Trial Outcomes & Findings for Safety and Efficacy of ACZ885 in Adult Patients With Established Rheumatoid Arthritis (NCT NCT00504595)

Last Updated: 2012-08-07

Results Overview

At each post-dose visit, an ACR20 responder was defined as someone who achieved at least 20% improvement in the tender and the swollen 28-joint count, and 20% improvement in at least 3 of the following 5 measures:: * Patient's pain assessment (Visual Analogue Scale (VAS) 100 mm) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein (hsCRP))

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

6 weeks and 12 weeks

Results posted on

2012-08-07

Participant Flow

Participant milestones

Participant milestones
Measure	ACZ885 (Canakinumab) : RA Patients Patients with Rheumatoid Arthritis RA taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.	ACZ885 (Canakinumab) : Healthy Volunteers Healthy Volunteers taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1	Placebo Comparator: RA Patients Rheumatoid Arthritis patients who received placebo Intravenous (IV) on Day 1, Day 15 and Day 43.	Placebo Comparator: Healthy Volunteers Healthy Volunteers who received placebo Intravenous (IV) at Day 1.
Overall Study STARTED	50	10	10	10
Overall Study COMPLETED	49	10	8	10
Overall Study NOT COMPLETED	1	0	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	ACZ885 (Canakinumab) : RA Patients Patients with Rheumatoid Arthritis RA taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.	ACZ885 (Canakinumab) : Healthy Volunteers Healthy Volunteers taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1	Placebo Comparator: RA Patients Rheumatoid Arthritis patients who received placebo Intravenous (IV) on Day 1, Day 15 and Day 43.	Placebo Comparator: Healthy Volunteers Healthy Volunteers who received placebo Intravenous (IV) at Day 1.
Overall Study Lack of Efficacy	1	0	0	0
Overall Study Other	0	0	2	0

Baseline Characteristics

Safety and Efficacy of ACZ885 in Adult Patients With Established Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ACZ885 (Canakinumab) : RA Patients n=50 Participants Patients with Rheumatoid Arthritis RA taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.	ACZ885 (Canakinumab) : Healthy Volunteers n=10 Participants Healthy Volunteers taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1	Placebo Comparator: RA Patients n=10 Participants Rheumatoid Arthritis patients who received placebo Intravenous (IV) on Day 1, Day 15 and Day 43.	Placebo Comparator: Healthy Volunteers n=10 Participants Healthy Volunteers who received placebo Intravenous (IV) at Day 1.	Total n=80 Participants Total of all reporting groups
Age Continuous	54.4 Years STANDARD_DEVIATION 13.42 • n=5 Participants	28.8 Years STANDARD_DEVIATION 7.42 • n=7 Participants	46.2 Years STANDARD_DEVIATION 12.83 • n=5 Participants	28.0 Years STANDARD_DEVIATION 5.52 • n=4 Participants	46.9 Years STANDARD_DEVIATION 16.22 • n=21 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants	2 Participants n=4 Participants	57 Participants n=21 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants	23 Participants n=21 Participants

PRIMARY outcome

Timeframe: 6 weeks and 12 weeks

Population: The Safety Analysis Set consisted of all subjects who received at least one dose of study medication. The analysis used last observation carried forward (LOCF) imputation for missing values.

Outcome measures

Outcome measures
Measure	ACZ885 (Canakinumab) : RA Patients n=50 Participants Patients with Rheumatoid Arthritis RA taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.	Placebo Comparator: RA Patients n=10 Participants Rheumatoid Arthritis patients who received placebo Intravenous (IV) on Day 1, Day 15 and Day 43.
Response to Treatment (ACR20) in Adult Patients With Established Rheumatoid Arthritis (RA) ACR20 response rate at 6 weeks	17 Participants	2 Participants
Response to Treatment (ACR20) in Adult Patients With Established Rheumatoid Arthritis (RA) ACR20 response rate at 12 weeks	27 Participants	2 Participants

SECONDARY outcome

Timeframe: 6 weeks and 12 weeks

SDAI is derived by the number of swollen joints and tender joints using the 28-joint count (tender28 and swollen28). SDAI measures the high sensitivity C-reactive protein (hsCRP) level, patient's global disease activity (PGDA) and evaluator's global disease activity (EGDA). PGDA and EGDA are measured on a 100 mm Visual Analogue Scale (VAS), ranging from no arthritis activity to maximal arthritis activity. SDAI = tender28 + swollen28 + CRP + (PGDA/10) + (EGDA/10). Lower scores indicate less disease activity.

