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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00613171
• Collaborator: (none)
• Enrollment: 27
• Locations: 7
• Arm: 1
• Actual Duration (Months): 24.4
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Systemic Sclerosis, Scleroderma	Drug: STI571	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jan 2, 2008
• Actual Primary Completion Date: Jan 13, 2010
• Actual Study Completion Date: Jan 13, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis [Baseline, Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS)]

   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.

2. Number of Participants With Adverse Events (AE's) and Serious Adverse Events (SAE's) [Baseline to Week 48/EOS]

   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.

Secondary Outcome Measures

1. Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values [Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS)]

   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%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigator Site	Chicago	Illinois	United States	60611
2	Novartis Investigator Site	Baltimore	Maryland	United States	21224
3	Novartis Investigator Site	Boston	Massachusetts	United States	02118
4	Novartis Investigator Site	Erlangen		Germany
5	Novartis Investigator Site	Florence		Italy
6	Novartis Investigator Site	Zurich		Switzerland
7	Novartis Investigator Site	London		United Kingdom

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Principal Investigator: NOVARTIS, Novartis investigator site

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00613171
• Other Study ID Numbers: CSTI571E2205
• First Posted: Feb 12, 2008
• Last Update Posted: Jul 7, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Systemic sclerosis, scleroderma, fibrosis, STI571, imatinib
• Additional relevant MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis; Fibrosis; Imatinib Mesylate

Study Results

Participant Flow

Recruitment Details	This study was conducted at 7 centers in 5 countries from 02 January 2008 to 13 January 2010.
Pre-assignment Detail	The study enrolled a total of 27 participants. The study consisted of a treatment period of 24 weeks and a follow-up period of 24 weeks with no study drug.

Arm/Group Title	STI571
Arm/Group Description	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.
Period Title: Overall Study
STARTED	27
COMPLETED	13
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	STI571
Arm/Group Description	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.
Overall Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.7 (11.99)
Sex: Female, Male (Count of Participants)
Female	21 77.8%
Male	6 22.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis
Description	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.
Time Frame	Baseline, Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS)

Outcome Measure Data

Analysis Population Description

Efficacy analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement. Number analyzed are the number of participants with data available for analyses at given time point.

Arm/Group Title	STI571
Arm/Group Description	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.
Measure Participants	27
Baseline	25.7 (5.83)
Week 2	6.58 (18.416)
Week 4	5.97 (17.382)
Week 6	8.34 (24.645)
Week 8	8.48 (27.096)
Week 12	3.34 (27.525)
Week 16	12.70 (28.399)
Week 20	12.41 (28.149)
Week 24	9.90 (23.675)
Week 28	-3.17 (19.891)
Week 32	-5.67 (18.013)
Week 36	-12.61 (27.383)
Week 40	-5.23 (27.506)
Week 44	-13.57 (26.763)
Week 48/ EOS	-20.89 (24.946)

2. Primary Outcome

Title	Number of Participants With Adverse Events (AE's) and Serious Adverse Events (SAE's)
Description	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.
Time Frame	Baseline to Week 48/EOS

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement.

Arm/Group Title	STI571
Arm/Group Description	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.
Measure Participants	27
Participants Experiencing AE's	27 100%
Participants Experiencing SAE's	5 18.5%

3. Secondary Outcome

Title	Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values
Description	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%.
Time Frame	Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS)

Outcome Measure Data

Analysis Population Description

Efficacy analysis set included all participants that received at least one dose of the study drug with at least one post-baseline measurement. Number analyzed are the number of participants with data available for analyses at given time points.

Arm/Group Title	STI571
Arm/Group Description	Participants received STI571 100 mg tablets, 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 Week24, if well tolerated.
Measure Participants	27
Non-response	27 100%
Partial Response	0 0%
Complete Response	0 0%
Remission	0 0%
Non-response	25 92.6%
Partial Response	2 7.4%
Complete Response	0 0%
Remission	0 0%
Non-response	24 88.9%
Partial Response	2 7.4%
Complete Response	1 3.7%
Remission	0 0%
Non-response	22 81.5%
Partial Response	2 7.4%
Complete Response	0 0%
Remission	0 0%
Non-response	15 55.6%
Partial Response	3 11.1%
Complete Response	0 0%
Remission	0 0%
Non-response	16 59.3%
Partial Response	2 7.4%
Complete Response	0 0%
Remission	0 0%
Non-response	16 59.3%
Partial Response	2 7.4%
Complete Response	0 0%
Remission	0 0%
Non-response	15 55.6%
Partial Response	1 3.7%
Complete Response	0 0%
Remission	0 0%
Non-response	13 48.1%
Partial Response	1 3.7%
Complete Response	0 0%
Remission	0 0%
Non-response	13 48.1%
Partial Response	1 3.7%
Complete Response	0 0%
Remission	0 0%
Non-response	9 33.3%
Partial Response	3 11.1%
Complete Response	0 0%
Remission	0 0%
Non-response	9 33.3%
Partial Response	3 11.1%
Complete Response	0 0%
Remission	0 0%
Non-response	8 29.6%
Partial Response	5 18.5%
Complete Response	0 0%
Remission	0 0%
Non-response	5 18.5%
Partial Response	8 29.6%
Complete Response	0 0%
Remission	0 0%

