Skin fibrosis in systemic sclerosis patients MedDRA version: 9.1 Level: LLT Classification code 10042953 Term: Systemic sclerosis
Conditions
Interventions
Trade Name: Glivec
Product Name: Glivec
Product Code: STI571
Pharmaceutical Form: Tablet
INN or Proposed INN: imatinib
CAS Number: 220127-57-1
Current Sponsor code: STI571
Concentration unit: mg milli
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Male and female patients equal to or older than 18 years of age and fulfilling the American College of Rheumatology criteria for systemic sclerosis (SSc) •Diffuse cutaneous SSc (dcSSc) according to the LeRoy criteria with disease duration less than 18 months from the appearance of the first non-Raynaud´s symptom judged by a physician to be part of SSc •Patients with a modified Rodnan Skin Score of at least 20 (maximum score 51) in the absence of trunk involvement or a modified Rodnan Skin Score of at least 16 in patients with trunk involvement •Female patients of child bearing potential must be using two acceptable methods of contraception (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through Study Completion. Period abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. •Male patients must be using a two acceptable methods of contraception, (e.g., spermicidal gel plus condom) for the entire duration of the study, up to Study Completion visit, and refrain from fathering a child in the three (3) months following last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception. •Able to communicate well with the Investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Concurrent connective tissue diseases other than SSc including SSc-like illnesses related to environmental, ingested or injected agents, and also including overlap syndromes and mixed connective tissue disease. 2.Significant pre-existing internal organ damage: •kidneys: •MDRD calculated creatinine clearance 3 seconds) •gut: •pseudo-obstruction •mal-absorption requiring parental nutrition. 3.Existing myositis: serum creatine phosphokinase > 3 fold of the upper-limit 4.Conditions that might mimic potential side effects of STI571: •hematological conditions: - thrombocytopenia 3 fold the upper limit of normal, or bilirubin > 2 fold the upper limit of normal •chronic diarrhea for more than 4 weeks •peripheral edemas 5.Concurrent interventional medical therapy that might potentially influence the outcome of the disease. Treatment with other potentially disease modifying agents during the last 6 weeks, including prednisone or corticosteroid equivalent in doses higher than 15 mg/d or changes in the prednisone doses during the last 1 month before first dosing. 6.Grapefruit juice should not be drunk whilst patients participate in the study. Special attention should be given to the co-prescription of CYP3A4 inhibitors (e.g. Amiodarone, Diltiazem, Verapamil, macrolide antibiotics, Itraconazole and Ketoconazole), and to some of the drugs metabolized by CYP450 isoenzymes (Phenytoin, Carbamazepin, Rifampicin, Phenobarbital, Saint-John’s Wort, Cyclosporine, Warfarin or Paracetamol). For guidance on drug-drug interactions see Section 6.5.3 on concomitant medication. 7.Other conditions that might be associated with an increased risk to the patient or interfere with successful conduction of the trial: •underlying chronic debilitating diseases such as cancer, •pregnancy, breast feeding or lack of safe contraception (IUD, diaphragm, bilateral tubal ligation, hysterectomy) in women of childbearing potential. 8.Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the patient in case of participation in the study. The Investigator should be guided by evidence of any of the following: •history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding; •history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; •history or clinical evidence of pancreatic injury or pancreatitis. 9.Participation in any treatment studies within 3 months prior to dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 10.Donation or loss of 400 ml or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation. 11.History of acute or chronic bronchospastic disease (at the discretion of Investigators) 12.History of clinically significant drug all
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To assess the efficacy of oral STI571 in skin fibrosis in systemic sclerosis (SSc) patients as measured by an improvement in the modified Rodnan Skin Score. •To assess the safety and tolerability of oral STI571 in SSc patients. ;Secondary Objective: Secondary objectives •To assess improvement in lung functions as measured by CO diffusion capacity (DLCO) and Forced Vital Capacity (FVC). •To assess biomarkers reflecting the direct effects of STI571 on its biological targets. •To determine the PK trough levels of STI571 and its major active metabolite CGP74588 during dose escalation and the maintenance phase of the study. Exploratory objective •To explore alternative biomarkers that may provide additional measures of efficacy of STI571 in skin, plasma/serum and urine samples.;Primary end point(s): Percentage change from baseline in MRSS at time point t is calculated for each patient as % change form baseline(t)=[mRSS(t)-mRSS(baseline)] / mRSS(baseline) | — |
Countries
Italy, United Kingdom
Outcome results
None listed