Trial Outcomes & Findings for Safety and Efficacy of Intravenous ACZ885 and Oral Methotrexate Therapy in Patients With Early Rheumatoid Arthritis (NCT NCT00487825)
NCT ID: NCT00487825
Last Updated: 2012-08-01
Results Overview
A patient was considered as improved according to the ACR50 criteria if she/he had at least a 50 % improvement in both the tender and the swollen 28-joint count, and 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
78 participants
Primary outcome timeframe
6, 14, and 26 weeks of treatment
Results posted on
2012-08-01
Participant Flow
A 26-week, phase II, multi-center, randomized, double-blind, placebo-controlled study to assess the response to treatment and to determine a biomarker profile in responders to Canakinumab plus MTX as com-pared to MTX alone in early rheumatoid arthritis patients. Study starting 16-Mar 2007 and ending 19 Dec 2008.
Participant milestones
| Measure |
Canakinumab + Methotrexate
Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly.
|
Methotrexate
Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.
|
|---|---|---|
|
Overall Study
STARTED
|
52
|
26
|
|
Overall Study
COMPLETED
|
46
|
21
|
|
Overall Study
NOT COMPLETED
|
6
|
5
|
Reasons for withdrawal
| Measure |
Canakinumab + Methotrexate
Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly.
|
Methotrexate
Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
2
|
|
Overall Study
Lack of Efficacy
|
1
|
1
|
|
Overall Study
Other
|
3
|
2
|
Baseline Characteristics
Safety and Efficacy of Intravenous ACZ885 and Oral Methotrexate Therapy in Patients With Early Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Canakinumab + Methotrexate
n=52 Participants
Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly.
|
Methotrexate
n=26 Participants
Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.
|
Total
n=78 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
51.6 Years
STANDARD_DEVIATION 12.78 • n=5 Participants
|
49.7 Years
STANDARD_DEVIATION 14.15 • n=7 Participants
|
50.9 Years
STANDARD_DEVIATION 13.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6, 14, and 26 weeks of treatmentPopulation: Intent-to-treat population (ITT)
A patient was considered as improved according to the ACR50 criteria if she/he had at least a 50 % improvement in both the tender and the swollen 28-joint count, and 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))
Outcome measures
| Measure |
Canakinumab + Methotrexate
n=52 Participants
Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly.
|
Methotrexate
n=26 Participants
Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.
|
|---|---|---|
|
Response to Intravenous Canakinumab and Oral Methotrexate (MTX) Compared to MTX Alone as Determined by 50% Improvement in Symptoms According to the American College of Rheumatology Criteria (ACR50)
ACR50 6 weeks after first dosing
|
10 Participants
|
5 Participants
|
|
Response to Intravenous Canakinumab and Oral Methotrexate (MTX) Compared to MTX Alone as Determined by 50% Improvement in Symptoms According to the American College of Rheumatology Criteria (ACR50)
ACR50 14 weeks after first dosing
|
19 Participants
|
9 Participants
|
|
Response to Intravenous Canakinumab and Oral Methotrexate (MTX) Compared to MTX Alone as Determined by 50% Improvement in Symptoms According to the American College of Rheumatology Criteria (ACR50)
ACR50 26 weeks after first dosing
|
24 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: At 6 weeks, 14 weeks, and 26 weeksPopulation: Intent-to-treat population (ITT)
A patient was considered as improved according to the criteria of ACR 20 equaling at least 20%, ACR70 = 70%, and ACR90 = 90% improvement in the tender and the swollen 28-joint count, and 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))
Outcome measures
| Measure |
Canakinumab + Methotrexate
n=52 Participants
Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly.
|
Methotrexate
n=26 Participants
Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.
