Trial Outcomes & Findings for Imatinib in Systemic Sclerosis (NCT NCT00506831)

NCT ID: NCT00506831

Last Updated: 2018-08-13

Results Overview

Modified Rodnan skin score (mRSS) on scale of 0 (no skin disease) to 51 severe skin disease. %change in mRSS=(score at 6 months - baseline score)/baseline score. Negative values indicate improvement in skin disease. Clinical important improvement defined as \> 25% improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 9 participants
• Primary outcome timeframe: 6 months compared to baseline
• Results posted on: 2018-08-13

Participant Flow

Participant milestones

Measure	Imatinib Mesylate All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Overall Study STARTED	9
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Imatinib Mesylate All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Overall Study Death	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Imatinib in Systemic Sclerosis

Baseline characteristics by cohort

Measure	Imatinib Mesylate n=9 Participants All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	56 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months compared to baseline

Population: Participants who completed the protocol were included in the analysis

Modified Rodnan skin score (mRSS) on scale of 0 (no skin disease) to 51 severe skin disease. %change in mRSS=(score at 6 months - baseline score)/baseline score. Negative values indicate improvement in skin disease. Clinical important improvement defined as > 25% improvement.

Outcome measures

Measure	Imatinib Mesylate n=7 Participants All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Percent Change in Modified Rodnan Skin Score at 6 Months Compared to Baseline	-32 percentage of change in MRSS Standard Deviation 22

SECONDARY outcome

Timeframe: 6 months compared to baseline

Population: Participants with available data were included in the analysis

Change in % predicted Forced Vital Capacity (FVC) at 6 months compared to baseline. FVC is the volume of air that can forcibly be blown out after taking a full breath. FVC% predicted is defined as FVC% of the patient divided by the average FVC% in the population for any person of similar age, sex and body composition.

Outcome measures

Measure	Imatinib Mesylate n=5 Participants All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Change in Pulmonary Function Tests at 6 Months Compared to Baseline	0 FVC% predicted Interval -7.0 to 10.0

SECONDARY outcome

Timeframe: 6 months compared to baseline

Population: No data were collected for this outcome measure

Number of digital ulcers as measured by physician assessment at 6 months compared to baseline

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months compared to baseline

Population: Participants with available data were included in the analysis

Change in Health Assessment Questionnaire disability index at 6 months compared to baseline. The Questionnaire is comprised of a 20 question instrument pertaining to specific activities with possible integer responses of 0 (without any difficulty) to 3 (unable to do), and five additional scleroderma-specific visual analog scale (VAS) domains with possible values ranging from 0.0 to 15.0. The 20 questions are divided into eight domains. A mean score is calculated for each domain ranging from 0 to 3. A composite score is calculated by dividing the summed domain scores by the number of domains answered. The composite score is reported, falling between 0 and 3 on an ordinal scale. The scores are interpreted as 0 (no impairment in function) to 3 (maximal impairment of function).

Outcome measures

Measure	Imatinib Mesylate n=5 Participants All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Change in Scleroderma Health Assessment Questionnaire at 6 Months Compared to Baseline	-.35 units on a scale Interval -0.88 to 0.38

SECONDARY outcome

Timeframe: 6 months compared to baseline

Population: Participants with available data were included in the analysis

Outcome measures

Measure	Imatinib Mesylate n=1 Participants All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Change in Dermal Thickness and Collagen Separation on Cutaneous Histopathology at 6 Months Compared to Baseline	-.5 mm

SECONDARY outcome

Timeframe: 6 months compared to baseline

Population: No data were collected for this outcome measure

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months compared to baseline

Population: Participants with available data were included in the analysis

To determine which cell types may be contributing to the gene expression changes associated with imatinib therapy, imatinib-responsive genes were isolated from from patient biopsies. From the total number of imatinib-responsive genes that were isolated, the percentage that came from endothelial cells, fibroblasts, B-cells, and multiple cell types was calculated. Reported values do not total to 100% because of rounding.

Outcome measures

Measure	Imatinib Mesylate n=1050 Isolated imantinib-responsive genes All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Cell Types That Contribute to the Gene Expression Changes Associated With Imatinib Therapy Endothelial cells	13 percentage of isolated genes
Cell Types That Contribute to the Gene Expression Changes Associated With Imatinib Therapy Fibroblasts	26 percentage of isolated genes
Cell Types That Contribute to the Gene Expression Changes Associated With Imatinib Therapy B-cells	8 percentage of isolated genes
Cell Types That Contribute to the Gene Expression Changes Associated With Imatinib Therapy Multiple cell types	52 percentage of isolated genes

SECONDARY outcome

Timeframe: 6 months compared to baseline

Population: No data were collected for this outcome measure

Outcome measures

Outcome data not reported

Adverse Events

Imatinib Mesylate

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Imatinib Mesylate n=9 participants at risk All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Infections and infestations Death	11.1% 1/9 • Number of events 1

Other adverse events

Measure	Imatinib Mesylate n=9 participants at risk All patients were treated with imatinib mesylate at a mean dosage of 300 mg daily.
Infections and infestations infection	77.8% 7/9 • Number of events 11
Blood and lymphatic system disorders edema	66.7% 6/9 • Number of events 6
Gastrointestinal disorders gastrointestinal symptoms	66.7% 6/9 • Number of events 10
Vascular disorders new digital ulcers	22.2% 2/9 • Number of events 2
Infections and infestations fever	11.1% 1/9 • Number of events 1
Immune system disorders neutropenia	11.1% 1/9 • Number of events 1
Renal and urinary disorders renal insufficiency	11.1% 1/9 • Number of events 1
Skin and subcutaneous tissue disorders hair loss	11.1% 1/9 • Number of events 1
Musculoskeletal and connective tissue disorders muscle cramps	11.1% 1/9 • Number of events 1
Skin and subcutaneous tissue disorders oral ulcer	11.1% 1/9 • Number of events 1
Eye disorders blurry vision	11.1% 1/9 • Number of events 1
Respiratory, thoracic and mediastinal disorders cough	11.1% 1/9 • Number of events 1
Nervous system disorders headache	11.1% 1/9 • Number of events 1
Renal and urinary disorders hypokalemia	11.1% 1/9 • Number of events 1
Skin and subcutaneous tissue disorders rash	11.1% 1/9 • Number of events 1
Eye disorders keratitis	11.1% 1/9 • Number of events 1

Additional Information

Lorinda Chung

Stanford University

Phone: 650-493-5000

Email: shauwei@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place