Canakinumab for Treatment of Adult-onset Still's Disease (CONSIDER)

Charité University Medicine Berlin

Status and phase: Terminated; Phase 2

Conditions: Adult-Onset Still´s Disease

Treatments: Drug: Canakinumab; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02204293

CACZ885GDE01T

2011-001027-20 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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36 participants in 2 patient groups, including a placebo group

Canakinumab

Experimental group

Description:

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.

Treatment:

Drug: Canakinumab

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Canakinumab

Drug: Placebo