Adverse Events

Time Frame	Baseline to Week 48/EOS
Adverse Event Reporting Description	Safety analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement.
Arm/Group Title	ST1571
Arm/Group Description	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.
All Cause Mortality
	ST1571
	Affected / at Risk (%)	# Events
Total	0/27 (0%)
Serious Adverse Events
	ST1571
	Affected / at Risk (%)	# Events
Total	5/27 (18.5%)
Blood and lymphatic system disorders
Neutropenia	1/27 (3.7%)
Gastrointestinal disorders
Gastritis erosive	1/27 (3.7%)
Nausea	1/27 (3.7%)
Vomiting	1/27 (3.7%)
General disorders
Face oedema	1/27 (3.7%)
Generalised oedema	1/27 (3.7%)
Oedema peripheral	1/27 (3.7%)
Infections and infestations
Neutropenic infection	1/27 (3.7%)
Upper respiratory tract infection	1/27 (3.7%)
Viral infection	1/27 (3.7%)
Investigations
Haematocrit decreased	1/27 (3.7%)
Other (Not Including Serious) Adverse Events
	ST1571
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Anaemia	6/27 (22.2%)
Leukopenia	1/27 (3.7%)
Lymphopenia	2/27 (7.4%)
Thrombocytosis	1/27 (3.7%)
Cardiac disorders
Cardiac disorder	1/27 (3.7%)
Ear and labyrinth disorders
Auricular swelling	1/27 (3.7%)
Ear pain	1/27 (3.7%)
Tinnitus	1/27 (3.7%)
Vertigo	1/27 (3.7%)
Eye disorders
Eye swelling	1/27 (3.7%)
Eyelid oedema	1/27 (3.7%)
Ocular hyperaemia	1/27 (3.7%)
Gastrointestinal disorders
Abdominal discomfort	3/27 (11.1%)
Abdominal distension	4/27 (14.8%)
Abdominal pain lower	1/27 (3.7%)
Abdominal pain upper	3/27 (11.1%)
Constipation	3/27 (11.1%)
Diarrhoea	7/27 (25.9%)
Diverticulum	1/27 (3.7%)
Dry mouth	1/27 (3.7%)
Dyspepsia	4/27 (14.8%)
Faeces discoloured	1/27 (3.7%)
Flatulence	3/27 (11.1%)
Gastrointestinal haemorrhage	2/27 (7.4%)
Gastrooesophageal reflux disease	1/27 (3.7%)
Gingival pain	1/27 (3.7%)
Hypoaesthesia oral	1/27 (3.7%)
Nausea	14/27 (51.9%)
Tongue dry	1/27 (3.7%)
Toothache	1/27 (3.7%)
Vomiting	5/27 (18.5%)
General disorders
Face oedema	5/27 (18.5%)
Fatigue	5/27 (18.5%)
Generalised oedema	1/27 (3.7%)
Influenza like illness	2/27 (7.4%)
Infusion site ulcer	1/27 (3.7%)
Oedema	1/27 (3.7%)
Oedema peripheral	15/27 (55.6%)
Pyrexia	1/27 (3.7%)
Infections and infestations
Herpes zoster	2/27 (7.4%)
Infected skin ulcer	2/27 (7.4%)
Influenza	2/27 (7.4%)
Infusion site infection	1/27 (3.7%)
Lower respiratory tract infection	3/27 (11.1%)
Nasopharyngitis	3/27 (11.1%)
Oral fungal infection	1/27 (3.7%)
Oral herpes	1/27 (3.7%)
Pharyngitis	1/27 (3.7%)
Respiratory tract infection	2/27 (7.4%)
Rhinitis	1/27 (3.7%)
Sinusitis	1/27 (3.7%)
Tonsillitis	1/27 (3.7%)
Upper respiratory tract infection	1/27 (3.7%)
Urinary tract infection	4/27 (14.8%)
Viral infection	1/27 (3.7%)
Vulvovaginal candidiasis	2/27 (7.4%)
Injury, poisoning and procedural complications
Back injury	1/27 (3.7%)
Contusion	1/27 (3.7%)
Joint injury	1/27 (3.7%)
Procedural site reaction	1/27 (3.7%)
