Methotrexate Treatment of Arthritis Caused by Chikungunya Virus (MARCH)

• Status: Not yet recruiting
• Trial end date: 2027-06-30
• Target enrollment: 0
• Participant gender: All

Summary

MARCH is the first randomized, double-blind, placebo-controlled evaluation of the efficacy and pathologic mechanism determined by synovial biopsy of 6 months of methotrexate (n=100) versus placebo (n=50) therapy for chronic chikungunya (CHIKV) arthritis in Colombia with the option for open-label use of the medication for up to one year for all participants. Our central hypothesis is that methotrexate will significantly decrease chronic CHIKV arthritis disease severity compared to placebo via suppression of leukocyte accumulation in synovial tissue and decreased expression of inflammatory cytokines from synovial macrophages and fibroblast-like synoviocytes (FLS).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: George Washington University
• Treatments: Methotrexate

Criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent form.

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

3. Male or female, aged >18 years

4. Ability to take oral medication and be willing to adhere to the methotrexate regimen

5. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 weeks after the end of methotrexate administration.

6. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

7. Have a diagnosis of CHIKV by CHIKV IgM or IgG antibody.

8. Have a diagnosis of arthritis as defined by having at least one joint with definite clinical synovitis (swelling)

9. The disease duration should be greater than 3 months (based on onset of symptoms).

10. Have active disease at the time of screening; active disease is defined as at least 4 swollen and 4 tender joints (using the 66-joint count).

11. Screen laboratory tests must meet the following criteria: Hemoglobin ≥ 9 g/dL, WBCs ≥ 3.5 x 109 cells/L, Neutrophils ≥ 1.5 x 109 cells/L, Platelets ≥ 100 x 109 cells/L, serum transaminase levels not exceeding 1.5 times the upper limit of normal, serum creatinine ≤ 1.6 mg/dL, and negative for hepatitis B surface antigen and hepatitis C antibodies.

12. Have a chest radiograph either at screening or within the past year that shows no evidence of malignancy or active infection.

13. Must have at least moderate Disease Activity Score.

14. Status-post complete Covid vaccination defined as at least 2 weeks after complete vaccination series.

Exclusion Criteria:

1. Pregnancy or lactation

2. Known allergic reactions to components of methotrexate or folic acid.

3. Treatment with another investigational drug or other intervention within 1 month.

4. History of chronic infection such as hepatitis, pneumonia, or pyelonephritis.

5. Current signs or symptoms of uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease.

6. Patients with a current diagnosis of class III or IV CHF.

7. History of lymphoproliferative disease including lymphoma.

8. Active TB or evidence of latent TB (positive PPD skin test or a history of old or latent TB on chest x-ray) without adequate therapy for TB.

9. Overt or laboratory evidence of immunodeficiency syndromes.

10. Any opportunistic infections, including but not limited to evidence of active cytomegalovirus, active Pneumocystis carinii, aspergillosis, histoplasmosis or atypical mycobacterium infection, within the previous 6 months at screening visit.

11. History of substance abuse (drug or alcohol) within the previous 2 years.

12. Intra-articular, soft tissue or intra-muscular corticosteroid injection during the 4 weeks prior to screening.

13. History of prior use of methotrexate or biologic therapy.

14. Evidence of active viral infection with fever >38°

15. Current use of any other disease modifying arthritis medication including but not limited to sulfasalazine, methotrexate, hydroxychloroquine, leflunomide, or biologics in the previous 2 months. Patients on stable doses of prednisone up to 10 mg per day for at least 4 weeks prior to enrollment may participate. Non-steroidal anti-inflammatories (NSAIDS) and acetaminophen are permitted for pain during the study.

16. Hematuria or proteinuria on urinalysis.

17. Diagnosis of rheumatoid arthritis prior to chikungunya infection or the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies >2 times the upper limit of normal.