Clinical trial NCT02204293: Canakinumab for Treatment of Adult-onset Still's Disease
Official title: Study Protocol for a Multi-Centre, Placebo-Controlled Phase II Study of Canakinumab for the Treatment of Adult-onset Still's Disease (AOSD) Including an Open-label Long Term Extension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adult-Onset Still´s Disease
Keywords: Adult-Onset Still´s Disease
Canakinumab
Joint involvement
AOSD
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2014-07-30
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Core Study Part I: Percentage of Responders as Assessed by Disease Activity Score 28 Joints (DAS28) Score at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Core Study Part I: Change From Baseline (CFB) in Disease Activity Score 28 Joints Erythrocyte Sedimentation Rate (DAS28 [ESR]) Score
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in DAS28 C-reactive Protein (CRP) Score
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in American College of Rheumatology (ACR) Component: 68 Tender Joint Count (TJC)
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in ACR Component: 66 Swollen Joint Count (SJC)
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in the 28 TJC
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in the 28 SJC
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in ACR Component: Acute Phase Reactant CRP
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in ACR Component: Acute Phase Reactant ESR
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in Serum Ferritin Level at Week 12
timeFrame: Week 12
measure: Core Study Part I: Percentage of Responders With Fever Episodes
timeFrame: Week 12
measure: Core Study Part I: CFB in ACR Component: Physician's Global Assessment of Disease Activity Score
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Disease Activity Score
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in ACR Component: Participant's Global Assessment of Pain Score
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Core Study Part I: CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
timeFrame: Baseline, Week 12
measure: Core Study Part I: Percentage of Responders With American College of Rheumatology Response of 20 (ACR20)
timeFrame: Baseline, Week 12
measure: Core Study Part I: Percentage of Responders With ACR30
timeFrame: Baseline, Week 12
measure: Core Study Part I: Percentage of Responders With Modified ACR30
timeFrame: Baseline, Week 12
measure: Core Study Part I: Percentage of Responders With ACR50
timeFrame: Baseline, Week 12
measure: Core Study Part I: Percentage of Responders With ACR70
timeFrame: Baseline, Week 12
measure: Core Study Part I: Percentage of Responders With ACR90
timeFrame: Baseline, Week 12
measure: Core Study Part I: Percentage of Responders With European League Against Rheumatism (EULAR) Response
timeFrame: Baseline, Week 12
measure: Core Study Part I: Percentage of Responders Achieving Low Disease Activity (LDA)
timeFrame: Week 12
measure: Core Study Part I: Percentage of Responders Achieving Disease Remission and Extended Disease Remission
timeFrame: Week 12
measure: Core Study Part I: Change in Joint Mobility (Degrees of Motion) Assessed by Neutral Zero Method
timeFrame: Baseline, Week 12
measure: Core Study Part I: CFB in Medical Outcome Short Form (SF-36) Health Survey Score
timeFrame: Baseline, Week 12
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Month 27
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Campus Mitte
city: Berlin
country: Germany
facility: Immanuel Krankenhaus Berlin
city: Erlangen
country: Germany
facility: Universität Erlangen
city: Essen
country: Germany
facility: Kliniken Essen-Süd/Krankenhaus St. Josef
city: Frankfurt a. M.
country: Germany
facility: Universitätsklinikum der J.W. Goethe-Universität Frankfurt
city: Hamburg
country: Germany
facility: Asklepios Klinikum Hamburg Altona
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitätskrankenhaus Schleswig Holstein
city: Köln
country: Germany
facility: Med. Klinik I für Innere Medizin Köln
city: München
country: Germany
facility: Klinikum der Universität München
city: Rostock
country: Germany
facility: Klinikum Südstadt Rostock
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Vogelsang
country: Germany
facility: Fachkrankenhaus
Study officials:
affiliation: Charité University Berlin Germany
name: Eugen Feist, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.