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Long-term Efficacy, Safety and Tolerability of ACZ885 in Patients With Rheumatoid Arthritis

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Canakinumab
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Anti-interleukin-1 beta, ACZ885

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients (male and non-pregnant, non-lactating females) who completed the core CACZ885A2204, CACZ885A2206, or CACZ885A2207 study without serious or severe drug-related adverse effects may enter the extension study upon signing informed consent

Exclusion Criteria:

  • Patients for whom continued treatment in the extension is not considered appropriate by the treating physician.
  • Patients who were non-compliant or who demonstrated a major protocol violation in the core study.
  • Patients who did not complete / discontinued from the core study.
  • Patients with drug related serious adverse events or severe adverse events.

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site
  • Novartis Investigator Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Canakinumab

Arm Description

Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events and Serious Adverse Events
Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

Secondary Outcome Measures

Percentage of Participants Who Achieved American College of Rheumatology Response 20 (ACR20)
ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Percentage of Participants Who Achieved American College of Rheumatology Response 50 (ACR50)
ACR50 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Percentage of Participants Who Achieved American College of Rheumatology Response 70 (ACR70)
ACR70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 70% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Percentage of Participants Who Achieved American College of Rheumatology Response 90 (ACR90)
ACR90 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 90% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Percentage of Participants Achieving Clinical Remission Based on Disease Activity Score (DAS) 28 and Simplified Disease Activity Index (SDAI)
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 ≤ (less than or equal to) 2.6 or SDAI ≤ (less than or equal to) to3.3.
Change From Baseline in ACR Component : Swollen Joint Count Through Week 54
Synovial fluid and/or soft tissue swelling but not bony overgrowth represents a positive result for swollen joint count. Joint counts were performed according to the visit schedule by the physician or by well trained personnel. Whenever possible, the same evaluator performed these assessments at all visits. The following 28 joints were assessed for tenderness and swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). If the number of joints for which data were available (e.g., S) was less than 28, the number of swollen joints (e.g., s) was scaled up proportionately (i.e., 28*(s/S)).
Change From Baseline in ACR Component : Tender Joint Count Through Week 54
The ACR tender joint count (28 joints) was done by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination. Joint counts were performed according to the visit schedule by the physician or by well trained personnel. The following 28 joints were assessed for tenderness and swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). If the number of joints for which data were available (e.g., T) was less than 28, the number of tender joints (e.g., t) was scaled up proportionately (i.e., 28*(t/T)).
Change From Baseline in ACR Component: Patient's Assessment of Pain Activity Through Week 54
ACR components included patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain).
Change From Baseline in ACR Component:- Patient's Global Assessment of Disease Activity Through Week 24
ACR component included patient's global assessment (PtGA) of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor).
Change From Baseline in ACR Component : Physician's Global Assessment of Disease Activity Through Week 54
ACR component included physician's global assessment (PGA) of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis).
Change From Baseline in ACR Component : C-reactive Protein (CRP) Through Week 54
Blood for this assessment was obtained in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. Assessment was performed by the central laboratory.
Core Study Change From Baseline in Edema, Erosion and Synovitis Score Was Assessed at Week 18
The MRI scan was scored according to OMERACT RAMRIS system. Erosions were scored on a scale of 0-10 per site, the scale is 0-10, based on the proportion of eroded bone compared to the "assessed bone volume", judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2; 11-20%, etc. For long bones, the "assessed bone volume" is from the articular surface (or its best estimated position if absent) to a depth of 1 cm, and in carpal bones it is the whole bone. Edema were scored on a scale of 0-10 per site, the scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%; and Synovitis on a scale of 0-3 per site, the scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment.
Core Study Change From Baseline in Van Der Heijde Modified Total Sharp Score Was Assessed for Erosion Score at Week 18
Digital radiographic (X-ray) assessment of 16 joints and bones in the hand and wrist were assessed for and 15 joints in the hand and wrist were assessed for joint space narrowing. Scoring of the radiographic assessment was according to modified Sharp/van der Heijde score. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.
Core Study Change From Baseline in Van Der Heijde Modified Total Sharp Score Was Assessed for Joint Narrowing Score at Week 18
Digital radiographic (X-ray) assessment of 16 joints and bones in the hand and wrist were assessed for and 15 joints in the hand and wrist were assessed for joint space narrowing. Scoring of the radiographic assessment was according to modified Sharp/van der Heijde score. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.
Core Study BMD of Total Lumbar Spine, Hip and Hand Was Assessed by DXA at Week 18
Bone Mineral Density was measured by dual-energy X-ray absorptiometry (DXA) of the hand with the most swollen wrist (determined at baseline by the investigator site), lumbosacral (LS) spine and hip, in selected study sites. The reading of the DXA scans were performed centrally, by an experienced independent reader who was blinded to clinical details and MRI findings.
Number of Subjects With Long-term Immunogenicity
Anti-ACZ885 antibodies concentrations were assessed in serum. All blood samples were taken by direct venipuncture in a forearm vein. Immunogenicity was analyzed by BIAcore technology. immunogenicity was categorized as NO (no immunogenicity), BLQ (positive immunogenicity < LLOQ (not quantifiable)), and ALQ (positive immunogenicity > LLOQ (quantifiable).
Pharmacokinetic (PK) of ACZ885: Systemic Clearance From Serum Following Intravenous Administration (CL) in Participants
The PK parameter were evaluated from serum concentration-time data using mixed effects modeling approach.
Pharmacokinetic (PK) of ACZ885: Volume Distribution From Serum Following Intravenous Administration (CL) in Participants
The PK parameter were evaluated from serum concentration-time data using mixed effects modeling approach.
Health-Related Quality of Life (HRQoL) Accessed by Short Form (SF) -36 Score (Physical Component)
The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score.The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
Health-Related Quality of Life (HRQoL) Accessed by Health Assessment Questionnaire (HAQ) Score
HAQ assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3 where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question.A decrease from baseline indicates improvement for HAQ-DI. The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. The HAQ-DI total score ranges from 0 to 3, with higher scores indicating greater disability.
Health-Related Quality of Life (HRQoL) Accessed by Short Form (SF) -36 Score (Mental Component)
The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score.The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.

