Trial Outcomes & Findings for Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA) (NCT NCT00886769)

NCT ID: NCT00886769

Last Updated: 2017-03-29

Results Overview

Adapted ACR Pediatric 30 criteria determined responders (improved from baseline of at least 30% in at least 3 response variables 1-6 and no intermittent fever in preceding week \[variable 7\], with no more than one variable 1-6 worsening \> 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2.Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4.Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 84 participants
• Primary outcome timeframe: Baseline, Day 15, Day 29
• Results posted on: 2017-03-29

Participant Flow

Participant milestones

Measure	Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo Patients received a single dose matching placebo of canakinumab on day 1.
Overall Study STARTED	43	41
Overall Study COMPLETED	37	4
Overall Study NOT COMPLETED	6	37

Reasons for withdrawal

Measure	Canakinumab Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo Patients received a single dose matching placebo of canakinumab on day 1.
Overall Study Unsatisfactory therapeutic effect	6	37

Baseline Characteristics

Single-dose Study to Assess Efficacy of Canakinumab (ACZ885) in Patients With Active Juvenile Idiopathic Arthritis (SJIA)

Baseline characteristics by cohort

Measure	Canakinumab n=43 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=41 Participants Patients received a single dose matching placebo of canakinumab on day 1.	Total n=84 Participants Total of all reporting groups
Age, Continuous	8.3 years STANDARD_DEVIATION 5.08 • n=5 Participants	9.7 years STANDARD_DEVIATION 4.32 • n=7 Participants	9.0 years STANDARD_DEVIATION 4.75 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	23 Participants n=7 Participants	50 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	18 Participants n=7 Participants	34 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 15, Day 29

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Adapted ACR Pediatric 30 criteria determined responders (improved from baseline of at least 30% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2.Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4.Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)

Outcome measures

Measure	Canakinumab n=43 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=41 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria Day 15	83.7 percentage of participants	9.8 percentage of participants
Percentage of Patients Who Meet the Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria Day 29	79.1 percentage of participants	9.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 15, Day 29

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Adapted ACR Pediatric 50 criteria determined responders (improved from baseline of at least 50% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30%) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP (mg/L)

Outcome measures

Measure	Canakinumab n=43 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=41 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria Day 15	67.4 percentage of participants	4.9 percentage of participants
Percentage of Patients Achieving the Adapted ACR Pediatric 50 Criteria Day 29	76.7 percentage of participants	4.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 15, Day 29

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Adapted ACR Pediatric 70 criteria determined responders (improved from baseline of at least 70% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)

Outcome measures

Measure	Canakinumab n=43 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=41 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Percentage of Patients Achieving the Adapted ACR Pediatric 70 Day 15	60.5 percent of participants	2.4 percent of participants
Percentage of Patients Achieving the Adapted ACR Pediatric 70 Day 29	65.1 percent of participants	2.4 percent of participants

SECONDARY outcome

Timeframe: Baseline, Day 15, Day 29

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Adapted ACR Pediatric 90 criteria determined responders (improved from baseline of at least 90% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation CRP(mg/L)

Outcome measures

Measure	Canakinumab n=43 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=41 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Percentage of Patients Achieving the Adapted ACR Pediatric 90 Day 15	41.9 percent of participants	0 percent of participants
Percentage of Patients Achieving the Adapted ACR Pediatric 90 Day 29	46.5 percent of participants	2.4 percent of participants

SECONDARY outcome

Timeframe: baseline, Day 15, Day 29

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug.

Adapted ACR Pediatric 100 criteria determined responders (ie improved from baseline of at least 100% in at least 3 response variables 1-6 and no intermittent fever in preceding week [variable 7], with no more than one variable 1-6 worsening > 30% ) 1. Physician's Global Assessment of disease activity: 0-100 mm VAS 2. Parent/Patient's Global Assessment of Patient's overall wellbeing: 0-100mmVAS in Child Health Assessment Questionnaire (CHAQ) 3. Functional ability: CHAQ 4. Number of joints with active arthritis 5. Number of joints with limited of motion 6. Laboratory measure of inflammation

Outcome measures

Measure	Canakinumab n=43 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=41 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Percentage of Patients Achieving the Adapted ACR Pediatric 100 Day 29	32.6 percent of participants	2.4 percent of participants
Percentage of Patients Achieving the Adapted ACR Pediatric 100 Day 15	32.6 percent of participants	0 percent of participants

SECONDARY outcome

Timeframe: Baseline, Day 15

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.

CHAQ assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty' (0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.

Outcome measures

Measure	Canakinumab n=43 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=25 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS)as Part of the Childhood Health Assessment Questionnaire(CHAQ)	20.3 Units on a scale Standard Error 5.08	66.7 Units on a scale Standard Error 6.35

SECONDARY outcome

Timeframe: Baseline, Day 29

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.

