Trial record 1 of 198 for:    "Diffuse scleroderma"
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IL1-TRAP, Rilonacept, in Systemic Sclerosis

This study is currently recruiting participants.
Verified November 2013 by Boston University
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Robert Lafyatis, Boston University
ClinicalTrials.gov Identifier:
NCT01538719
First received: February 21, 2012
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Scleroderma
Systemic Sclerosis
Diffuse Scleroderma
Diffuse Systemic Sclerosis
Drug: Rilonacept
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Boston University:

Primary Outcome Measures:
  • 4- gene biomarker [ Time Frame: 5 year(anticipated) ] [ Designated as safety issue: No ]
    To investigate the effect of rilonacept on 4-gene biomarker expression in skin after treatment with rilonacept compared to pre-treatment 4-gene biomarker expression


Secondary Outcome Measures:
  • Modified Rodnan Skin Score [ Time Frame: 5 year(anticipated) ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2011
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
2:1 randomization
Drug: 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01538719

Contacts
Contact: Jessica Ziemek 617-638-5383 jziemek@bu.edu

Locations
United States, Massachusetts
Boston University Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Jessica Ziemek    617-638-5383    jziemek@bu.edu   
Principal Investigator: Robert Lafyatis, MD         
Sponsors and Collaborators
Boston University
Regeneron Pharmaceuticals
Investigators
Principal Investigator: Robert Lafyatis, MD Boston University Medical Center-Rheum/Arthritis Center
  More Information

No publications provided

Responsible Party: Robert Lafyatis, Professor of Medicine, Boston University
ClinicalTrials.gov Identifier: NCT01538719     History of Changes
Other Study ID Numbers: H31332
Study First Received: February 21, 2012
Last Updated: November 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Sclerosis
Connective Tissue Diseases
Skin Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014