AzTrials
AzTrials

Familial Cold Autoinflammatory Syndrome (FCAS)Phase 3NCT00288704

Rilonacept for Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS)

A Phase 3 study testing rilonacept 160 mg in people with Familial Cold Autoinflammatory Syndrome (FCAS) and Familial Cold Urticaria, run by Regeneron Pharmaceuticals at 24 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Inflammatory symptoms of Cryopyrin-Associated Periodic Syndrome (CAPS) are due to mutations in a the NLRP-3 gene (previously known as Cold Induced Autoinflammatory Syndrome-1 or CIAS1). These mutations result in the body's overproduction of interleukin-1 (IL-1), a protein that stimulates the inflammatory process. Read more about this study

Who is it for?
Ages 7 years and older
What is being tested?
rilonacept 160 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
104 participants
Where
24 sitesUnited States
Study dates
Dec 2005to Aug 2008
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 7 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Double-blind phases: adults age 18 and above; Open-label extension: Adults and children aged 7 years and older.
  • Was diagnosed with Familial Cold Auto-inflammatory Syndrome (FCAS) or Muckle-Wells Syndrome (MWS) based upon clinical signs and symptoms
  • Had documented mutation in NLRP-3 (Cold Induced Autoinflammatory Syndrome-1 or CIAS1) in subject or relative, and willingness to have a confirmatory genetic (Deoxyribonucleic acid or DNA) test (cheek swab).
  • Was able to understand and comply with study procedures and was able to provide informed consent
  • If female, was not currently pregnant and was willing to use contraception during the study

Who cannot join

  • Had evidence of untreated tuberculosis or other conditions/therapies that made the subject inappropriate for this study.

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

United States24 sites
  • Study site

    Atlanta, Georgia, 30342

  • Study site

    Aurora, Illinois, 60504

  • Study site

    Cedar City, Utah, 84720

  • Study site

    Chattanooga, Tennessee, 37403

  • Study site

    Chesterfield, Michigan, 48047

  • Study site

    Cincinnati, Ohio, 45236

  • Study site

    Columbia, South Carolina, 29201

  • Study site

    Columbus, Georgia, 31904

  • Study site

    Dallas, Texas, 75235

  • Study site

    Duncansville, Pennsylvania, 16635

  • Study site

    Forest, Virginia, 24551

  • Study site

    Greer, South Carolina, 29651

  • Study site

    Jacksonville, Florida, 32216

  • Study site

    Lakewood, Washington, 98499

  • Study site

    Little Rock, Arkansas, 72204

  • Study site

    Louisville, Kentucky, 40215

  • Study site

    New York, New York, 10023

  • Study site

    Palm Desert, California, 92260

  • Study site

    Raleigh, North Carolina, 27609

  • Study site

    Shreveport, Louisiana, 71105

  • Study site

    St Louis, Missouri, 63141

  • Study site

    Stuart, Florida, 34996

  • Study site

    Upland, California, 91786

  • Study site

    Waco, Texas, 76712

Other trials in United States

About this 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

Inflammatory symptoms of Cryopyrin-Associated Periodic Syndrome (CAPS) are due to mutations in a the NLRP-3 gene (previously known as Cold Induced Autoinflammatory Syndrome-1 or CIAS1). These mutations result in the body's overproduction of interleukin-1 (IL-1), a protein that stimulates the inflammatory process. IL-1 Trap (rilonacept) was designed to bind to the interleukin-1 cytokine and prevent it from binding to its receptors in the body.

Read the detailed description

Primary Objective:

The primary objective of this study was to assess the effect of rilonacept on the clinical signs and symptoms of Cryopyrin-Associated Periodic Syndrome (CAPS) when used for chronic therapy as evaluated by the subjects themselves over time using a validated patient-reported outcomes tool.

Secondary Objective(s):

The secondary objectives were 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 was a multi-center, two-part, double-blind, placebo-controlled study (Parts A and B) designed to assess the efficacy, safety, and tolerability of weekly subcutaneous (SC) doses of 160 mg of rilonacept in adult subjects with active CAPS. These phases were followed by extended open-label phases. 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 Part A, a 6-week long double-blind, randomized phase of the study. All subjects were then treated with single-blind rilonacept for 9-weeks, followed by a subsequent 9-week, double-blind, withdrawal phase during which subjects were re-randomized to either rilonacept or placebo. Subjects then continued treatment in a 24-week open-label extension phase (OLE) and a further 112-week long-term open-label extension (LTOLE), during which all subjects received rilonacept and a 6-week post-treatment follow-up period. Amendments 4 and 6 allowed eligible adult and pediatric subjects aged 7 and above to enroll directly into the open-label phases of the trial.

