Systemic Sclerosis Clinical Trial
Official title:
Phase IIA Study of the Safety and Tolerability of the Use of Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis
Verified date | January 2018 |
Source | Hospital for Special Surgery, New York |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is to assess the safety and tolerability of imatinib mesylate
(Gleevec) in patients with systemic sclerosis (scleroderma). Gleevec is a medication already
FDA approved for the treatment of chronic myelogenous leukemia (CML), gastrointestinal
stromal tumors (GIST), dermatofibrosarcoma protuberans tumors, Philadelphia
chromosome-positive acute lymphoblastic leukemia, hypereosinophilic syndrome, and aggressive
systemic mastocytosis. In-vitro studies have suggested that imatinib may inhibit collagen
production by scleroderma fibroblasts, and in mouse models of fibrosis imatinib has been
shown to decrease skin thickness.
This is a Phase IIa, single center, prospective open label clinical trial of Gleevec in
patients with systemic sclerosis. All patients will be treated with active drug for 12
months. The primary objective of this study will be to determine the safety and tolerability
of Gleevec in patients with systemic sclerosis, but important secondary outcomes of relevance
will be improvement in disease status as defined by skin scores and indices of pulmonary
function.
Patients who complete the initial phase (described above) of the study will be eligible to
participate in an extension phase. The purpose of the extension phase of the study is to give
patients who participated in the phase IIa clinical trial of Gleevec at the Hospital for
Special Surgery the opportunity to continue Gleevec treatment if both the treating physicians
and the patient are in agreement that Gleevec had acceptable safety and tolerability, as well
as possible efficacy during the initial year of therapy.
Status | Completed |
Enrollment | 30 |
Est. completion date | December 2011 |
Est. primary completion date | December 2011 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 1. Age greater than or equal to eighteen years. 2. Clinical diagnosis of diffuse systemic sclerosis by ACR criteria, with a stable modified Rodnan skin score in the one month preceding introduction of oral Gleevec therapy. The modified Rodnan skin score must be greater than or equal to sixteen at screening and initiation of therapy. 3. Disease duration of less than or equal to 10 years. 4. Estimated ejection fraction of greater than 50% by echocardiography Exclusion Criteria: 1. Inability to render informed consent in accordance with institutional guidelines. 2. Disease duration of greater than 10 years. 3. Patients with mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease.) 4. Ongoing treatment with other immunosuppressive therapies including cyclophosphamide, azathioprine, mycophenolic acid, methotrexate, or cyclosporine, or use of those medications within 3 months of trial entry. 5. Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for this study such as uncontrollable CHF, arrhythmia, severe pulmonary or systemic hypertension, severe GI involvement, serum creatinine of greater than 2.0, active infection, severe diabetes, unstable atherosclerotic cardiovascular disease, malignancy, HIV, or severe peripheral vascular disease. 6. The use of other anti-fibrotic agents including colchicine, D-penicillamine, minocycline, or Type 1 oral Collagen in the three months prior to enrollment. 7. Limited scleroderma. 8. Systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin. 9. A positive pregnancy at entry into this study. Men and women with reproductive potential will be required to use effective means of contraception through the course of the study. 10. Use in the prior month of corticosteroids at doses exceeding the equivalent of prednisone 10 mg daily. Use of corticosteroid at < 10 mg of prednisone can continue but not be increased during the course of the study. 11. Participation in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study. 12. The presence of severe lung disease as defined by a diffusion capacity of less than 30% of predicted. |
Country | Name | City | State |
---|---|---|---|
United States | Hospital for Special Surgery | New York | New York |
Lead Sponsor | Collaborator |
---|---|
Hospital for Special Surgery, New York | Novartis Pharmaceuticals |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Improvement in the Modified Rodnan Skin Score | 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. | 12 months | |
Secondary | Improvement in Indices of Pulmonary Function Measured by Change in FVC % Predicted | 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. | 12 months | |
Secondary | Improvement in Indices of Pulmonary Function Measured by Change DLCO hb Adj % Predicted | 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). | 12 months | |
Secondary | Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire:Mental Component Summary | 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). | 12 months | |
Secondary | Scleroderma Health Assessment Questionnaire Disability Index | 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). |
12 months | |
Secondary | Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire: Physical Component Summary | 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). | 12 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03274076 -
Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc)
|
Phase 1/Phase 2 | |
Completed |
NCT04300426 -
Safety and Efficacy of Anaerobic Cultivated Human Intestinal Microbiome Transplantation in Systemic Sclerosis (ReSScue)
|
Phase 2 | |
Recruiting |
NCT06058091 -
RY_SW01 Cell Injection Therapy in Systemic Sclerosis
|
Phase 1/Phase 2 | |
Recruiting |
NCT04356755 -
Subcutaneous Injections of ASC to Heal Digital Ulcers in Patients With Scleroderma.
|
Phase 2 | |
Suspended |
NCT06210945 -
Study to Evaluate the Safety, Tolerability, and Activity of CM-101 in Patients With Systemic Sclerosis
|
Phase 2 | |
Not yet recruiting |
NCT05947682 -
Manufacturing of Allogeneic Adipose Tissue-derived Mesenchymal Stromal Cells for Treatment of Severe Systemic Sclerosis
|
N/A | |
Not yet recruiting |
NCT04303208 -
Sirtuin 3 and Sirtuin 7 in Systemic Sclerosis
|
N/A | |
Not yet recruiting |
NCT05177380 -
Efficacy of a Personalized Rehabilitation Program of Facial Involvement in Systemic Sclerosis
|
N/A | |
Recruiting |
NCT02551042 -
CSL Behring Sclero XIII
|
Phase 2 | |
Terminated |
NCT02246348 -
Evaluating Lung Doppler Signals in Patients With Systemic Sclerosis (SSc)
|
N/A | |
Terminated |
NCT02243111 -
Detecting Pulmonary Arterial Hypertension (PAH) in Patients With Systemic Sclerosis (SSc) by Ultrasound
|
N/A | |
Completed |
NCT01933334 -
Safety and Tolerability of Pirfenidone in Patients With Systemic SclerosisâRelated Interstitial Lung Disease (SSc-ILD) (LOTUSS)
|
Phase 2 | |
Completed |
NCT01468792 -
Hemodynamic Changes in Connective Tissue Disease
|
N/A | |
Terminated |
NCT00848107 -
Open-Label Study of Oral Treprostinil in Digital Ulcers
|
Phase 2 | |
Completed |
NCT00984932 -
Effect of Rosuvastatin on Systemic Sclerosis-related Pulmonary Hypertension
|
Phase 3 | |
Completed |
NCT00074568 -
Scleroderma Registry
|
||
Not yet recruiting |
NCT06412614 -
Evaluation of Patients With Systemic Sclerosis Without Specific or Associated Autoantibodies
|
||
Terminated |
NCT00622687 -
Effect of Different Iloprost Doses on Symptoms in Systemic Sclerosis
|
Phase 2 | |
Recruiting |
NCT04464434 -
Upfront Autologous HSCT Versus Immunosuppression in Early Diffuse Cutaneous Systemic Sclerosis
|
Phase 4 | |
Recruiting |
NCT04246528 -
SPIN Self-Management Feasibility Trial With Progression to Full-scale Trial (SPIN-SELF)
|
N/A |