Anakinra for Behcet s Disease

NCT01441076 | Completed Phase 1 Results DMC

• 2 other identifiers: 11024111-AR-0241
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Behcet's disease (BD) is an autoimmune disease where the immune system attacks the body. People with BD may develop oral or genital ulcers, skin problems, and eye disease. Most drugs used to treat BD suppress the immune system, but they are not always helpful and may have side effects. A new drug, anakinra, may be able to treat BD with fewer side effects. Because it has not been studied in people with BD, anakinra is considered an experimental treatment. Objectives: \- To test whether anakinra can be a safe and effective treatment for Behcet s disease. Eligibility: \- People who have Behcet's disease with ongoing oral or genital ulcers for at least one month, or three or more flares of eye disease in the past 6 months. Design:

• Participants will be screened with a physical exam and medical history. They will also have blood and urine tests. They will be divided into two groups: those with oral or genital ulcers and those with eye disease.
• All participants will keep a diary of symptoms for a month before starting the study drug.
• Participants with oral or genital ulcers will receive daily injections of anakinra for 3 to 6 months. Treatment will be monitored with frequent blood draws and daily diaries. Those who improve but do not have a full response to the drug may receive a higher dose. Those who improve after 6 months may have an extra 6 months on either anakinra or placebo to study the differences in response.
• Participants with eye disease will receive anakinra for up to 12 months. Treatment will be monitored with frequent blood draws, daily diaries, and regular eye exams.
• All participants will have a final study visit 1 month after stopping the study drug.

Conditions

Autoimmune Connective Tissue Disorder; Immune System Diseases

Keywords

Behcet's Disease; Aphthous Ulcer; Uveitis; IL-1; Autoinflammation; BD

Outcome Measures

Primary Outcomes (1)

• Clinical Remission From Months 3-6

  Clinical remission was defined as no oral or vaginal ulcers on physical examination for 2 consecutive monthly visits from months 3-6.

  Monthly study visits from months 3-6 during the trial

Secondary Outcomes (14)

• Behcet's Disease Related Quality of Life (BDRQOL) Assessment Score

  Month 6 study visit

• Behcet's Syndrome Activity Scale (BSAS) Score

  Month 6 study visit

• Behcets Disease Current Activity Form (BDCAF) Score

  Month 6 study visit

• Number of Genital Ulcers by Physician Evaluation

  Month 6 study visit

• Number of Oral Ulcers by Physician Evaluation

  Month 6 study visit

Study Arms (1)

Anakinra

EXPERIMENTAL

Treatment with Anakinra 100mg subcutaneous daily with option to escalate dose up to 300mg subcutaneous daily

Drug: Anakinra

Interventions

Anakinra DRUG

Anakinra/Kineret\[registered\] is a recombinant, non-glycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra)

Anakinra

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects with BD associated inflammatory disease greater than or equal 18 years of age
• Participation in NIH study #03-AR-0173 ( Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases )
• Diagnosis of Behcet s disease as determined by the International Study Group Criteria \[17\] or by complete Japanese Criteria \[18\].
• Active mucocutaneous disease as defined by at least one oral or genital ulcer within the past month.
• Stable dose of steroids, NSAIDs, DMARDs, or colchicine for four weeks prior to enrollment visit.
• For patients with ocular disease, no active intermediate or posterior disease at enrolment but history of an ocular flare (greater than or equal to 3 in the last 6 months) in the presence of any systemic anti-inflammatory therapy such as prednisone, azathioprine, Mycophenolate, methotrexate, cyclosporine, a tumor necrosis factor (TNF) inhibitor, or a combination of these medications. Patients must have developed active disease in the presence of at treatment with at least one of the following medications for at least six months: azathioprine, cyclosporine, or a TNF inhibitor.
• Females of childbearing potential (young women who have had at least one menstrual period regardless of age) must have a negative urine pregnancy test at screening and a negative serum pregnancy test at baseline prior to performance of any radiologic procedure or administration of study medication. Female patients will be screened for pregnancy at all NIH visits.
• Women of childbearing age and men able to father a child, who are sexually active, who agree to use a form of effective birth control, including abstinence.
• Either (1) a negative PPD test using 5 T.U. intradermal testing per Center for Disease Control and Prevention guidelines and no evidence of active tuberculosis (TB) on chest X-ray at the time of enrollment or (2) a positive PPD with no evidence of active TB by history or on chest X-ray at the time of enrollment and either past or present treatment with adequate therapy for at least one month prior to first dose of study medication. Full prophylaxis regimens will be completed. Subjects who have been Bacillus Calmette-Guerin (BCG)-vaccinated will also be skin-tested.
• Able to understand, and complete study-related questionnaires.
• Able and willing to give informed consent and abide with the study procedures.