Full Information

First Posted
November 5, 2007
Last Updated
June 17, 2021
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00554606
Brief Title
Long-term Efficacy, Safety and Tolerability of ACZ885 in Patients With Rheumatoid Arthritis
Official Title
A 54-week, Phase II, Multi-center, Open-label Extension Study to Evaluate the Efficacy, Safety and Tolerability of ACZ885 (Anti-interleukin-1B Monoclonal Antibody) in Patients With Rheumatoid Arthritis
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
October 11, 2007 (Actual)
Primary Completion Date
August 13, 2009 (Actual)
Study Completion Date
August 13, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will assess the long-term safety and tolerability of ACZ885 in patients with rheumatoid arthritis, as well as long-term efficacy, long-term preservation and/or improvement of joint structure and bone mineral density, and long term maintenance of health-related quality of life.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, Anti-interleukin-1 beta, ACZ885

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
115 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Canakinumab
Arm Type
Experimental
Arm Description
Participants received one single dose of 600 mg canakinumab via intravenous infusion on Day 1 and thereafter every 6 weeks until completion of the 54-week treatment period.
Intervention Type
Drug
Intervention Name(s)
Canakinumab
Other Intervention Name(s)
ACZ885
Intervention Description
Canakinumab
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events and Serious Adverse Events
Description
Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Time Frame
From start of the study up to End Of Study (Week 60)
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieved American College of Rheumatology Response 20 (ACR20)
Description
ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Percentage of Participants Who Achieved American College of Rheumatology Response 50 (ACR50)
Description
ACR50 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Percentage of Participants Who Achieved American College of Rheumatology Response 70 (ACR70)
Description
ACR70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 70% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Percentage of Participants Who Achieved American College of Rheumatology Response 90 (ACR90)
Description
ACR90 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 90% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Percentage of Participants Achieving Clinical Remission Based on Disease Activity Score (DAS) 28 and Simplified Disease Activity Index (SDAI)
Description
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 ≤ (less than or equal to) 2.6 or SDAI ≤ (less than or equal to) to3.3.
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Change From Baseline in ACR Component : Swollen Joint Count Through Week 54
Description
Synovial fluid and/or soft tissue swelling but not bony overgrowth represents a positive result for swollen joint count. Joint counts were performed according to the visit schedule by the physician or by well trained personnel. Whenever possible, the same evaluator performed these assessments at all visits. The following 28 joints were assessed for tenderness and swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). If the number of joints for which data were available (e.g., S) was less than 28, the number of swollen joints (e.g., s) was scaled up proportionately (i.e., 28*(s/S)).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Change From Baseline in ACR Component : Tender Joint Count Through Week 54
Description
The ACR tender joint count (28 joints) was done by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination. Joint counts were performed according to the visit schedule by the physician or by well trained personnel. The following 28 joints were assessed for tenderness and swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2). If the number of joints for which data were available (e.g., T) was less than 28, the number of tender joints (e.g., t) was scaled up proportionately (i.e., 28*(t/T)).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Change From Baseline in ACR Component: Patient's Assessment of Pain Activity Through Week 54
Description
ACR components included patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Change From Baseline in ACR Component:- Patient's Global Assessment of Disease Activity Through Week 24
Description
ACR component included patient's global assessment (PtGA) of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Change From Baseline in ACR Component : Physician's Global Assessment of Disease Activity Through Week 54
Description
ACR component included physician's global assessment (PGA) of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Change From Baseline in ACR Component : C-reactive Protein (CRP) Through Week 54
Description
Blood for this assessment was obtained in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. Assessment was performed by the central laboratory.
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Core Study Change From Baseline in Edema, Erosion and Synovitis Score Was Assessed at Week 18