|
|---|---|---|
|
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
ACR20 6 weeks after first dosing
|
32 Participants
|
13 Participants
|
|
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
ACR20 14 weeks after first dosing
|
38 Participants
|
16 Participants
|
|
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
ACR20 26 weeks after first dosing
|
39 Participants
|
20 Participants
|
|
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
ACR70 6 weeks after first dosing
|
1 Participants
|
3 Participants
|
|
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
ACR70 14 weeks after first dosing
|
6 Participants
|
3 Participants
|
|
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
ACR70 26 weeks after first dosing
|
17 Participants
|
9 Participants
|
|
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
ACR90 6 weeks after first dosing
|
0 Participants
|
0 Participants
|
|
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
ACR90 14 weeks after first dosing
|
1 Participants
|
0 Participants
|
|
Response to Intravenous (IV) Canakinumab and Oral Methotrexate (MTX) Therapy (ACR20, 70, 90) Compared to MTX Alone
ACR90 26 weeks after first dosing
|
4 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: At 26 weeksPopulation: Intention to treat (ITT) population
At each visit (including baseline) the DAS28 is derived as: DAS28 = 0.56\*√ (tender28) + 0.28 \* √ (swollen28) + 0.36 \* loge(CRP+1) + 0.014\*PGDA+ 0.96; where tender28 is the tender 28-joint count, swollen28 is the swollen 28-joint count, PGDA is the patient's global assessment of disease activity. Patients can be scored on a range of 0 to 10. When current DAS \< 3.2, good response is defined as \>1.2 improvement in DAS from baseline and non-response is improvement of ≤0.6. When current DAS \>5.1, non-response is improvement of \>0.6 but ≤1.2 . All others are moderate responses.
Outcome measures
| Measure |
Canakinumab + Methotrexate
n=52 Participants
Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly.
|
Methotrexate
n=26 Participants
Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.
|
|---|---|---|
|
Percentage of Participants Achieving a Good European League Against Rheumatism (EULAR) Response (Based on the Disease Activity Score (DAS28)) at 26 Weeks
Good responders
|
46.2 Percentage of Participants
|
30.8 Percentage of Participants
|
|
Percentage of Participants Achieving a Good European League Against Rheumatism (EULAR) Response (Based on the Disease Activity Score (DAS28)) at 26 Weeks
Mild responders
|
28.8 Percentage of Participants
|
42.3 Percentage of Participants
|
|
Percentage of Participants Achieving a Good European League Against Rheumatism (EULAR) Response (Based on the Disease Activity Score (DAS28)) at 26 Weeks
Non responders
|
17.3 Percentage of Participants
|
11.5 Percentage of Participants
|
SECONDARY outcome
Timeframe: At 6 weeks, 14 weeks and 24 weeksPopulation: Intention to treat (ITT) population
At each visit (including baseline) the DAS28 and SDAI variables were derived using the following formulas: DAS28 = 0.56\*√ (tender28) + 0.28 \* √ (swollen28) + 0.36 \* loge(CRP+1) + 0.014\*PGDA+ 0.96; SDAI = tender28 + swollen28 + CRP + (PGDA / 10) + (EGDA / 10) where tender28 is the tender 28-joint count, swollen28 is the swollen 28-joint count, CRP is C-reactive protein, PGDA is the patient's global assessment of disease activity and EGDA is the physician's global assessment of disease activity. The Number of Participants in clinical remission is defined as the DAS28 ≤ 2.6 or SDAI ≤ 3.3.
Outcome measures
| Measure |
Canakinumab + Methotrexate
n=52 Participants
Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly.
|
Methotrexate
n=26 Participants
Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.
|
|---|---|---|
|
The Number of Participants in Clinical Remission Based on Disease Activity Score (DAS)28 and Simplified Disease Activity Index (SDAI)
After 6 weeks
|
6 Participants
|
3 Participants
|
|
The Number of Participants in Clinical Remission Based on Disease Activity Score (DAS)28 and Simplified Disease Activity Index (SDAI)
After 14 weeks
|
13 Participants
|
3 Participants
|
|
The Number of Participants in Clinical Remission Based on Disease Activity Score (DAS)28 and Simplified Disease Activity Index (SDAI)
After 26 weeks
|
20 Participants
|
6 Participants
|
Adverse Events
Canakinumab + Methotrexate
Serious events: 1 serious events
Other events: 36 other events
Deaths: 0 deaths
Methotrexate
Serious events: 2 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Canakinumab + Methotrexate
n=52 participants at risk
Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly.
|
Methotrexate
n=26 participants at risk
Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.
