NordicAOSD05: Treatment of Refractory Adult-onset Still's Disease With Anakinra: a Randomized Study

Sponsor

University of Helsinki (Other)

Overall Status

Completed

CT.gov ID

NCT01033656

Collaborator

Uppsala University Hospital (Other), Helse Stavanger HF (Other), Tampere University Hospital (Other), Turku University Hospital (Other), Oulu University Hospital (Other), Kuopio University Hospital (Other), Jyväskylä Central Hospital (Other), Satakunta Central Hospital (Other), University Hospital, Umeå (Other), University Hospital, Linkoeping (Other)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

An open, randomized, parallel-group, comparative, multicentre study. Patients on corticosteroids (plus conventional therapy) will be randomized to receive anakinra (Kineret®), or one of the following: methotrexate, azathioprine, leflunomide, cyclosporin A or sulphasalazine. Patients enter the study if considered refractory to corticosteroids (prednisolone equivalent ≥10 mg/day) at the time of randomization.

The randomized phase of the study will be followed by an open-label extension (OLE) phase, to follow-up drug survival, efficacy, tolerability and disease-related parameters of long-term treatment with anakinra or one of the study DMARDs or a combination of study drugs for additional 28 weeks.

Condition or Disease	Intervention/Treatment	Phase
Adult-Onset Still's Disease	Drug: anakinra Drug: comparators	Phase 2

Detailed Description

Product: Kineret (anakinra) Comparative agents: Methotrexate or azathioprine or leflunomide or cyclosporin A or sulphasalazine Protocol title: An open, randomized study treating refractory adult-onset Still's disease with IL-1ra anakinra (Kineret, compared to an established, single anti-rheumatic treatment Target Disease: Adult-onset Still's disease Patients: 23 patients diagnosed with AOSD, living in the four Nordic countries.

Study Objectives: To follow the changes in clinical status and disease activity in patients receiving anakinra, compared to those treated with an established DMARD, in addition to corticosteroids in patients with refractory AOSD. To compare the changes in disease-related parameters (global health, patient's assessment on disease, laboratory values) in the two randomized groups. To assess the safety of anakinra in AOSD. To follow-up drug survival, efficacy, tolerability and disease-related parameters of long-term treatment in AOSD (open phase).

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open, Randomized Study Treating Refractory Adult-onset Still's Disease With Interleukin-1 Receptor Antagonist Anakinra (Kineret), Compared to an Established, Single Anti-rheumatic Drug Treatment

Study Start Date :

Dec 1, 2005

Actual Primary Completion Date :

Mar 1, 2010

Actual Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anakinra experimental drug of study	Drug: anakinra 100 mg subcutaneous injection daily Other Names: Interleukin-1 receptor antagonist
Active Comparator: comparator comparators:methotrexate, azathioprine, leflunomide or supfasalazine	Drug: comparators po drugs, comparators Other Names: methotrexate, azathioprine, leflunomide, sufalalazine

Arm

Intervention/Treatment

Experimental: Anakinra

experimental drug of study

Drug: anakinra

100 mg subcutaneous injection daily

Other Names:

Interleukin-1 receptor antagonist

Active Comparator: comparator

comparators:methotrexate, azathioprine, leflunomide or supfasalazine

Drug: comparators

po drugs, comparators

Other Names:

methotrexate, azathioprine, leflunomide, sufalalazine

Outcome Measures

Primary Outcome Measures

Number of patients reaching remission of the disease, after eight weeks of the randomized study treatment (Remission: afebrile and normalization of acute phase reactants) [8 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must be diagnosed with AOSD according to preliminary classification by Yamaguchi (1992).
Other diseases with similar symptoms must be excluded. Has been exposed to a corticosteroid for ≥2 months prior to randomization for AOSD.
Needs a prednisolone dose ≥10 mg/day or equivalent, yet unacceptable disease activity determined by the investigator.
Anti-TNF agents must be discontinued 4 to 8 weeks prior to commencing study medication.

Exclusion Criteria:

Use of corticosteroids (prednisolone equivalent <10 mg/day.
History of recurrent or chronic infection, including:
tuberculosis
any malignancy
any other major chronic inflammatory disease syndrome
drug or alcohol abuse
known positivity for hepatitis B, C or HIV.
Use of anti-TNF agents during ≤4 weeks (etanercept) or≤8 weeks (infliximab or adalimumab) prior to randomization.