IL1-TRAP, Rilonacept, in Systemic Sclerosis
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|ClinicalTrials.gov Identifier: NCT01538719|
Recruitment Status : Completed
First Posted : February 24, 2012
Results First Posted : May 1, 2018
Last Update Posted : May 1, 2018
Scleroderma,also known as systemic sclerosis (SSc), is a multisystem disease affecting skin and other tissues including joints, muscles, lungs, the gastrointestinal tract and kidneys and tissue fibrosis is widespread. SSc presents special problems for developing therapies due to the heterogeneous clinical presentation, the variability of disease progression and the difficulty quantifying the extent of disease. For most disease manifestations, treatment is primarily symptomatic and generally inadequate.
This study will utilize a 4-gene biomarker of skin disease as the primary efficacy outcome in a short duration, placebo-controlled clinical trial of rilonacept, designed to provide preliminary data for a larger trial. These gene biomarkers should provide a strong surrogate for such trials in the future and, if IL-1 is indeed the cytokine leading to fibrosis in this disease, provide a highly significant start to finding a therapeutic for SSc that for the first time might dramatically affect fibrosis. A central hypothesis of this study is that IL-1 inhibition will downregulate the 4-gene biomarker over a relatively short period of time, much shorter than is historically thought necessary to see changes in the MRSS, a skin score measurement tool. Entry criteria will include the recent onset of diffuse cutaneous SSc as this is the population most likely to show progressive skin disease and also the population examined in previous studies showing correlations between MRSS and the 4-gene biomarker.
Secondary outcomes will include other validated measures of SSc disease activity. MRSS and SSc health assessment questionnaire (SHAQ), will be followed during the trial. This study will also test the effect of rilonacept on global skin gene expression using microarray analyses of skin biopsies. In addition, serum biomarkers of SSc disease activity (COMP, THS-1 and IFI44) and a biomarker of inflammasome activation (CRP) will be tested before and after treatment.
|Condition or disease||Intervention/treatment||Phase|
|Scleroderma Systemic Sclerosis Diffuse Scleroderma Diffuse Systemic Sclerosis||Drug: Rilonacept Other: Placebo||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Randomized, Double-Blind, Placebo-Controlled Trial if IL1-TRAP, Rilonacept, in Systemic Sclerosis -A Phase I/II Biomarker Trial|
|Actual Study Start Date :||December 2011|
|Actual Primary Completion Date :||January 2017|
|Actual Study Completion Date :||August 11, 2017|
Placebo Comparator: Placebo
Patients randomized to placebo will receive saline subcutaneously (SQ) on day 0 and each week for 5 additional weeks
Active Comparator: Rilonacept
Patients randomized to active study drug will receive Rilonacept 320 mg subcutaneously (SQ) on day 0 and 160 mg SQ each week for 5 additional weeks
Other Name: IL1-TRAP
- Change in 2- Gene Biomarker [ Time Frame: Visit 3 (Day 42) - Visit 1 (Day 0) ]To investigate the effect of rilonacept on 2-gene biomarker expression in skin after treatment with rilonacept compared to pre-treatment 2-gene biomarker expression. These were measured at visit 3 (Day 42) and visit 1 (Day 0). This was calculated using a previously validated equation (MRSS = -27.6844 + [4.46(baseline THBS1)] + [5.31(ΔMS4A4A) + 4.96(ΔTHBS1)]). In this equation the expression of two genes (THBS1 and MS4A4) in collected samples are measured via nanostring, and then the expression levels of each gene are inserted into the equation in order to obtain the 2- gene biomarker score. A high biomarker score is equivalent to a high skin score, suggesting a higher severity of the disease.
- Change in Modified Rodnan Skin Score [ Time Frame: Visit 3 (Day 42) - Visit 1 (Day 0) ]Change in Modified Rodnan Skin Score over time. The fully validated modified version of the Rodnan skin thickness score was used. On this scale, a total of 17 skin sites are evaluated, including the face, upper arms, forearms, dorsum of the hands, fingers, chest, abdomen, thighs, forearms and feet. The total score can range from 0 to 51, with higher scores indicating greater severity of skin thickening and involvement (MRSS-51). Each of the 17 skin sites are scored from 0 to 3, where the following criteria apply: 0, normal skin; 1, thickened skin; 2, thickened and unable to pinch; and 3, thickened and unable to move. Scores from visit 3 (Day 42) and visit 1 (Day 0) were compared.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01538719
|United States, Massachusetts|
|Boston University Medical Center|
|Boston, Massachusetts, United States, 02118|
|Principal Investigator:||Robert W Simms, MD||Boston University Medical Center-Rheum/Arthritis Center|