1) Fatigue, 2) Breathing, 3) Memory, thinking, and communication, 4) Muscles and joints, 5) Circulation.
5. To measure specific pathophysiological biomarker of study drugs versus placebo indicated by the normalization of blood biomarkers after treatment in picograms per milliliter (pg/mL).
6. To assess changes in exercise capacity over time of participants with Long Covid treated with study drugs versus placebo. The score is determined by the distance a participant walks in six minutes around the perimeter of a designated circuit.
7. The frequency and severity of adverse events and laboratory abnormalities will be monitored to assess safety and tolerability. A lower incidence and severity will indicate that the drugs are safer and more tolerable.
8. Plasma proteomics will be analyzed to assess protein differential expression and signaling pathway mechanisms related to the study drugs. Analyses will focus on the expression normalization of proteins/pathways associated with Long Covid. Plasma metabolomics will be analyzed to evaluate metabolic changes and the overall effects of the study drugs. Analyses will focus on the concentration normalization of metabolites linked to the pathophysiology of Long Covid.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dr. Douglas D. Fraser

Sponsor organisation

Dr. Douglas D. Fraser

Address

800 Commissioners Rd E

City

London

Postcode

N6A 5W9

Country

Canada

Scientific contact point

Organisation

Dr. Douglas D. Fraser

Contact name

Douglas D. Fraser

Public contact point

Organisation

Dr. Douglas D. Fraser

Contact name

Stephanie Perkin

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications