Trial Outcomes & Findings for Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis (NCT NCT00555581)

Last Updated: 2018-02-06

Results Overview

Improvement in the Modified Rodnan Skin Score (MRSS) is measured by Mean change (and 95% Confidence Interval) from Baseline mean to Month 12 mean.Measure Description: The Modified Rodnan Skin Score (MRSS) measures dermal skin thickness through the examination of 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (in pairs), and face, chest, and abdomen. The skin score is 0 for uninvolved skin through 3 for severe thickening (hidebound skin). The total skin score is the sum of the skin scores of the individual areas. The minimum score is 0 and the maximum score is 51. A higher score indicates greater severity of disease. The mean change in MRSS represents the average change in total skin score from baseline to month 12.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

12 months

Results posted on

2018-02-06

Participant Flow

Participant milestones

Participant milestones
Measure	400 mg Daily of Imatinib Mesylate All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Overall Study STARTED	30
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	400 mg Daily of Imatinib Mesylate n=30 Participants All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	48 years n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	30 Participants n=5 Participants
Disease Duration Early	2.1 years STANDARD_DEVIATION 1.2 • n=5 Participants
Disease Duration Late	6.1 years STANDARD_DEVIATION 1.6 • n=5 Participants
Anti-Scl70 positive	9 Participants n=5 Participants
MRSS at baseline	30.3 units on a scale STANDARD_DEVIATION 8.7 • n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	400 mg Daily of Imatinib Mesylate n=24 Participants All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Improvement in the Modified Rodnan Skin Score	-6.6 units on a scale Interval -8.7 to -4.5

SECONDARY outcome

Timeframe: 12 months

This outcome measure includes patients with and without the presence of Interstitial Lung Disease (ILD). Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking a deep breath. It is used to determine the severity of lung disease. Improvement in FVC % predicted is measured by Mean change (and 95% Confidence Interval) from Baseline mean to Month 12 mean. Results are compared to the predicted values that are calculated from a patients age, size, weight, and sex. Results are considered normal if FVC is 80 percent or more of the predicted value. Mean change in FVC % predicted is measured by the average change in FVC% percent predicted from baseline to month 12.

Outcome measures

Outcome measures
Measure	400 mg Daily of Imatinib Mesylate n=22 Participants All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Improvement in Indices of Pulmonary Function Measured by Change in FVC % Predicted	6.4 FVC% Interval 1.9 to 10.9

SECONDARY outcome

Timeframe: 12 months

This outcome measure includes patients with and without the presence of Interstitial Lung Disease (ILD). Diffusion capacity of the lungs for carbon monoxide (DLCO) measures how much oxygen travels from the alveoli of the lungs to the blood stream. DLCO is adjusted for hemoglobin as small changes in hemoglobin concentration can affect the carbon monoxide transfer. DLCO results are compared to normal values for a patient's height, age, sex, and ethnicity. A DLCO result that is at least 80% of the predicted value is considered normal. Improvement in DLCO hb adj % predicted is measured by Mean change (and 95% Confidence Interval) from Baseline mean to Month 12 mean (the average change in DLCO hb adj% from baseline to month 12).

Outcome measures

Outcome measures
Measure	400 mg Daily of Imatinib Mesylate n=22 Participants All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Improvement in Indices of Pulmonary Function Measured by Change DLCO hb Adj % Predicted	5.5 DLCO% Interval -1.5 to 12.4

SECONDARY outcome

Timeframe: 12 months

The Short Form 36 (SF-36) is a validated 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The mental component score is composed of a subset of the 8 health domains. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability.The SF-36 mental component can be obtained by looking at the mean average of all the emotionally relevant items. Change in Short Form 36 mental (SF-36 MC) is measured by Mean change (and 95 % Confidence Interval) from Baseline mean to Month 12 mean (the average change in SF-36 mental component from baseline to month 12).

Outcome measures

Outcome measures
Measure	400 mg Daily of Imatinib Mesylate n=24 Participants All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire:Mental Component Summary	-6.6 units on a scale Interval -12.5 to -0.7

SECONDARY outcome

Timeframe: 12 months

The Scleroderma Health Assessment Questionnaire (SHAQ) consist of the Health Assessment Questionnaire (HAQ) and 8 other domains which include scales looking at pain, patient global assessment, vascular, digital ulcers, lung involvement, and gastrointestinal involvement. It addresses scleroderma related manifestations that contribute to disability. It is a quality of life measure. Each question is scored from 0 (without difficulty) to 3 (unable to do). Some domains in the SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale. The maximum from each category is added together and divided by the number of categories completed. Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) is measured as Mean Change (and 95% Confidence Interval) from Baseline mean to Month 12 mean (the average change in SHAQ-DI from baseline to month 12).

Outcome measures

Outcome measures
Measure	400 mg Daily of Imatinib Mesylate n=24 Participants All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Scleroderma Health Assessment Questionnaire Disability Index	0.02 units on a scale Interval -0.15 to 0.18

SECONDARY outcome

Timeframe: 12 months

The Short Form 36 (SF-36) is a 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The physical component score is composed of a subset of the 8 health domains.The SF-36 physical component can be obtained by looking at the mean average of all the physically relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. Change in Short Form 36 physical component (SF-36 PC) is measured by Mean change (and 95 % Confidence Interval) from Baseline mean to Month 12 mean (the average change in SF-36 physical component from baseline to month 12).

Outcome measures

Outcome measures
Measure	400 mg Daily of Imatinib Mesylate n=24 Participants All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire: Physical Component Summary	6.8 units on a scale Interval 1.7 to 15.3

Adverse Events

400 mg Daily of Imatinib Mesylate

Serious events: 12 serious events

Other events: 25 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	400 mg Daily of Imatinib Mesylate n=30 participants at risk All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Renal and urinary disorders Haematuria (hospitalisations)	3.3% 1/30 • Number of events 7 • 12 months
Respiratory, thoracic and mediastinal disorders Pneumonia	6.7% 2/30 • Number of events 2 • 12 months
Infections and infestations C difficile infection	3.3% 1/30 • Number of events 2 • 12 months
Infections and infestations Infected ulcer	6.7% 2/30 • Number of events 2 • 12 months
Respiratory, thoracic and mediastinal disorders Death (pneumonia)	3.3% 1/30 • Number of events 1 • 12 months
Gastrointestinal disorders Acute gastroenteritis	3.3% 1/30 • Number of events 1 • 12 months
Cardiac disorders Acute myocardial infarction	3.3% 1/30 • Number of events 1 • 12 months
Surgical and medical procedures Anaemia Blood Transfusion	3.3% 1/30 • Number of events 1 • 12 months
Injury, poisoning and procedural complications Fall	3.3% 1/30 • Number of events 1 • 12 months
Blood and lymphatic system disorders Fluid Overload	3.3% 1/30 • Number of events 1 • 12 months
Renal and urinary disorders Rectal proplapse, haemorrhoidal bleed	3.3% 1/30 • Number of events 1 • 12 months
Renal and urinary disorders Nephrolithiasis	3.3% 1/30 • Number of events 1 • 12 months
Gastrointestinal disorders Partial small bowel obstruction	3.3% 1/30 • Number of events 1 • 12 months
Surgical and medical procedures Bleeding post renal biopsy (hospitalisation)	3.3% 1/30 • Number of events 1 • 12 months
Cardiac disorders Tachyarrhythmia/cardiomyopathy	3.3% 1/30 • Number of events 1 • 12 months

Other adverse events

Other adverse events
Measure	400 mg Daily of Imatinib Mesylate n=30 participants at risk All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial. Imatinib Mesylate: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
General disorders Edema	83.3% 25/30 • Number of events 33 • 12 months
Metabolism and nutrition disorders Nausea	73.3% 22/30 • Number of events 22 • 12 months
Musculoskeletal and connective tissue disorders Myalgias	70.0% 21/30 • Number of events 21 • 12 months
Blood and lymphatic system disorders CK elevation	43.3% 13/30 • Number of events 13 • 12 months
General disorders Fatigue	60.0% 18/30 • Number of events 18 • 12 months
Gastrointestinal disorders Pyrosis	23.3% 7/30 • Number of events 7 • 12 months
Metabolism and nutrition disorders Vomiting	23.3% 7/30 • Number of events 7 • 12 months
Metabolism and nutrition disorders Weight Loss	16.7% 5/30 • Number of events 5 • 12 months
Nervous system disorders Headaches	23.3% 7/30 • Number of events 7 • 12 months
Respiratory, thoracic and mediastinal disorders Effusions	10.0% 3/30 • Number of events 3 • 12 months
Metabolism and nutrition disorders Hypocalcemia	10.0% 3/30 • Number of events 3 • 12 months
Skin and subcutaneous tissue disorders Dry Skin	6.7% 2/30 • Number of events 2 • 12 months
Reproductive system and breast disorders Erectile Dysfunction	6.7% 2/30 • Number of events 2 • 12 months
General disorders Generalised weakness	16.7% 5/30 • Number of events 5 • 12 months
Blood and lymphatic system disorders Light-headedness	10.0% 3/30 • Number of events 3 • 12 months

Additional Information

Robert F. Spiera

Hospital for Special Surgery

Phone: 212-774-2048

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place