IL-1 Trap for Treatment of CIAS1 Associated Periodic Syndromes (CAPS) - Full Text View

Sponsored by:	Regeneron Pharmaceuticals
Information provided by:	Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00288704

Purpose

Inflammatory symptoms of CAPS are due to mutations in a gene called "cryopyrin" (CIAS1; also known as NALP3 or PYPAF1). These mutations result in the body's overproduction of interleukin-1 (IL-1), a protein that stimulates the inflammatory process. IL-1 Trap is an experimental drug candidate that is designed to bind to the interleukin-1 cytokine and prevent it from binding to its receptors in the body.

Condition	Intervention	Phase
Familial Cold Autoinflammatory Syndrome Familial Cold Urticaria Muckle-Wells Syndrome Genetic Diseases, Inborn	Biological: IL-1 Trap	Phase II Phase III

Genetics Home Reference related topics: familial cold autoinflammatory syndrome Muckle-Wells syndrome

MedlinePlus related topics: Hives

Drug Information available for: Rilonacept

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	IL1T-AI-0505: A Multi-Center, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, & Efficacy of Rilonacept in Subjects With Cryopyrin-Associated Periodic Syndromes (CAPS) Using Parallel Group & Randomized Withdrawal Designs

Further study details as provided by Regeneron Pharmaceuticals:

Primary Outcome Measures:

The primary objective of this study was to assess the effect of rilonacept on the clinical signs and symptoms of CAPS when used for chronic therapy [ Time Frame: Assessment of disease activity was conducted daily using the Daily Health Assessment Form (DHAF), a one-page questionnaire that asked subjects to rate the severity of the key symptoms experienced over the previous 24 hours. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

• To determine the safety and tolerability of rilonacept in subjects with CAPS [ Time Frame: Day 0 and Weeks 3, 6, 9, 12, 15, 18, 21 and 24 (Parts A & B), open-label extension Day 0 and Weeks 6, 12, 18, and 24 (for Amendment #4) & Day 0 & Weeks 6, 12, and 24 for Amendment #6. Weeks 40, 72, 88, and FU (42 days post last dose) ] [ Designated as safety issue: Yes ]

Enrollment:	104
Study Start Date:	December 2005
Study Completion Date:	August 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Part A: Placebo Comparator Double blind, placebo controlled	Biological: IL-1 Trap Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, polysorbate 20, glycine, arginine, and sucrose (pH 6.5). Biological: IL-1 Trap Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, polysorbate 20, glycine, arginine, and sucrose (pH 6.5). polysorbate 20, glycine, arginine, and sucrose (pH 6.5).
Part B: Placebo Comparator Double Blind, placebo controlled	Biological: IL-1 Trap Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, polysorbate 20, glycine, arginine, and sucrose (pH 6.5). Biological: IL-1 Trap Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, polysorbate 20, glycine, arginine, and sucrose (pH 6.5). polysorbate 20, glycine, arginine, and sucrose (pH 6.5).
24 Week Open Label Extension: Active Comparator 24 week open label extension phase	Biological: IL-1 Trap Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, polysorbate 20, glycine, arginine, and sucrose (pH 6.5). Biological: IL-1 Trap Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, polysorbate 20, glycine, arginine, and sucrose (pH 6.5). polysorbate 20, glycine, arginine, and sucrose (pH 6.5).
64 Week Open Label extension: Active Comparator 64 week open label extension phase	Biological: IL-1 Trap Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, polysorbate 20, glycine, arginine, and sucrose (pH 6.5). Biological: IL-1 Trap Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, Rilonacept was supplied by Regeneron as a lyophilized powder in sealed, sterile, single-use, 20-mL vials at a concentration of 80 mg/mL when reconstituted with 2.3-mL of sterile water for injection. The lyophilized formulation contained histidine, sodium citrate, PEG 3350, polysorbate 20, glycine, arginine, and sucrose (pH 6.5). polysorbate 20, glycine, arginine, and sucrose (pH 6.5).

Detailed Description:

Primary Objective:

The primary objective of this study are to assess the effect of rilonacept on the clinical signs and symptoms of CAPS when used for chronic therapy

Secondary Objective(s):

The secondary objectives are as follows:

To determine the safety and tolerability of rilonacept in subjects with CAPS
To assess the effect of rilonacept on laboratory measures of inflammation such as acute phase reactants

This is a multi-center, initially double-blind, placebo-controlled study (Parts A and B) followed by extended open-label phases designed to assess the efficacy, safety, and tolerability of weekly subcutaneous (SC) doses of 160 mg of rilonacept in adult subjects with active CAPS. After written informed consent was obtained, subjects who met the protocol eligibility criteria were enrolled at one of 27 study sites in the United States. The study consisted of a 3-week screening period preceding the 24-week long Parts A and B phase of the study. Subjects then continued treatment in a 24-week open-label extension phase (OLE) and a further 64-week long-term open-label extension (LTOLE), and a 6-week post-treatment follow-up period. Amendments 4 and 6 allowed eligible adult and pediatric subjects to enroll directly into the open-label phases of the trial.

Eligibility

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

Criteria

Inclusion Criteria:

Diagnosis of familial cold autoinflammatory syndrome (FCAS) or Muckle-Wells Syndrome (MWS) based on clinical signs and symptoms
Previously documented mutation in CIAS1 in subject or relative, and willingness to have a confirmatory genetic (DNA) test (cheek swab).
Able to understand and comply with study procedures and willing to provide informed consent
If female, not currently pregnant and willing to use contraception during the study

Exclusion Criteria:

Evidence of untreated tuberculosis or other conditions/therapies that would make subject inappropriate for this study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00288704

Show 24 Study Locations

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

Study Director:	Scott Mellis, MD, PhD	Regeneron Pharmaceuticals
Study Director:	Steven P Weinstein, MD, PhD	Regeneron Pharmaceuticals

More Information

No publications provided by Regeneron Pharmaceuticals

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ, Kavanaugh A, Weinstein SP, Belomestnov P, Yancopoulos GD, Stahl N, Mellis SJ. Efficacy and safety of rilonacept (interleukin-1 trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008 Aug;58(8):2443-52.

Responsible Party:	Regeneron Pharmaceuticals, Inc. ( Robert Evans, PharmD )
Study ID Numbers:	IL1T-AI-0505
Study First Received:	February 6, 2006
Last Updated:	March 2, 2009
ClinicalTrials.gov Identifier:	NCT00288704 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Regeneron Pharmaceuticals:

Familial Cold Autoinflammatory Syndrome (FCAS)
Muckle-Wells Syndrome (MWS)
CIAS1
NALP3

PYPAF1
Cryopyrin
CAPS
Interleukin-1

Study placed in the following topic categories:

Metabolic Diseases
Skin Diseases
Glycine
Citric Acid
Urticaria
Wells Syndrome
Familial Cold Autoinflammatory Syndrome

Amyloidosis
Hypersensitivity
Genetic Diseases, Inborn
Hypersensitivity, Immediate
Muckle-Wells Syndrome
Metabolic Disorder

Additional relevant MeSH terms:

Hypersensitivity
Skin Diseases, Vascular
Amyloidosis
Metabolic Diseases
Pathologic Processes
Disease

Immune System Diseases
Skin Diseases
Genetic Diseases, Inborn
Syndrome
Hypersensitivity, Immediate
Urticaria

ClinicalTrials.gov processed this record on May 07, 2009