Efficacy and Tolerability of STI571 (Imatinib Mesylate) for the Treatment of Fibrosis in Participants With Systemic Sclerosis

A Multi-centre, Open-label, Proof of Concept (PoC) Study to Evaluate the Efficacy and Tolerability of STI571 for the Treatment of Fibrosis in Patients With Systemic Sclerosis

This study investigates the efficacy and safety of STI571 for the treatment of fibrosis in participants with systemic sclerosis. Other purposes of the study were to investigate whether STI571 is effective in improving lung functions and other test results called biomarkers. Whether STI571 is well-absorbed in systemic sclerosis participants' gut was also investigated by testing the drug level in the blood (pharmacokinetics).

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis, Scleroderma
• Intervention / Treatment: Drug: STI571

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany
    • Novartis Investigator Site
• Italy
  • Florence, Italy
    • Novartis Investigator Site
• Switzerland
  • Zurich, Switzerland
    • Novartis Investigator Site
• United Kingdom
  • London, United Kingdom
    • Novartis Investigator Site
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Novartis Investigator Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Novartis Investigator Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female participants who are equal to or older than 18 years of age and who have early diffuse cutaneous systemic sclerosis (Disease duration < 18 months from the first non-Raynaud's symptom)
• Participants with a modified Rodnans Skin Score (MRSS) of at least 20 in the absence of trunk involvement or a MRSS of at least 16 in patients with trunk involvement
• Female patients of childbearing potential practicing two acceptable forms of contraception

Exclusion Criteria:

• SSc patients with a MRSS greater than 35
• Concurrent connective tissue diseases other than systemic sclerosis
• Significant pre-existing heart, liver, lungs, digestive system, blood and other diseases, cancer
• Conditions that might mimic the potential side effects of STI571 (blood conditions, liver damage, chronic diarrhea, edema)
• Concurrent medical therapies (or during last 6 weeks before first dosing) that may potentially influence outcome of the study
• Allergic to the study medication
• Pregnancy
• Breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ST1571; Participants received ST1571 100 mg tablets, orally, once daily. Initiated at an oral dose of 200 mg/day for 4 weeks then titrated up to 400 mg/day for 2 weeks followed by 600 mg/day until Week 24, if well tolerated.	Drug: STI571; STI571 tablets taken orally once a day; Other Names: Gleevec, Glivec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis	The efficacy of oral STI571 in participants with systemic sclerosis is defined by an improvement in MRSS. Skin thickness was assessed clinically in each of 17 body areas and scored using a 0-3 scale, where 0= normal, 1= mild thickness, 2= moderate thickness, and 3= severe thickness (maximum score 51). A higher score indicates greater severity of the disease.	Baseline, Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS)
Number of Participants With Adverse Events (AE's) and Serious Adverse Events (SAE's)	An AE is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to the study drug. An SAE is defined as an event that is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization, is medically significant, i.e., defined as an event that jeopardizes the patient or may require medical or surgical intervention to prevent one of the outcomes listed above.	Baseline to Week 48/EOS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values	The following MRSS categories were calculated for up to Week 48: Non-response: a reduction in MRSS <25%, Partial response: a reduction in MRSS between 25-<50%, Complete response: a reduction in MRSS between 50-<80%, Remission: a reduction in MRSS ≥80%.	Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2008
• Primary Completion (Actual): January 13, 2010
• Study Completion (Actual): January 13, 2010

Study Registration Dates

• First Submitted: January 25, 2008
• First Submitted That Met QC Criteria: January 29, 2008
• First Posted (Estimate): February 12, 2008

Study Record Updates

• Last Update Posted (Actual): July 7, 2021
• Last Update Submitted That Met QC Criteria: July 5, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Systemic sclerosis, scleroderma, fibrosis, STI571, imatinib
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Fibrosis; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: CSTI571E2205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No