Outcome measures

Outcome measures
Measure	ACZ885 (Canakinumab) : RA Patients n=50 Participants Patients with Rheumatoid Arthritis RA taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.	Placebo Comparator: RA Patients n=10 Participants Rheumatoid Arthritis patients who received placebo Intravenous (IV) on Day 1, Day 15 and Day 43.
Efficacy of ACZ885 by Assessing the Response to Treatment Using the Simple Disease Index (SDAI) 6 Weeks	32.623 Scores on a scale Standard Deviation 13.6218 • Interval -1.04 to 0.17	33.841 Scores on a scale Standard Deviation 15.0053 • Interval -10.75 to 4.83
Efficacy of ACZ885 by Assessing the Response to Treatment Using the Simple Disease Index (SDAI) 12 Weeks	29.163 Scores on a scale Standard Deviation 13.0927 • Interval -1.38 to -0.01	32.412 Scores on a scale Standard Deviation 12.2633 • Interval -12.41 to 2.89

SECONDARY outcome

Timeframe: 6 weeks and 12 weeks

DAS28 is derived by the number of swollen joints and tender joints using the 28-joint count (tender28 and swollen28). DAS28 measures the C-reactive protein (CRP) (in mg/L) and the patient's general health (GH). GH is measured on a 100 mm Visual Analogue Scale (VAS), ranging from no arthritis activity to maximal arthritis activity. DAS28 = 0.56\*√(tender28) + 0.28\*√(swollen28) + 0.36\*log\_e(CRP+1) + 0.014\*PGDA + 0.96. Lower scores indicate less disease activity.

Outcome measures

Outcome measures
Measure	ACZ885 (Canakinumab) : RA Patients n=50 Participants Patients with Rheumatoid Arthritis RA taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.	Placebo Comparator: RA Patients n=10 Participants Rheumatoid Arthritis patients who received placebo Intravenous (IV) on Day 1, Day 15 and Day 43.
Efficacy of ACZ885 (Canakinumab) by Assessing the Response to Treatment Using the Disease Activity Score (DAS28) 6 Weeks	5.088 Scores on a scale Standard Deviation 1.1148	5.397 Scores on a scale Standard Deviation 1.0591
Efficacy of ACZ885 (Canakinumab) by Assessing the Response to Treatment Using the Disease Activity Score (DAS28) 12 Weeks	4.853 Scores on a scale Standard Deviation 1.1879	5.400 Scores on a scale Standard Deviation 0.9321

Adverse Events

ACZ885 (Canakinumab): Healthy Volunteers

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo Comparator: Healthy Volunteers

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

ACZ885 (Canakinumab): RA Patients

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo Comparator: RA Patients

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ACZ885 (Canakinumab): Healthy Volunteers n=10 participants at risk Healthy Volunteers taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1.	Placebo Comparator: Healthy Volunteers n=10 participants at risk Healthy Volunteers who received placebo Intravenous (IV) at Day 1.	ACZ885 (Canakinumab): RA Patients n=50 participants at risk Patients with Rheumatoid Arthritis RA taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.	Placebo Comparator: RA Patients n=10 participants at risk Rheumatoid Arthritis patients who received placebo Intravenous (IV) on Day 1, Day 15 and Day 43.
Ear and labyrinth disorders Deafness Neurosensory	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	2.0% 1/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Infections and infestations Ear Infection	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	2.0% 1/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Infections and infestations Sinusitis	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	2.0% 1/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	2.0% 1/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)

Other adverse events

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 the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	ACZ885 (Canakinumab): Healthy Volunteers n=10 participants at risk Healthy Volunteers taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1.	Placebo Comparator: Healthy Volunteers n=10 participants at risk Healthy Volunteers who received placebo Intravenous (IV) at Day 1.	ACZ885 (Canakinumab): RA Patients n=50 participants at risk Patients with Rheumatoid Arthritis RA taking 600 mg of ACZ885 (Canakinumab) Intravenous (IV) on Day 1, Day 15, and Day 43.	Placebo Comparator: RA Patients n=10 participants at risk Rheumatoid Arthritis patients who received placebo Intravenous (IV) on Day 1, Day 15 and Day 43.
Ear and labyrinth disorders Vertigo	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	6.0% 3/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Gastrointestinal disorders Abdominal Pain	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	6.0% 3/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Gastrointestinal disorders Enterocolitis	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Gastrointestinal disorders Nausea	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	2.0% 1/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	20.0% 2/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Gastrointestinal disorders Toothache	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Gastrointestinal disorders Vomiting	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
General disorders Influenza Like Illness	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
General disorders Oedema Peripheral	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	2.0% 1/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Infections and infestations Acute Tonsillitis	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Infections and infestations Pyelonephritis Acute	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Infections and infestations Respiratory Tract Infection Viral	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	6.0% 3/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	20.0% 2/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Infections and infestations Upper Respiratory Tract Infection	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Infections and infestations Viral Infection	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Investigations Hepatic Enzyme Increased	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Metabolism and nutrition disorders Iron Deficiency	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	2.0% 1/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	4.0% 2/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	30.0% 3/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Nervous system disorders Headache	20.0% 2/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	6.0% 3/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	2.0% 1/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Skin and subcutaneous tissue disorders Rash	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Vascular disorders Hypertension	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	4.0% 2/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)
Vascular disorders Phlebitis	10.0% 1/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	2.0% 1/50 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)	0.00% 0/10 • 18 Weeks (12 Week treatment period + 6 Week Follow-up period)