Nilotinib in the Treatment of Systemic Sclerosis

NCT01166139 | Completed Phase 2 Results DMC

• 1 other identifier: 10041
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Systemic Sclerosis

Keywords

Systemic Sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  6 Months and 12 months treatment

Secondary Outcomes (2)

• Improvement of Modified Rodnan Skin Score Reported as a Mean (Units Equals Number of Points)

  6 Months of treatment

• Efficacy of Nilotinib in Patients With Systemic Sclerosis, as Defined by an Improvement in the Modified Rodnan Skin Score

  12 months treatment

Study Arms (1)

Nilotinib 400 mg twice daily

EXPERIMENTAL

Drug: Nilotinib (Tasigna)

Interventions

Nilotinib (Tasigna) DRUG

Patients will be treated with Nilotinib 400 mg two times a day for 6 months.

Nilotinib 400 mg twice daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to eighteen years.
• 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.
• Disease duration of less than or equal to 3 years as defined by the date of onset of the first non-Raynaud's symptom.
• Estimated ejection fraction of greater than 50% by echocardiography

You may not qualify if:

• Inability to render informed consent in accordance with institutional guidelines.
• Disease duration of greater than 3 years.
• Patients with mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease.)
• Limited scleroderma.
• Systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin.
• Ongoing treatment with immunosuppressive therapies including cyclophosphamide, azathioprine, mycophenolic acid, methotrexate, or cyclosporine, or use of those medications within 1 month of trial entry.
• The use of other anti-fibrotic agents including colchicine, D-penicillamine, minocycline, or Type 1 oral Collagen in the month prior to enrollment.
• 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.
• 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.
• History of pancreatitis.
• Prolonged QTc interval defined as a QTc \> 450 msec
• 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.
• Patients requiring the ongoing use of medications that are potent inhibitors or inducers of CYP3A4.
• 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.
• Participation in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study.

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead
• Rudolph Rupert Scleroderma Program: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Related Publications (2)

• Haddon DJ, Wand HE, Jarrell JA, Spiera RF, Utz PJ, Gordon JK, Chung LS. Proteomic Analysis of Sera from Individuals with Diffuse Cutaneous Systemic Sclerosis Reveals a Multianalyte Signature Associated with Clinical Improvement during Imatinib Mesylate Treatment. J Rheumatol. 2017 May;44(5):631-638. doi: 10.3899/jrheum.160833. Epub 2017 Mar 15.

  PMID: 28298564 DERIVED

• Gordon JK, Martyanov V, Magro C, Wildman HF, Wood TA, Huang WT, Crow MK, Whitfield ML, Spiera RF. Nilotinib (Tasigna) in the treatment of early diffuse systemic sclerosis: an open-label, pilot clinical trial. Arthritis Res Ther. 2015 Aug 18;17(1):213. doi: 10.1186/s13075-015-0721-3.

  PMID: 26283632 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Results Point of Contact

• Title: Annel Fernandez
• Organization: Hospital For Special Surgery

fernandeza@hss.edu

212 774 2123

Study Officials

• Robert Spiera, MD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2010
• First Posted: July 20, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: January 1, 2015
• Last Updated: October 4, 2017
• Results First Posted: October 4, 2017

Record last verified: 2017-10

Locations

US (1)