Study of Efficacy and Safety of Canakinumab in Japanese Patients With AOSD

Novartis Pharmaceuticals14 enrolled

Overview

This is a phase III study designed to provide efficacy and safety data for canakinumab administered for at least 48 weeks as subcutaneous (s.c.) injection every 4 weeks (q4wk) in Japanese patients with Adult Onset Still's Disease (AOSD). Interim analysis (IA) data at Week 28 and 48 from this study supports a registration submission of canakinumab in the indication of Adult still's disease (ASD) in Japan.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Adult Onset Still's Disease

Interventions

CanakinumabBIOLOGICAL

Provide as 150 mg/1 mL solution for subcutaneous injection and administer 4mg/kg every 4 weeks.

Eligibility

Sex: ALLMin age: 16 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study. Parent's or legal guardian's written informed consent and child's assent, if appropriate, are required before any assessment is performed for participants \< 20 years of age * Japanese male and female participants aged ≥ 16 years * Confirmed diagnosis of AOSD as per Yamaguchi criteria (Yamaguchi M, 1992) with an onset of disease ≥ 16 years of age. Yamaguchi criteria requires at least five criteria, including two major criteria and no exclusion criteria * Active disease at the time of baseline defined as follows * Fever (body temperature \> 38°C) due to AOSD for at least 1 day within 1 week before baseline * At least 2 active joints (tender or swollen) * CRP ≥ 10 mg/L Exclusion Criteria: * Pregnant or nursing (lactating) female participants, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/ mL) at screening visit. * History of significant hypersensitivity to study drug or to biologics. * History/evidence of active macrophage activation syndrome or disseminated intravascular coagulation prior to 6 months of enrollment. * With underlying metabolic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator compromises the articipant and/ or places the participant at unacceptable risk for participation in an immunomodulatory therapy. * With active or recurrent bacterial, fungal or viral infection at the time of enrollment, including participants with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection. * Participants with absolute neutrophil count \< 1500/mm3 at screening.

Locations (9)

Novartis Investigative Site

Sapporo, Hokkaido, Japan

Novartis Investigative Site

Kanazawa, Ishikawa-ken, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Iruma-gun, Saitama, Japan

Outcomes

Primary Outcomes

Proportion of participants who achieve adapted American College of Rheumatology (ACR) 30 response at Week 8

Adapted ACR30 response is defined as 30% reduction between baseline and post-baseline values in at least 3 of the 5 response variables 1 to 5 and no intermittent fever in the preceding week (variable 6), with no more than one of variables 1-5 worsening by more than 30%: 1. Physicians global assessment of disease activity 2. Participant's assessment of disease activity (PtGA) 3. Functional ability assessed using Health Assessment Questionnaire (HAQ) 4. Number of active joints (68 joints evaluated for pain/tenderness and 66 for swelling) 5. Laboratory measure of inflammation: CRP (mg/L) 6. Absence of intermittent fever in the preceding week

Time frame: Week 8

Secondary Outcomes

Proportion of participants who are able to taper corticosteroids based on success criteria at Week 28.

To evaluate ability of canakinumab to taper corticosteroids based on success criteria starting from Week 8 to Week 28

Time frame: Week 28

Proportion of participants who achieved adapted ACR 30/50/70/90/100 response criteria at Day 15 and all subsequent visits.

The adapted ACR 50, 70, 90 and 100 criteria will be used as additional efficacy assessments, i.e., an improvement ≥ 50%, ≥ 70%, ≥ 90%, or = 100% in at least 3 of 5 response variables and no intermittent fever in the preceding week (variable 6) with no more than one variable of 1-5 worsening by more than 30%.

Time frame: Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, End of Study(EOS)(up to Week 152)

Change from baseline in Systemic Feature Score (total score and each components) at Day 15 and all subsequent visits.

