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Autoimmune Connective Tissue DisorderPhase 1/2NCT01441076

Anakinra for Behcet s Disease

A Phase 1/2 study testing Anakinra in people with Autoimmune Connective Tissue Disorder and Immune System Diseases, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site 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

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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Anakinra
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
Sep 2011to Nov 2014
Phase
Phase 1/2
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Presence of other severe acute or chronic medical or psychiatric condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the subject s safety, inhibit protocol participation, or interfere with interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
  • Treatment within the past 12 months with canakinumab
  • Active neurologic disease which would require cyclophosphamide treatment. Active neurologic disease is defined as either new evidence of parenchymal (meningoencephalitis) or non-parenchymal (vascular complications including thrombosis) disease.
  • Subjects who experience an end organ flare after discontinuation of a TNF inhibitor as part of this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Pilot Study of Anakinra in Behcet's Disease (BD)

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.
Read more

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.
Read the detailed description

Autoinflammatory diseases are illnesses characterized by episodes of inflammation that, unlike autoimmune disorders, lack the production of high titer autoantibodies or antigen-specific T cells. There is growing genetic and clinical evidence that Interleukin-1 (IL-1) plays a pathogenic role in several of these diseases. This exploratory study aims to examine the utility of anakinra in the treatment of adult subjects with Behcet s Disease (BD), a disease which shows similarities to the known anakinra-responsive autoinflammatory disorders, familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells Syndrome (MWS). Anakinra is a recombinant form of the human interleukin-1 receptor antagonist that has been studied in rheumatoid arthritis (RA) and the autoinflammatory disorders. It has a half life of 4 to 6 hours with a FDA approved recommended dose of 100 mg/day subcutaneously for the treatment of rheumatoid arthritis.

This pilot study is designed to address: 1) the utility of anakinra in the treatment of BD; 2) the effect of anakinra on laboratory biomarkers in BD; and 3) an exploratory assessment of the safety of anakinra in individuals with Behcet's Disease.

Subjects with oral or genital ulcers will receive anakinra for three to six months. If five of the initial seven patients have a positive response, up to 20 patients with oral or genital ulcers will then be randomized to withdrawal or continuation of drug for six months once placebo is available. Patients with eye disease will be treated with anakinra for a total of twelve months without randomization to withdrawal. Clinical and biochemical correlates of inflammation will be measured at appropriate intervals to assess response and to further understand disease mechanisms.

Being tested
Anakinra
Keywords
Behcet's Disease, Aphthous Ulcer, Uveitis, IL-1, Autoinflammation, BD
Medical subject headings
Immune System Diseases, Behcet Syndrome, Stomatitis, Aphthous, Uveitis

What participants receive

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

  • AnakinraDrug

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

Study groups in NCT01441076
Study groupRoleWhat they receive
AnakinraExperimentalTreatment with Anakinra 100mg subcutaneous daily with option to escalate dose up to 300mg subcutaneous daily
Receives: Drug: Anakinra

What is being measured

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

  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.

    Measured: Monthly study visits from months 3-6 during the trial

Secondary outcomes (14)

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

    The BDRQOL is a standardized assessment form in Behcet's disease composed of 30 items (answered true or not true) and each item is scored 0 or 1 (scoring range from 0 to 30). A total lower score indicates a better quality of life and a total higher score indicates a worse quality of life.

    Measured: Month 6 study visit

  2. Behcet's Syndrome Activity Scale (BSAS) Score

    The BSAS is a standardized assessment form in Behcet's disease. The BSAS score comprises 10 items. The total score possible is between 0-100. A total lower score indicates a less syndrome activity and a higher total score indicates more syndrome activity.

    Measured: Month 6 study visit

  3. Behcets Disease Current Activity Form (BDCAF) Score

    The BDCAF is a standardized assessment form in Behcet's disease to measure patient activity. Scoring is based on the history of new clinical features present over the preceding 4 weeks prior to assessment. The range of score is 0 - 12. A total lower score indicates less disease activity and a higher total score indicates more disease activity.

    Measured: Month 6 study visit

  4. Number of Genital Ulcers by Physician Evaluation

    Number of genital ulcers noted by physician evaluation

    Measured: Month 6 study visit

  5. Number of Oral Ulcers by Physician Evaluation

    Number of oral ulcers noted by physician evaluation

    Measured: Month 6 study visit

  6. Patient Global Score

    Global visual analogue scale taken by patients with a range of score of 0-100. Lower scores indicate least symptoms and higher scores indicate worst symptoms faced by the patient.

    Measured: Month 6 study visit

  7. Physician Global Score

    Global visual analogue scale administered by physicians with a range of score of 0-100. Lower scores indicate least symptoms and higher scores indicate worst symptoms faced by the patient.

    Measured: Month 6 study visit

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

    The BDRQOL is a standardized assessment form in Behcet's disease composed of 30 items (answered true or not true) and each item is scored 0 or 1 (scoring range from 0 to 30). A total lower score indicates a better quality of life and a total higher score indicates a worse quality of life.

    Measured: Baseline

  9. Behcet's Syndrome Activity Scale (BSAS) Score

    The BSAS is a standardized assessment form in Behcet's disease. The BSAS score comprises 10 items. The total score possible is between 0-100. A total lower score indicates a less syndrome activity and a higher total score indicates more syndrome activity.

    Measured: Baseline

  10. Behcets Disease Current Activity Form (BDCAF) Score

    The BDCAF is a standardized assessment form in Behcet's disease to measure patient activity. Scoring is based on the history of new clinical features present over the preceding 4 weeks prior to assessment. The range of score is 0 - 12. A total lower score indicates less disease activity and a higher total score indicates more disease activity.

    Measured: Baseline

  11. Number of Genital Ulcers by Physician Evaluation

    Number of genital ulcers noted by physician evaluation

    Measured: Baseline

  12. Number of Oral Ulcers by Physician Evaluation

    Number of oral ulcers noted by physician evaluation

    Measured: Baseline

  13. Patient Global Score

    Global visual analogue scale taken by patients with a range of score of 0-100. Lower scores indicate least symptoms and higher scores indicate worst symptoms faced by the patient.

    Measured: Baseline

  14. Physician Global Score

    Global visual analogue scale administered by physicians with a range of score of 0-100. Lower scores indicate least symptoms and higher scores indicate worst symptoms faced by the patient.

    Measured: Baseline

Timeline

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

  1. First posted27 Sep 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionOct 2014
  4. Study completionNov 2014

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01441076
Sponsor's protocol ID
110241
Other IDs
11-AR-0241
Status last verified
Apr 2017
First submitted
24 Sep 2011
Last updated
12 May 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 17393462

  • 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.

    PubMed 12483741

  • 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.

    PubMed 12032915

  • 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.

    PubMed 28335798

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Anakinra in people with Autoimmune Connective Tissue Disorder and Immune System Diseases, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site 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 11 inclusion and 19 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 12 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 12 May 2017). 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?

Clinical Remission From Months 3-6 (time frame: Monthly study visits from months 3-6 during the trial). 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 NCT01441076, which also lists 4 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 12 May 2017.

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