Rilonacept for Deficiency of the Interleukin-1 Receptor Antagonist (DIRA)

NCT01801449 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 13008613-AR-0086
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Deficiency of the IL-1 receptor antagonist (DIRA) is a condition that causes repeated episodes of inflammation. People with DIRA can have rashes, fever, and joint pain. Most treatments for DIRA are intended to control the immune system to stop these inflammations. There are drugs that can treat DIRA, but they have to be given daily as injections. Researchers want to try another drug, rilonacept, as a treatment for DIRA. It needs to be given only once a week. Rilonacept will be given to individuals who are at least 3 months old and who have DIRA. Objectives: \- To test the safety and effectiveness of rilonacept for children and adults with DIRA. Eligibility: \- Individuals at least 3 months old who have DIRA. Design:

• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Other tests to study pain and movement will be given. Imaging studies such as bone density scans and x-rays may also be taken.
• Participants will have a minimum of four to five study visits over 12 months. Those who are on different anti-inflammatory drugs (such as anakinra) will stop taking them before beginning the study visits.
• Participants will have rilonacept injections weekly while on this study. The dose will be adjusted as needed to help treat the DIRA symptoms. Participants will keep a diary to monitor their symptoms and any side effects.
• Treatment with rilonacept will be given for 1 year. Participants will have study visits to monitor the treatment. They will provide blood samples and have other tests at these study visits.

Conditions

DIRA

Keywords

DIRA; Clinical Trial; IL-1; Autoinflammatory Syndrome; Rilonacept

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Who Maintained Inflammatory Remission With Rilonacept

  Inflammatory remission criteria remission criteria were defined as meeting all of the following criteria: a diary score of \<0.5 (reflecting no fever, skin rash or bone pain), normal acute phase reactants (C-reactive protein (CRP) \<0.5 mg/dL), no objective skin rash or radiological evidence of active bone lesions on x-ray.

  6 months

Secondary Outcomes (10)

• Height

  24 months after rilonacept initiation

• Height

  Baseline

• Weight

  24 months after rilonacept initiation

• Weight

  Baseline

• Childhood Health Assessment Questionnaire (CHAQ)

  24 months after rilonacept initiation

Study Arms (1)

Rilonacept Treatment

EXPERIMENTAL

Rilonacept loading dose of 4.4 mg/kg/week followed by maintenance dose of 2.2 mg/kg/week. Total duration of the study 24 months. Maintenance dose could be escalated to 4.4 mg/kg/week or further to 6.6 mg/kg/week for 3 months only.

Drug: Rilonacept

Interventions

Rilonacept DRUG

Rilonacept Treatment

Eligibility Criteria

• Age: 3 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female pediatric and adult subjects with mutation positive IL1RN indicating DIRA. For the first five patients enrolled, they must have been on a stable dose of anakinra during the 2-week period prior to screening visit. If the subject is on other medications such as NSAIDs, methotrexate and/or oral steroids, it is a requirement that these doses have been stable during the 2-week period prior to screening visit.
• Subjects greater or equal to 3 months of age (however the first 5 patients enrolled will be over 2 years of age). Subjects 3 months old or older will be enrolled after SMC data review of the first 5 enrolled patients.
• Participation in NIH study #03-AR-0173 ( Studies of the Natural History, Pathogenesis and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CRMO, Still s Disease, Behcet s Disease, and other Undifferentiated Autoinflammatory Diseases )
• Subjects currently treated with anakinra may be enrolled in this study even though their DIRA may be quiescent. For these subjects, a history of active DIRA prior to treatment with anakinra will be sufficient. Subjects will not take anakinra 24 hours before initiation of drug treatment. Treatment naive patients will also be enrolled after SMC data review of the first 5 enrolled patients.
• Females of childbearing potential (young women who have had at least one menstrual period regardless of age) must have a negative serum pregnancy test at screening and a urine pregnancy test prior to administration of study medication.
• Females of childbearing age and men able to father a child and who are sexually active, who agree to use two forms of effective birth control, including abstinence.
• Negative Purified Protein Derivative (PPD) test using 5 T.U. intradermal testing or the QuantiFERON(SqrRoot) - TB Gold test per the Centers for Disease Control and Prevention (CDC) guidelines, and no evidence of active tuberculosis (TB) on chest X-ray.
• Subjects with latent TB (positive PPD or QuantiFERON - TB Gold test) currently treated with adequate therapy for at least one month prior to first dose of study medication may be included. Full prophylaxis regimens will be continued while on the study.
• Subjects who have had active TB in the past with documentation of adequate treatment may be included with strict clinical and radiological follow-up as per current guidelines.
• The Infectious diseases service will be consulted regarding all patients with evidence of TB infection (latent or active, current or history) prior to enrollment, and as appropriate during the study.
• Subjects who have been BCG-vaccinated will also be tested. Interpretation of PPD and QuantiFERON - TB Gold test in BCG recipients will be the same as for subjects who have not received BCG vaccine.
• Guardian/parent able to understand, and complete study-related questionnaires.
• Guardian/parent able and willing to give informed consent and abide with the study procedures.

