Systemic Sclerosis, Scleroderma
Conditions
Keywords
Systemic sclerosis, scleroderma, fibrosis, STI571, imatinib
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).
Interventions
DRUGSTI571
STI571 tablets taken orally once a day
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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%. |
Countries
Germany, Italy, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 7 centers in 5 countries from 02 January 2008 to 13 January 2010.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| STI571 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. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Reason not Specified | 4 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | STI571 |
|---|---|
| Age, Continuous | 45.7 years STANDARD_DEVIATION 11.99 |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 27 |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 5 / 27 |
Outcome results
Primary
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.
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 16 | 12.70 units on a scale | Standard Deviation 28.399 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Baseline | 25.7 units on a scale | Standard Deviation 5.83 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 2 | 6.58 units on a scale | Standard Deviation 18.416 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 4 | 5.97 units on a scale | Standard Deviation 17.382 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 6 | 8.34 units on a scale | Standard Deviation 24.645 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 8 | 8.48 units on a scale | Standard Deviation 27.096 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 12 | 3.34 units on a scale | Standard Deviation 27.525 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 20 | 12.41 units on a scale | Standard Deviation 28.149 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 24 | 9.90 units on a scale | Standard Deviation 23.675 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 28 | -3.17 units on a scale | Standard Deviation 19.891 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 32 | -5.67 units on a scale | Standard Deviation 18.013 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 36 | -12.61 units on a scale | Standard Deviation 27.383 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 40 | -5.23 units on a scale | Standard Deviation 27.506 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 44 | -13.57 units on a scale | Standard Deviation 26.763 |
| STI571 | Change From Baseline in Modified Rodnan Skin Score (MRSS) at Each Time Point of Analysis | Week 48/ EOS | -20.89 units on a scale | Standard Deviation 24.946 |
Primary
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.
Time frame: Baseline to Week 48/EOS
Population: Safety analysis set included all participants who received at least one dose of the study drug with at least one post-baseline measurement.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| STI571 | Number of Participants With Adverse Events (AE's) and Serious Adverse Events (SAE's) | Participants Experiencing AE's | 27 Participants |
| STI571 | Number of Participants With Adverse Events (AE's) and Serious Adverse Events (SAE's) | Participants Experiencing SAE's | 5 Participants |
Secondary
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%.
Time frame: Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48/End of Study (EOS)
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 2 | Non-response | 27 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 2 | Partial Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 2 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 2 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 4 | Non-response | 25 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 4 | Partial Response | 2 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 4 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 4 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 6 | Non-response | 24 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 6 | Partial Response | 2 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 6 | Complete Response | 1 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 6 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 8 | Non-response | 22 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 8 | Partial Response | 2 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 8 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 8 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 12 | Non-response | 15 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 12 | Partial Response | 3 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 12 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 12 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 16 | Non-response | 16 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 16 | Partial Response | 2 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 16 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 16 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 20 | Non-response | 16 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 20 | Partial Response | 2 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 20 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 20 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 24 | Non-response | 15 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 24 | Partial Response | 1 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 24 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 24 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 28 | Non-response | 13 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 28 | Partial Response | 1 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 28 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 28 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 32 | Non-response | 13 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 32 | Partial Response | 1 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 32 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 32 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 36 | Non-response | 9 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 36 | Partial Response | 3 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 36 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 36 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 40 | Non-response | 9 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 40 | Partial Response | 3 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 40 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 40 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 44 | Non-response | 8 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 44 | Partial Response | 5 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 44 | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 44 | Remission | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 48/EOS | Non-response | 5 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 48/EOS | Partial Response | 8 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 48/EOS | Complete Response | 0 Participants |
| STI571 | Number of Participants With Non-response, Partial Response, Complete Response, and Remission Assessed by MRSS Values | Week 48/EOS | Remission | 0 Participants |