Systemic feature score consists of 5 clinical and 5 laboratory assessments. Clinical features include fever, rash, lymphadenopathy, hepatosplenomegaly and serositis. Laboratory features include erythrocyte sedimentation rate, C reactive protein, leucocyte count, hemoglobin level and platelet count. Each clinical and laboratory feature will be assigned a score of 1 (present) or 0 (absent):

Data from ClinicalTrials.gov

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Novartis Investigative Site

Bunkyo Ku, Tokyo, Japan

Novartis Investigative Site

Chuo Ku, Tokyo, Japan

Novartis Investigative Site

Mitaka, Tokyo, Japan

Novartis Investigative Site

Shinjuku-ku, Tokyo, Japan

Novartis Investigative Site

Chiba, Japan

Time frame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)

Absolute change from baseline in the component of adapted ACR at Day 15 and all subsequent visits: Physician's global assessment of disease activity

The physician will rate the participant's current condition on a 0-100 mm Visual Analog Scale (VAS), ranging from no disease activity (0 mm) to very severe disease activity (100 mm).

Time frame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)

Absolute change from baseline in the component of adapted ACR at Day 15 and all subsequent visits: Patient's global assessment of disease activity

The participant's assessment of disease activity will be assessed on the VAS. The VAS scale ranges from 0-100 mm, from no pain/very well (0 mm) to very severe pain/very poor (100 mm).

Time frame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)

Absolute change from baseline in the component of adapted ACR at Day 15 and all subsequent visits: Health Assessment Questionnaire

The health assessment questionnaire, HAQ©, will be used to assess physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing, arising, eating, walking, hygiene, reach, grip and usual activities. Participants choose from four response categories, ranging from 'without any difficulty' to 'unable to do'.

Time frame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)

Absolute change from baseline in the component of adapted ACR at Day 15 and all subsequent visits: Tender and swollen joint counts

Active joints are defined as joints with swelling or pain/tenderness. 68 joints will be assessed for tenderness and 66 joints for swelling.

Time frame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)

Absolute change from baseline in the component of adapted ACR at all visits: C-Reactive Protein(CRP)

CRP values were standardized to a normal range of 0 to 10 mg/L.

Time frame: Baseline, Days 3, 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, EOS(up to Week 152)

Absolute change from baseline in the component of adapted ACR at all visits: Fever assessment

The absence or presence of intermittent fever due to AOSD (oral, rectal, or axillary body temperature \> 38°C only for several hours during the day) will be assessed.

Change from baseline of corticosteroid dose at all visits after Week 8.

To evaluate ability of canakinumab to taper corticosteroids dose over time after Week 8

Time frame: Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, EOS(up to Week 152)

Presence of rash (typical/atypical) at all visits during study.

The absence or presence of skin rash will be assessed based on physical exam findings including whether it is typical or atypical.

Time frame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108, 112, 116, 120, 124, 128, 132, 136, 140, 144, 148, EOS(up to Week 152)

Change from baseline in DAS28-CRP at Day 15 and all subsequent visits.

DAS28-CRP is a composite index, validated for RA patients and takes into account the following items: Tender joint count (number of tender joints; 0-28); swollen joint count (number of swollen joints; 0-28); C-reactive protein (mg/l) and Global Health (Patient's Global Assessment of Disease Activity; from 0=best to 100=worst). Thus, given the reliability, validity, and ability of DAS28 to discriminate the severity of joint involvement, this index has been used in other rheumatic diseases characterized by RA-like poly-articular involvement. Of note, a DAS28 score \> 5.1 implies active disease, ≤3.2 low disease activity, and \<2.6 remission. Moderate/high disease activity is defined as a DAS28 higher than 3.2.

Time frame: Baseline, Day 15, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72, 84, 96, 108, 120, 132, 144, EOS(up to Week 152)

Canakinumab concentrations over time

To evaluate the pharmacokinetics (PK) of canakinumab

Time frame: Baseline, Days 3, 15, Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144

Total IL-1β (sum of IL-1β free and bound to canakinumab) level s over time

To evaluate the pharmacodynamic (PD) of canakinumab

Time frame: Baseline, Days 3, 15, Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144

Anti-canakinumab antibody identification and titer

To assess the immunogenicity of canakinumab

Time frame: Baseline, Weeks 24, 48, 72, 96, 120