You may not qualify if:

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• Treatment receiving a live virus vaccine (such as the measles, mumps, and rubella vaccine) during the 3 months prior to baseline visit. No live vaccines will be allowed throughout the course of this study.
• Presence of active infections or a history of pulmonary TB infection without documented adequate therapy. Subjects with current active TB, or recent close exposure to an individual with active TB, are excluded from the study. Exceptions include patients with latent TB treated with adequate therapy for at least one month prior to the first dose of study medication, and patients with history of TB with documentation of adequate treatment.
• Positive test for, or prior history of, HIV, or Hepatitis B or C.
• History of malignancy. Subjects deemed cured of superficial malignancies such as cutaneous basal or squamous cell carcinomas, or in situ cervical cancer may be enrolled.
• Known hypersensitivity to Chinese Hamster Ovary cell-derived biological or any components of rilonacept.
• Presence of any additional rheumatic disease or significant systemic disease. For example, major chronic infectious/ inflammatory/ immunologic disease (such as inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, SLE in addition to autoinflammatory disease).
• Presence of any of the following laboratory abnormalities at enrollment visit:
• creatinine greater than 1.5xULN
• WBC less than 3.0x103/mm3
• ANC less than 800 cells/mL
• platelet count less than 150,000 mm3
• ALT or AST greater than 2.0x ULN.
• Lactating, breastfeeding or pregnant females.
• Enrollment in any other investigational treatment study or use of an investigational agent, or has not yet completed at least 4 weeks or 5 half-lives, whichever is longer, since ending another investigational device or drug trial.

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead
• National Institutes of Health Clinical Center (CC): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, Laxer R, Tedgard U, Cowen EW, Pham TH, Booty M, Estes JD, Sandler NG, Plass N, Stone DL, Turner ML, Hill S, Butman JA, Schneider R, Babyn P, El-Shanti HI, Pope E, Barron K, Bing X, Laurence A, Lee CC, Chapelle D, Clarke GI, Ohson K, Nicholson M, Gadina M, Yang B, Korman BD, Gregersen PK, van Hagen PM, Hak AE, Huizing M, Rahman P, Douek DC, Remmers EF, Kastner DL, Goldbach-Mansky R. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009 Jun 4;360(23):2426-37. doi: 10.1056/NEJMoa0807865.

  PMID: 19494218 BACKGROUND

• Garg M, de Jesus AA, Chapelle D, Dancey P, Herzog R, Rivas-Chacon R, Muskardin TLW, Reed A, Reynolds JC, Goldbach-Mansky R, Sanchez GAM. Rilonacept maintains long-term inflammatory remission in patients with deficiency of the IL-1 receptor antagonist. JCI Insight. 2017 Aug 17;2(16):e94838. doi: 10.1172/jci.insight.94838. eCollection 2017 Aug 17.

  PMID: 28814674 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

rilonacept

Results Point of Contact

• Title: Montealegre, Gina
• Organization: National Inst of Arthritis and Musculoskeletal and Skin Diseases

montealegrega@mail.nih.gov

+1 301 761 7747

Study Officials

• Gina A Montealegre, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: February 28, 2013
• Study Start: February 12, 2013
• Primary Completion: April 28, 2016
• Study Completion: April 28, 2016
• Last Updated: October 16, 2017
• Results First Posted: October 16, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)