Description
The MRI scan was scored according to OMERACT RAMRIS system. Erosions were scored on a scale of 0-10 per site, the scale is 0-10, based on the proportion of eroded bone compared to the "assessed bone volume", judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2; 11-20%, etc. For long bones, the "assessed bone volume" is from the articular surface (or its best estimated position if absent) to a depth of 1 cm, and in carpal bones it is the whole bone. Edema were scored on a scale of 0-10 per site, the scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%; and Synovitis on a scale of 0-3 per site, the scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment.
Time Frame
Baseline, Week 18
Title
Core Study Change From Baseline in Van Der Heijde Modified Total Sharp Score Was Assessed for Erosion Score at Week 18
Description
Digital radiographic (X-ray) assessment of 16 joints and bones in the hand and wrist were assessed for and 15 joints in the hand and wrist were assessed for joint space narrowing. Scoring of the radiographic assessment was according to modified Sharp/van der Heijde score. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.
Time Frame
Baseline, Week 18
Title
Core Study Change From Baseline in Van Der Heijde Modified Total Sharp Score Was Assessed for Joint Narrowing Score at Week 18
Description
Digital radiographic (X-ray) assessment of 16 joints and bones in the hand and wrist were assessed for and 15 joints in the hand and wrist were assessed for joint space narrowing. Scoring of the radiographic assessment was according to modified Sharp/van der Heijde score. The maximum number of erosions is 160 in the hands and 120 in the feet; and the maximum scores for joint space narrowing are 120 and 48, respectively. Erosions are scored 1 for a discrete interruption of the cortical surface, and scored 2-5 for a larger defect according to the surface area of the joint involved. Notably, the maximum erosion score in each joint in hands is 5, while it is 10 in the feet. For joint space narrowing, 0=normal; 1=focal or doubtful; 2=general, <50% of the original joint space; 3=general, >50% of the original joint space or subluxation; 4=ankylosis.
Time Frame
Baseline, Week 18
Title
Core Study BMD of Total Lumbar Spine, Hip and Hand Was Assessed by DXA at Week 18
Description
Bone Mineral Density was measured by dual-energy X-ray absorptiometry (DXA) of the hand with the most swollen wrist (determined at baseline by the investigator site), lumbosacral (LS) spine and hip, in selected study sites. The reading of the DXA scans were performed centrally, by an experienced independent reader who was blinded to clinical details and MRI findings.
Time Frame
Baseline, Week 18
Title
Number of Subjects With Long-term Immunogenicity
Description
Anti-ACZ885 antibodies concentrations were assessed in serum. All blood samples were taken by direct venipuncture in a forearm vein. Immunogenicity was analyzed by BIAcore technology. immunogenicity was categorized as NO (no immunogenicity), BLQ (positive immunogenicity < LLOQ (not quantifiable)), and ALQ (positive immunogenicity > LLOQ (quantifiable).
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Pharmacokinetic (PK) of ACZ885: Systemic Clearance From Serum Following Intravenous Administration (CL) in Participants
Description
The PK parameter were evaluated from serum concentration-time data using mixed effects modeling approach.
Time Frame
Pre dose at Day 1, Pre dose at week 6, 12, 18, 24, 30, 36, 42, 48, follow up and at study completion (week 60)
Title
Pharmacokinetic (PK) of ACZ885: Volume Distribution From Serum Following Intravenous Administration (CL) in Participants
Description
The PK parameter were evaluated from serum concentration-time data using mixed effects modeling approach.
Time Frame
Pre dose at Day 1, Pre dose at week 6, 12, 18, 24, 30, 36, 42, 48, follow up and at study completion (week 60)
Title
Health-Related Quality of Life (HRQoL) Accessed by Short Form (SF) -36 Score (Physical Component)
Description
The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score.The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Health-Related Quality of Life (HRQoL) Accessed by Health Assessment Questionnaire (HAQ) Score
Description
HAQ assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions. The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3 where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question.A decrease from baseline indicates improvement for HAQ-DI. The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. The HAQ-DI total score ranges from 0 to 3, with higher scores indicating greater disability.
Time Frame
Baseline Up to End Of Study (up to week 60)
Title
Health-Related Quality of Life (HRQoL) Accessed by Short Form (SF) -36 Score (Mental Component)
Description
The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score.The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
Time Frame
