Canakinumab for Treatment of Adult-onset Still's Disease

NCT ID: NCT02204293

Last Updated: 2020-08-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-21
• Study Completion Date: 2018-05-05

Brief Summary

The purpose of this trial is to investigate the efficacy of the treatment with canakinumab in participants with Adult-onset Still's Disease (AOSD) and active joint involvement.

Conditions

Adult-Onset Still´s Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Canakinumab

Participants received canakinumab 4 mg/kg up to a maximum of 300 mg subcutaneous (SC) injection, once in morning on Day 0, Weeks 4, 8, and 12 in Part I of the core study. Participants with response (change in DAS score \> 1.2 at Week 12) continued to receive same dose of canakinumab in Part II for Weeks 12, 16, and 20. Participants who had remission (change in DAS score \> 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) entered Long-term extension (LTE) phase and received same dose of canakinumab at Weeks 24 and 28, which was down titrated to 2 mg/kg if applicable from Week 28 up to Month 27.

Group Type: EXPERIMENTAL

Canakinumab

Intervention Type: DRUG

Canakinumab, single-dose 4 mg/kg up to 300 mg administered subcutaneously.

Placebo

Participants received placebo, SC injection, once in morning on Day 0, Weeks 4, 8, and 12 in Part I of the core study. Participants with response (change in DAS score \> 1.2 at Week 12) continued to receive placebo at Weeks 12, 16, and 20. Non-responders (who had change in DAS score ≤ 1.2) were unblinded to receive canakinumab 4 mg/kg (up to 300 mg maximum), SC injection, at Weeks 12, 16, and 20. Participants who had remission (change in DAS score \> 1.2 and no signs of systemic activity for adult-onset Still's disease at Week 20) entered Long-term extension (LTE) phase and received same dose of canakinumab at Weeks 24 and 28, which was down titrated to 2 mg/kg if applicable from Week 28 up to Month 27.

Group Type: PLACEBO_COMPARATOR

Canakinumab

Intervention Type: DRUG

Canakinumab, single-dose 4 mg/kg up to 300 mg administered subcutaneously.

Placebo

Intervention Type: DRUG

Matching placebo administered subcutaneously.

Interventions

Canakinumab

Canakinumab, single-dose 4 mg/kg up to 300 mg administered subcutaneously.

Intervention Type: DRUG

Placebo

Matching placebo administered subcutaneously.

Intervention Type: DRUG

Other Intervention Names

Ilaris

Eligibility Criteria

Inclusion Criteria

1. Written and signed consent from the participant to take part in the study

2. Men and women aged ≥ 18 years and ≤ 75 years

3. Fulfilment of AOSD classification criteria (according to Yamaguchi et al, J. Rheumatology, 1992)

4. Disease activity based on Disease Activity Score 28 (DAS28) of ≥3.2 at screening

5. At least 4 painful and 4 swollen joints at screening and baseline (of the 28 joints according to DAS28)

6. If undergoing treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable dose for at least 4 weeks prior to randomisation

7. If undergoing treatment with glucocorticoids, stable dose of ≤10 milligrams per day (mg/day) (prednisolone or equivalent) for at least 4 weeks prior to randomisation

8. If undergoing treatment with conventional disease-modifying anti-rheumatic drugs (DMARD), stable dose for at least 3 months prior to randomisation

9. Normalisation period for biological DMARDS (anakinra 1 week, etanercept 1 month, adalimumab and certolizumab 2 months, infliximab, golimumab, abatacept and tocilizumab 3 months, rituximab 9 months, canakinumab 6 months) prior to randomisation

10. In participants of reproductive age, use of an effective method of contraception as well as negative pregnancy test prior to the study commencing.

Exclusion Criteria

1. Previous treatment with the study drug with repeated administration of canakinumab

2. Intraarticular or intravenous administration of glucocorticoids within 4 weeks prior to the baseline or use of narcotic analgesics except for analgesics permitted within the framework of the investigation (codeine and tramadol)

3. Presence of another, serious chronic-inflammatory disease

4. Positive hepatitis B antigen (HBsAg), hepatitis C antibodies and/or human immunodeficiency virus (HIV) antibodies.

5. Presence of a relevant, active infection or other diseases, which entail a tendency towards infection

6. Positive screening for latent tuberculosis, in accordance with usual local practice

7. Raised liver count (raised bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3-fold the normal range)

8. Serum-creatinine concentration >1.5 milligrams per deciliter (mg/dL)

9. Inadequate haematological findings (hemoglobin [Hb] ≤ 10 grams per deciliter (g/dL), neutrophils ≤2,500/microliter (µl) and thrombocytes ≤100,000/µl)

10. Simultaneous participation in any other interventional clinical study within the last 30 days preceding the commencement of the study

11. History of neoplasia with the exception of a curatively treated non-melanoma skin tumour or carcinoma of the cervix treated in situ without any indication of recurrence within the last 10 years

12. Relevant cardiac or pulmonary disorders

13. Severe intercurrent neurological or psychiatric disorders

14. Macrophage activation syndrome (MAS) as part of previous treatment with IL-1 blockade (e.g. anakinra, rilonacept)

15. Vaccination with a live vaccine within 3 months before the baseline

16. Alcohol or drug abuse in the past 12 months

17. ≥400 milliliter (mL) donation of blood or loss up to 8 weeks before the baseline

18. Pregnancy or breast-feeding

19. Commitment of the patient to an institution at the direction of an authority or court

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Eugen Feist

Prof. Dr Eugen Feist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eugen Feist, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Charité University Berlin Germany

Locations

Charité Campus Mitte

Berlin, , Germany

Immanuel Krankenhaus Berlin

Berlin, , Germany

Med. Klinik I für Innere Medizin Köln

Cologne, , Germany

Universität Erlangen

Erlangen, , Germany

Kliniken Essen-Süd/Krankenhaus St. Josef

Essen, , Germany

Universitätsklinikum der J.W. Goethe-Universität Frankfurt

Frankfurt A. M., , Germany

Asklepios Klinikum Hamburg Altona

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätskrankenhaus Schleswig Holstein

Kiel, , Germany

Klinikum der Universität München

München, , Germany

Klinikum Südstadt Rostock

Rostock, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

Fachkrankenhaus

Vogelsang, , Germany

Countries

Germany

References

Nirmala N, Brachat A, Feist E, Blank N, Specker C, Witt M, Zernicke J, Martini A, Junge G. Gene-expression analysis of adult-onset Still's disease and systemic juvenile idiopathic arthritis is consistent with a continuum of a single disease entity. Pediatr Rheumatol Online J. 2015 Nov 20;13:50. doi: 10.1186/s12969-015-0047-3.

Reference Type: DERIVED

PMID: 26589963 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://ard.bmj.com/content/early/2020/05/13/annrheumdis-2020-217155

Related Info

Other Identifiers

2011-001027-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CACZ885GDE01T

Identifier Type: -

Identifier Source: org_study_id