You may not qualify if:

• Treatment with a live virus vaccine during 3 months prior to baseline visit. No live vaccines will be allowed throughout the course of this study.
• Patients with ocular disease who received local treatments other than eye drops (i.e. periocular or intraocular steroids, implants or other anti-inflammatory agents within 4 weeks prior to enrolment)
• Current treatment with TNF inhibitors or discontinuation of TNF inhibitors within 8 weeks.
• Presence of active infections or a history of pulmonary TB infection. Patients with a history of exposure to TB (positive PPD) who have not been treated with a TB prophylaxis regimen for at least one month.
• Chest x-ray read by a radiologist with pleural scarring and/or calcified granuloma consistent with prior TB.
• Positive test for or prior history of HIV, Hepatitis B or C.
• History or concomitant diagnosis of congestive heart failure.
• 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 (CHO) cell derived biologicals or any components of anakinra.
• 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, systemic lupus erythematosus in addition to autoinflammatory disease).
• Presence of any of the following laboratory abnormalities at enrollment visit: creatinine \> 1.5 times the upper limit of normal , white blood cell \< 3.6 times10(9)/mm(3); platelet count \< 75,000 mm(3); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.0 times the upper limit of normal
• Lactating females or pregnant females.
• Subjects with asthma not adequately controlled on current inhaled therapy for at least four weeks.
• 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.
• Subjects for whom there is concern about compliance with the protocol procedures.

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Aksentijevich I, Putnam CD, Remmers EF, Mueller JL, Le J, Kolodner RD, Moak Z, Chuang M, Austin F, Goldbach-Mansky R, Hoffman HM, Kastner DL. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum. 2007 Apr;56(4):1273-1285. doi: 10.1002/art.22491.

  PMID: 17393462 BACKGROUND

• Aksentijevich I, Nowak M, Mallah M, Chae JJ, Watford WT, Hofmann SR, Stein L, Russo R, Goldsmith D, Dent P, Rosenberg HF, Austin F, Remmers EF, Balow JE Jr, Rosenzweig S, Komarow H, Shoham NG, Wood G, Jones J, Mangra N, Carrero H, Adams BS, Moore TL, Schikler K, Hoffman H, Lovell DJ, Lipnick R, Barron K, O'Shea JJ, Kastner DL, Goldbach-Mansky R. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum. 2002 Dec;46(12):3340-8. doi: 10.1002/art.10688.

  PMID: 12483741 BACKGROUND

• Feldmann J, Prieur AM, Quartier P, Berquin P, Certain S, Cortis E, Teillac-Hamel D, Fischer A, de Saint Basile G. Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet. 2002 Jul;71(1):198-203. doi: 10.1086/341357. Epub 2002 May 24.

  PMID: 12032915 BACKGROUND

• Grayson PC, Yazici Y, Merideth M, Sen HN, Davis M, Novakovich E, Joyal E, Goldbach-Mansky R, Sibley CH. Treatment of mucocutaneous manifestations in Behcet's disease with anakinra: a pilot open-label study. Arthritis Res Ther. 2017 Mar 24;19(1):69. doi: 10.1186/s13075-017-1222-3.

  PMID: 28335798 DERIVED

MeSH Terms

Conditions

Immune System Diseases; Behcet Syndrome; Stomatitis, Aphthous; Uveitis

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Uveitis, Anterior; Panuveitis; Uveal Diseases; Eye Diseases; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vascular; Stomatitis

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Grayson, Peter
• Organization: National Inst of Arthritis and Musculoskeletal and Skin Diseases

peter.grayson@nih.gov

+1 301 827 9187

Study Officials

• Peter C Grayson, M.D.

  National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2011
• First Posted: September 27, 2011
• Study Start: September 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2014
• Last Updated: May 12, 2017
• Results First Posted: May 12, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)