For reporting purposes, the 24-week OLE and the 112-week LTOLE was considered one Open Label Extension (OLE) phase. This occurred after the 24-week double blind (Parts A and B ) phase. In other words, OLE Week 1 corresponded to the week 25 in the study.

OLE Week 72 was the final timepoint where efficacy was measured. Safety continued after that timepoint until the end of the study.

Being tested
rilonacept 160 mg, Placebo
Keywords
Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), CIAS1, NLRP-3, PYPAF1, Cryopyrin, CAPS, Interleukin-1
Medical subject headings
Cryopyrin-Associated Periodic Syndromes, Genetic Diseases, Inborn

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rilonacept 160 mgDrug

    Also called Rilonacept

    Rilonacept was given by subcutaneous injection. It was administered weekly at the dose of 160mg. On Day 1, subjects received two injections of rilonacept (for a total of 320 mg).

  • PlaceboDrug

    Subcutaneous injection of Placebo occurred during first 6 weeks of the study or during randomized withdrawal (weeks 15-24). On Day 1, subjects received two placebo injections.

  • rilonacept 160 mgDrug

    Rilonacept was given by subcutaneous injection. It was administered weekly at the dose of 160mg. No loading dose was given for subjects who entered directly into the open-label.

Study groups in NCT00288704
Study groupRoleWhat they receive
PlaceboPlacebo comparatorSome subjects were treated with Placebo in the Study. This occurred (if subject randomized to Placebo) either during the first 6 weeks of the study or during the randomized withdrawal (weeks 15-24).
Receives: Drug: Placebo
rilonacept 160 mgActive comparatorIf randomized to rilonacept, subjects received this treatment during the first 6 weeks of the study or during the randomized withdrawal (weeks 15-24). All subjects received rilonacept 160 mg during weeks 6-14 (between Parts A and B). Study drug is administered as a 2.0 mL subcutaneous injection once a week. At baseline (week 0) subjects receive a loading dose of rilonacept 320 mg.
Receives: Drug: rilonacept 160 mg
Open-Label rilonacept 160 mgOtherAfter week 24 (the end of part B), all subjects went into weekly dosing of open label rilonacept 160 mg. During this phase of the study, adolescents aged 7 and above were entered into the study and rilonacept was dosed as 2.2 mg/kg injections, up to 160 mg, per week. Study drug is administered as a 2.0 mL subcutaneous injection once a week.
Receives: Drug: rilonacept 160 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS)

    The mean Key Symptom Score (KSS --from the validated, patient-administered Daily Health Assessment Form(DHAF)) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue). KSS was averaged over two 21-day daily reporting periods (the 3 weeks prior to both baseline and week 6). In part A, a negative change in mean values indicated improvement under treatment with rilonacept in symptoms.

    The DHAF was used because it is a validated instrument to collect subject's self-reported responses.

    Measured: Baseline (Days -21 to -1) and Week 6 (Days 21-42)

  2. Mean Change in Key Symptom Score (KSS) From Week 15 to Week 24 (During the Randomized Withdrawal Phase or Part B)

    The mean Key Symptom Score (KSS --from the validated, patient-administered DHAF) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue).

    Subjects all received rilonacept 160 mg from week 6 through week 14. At week 15, subjects were re-randomized in a 1:1 ratio between Placebo and rilonacept 160 mg. Subjects baseline period was the 21-day period prior to week 15 randomization.

    A positive score indicated a worsening of symptoms versus an active treatment rilonacept baseline period.

    Measured: Week 15 through Week 24 (randomized withdrawal)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2006 (estimated)
  2. Study startDec 2005
  3. Primary completionJun 2008
  4. Study completionAug 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
104 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00288704
Sponsor's protocol ID
IL1T-AI-0505
Status last verified
Dec 2011
First submitted
6 Feb 2006
Last updated
6 Dec 2011
Data monitoring committee
Yes

Publications

  • Hoffman HM, Throne ML, Amar NJ, Cartwright RC, Kivitz AJ, Soo Y, Weinstein SP. Long-term efficacy and safety profile of rilonacept in the treatment of cryopryin-associated periodic syndromes: results of a 72-week open-label extension study. Clin Ther. 2012 Oct;34(10):2091-103. doi: 10.1016/j.clinthera.2012.09.009. Epub 2012 Sep 29.

    PubMed 23031624
  • 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. doi: 10.1002/art.23687.

    PubMed 18668535

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rilonacept 160 mg in people with Familial Cold Autoinflammatory Syndrome (FCAS) and Familial Cold Urticaria, run by Regeneron Pharmaceuticals at 24 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Nov 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS) (time frame: Baseline (Days -21 to -1) and Week 6 (Days 21-42)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00288704, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2011.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in