|
|---|---|---|
|
Gastrointestinal disorders
Lip oedema
|
1.9%
1/52 • 26 weeks plus a follow-up period of 3 months
|
0.00%
0/26 • 26 weeks plus a follow-up period of 3 months
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/52 • 26 weeks plus a follow-up period of 3 months
|
3.8%
1/26 • 26 weeks plus a follow-up period of 3 months
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/52 • 26 weeks plus a follow-up period of 3 months
|
3.8%
1/26 • 26 weeks plus a follow-up period of 3 months
|
Other adverse events
| Measure |
Canakinumab + Methotrexate
n=52 participants at risk
Canakinumab, human anti-interleukin-1beta monoclonal antibody plus Methotrexate (MTX). Intravenous (IV) Infusion of 600mg canakinumab on Day 1, 15 continuing every 4 weeks up to week 26. Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly.
|
Methotrexate
n=26 participants at risk
Methotrexate is given as variable dosing regimen of 7.5 mg-15 mg weekly. Intravenous (IV) Placebo Solution, given in the same mode of administration as the canakinumab solution.
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
3.8%
2/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.6%
5/52 • 26 weeks plus a follow-up period of 3 months
|
0.00%
0/26 • 26 weeks plus a follow-up period of 3 months
|
|
Gastrointestinal disorders
Diarrhoea
|
9.6%
5/52 • 26 weeks plus a follow-up period of 3 months
|
23.1%
6/26 • 26 weeks plus a follow-up period of 3 months
|
|
Gastrointestinal disorders
Dyspepsia
|
7.7%
4/52 • 26 weeks plus a follow-up period of 3 months
|
0.00%
0/26 • 26 weeks plus a follow-up period of 3 months
|
|
Gastrointestinal disorders
Nausea
|
15.4%
8/52 • 26 weeks plus a follow-up period of 3 months
|
34.6%
9/26 • 26 weeks plus a follow-up period of 3 months
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
4/52 • 26 weeks plus a follow-up period of 3 months
|
11.5%
3/26 • 26 weeks plus a follow-up period of 3 months
|
|
General disorders
Fatigue
|
13.5%
7/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
General disorders
Nodule
|
0.00%
0/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
General disorders
Oedema peripheral
|
7.7%
4/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Infections and infestations
Bronchitis
|
3.8%
2/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Infections and infestations
Influenza
|
5.8%
3/52 • 26 weeks plus a follow-up period of 3 months
|
0.00%
0/26 • 26 weeks plus a follow-up period of 3 months
|
|
Infections and infestations
Nasopharyngitis
|
11.5%
6/52 • 26 weeks plus a follow-up period of 3 months
|
19.2%
5/26 • 26 weeks plus a follow-up period of 3 months
|
|
Infections and infestations
Upper respiratory tract infection
|
7.7%
4/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Injury, poisoning and procedural complications
Fall
|
1.9%
1/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.8%
2/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.6%
5/52 • 26 weeks plus a follow-up period of 3 months
|
19.2%
5/26 • 26 weeks plus a follow-up period of 3 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.8%
2/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Nervous system disorders
Dizziness
|
7.7%
4/52 • 26 weeks plus a follow-up period of 3 months
|
15.4%
4/26 • 26 weeks plus a follow-up period of 3 months
|
|
Nervous system disorders
Headache
|
13.5%
7/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Psychiatric disorders
Depression
|
5.8%
3/52 • 26 weeks plus a follow-up period of 3 months
|
7.7%
2/26 • 26 weeks plus a follow-up period of 3 months
|
|
Psychiatric disorders
Sleep disorder
|
5.8%
3/52 • 26 weeks plus a follow-up period of 3 months
|
0.00%
0/26 • 26 weeks plus a follow-up period of 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
4/52 • 26 weeks plus a follow-up period of 3 months
|
11.5%
3/26 • 26 weeks plus a follow-up period of 3 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.6%
5/52 • 26 weeks plus a follow-up period of 3 months
|
11.5%
3/26 • 26 weeks plus a follow-up period of 3 months
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.8%
3/52 • 26 weeks plus a follow-up period of 3 months
|
3.8%
1/26 • 26 weeks plus a follow-up period of 3 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.8%
2/52 • 26 weeks plus a follow-up period of 3 months
|
11.5%
3/26 • 26 weeks plus a follow-up period of 3 months
|
|
Vascular disorders
Hypertension
|
5.8%
3/52 • 26 weeks plus a follow-up period of 3 months
|
3.8%
1/26 • 26 weeks plus a follow-up period of 3 months
|
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