A Study Evaluating the Efficacy and Safety of Baricitinib in Systemic Sclerosis

• Status: Recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Systemic Sclerosis (Ssc) is a rare, systemic autoimmune disease characterized by skin fibrosis and vasculopathy. In addition to the skin, it is a heterogeneous disease that affects multiple organs, including the musculoskeletal, cardiac, pulmonary, and gastrointestinal systems. Patients may experience many symptoms such as pain, fatigue, dyspnea, impaired hand function, dry mouth, and difficulty sleeping. As a result of these symptoms, these patients may experience a decrease in activities of daily living, physical activity level and quality of life, while psychological problems such as anxiety and depression may increase.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tongji Hospital
• Treatments: Cyclophosphamide

Criteria

Inclusion Criteria:

1. Diagnosis of Systematic Sclerosis (SSc), as defined using the 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc

2. Diffuse Systemic Sclerosis (dcSSc) as defined by LeRoy and Medsger

3. Disease duration of ≤ 36 months (defined as time from the first non-Raynaud phenomenon manifestation)

4. For disease duration of ≤ 18 months: ≥ 10 and ≤ 35 mRSS units at the screening visit

5. For disease duration of >18-36 months: ≥ 15 and ≤ 45 mRSS units at the screening visit and one of the following:

1)Increase ≥ 3 in mRSS units compared with the last visit within previous 1-6 months 2)Involvement of one new body area with ≥ 2 mRSS units compared with the last visit within the previous 1-6 months 3)Involvement of two new body areas with ≥ 1 mRSS units compared with the last visit within the previous 1-6 months 4)Presence of 1 or more Tendon Friction Rub 6.Age ≥ 18 years at the screening visit 7.If female of childbearing potential, the patient must have a negative pregnancy test at screening and baseline visits 8.Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) and NSAIDs are permitted if the patient is on a stable dose regimen for 2 weeks prior to and including the baseline visit.

9.ACE inhibitors, calcium-channel blockers, proton-pump inhibitors, and/or oral vasodilators are permitted if the patient is on a stable dose for ≥ 2 weeks prior to and including the baseline visit.

Exclusion Criteria:

1. Rheumatic disease other than dcSSc; it is acceptable to include patients with fibromyalgia and scleroderma-associated myopathy

2. Limited cutaneous systemic sclerosis or sine scleroderma at the screening visit

3. Major surgery (including joint surgery) within 8 weeks prior to screening visit

4. Infected ulcer prior to treatment

5. Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the baseline visit

6. Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and ABA

7. Anti-CD20 within 12 months prior to baseline visit.

8. Use of Intravenous Immunoglobulin (IVIG) within 12 weeks prior to baseline visit

9. Previous treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation

10. Immunization with a live/attenuated vaccine within ≤ 4 weeks prior to the baseline visit

11. Treatment with methotrexate, hydroxychloroquine, cyclosporine A, azathioprine, mycophenolate mofetil rapamycin, colchicine, or D-penicillamine, within≤ 4 weeks prior to the baseline visit

12. Treatment with etanercept within ≤ 2 weeks, infliximab, certolizumab, golimumab, ABA or adalimumab within ≤ 8 weeks, anakinra within ≤ 1 week prior to the baseline visit

13. Pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤ 40% of predicted at the screening visit

14. Pulmonary arterial hypertension (PAH) as determined by right heart catheterization or on PAH approved medications for PAH. It is acceptable to use PDFE-5 inhibitors for Raynaud's and digital ulcers.

15. Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be participants with a history of active TB within the last 3 years, even if it was treated; a history of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type; current clinical, radiographic, or laboratory evidence of active TB; and latent TB that was not successfully treated (≥ 4 weeks).

16. Positive for hepatitis B surface antigen prior to the baseline visit

17. Positive for hepatitis C antigen, if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay prior to baseline visit

18. Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be participants with a history of active TB within the last 3 years, even if it was treated; a history of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type; current clinical, radiographic, or laboratory evidence of active TB; and latent TB that was not successfully treated (≥ 4 weeks).

19. Any of the following at the screening visit: Hemoglobin <8 g/dL; ANC < 1,000/mm3 (<1 x 109/L); platelets < 100,000/mm3 (<100 x 109/L); serum creatinine > 2 x ULN; serum ALT or AST > 2 x ULN

20. Severe skin thickening (mRSS 3) on the inner aspects of thighs, upper arms, or abdomen

21. Patients with a history of anaphylaxis to Baricitinib or cyclophosphamide