Wound necrosis	1/27 (3.7%)
Investigations
Alanine aminotransferase increased	1/27 (3.7%)
Aspartate aminotransferase increased	2/27 (7.4%)
Blood albumin decreased	1/27 (3.7%)
Blood alkaline phosphatase increased	1/27 (3.7%)
Blood amylase increased	1/27 (3.7%)
Blood cholesterol increased	1/27 (3.7%)
Blood creatine phosphokinase increased	3/27 (11.1%)
Blood triglycerides increased	2/27 (7.4%)
Blood urea increased	1/27 (3.7%)
Blood uric acid decreased	1/27 (3.7%)
C-reactive protein increased	3/27 (11.1%)
Electrocardiogram QRS complex abnormal	1/27 (3.7%)
Electrocardiogram abnormal	1/27 (3.7%)
Gamma-glutamyltransferase increased	3/27 (11.1%)
Haematocrit decreased	1/27 (3.7%)
Haemoglobin decreased	1/27 (3.7%)
Heart rate irregular	1/27 (3.7%)
High density lipoprotein decreased	1/27 (3.7%)
Laboratory test interference	1/27 (3.7%)
Lipase increased	1/27 (3.7%)
Neutrophil count decreased	1/27 (3.7%)
Platelet count increased	1/27 (3.7%)
Protein total abnormal	1/27 (3.7%)
Red blood cell count decreased	1/27 (3.7%)
Red blood cell sedimentation rate increased	4/27 (14.8%)
Troponin I increased	2/27 (7.4%)
Weight decreased	2/27 (7.4%)
Weight increased	1/27 (3.7%)
White blood cell count decreased	3/27 (11.1%)
Metabolism and nutrition disorders
Decreased appetite	3/27 (11.1%)
Dehydration	1/27 (3.7%)
Hypokalaemia	1/27 (3.7%)
Iron deficiency	1/27 (3.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/27 (25.9%)
Back pain	1/27 (3.7%)
Groin pain	1/27 (3.7%)
Joint range of motion decreased	1/27 (3.7%)
Joint stiffness	1/27 (3.7%)
Musculoskeletal chest pain	1/27 (3.7%)
Musculoskeletal pain	1/27 (3.7%)
Musculoskeletal stiffness	1/27 (3.7%)
Myalgia	3/27 (11.1%)
Pain in extremity	3/27 (11.1%)
Sensation of heaviness	1/27 (3.7%)
Systemic sclerosis	1/27 (3.7%)
Tenosynovitis stenosans	1/27 (3.7%)
Nervous system disorders
Dizziness	1/27 (3.7%)
Dysgeusia	1/27 (3.7%)
Headache	5/27 (18.5%)
Hypoaesthesia	1/27 (3.7%)
Neuralgia	1/27 (3.7%)
Paraesthesia	1/27 (3.7%)
Psychiatric disorders
Depression	2/27 (7.4%)
Insomnia	2/27 (7.4%)
Sleep disorder	1/27 (3.7%)
Reproductive system and breast disorders
Menorrhagia	1/27 (3.7%)
Respiratory, thoracic and mediastinal disorders
Cough	2/27 (7.4%)
Dysphonia	1/27 (3.7%)
Dyspnoea	1/27 (3.7%)
Oropharyngeal pain	2/27 (7.4%)
Pleurisy	1/27 (3.7%)
Pulmonary hypertension	1/27 (3.7%)
Skin and subcutaneous tissue disorders
Alopecia	1/27 (3.7%)
Dermatitis	1/27 (3.7%)
Dry skin	1/27 (3.7%)
Hypoaesthesia facial	1/27 (3.7%)
Lentigo	1/27 (3.7%)
Panniculitis	1/27 (3.7%)
Periorbital oedema	5/27 (18.5%)
Pruritus	9/27 (33.3%)
Rash	1/27 (3.7%)
Rash generalised	1/27 (3.7%)
Rash maculo-papular	1/27 (3.7%)
Skin tightness	3/27 (11.1%)
Skin ulcer	5/27 (18.5%)
Swelling face	1/27 (3.7%)
Vascular disorders
Erythromelalgia	1/27 (3.7%)
Raynaud's phenomenon	4/27 (14.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.