CHAQ, assessed physical ability and functional status of patients as well as quality of life. The disability dimension consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). The parent's or patient's pain assessment was on VAS that was part of CHAQ. The VAS scale ranges from no pain (0 mm) to very severe pain (100 mm). Negative change indicates improvement.

Outcome measures

Measure	Canakinumab n=38 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=7 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Change in Patient's Pain Intensity as Assessed on a 100-mm Visual Analog Scale (VAS) as Part of CHAQ	20.6 Units on a scale Standard Error 5.59	62.5 Units on a scale Standard Error 9.7

SECONDARY outcome

Timeframe: Day 3

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.

Body temperature was derived from vital signs evaluation. No conversion of body temperature was performed, no matter how it was measured.

Outcome measures

Measure	Canakinumab n=43 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=38 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Percentage of Patients Who Had Body Temperature ≤ 38°C	100 Percent of participants	86.8 Percent of participants

SECONDARY outcome

Timeframe: Over 4 week study period (Baseline, Day 15, Day 29)

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Observed cases only were analyzed.

CHQ-PF50 measures HRQoL in children 5-18 years old from parent's perspective. Questionnaire completed by parent without input from patient. Total score ranges from 0-100. Increases in scores represent improved well-being in subjects as assessed by their parents. Mixed linear model on change from baseline in CHQ-PF50 score with treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Covariance analysis used a repeated measures approach, so all timepoints over time were taken into account.

Outcome measures

Measure	Canakinumab n=28 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=34 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50) CHQ-PF50 physical score	16.9 units on a scale Standard Error 3.46	4.9 units on a scale Standard Error 3.97
Change in Health-related Quality of Life (HRQoL)Over Time by Use of the Child Health Questionnaire - Parent Form (CHQ-PF50) CHQ-PF50 psychosocial score	6.2 units on a scale Standard Error 2.15	-1.1 units on a scale Standard Error 2.49

SECONDARY outcome

Timeframe: At 4 week study period

Population: The Full Analysis Set (FAS) consisted of all randomized patients who received at least one dose of study drug. Only observed cases were used in the analysis.

The disability dimension of CHAQ consisted of 20 multiple choice items about difficulty in doing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Four response categories range from 'without any difficulty'(0) to 'unable to do' (3). Mixed linear model on change from baseline in CHAQ score included treatment group, stratification factors, day of assessment and interaction between group and day as covariates. Negative change indicates improvement.

Outcome measures

Measure	Canakinumab n=43 Participants Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=41 Participants Patients received a single dose matching placebo of canakinumab on day 1.
Change in Disability Score Over Time by Use of the CHAQ	-0.8 Units on a Scale Standard Error 0.15	-0.2 Units on a Scale Standard Error 0.20

Adverse Events

Canakinumab

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Canakinumab n=43 participants at risk Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=41 participants at risk Patients received a single dose matching placebo of canakinumab on day 1.
Blood and lymphatic system disorders Leukopenia	2.3% 1/43	0.00% 0/41
Blood and lymphatic system disorders Neutropenia	2.3% 1/43	0.00% 0/41
Hepatobiliary disorders Hepatitis	2.3% 1/43	0.00% 0/41
Infections and infestations Bronchopneumonia	2.3% 1/43	0.00% 0/41
Infections and infestations Varicella	2.3% 1/43	0.00% 0/41
Infections and infestations Gastroenteritis	0.00% 0/43	2.4% 1/41
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Histiocytosis haematophagic	2.3% 1/43	2.4% 1/41
Skin and subcutaneous tissue disorders Rash maculo-papular	2.3% 1/43	0.00% 0/41

Other adverse events

Measure	Canakinumab n=43 participants at risk Patients received a single dose of subcutaneous(sc) injection of canakinumab (4 mg/kg) on Day 1. Maximal total single dose of canakinumab allowed was 300 mg. Any patient who required a dose greater than 150 mg (patients\>37.5 kg) received two sc injections.	Placebo n=41 participants at risk Patients received a single dose matching placebo of canakinumab on day 1.
Gastrointestinal disorders Diarrhoea	7.0% 3/43	2.4% 1/41
Gastrointestinal disorders Abdominal pain	4.7% 2/43	0.00% 0/41
General disorders Pyrexia	4.7% 2/43	0.00% 0/41
Infections and infestations Nasopharyngitis	7.0% 3/43	2.4% 1/41
Infections and infestations Upper respiratory tract infection	7.0% 3/43	0.00% 0/41
Infections and infestations Bronchitis	4.7% 2/43	0.00% 0/41
Nervous system disorders Headache	4.7% 2/43	2.4% 1/41

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until publication of the pooled data (i.e., data from all sites) in the clinical trial or publication of trial results in their entirety.
• Publication restrictions are in place

Restriction type: OTHER