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IL1-TRAP, Rilonacept, in Systemic Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01538719
Recruitment Status : Completed
First Posted : February 24, 2012
Results First Posted : May 1, 2018
Last Update Posted : May 1, 2018
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Robert Simms, Boston University

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Arm Intervention/treatment
Placebo Comparator: Placebo
2:1 randomization
Other: Placebo
Patients randomized to placebo will receive saline subcutaneously (SQ) on day 0 and each week for 5 additional weeks

Active Comparator: Rilonacept
2:1 randomization
Drug: 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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Must meet the American College of Rheumatology criteria for systemic sclerosis with diffuse cutaneous involvement and < 24 months since the onset of the first SSc manifestation other than Raynaud's phenomenon; or has had an increase of MRSS by 5 in the last 6 months.
  • Must have a MRSS of ≥ 15.
  • Male or female patients ≥ 18 years of age.
  • Able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria:

  • Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer).
  • Ongoing use of high dose steroids (> 10mg/day prednisone or equivalent) or unstable steroid dose in the past 4 weeks.
  • Treatment with immunosuppressive (other than low dose steroids), cytotoxic or anti-fibrotic drug within 4 weeks of screening.
  • The patient has positive viral hepatitis B, hepatitis C or HIV serologies on screening laboratories. (Patients with a positive hepatitis B surface antibody (HBsAb) test with a history of prior hepatitis B immunization are eligible as long as other criteria are met (i.e., negative tests for: hepatitis B surface antigen [HBsAg], hepatitis B core antibody [HBcAb], and hepatitis C virus antibody [HCVAb]).)
  • Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening.
  • Patients must have a negative PPD tested within 6 months of the time of screening, or past positive PPD treated with appropriate antibiotic prophylaxis.
  • Patients with a history of malignancy within the past 5 years.
  • Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
  • Scleroderma renal crisis within 6 months or creatinine greater than 2.0
  • Pregnancy (a negative pregnancy test will be performed for all women of childbearing potential on study day 0 and 42).
  • Male and female patients of child-producing potential must agree to use effective contraception while enrolled on study and receiving the experimental drug, and for at least 3 months after the last treatment.
  • Nursing mothers
  • Gastrointestinal involvement requiring total parenteral nutrition or hospitalization within the past 3 months for pseudo-obstruction
  • Moderately severe pulmonary disease with FVC < 60%, or DLCO < 50% predicted.
  • Moderately severe cardiac disease with either a history of significant arrhythmia (not to include conduction delays other than trifascicular block, or PVCs or PACs < 5/minute), clinically significant heart failure, or unstable angina.
  • Hemoglobin: < 8.5 gm/dL
  • White blood count < 3,000/mm3 or total neutrophil count < 1,500
  • Platelets: < 100,000/mm3
  • AST or ALT > 2.5 x Upper Limit of Normal.
  • Total bilirubin > 1.5 x upper limit of normal (ULN). Patients with Gilbert's Disease may be included if their total bilirubin is ≤ 3.0 mg/dL.
  • Patients should not have received any live vaccine within 30 days of trial entry
  • Patients with a history of rilonacept allergy will be excluded.
  • Patients who, in the opinion of the Investigator, have significant medical or psychosocial problems that warrant exclusion. Examples of significant problems include, but are not limited to:
  • Other serious non-malignancy-associated medical conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs.
  • Any condition, psychiatric, substance abuse, or otherwise, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance with any aspect of the study
  • Current use of TNF-blockers within 4 weeks of screening

Information from the National Library of Medicine

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 identifier (NCT number): NCT01538719

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United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston University
Regeneron Pharmaceuticals
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Principal Investigator: Robert W Simms, MD Boston University Medical Center-Rheum/Arthritis Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Robert Simms, Professor of Medicine, Boston University Identifier: NCT01538719    
Other Study ID Numbers: H31332
First Posted: February 24, 2012    Key Record Dates
Results First Posted: May 1, 2018
Last Update Posted: May 1, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Anti-Inflammatory Agents