Canakinumab for Treatment of Adult-onset Still's Disease

NCT02204293 | Terminated Phase 2 Results

• 2 other identifiers: CACZ885GDE01T2011-001027-20
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 14

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

Keywords

Adult-Onset Still´s Disease; Canakinumab; Joint involvement; AOSD

Outcome Measures

Primary Outcomes (1)

• Core Study Part I: Percentage of Responders as Assessed by Disease Activity Score 28 Joints (DAS28) Score at Week 12

  Responders included participants with change in disease activity score based on 28 joint counts and ESR (DAS28) score \> 1.2. The DAS28 score index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity score, and the erythrocyte sedimentation rate (ESR) value. Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value \< 2.6 = disease remission.

  Week 12

Secondary Outcomes (26)

• Core Study Part I: Change From Baseline (CFB) in Disease Activity Score 28 Joints Erythrocyte Sedimentation Rate (DAS28 [ESR]) Score

  Baseline, Weeks 4, 8 and 12

• Core Study Part I: CFB in DAS28 C-reactive Protein (CRP) Score

  Baseline, Weeks 4, 8 and 12

• Core Study Part I: CFB in American College of Rheumatology (ACR) Component: 68 Tender Joint Count (TJC)

  Baseline, Weeks 4, 8 and 12

• Core Study Part I: CFB in ACR Component: 66 Swollen Joint Count (SJC)

  Baseline, Weeks 4, 8 and 12

• Core Study Part I: CFB in the 28 TJC

  Baseline, Weeks 4, 8 and 12

Study Arms (2)

Canakinumab

EXPERIMENTAL

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.

Drug: Canakinumab

Placebo

PLACEBO COMPARATOR

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.

Drug: Canakinumab; Drug: Placebo

Interventions

Canakinumab DRUG

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

Also known as: Ilaris

Canakinumab; Placebo

Placebo DRUG

Matching placebo administered subcutaneously.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written and signed consent from the participant to take part in the study
• Men and women aged ≥ 18 years and ≤ 75 years
• Fulfilment of AOSD classification criteria (according to Yamaguchi et al, J. Rheumatology, 1992)
• Disease activity based on Disease Activity Score 28 (DAS28) of ≥3.2 at screening
• At least 4 painful and 4 swollen joints at screening and baseline (of the 28 joints according to DAS28)
• If undergoing treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable dose for at least 4 weeks prior to randomisation
• 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
• If undergoing treatment with conventional disease-modifying anti-rheumatic drugs (DMARD), stable dose for at least 3 months prior to randomisation
• 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
• In participants of reproductive age, use of an effective method of contraception as well as negative pregnancy test prior to the study commencing.

You may not qualify if:

• Previous treatment with the study drug with repeated administration of canakinumab
• 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)
• Presence of another, serious chronic-inflammatory disease
• Positive hepatitis B antigen (HBsAg), hepatitis C antibodies and/or human immunodeficiency virus (HIV) antibodies.
• Presence of a relevant, active infection or other diseases, which entail a tendency towards infection
• Positive screening for latent tuberculosis, in accordance with usual local practice
• Raised liver count (raised bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3-fold the normal range)
• Serum-creatinine concentration \>1.5 milligrams per deciliter (mg/dL)
• Inadequate haematological findings (hemoglobin \[Hb\] ≤ 10 grams per deciliter (g/dL), neutrophils ≤2,500/microliter (µl) and thrombocytes ≤100,000/µl)
• Simultaneous participation in any other interventional clinical study within the last 30 days preceding the commencement of the study
• 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
• Relevant cardiac or pulmonary disorders
• Severe intercurrent neurological or psychiatric disorders
• Macrophage activation syndrome (MAS) as part of previous treatment with IL-1 blockade (e.g. anakinra, rilonacept)
• Vaccination with a live vaccine within 3 months before the baseline

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (14)

Charité Campus Mitte

Berlin, 10117, Germany

Location

Immanuel Krankenhaus Berlin

Berlin, 13125, Germany

Location

Med. Klinik I für Innere Medizin Köln

Cologne, 50937, Germany

Location

Universität Erlangen

Erlangen, 91054, Germany

Location

Kliniken Essen-Süd/Krankenhaus St. Josef

Essen, 45239, Germany

Location

Universitätsklinikum der J.W. Goethe-Universität Frankfurt

Frankfurt A. M., 60590, Germany

Location

Asklepios Klinikum Hamburg Altona

Hamburg, 22763, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätskrankenhaus Schleswig Holstein

Kiel, 24105, Germany

Location

Klinikum der Universität München

München, 80336, Germany

Location

Klinikum Südstadt Rostock

Rostock, 18059, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Fachkrankenhaus

Vogelsang, 39245, Germany

Location

Related Publications (1)

• 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.

  PMID: 26589963 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

canakinumab

Limitations and Caveats

The study terminated prior to the planned completion date due to recruitment issues because of the marketing authorization of the study drug.

Results Point of Contact

• Title: Prof. Dr Eugen Feist
• Organization: Helios Fachklinik Vogelsang-Gommern GmbH, Germany

eugen.feist@charite.de

+49 30 450 513 192

Study Officials

• Eugen Feist, Prof. Dr.

  Charité University Berlin Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr Eugen Feist

Study Record Dates

• First Submitted: July 29, 2014
• First Posted: July 30, 2014
• Study Start: June 21, 2012
• Primary Completion: May 5, 2018
• Study Completion: May 5, 2018
• Last Updated: August 7, 2020
• Results First Posted: August 7, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (14)