Nilotinib in the Treatment of Systemic Sclerosis

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

Summary

A phase IIa open-label single center pilot study to assess the safety and efficacy of Nilotinib in patients with Scleroderma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hospital for Special Surgery, New York
• Collaborators: Novartis Pharmaceuticals; Rudolph Rupert Scleroderma Program

Criteria

Inclusion Criteria:

1. Age greater than or equal to eighteen years.

2. Clinical diagnosis of diffuse systemic sclerosis by ACR criteria, with a stable modified Rodnan skin score in the one month preceding introduction of oral nilotinib therapy. The modified Rodnan skin score must be greater than or equal to sixteen at screening and initiation of therapy.

3. Disease duration of less than or equal to 3 years as defined by the date of onset of the first non-Raynaud's symptom.

4. Estimated ejection fraction of greater than 50% by echocardiography

Exclusion Criteria:

1. Inability to render informed consent in accordance with institutional guidelines.

2. Disease duration of greater than 3 years.

3. Patients with mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease.)

4. Limited scleroderma.

5. Systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin.

6. Ongoing treatment with immunosuppressive therapies including cyclophosphamide, azathioprine, mycophenolic acid, methotrexate, or cyclosporine, or use of those medications within 1 month of trial entry.

7. The use of other anti-fibrotic agents including colchicine, D-penicillamine, minocycline, or Type 1 oral Collagen in the month prior to enrollment.

8. Use in the prior month of corticosteroids at doses exceeding the equivalent of prednisone 10 mg daily. Use of corticosteroid at < 10 mg of prednisone can continue during the course of the study.

9. Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for this study such as uncontrollable CHF, arrhythmia, severe pulmonary or systemic hypertension, severe GI involvement, hepatic impairment, serum creatinine of greater than 2.0, active infection, severe diabetes, unstable atherosclerotic cardiovascular disease, malignancy, HIV, or severe peripheral vascular disease.

10. History of pancreatitis.

11. Prolonged QTc interval defined as a QTc > 450 msec

12. Patients requiring the ongoing use of medications that are antiarrhythmics (including, but not limited to amiodarone, disopyramide, procainamide, quinidine and sotalol) or that prolong the QTc interval (including, but not limited to chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, bepridil and pimozide) will be excluded.

13. Patients requiring the ongoing use of medications that are potent inhibitors or inducers of CYP3A4.

14. A positive pregnancy test at entry into this study. Men and women with reproductive potential will be required to use effective means of contraception through the course of the study.

15. Participation in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study.

16. The presence of severe lung disease as defined by a diffusion capacity of less than 30% of predicted.