Baseline Up to End Of Study (up to week 60)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients (male and non-pregnant, non-lactating females) who completed the core CACZ885A2204, CACZ885A2206, or CACZ885A2207 study without serious or severe drug-related adverse effects may enter the extension study upon signing informed consent Exclusion Criteria: Patients for whom continued treatment in the extension is not considered appropriate by the treating physician. Patients who were non-compliant or who demonstrated a major protocol violation in the core study. Patients who did not complete / discontinued from the core study. Patients with drug related serious adverse events or severe adverse events. Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
NOVARTIS
Organizational Affiliation
Novartis investigator site
Official's Role
Principal Investigator
Facility Information:
Facility Name
Novartis Investigator Site
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
Facility Name
Novartis Investigator Site
City
Tuscaloosa
State/Province
Alabama
ZIP/Postal Code
35406
Country
United States
Facility Name
Novartis Investigator Site
City
Paradise Valley
State/Province
Arizona
ZIP/Postal Code
85253
Country
United States
Facility Name
Novartis Investigator Site
City
Trumbull
State/Province
Connecticut
ZIP/Postal Code
06611
Country
United States
Facility Name
Novartis Investigator Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
Novartis Investigator Site
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Novartis Investigator Site
City
Tamarac
State/Province
Florida
ZIP/Postal Code
33321
Country
United States
Facility Name
Novartis Investigator Site
City
Rockford
State/Province
Illinois
ZIP/Postal Code
61107
Country
United States
Facility Name
Novartis Investigator Site
City
Urbandale
State/Province
Indiana
ZIP/Postal Code
50322
Country
United States
Facility Name
Novartis Investigator Site
City
Richmond Heights
State/Province
Missouri
ZIP/Postal Code
63117
Country
United States
Facility Name
Novartis Investigator Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Novartis Investigator Site
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Novartis Investigator Site
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
Facility Name
Novartis Investigator Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78704
Country
United States
Facility Name
Novartis Investigator Site
City
Carrollton
State/Province
Texas
ZIP/Postal Code
75007
Country
United States
Facility Name
Novartis Investigator Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Novartis Investigator Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Novartis Investigator Site
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75150
Country
United States
Facility Name
Novartis Investigator Site
City
Arlington
State/Province
Virginia
ZIP/Postal Code
22205
Country
United States
Facility Name
Novartis Investigator Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Novartis Investigator Site
City
Antwerpen
Country
Belgium
Facility Name
Novartis Investigator Site
City
Diepenbeek
Country
Belgium
Facility Name
Novartis Investigator Site
City
Liege
Country
Belgium
Facility Name
Novartis Investigator Site
City
Berlin
Country
Germany
Facility Name
Novartis Investigator Site
City
Hamburg
Country
Germany
Facility Name
Novartis Investigator Site
City
Hannover
Country
Germany
Facility Name
Novartis Investigator Site
City
Ratingen
Country
Germany
Facility Name
Novartis Investigator Site
City
Sendenhorst
Country
Germany
Facility Name
Novartis Investigator Site
City
Wiesbaden
Country
Germany
Facility Name
Novartis Investigator Site
City
Arenzano
State/Province
GE
Country
Italy
Facility Name
Novartis Investigator Site
City
Valeggio sul Mincio
State/Province
VR
Country
Italy
Facility Name
Novartis Investigator Site
City
Genova
Country
Italy
Facility Name
Novartis Investigator Site
City
Padova
Country
Italy
Facility Name
Novartis Investigator Site
City
Leeuwarden
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Leiden
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Venlo
Country
Netherlands
Facility Name
Novartis Investigator Site
City
Moscow
Country
Russian Federation
Facility Name
Novartis Investigator Site
City
Yaroslavl
Country
Russian Federation
Facility Name
Novartis Investigator Site
City
Yekaterinburg
Country
Russian Federation
Facility Name
Novartis Investigator Site
City
Alicante
Country
Spain
Facility Name
Novartis Investigator Site
City
Barcelona
Country
Spain
Facility Name
Novartis Investigator Site
City
Bilbao
Country
Spain
Facility Name
Novartis Investigator Site
City
Madrid
Country
Spain
Facility Name
Novartis Investigator Site
City
Santiago de Compostela
Country
Spain
Facility Name
Novartis Investigator Site
City
Sevilla
Country
Spain
Facility Name
Novartis Investigator Site
City
Valencia
Country
Spain
Facility Name
Novartis Investigator Site
City
Basel
Country
Switzerland
Facility Name
Novartis Investigator Site
City
Zurich
Country
Switzerland
Facility Name
Novartis Investigator Site
City
Istanbul
Country
Turkey
Facility Name
Novartis Investigator Site
City
Izmir
Country
Turkey
Facility Name
Novartis Investigator Site
City
Sihhiye/Ankara
Country
Turkey

12. IPD Sharing Statement

Learn more about this trial

Long-term Efficacy, Safety and Tolerability of ACZ885 in Patients With Rheumatoid Arthritis

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