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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00554606
• Other study ID #: CACZ885A2211
• Status: Completed
• Phase: Phase 2
• Start date: October 11, 2007
• Est. completion date: August 13, 2009

Study information

• Verified date: June 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: August 13, 2009
• Est. primary completion date: August 13, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Canakinumab
Canakinumab

Locations

Country	Name	City	State
Belgium	Novartis Investigator Site	Antwerpen
Belgium	Novartis Investigator Site	Diepenbeek
Belgium	Novartis Investigator Site	Liege
Germany	Novartis Investigator Site	Berlin
Germany	Novartis Investigator Site	Hamburg
Germany	Novartis Investigator Site	Hannover
Germany	Novartis Investigator Site	Ratingen
Germany	Novartis Investigator Site	Sendenhorst
Germany	Novartis Investigator Site	Wiesbaden
Italy	Novartis Investigator Site	Arenzano	GE
Italy	Novartis Investigator Site	Genova
Italy	Novartis Investigator Site	Padova
Italy	Novartis Investigator Site	Valeggio sul Mincio	VR
Netherlands	Novartis Investigator Site	Leeuwarden
Netherlands	Novartis Investigator Site	Leiden
Netherlands	Novartis Investigator Site	Venlo
Russian Federation	Novartis Investigator Site	Moscow
Russian Federation	Novartis Investigator Site	Yaroslavl
Russian Federation	Novartis Investigator Site	Yekaterinburg
Spain	Novartis Investigator Site	Alicante
Spain	Novartis Investigator Site	Barcelona
Spain	Novartis Investigator Site	Bilbao
Spain	Novartis Investigator Site	Madrid
Spain	Novartis Investigator Site	Santiago de Compostela
Spain	Novartis Investigator Site	Sevilla
Spain	Novartis Investigator Site	Valencia
Switzerland	Novartis Investigator Site	Basel
Switzerland	Novartis Investigator Site	Zurich
Turkey	Novartis Investigator Site	Istanbul
Turkey	Novartis Investigator Site	Izmir
Turkey	Novartis Investigator Site	Sihhiye/Ankara
United States	Novartis Investigator Site	Arlington	Virginia
United States	Novartis Investigator Site	Austin	Texas
United States	Novartis Investigator Site	Carrollton	Texas
United States	Novartis Investigator Site	Dallas	Texas
United States	Novartis Investigator Site	Fort Worth	Texas
United States	Novartis Investigator Site	Huntsville	Alabama
United States	Novartis Investigator Site	Jacksonville	Florida
United States	Novartis Investigator Site	Mesquite	Texas
United States	Novartis Investigator Site	Omaha	Nebraska
United States	Novartis Investigator Site	Paradise Valley	Arizona
United States	Novartis Investigator Site	Reno	Nevada
United States	Novartis Investigator Site	Richmond Heights	Missouri
United States	Novartis Investigator Site	Rockford	Illinois
United States	Novartis Investigator Site	South Miami	Florida
United States	Novartis Investigator Site	Spokane	Washington
United States	Novartis Investigator Site	Tamarac	Florida
United States	Novartis Investigator Site	Trumbull	Connecticut
United States	Novartis Investigator Site	Tulsa	Oklahoma
United States	Novartis Investigator Site	Tuscaloosa	Alabama
United States	Novartis Investigator Site	Urbandale	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy,  Netherlands,  Russian Federation,  Spain,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From start of the study up to End Of Study (Week 60)
Secondary	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).	Baseline Up to End Of Study (up to week 60)
Secondary	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).	Baseline Up to End Of Study (up to week 60)
Secondary	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).	Baseline Up to End Of Study (up to week 60)
Secondary	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).	Baseline Up to End Of Study (up to week 60)
Secondary	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*v (tender28) + 0.28 * v (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.	Baseline Up to End Of Study (up to week 60)
Secondary	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)).	Baseline Up to End Of Study (up to week 60)
Secondary	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)).	Baseline Up to End Of Study (up to week 60)
Secondary	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).	Baseline Up to End Of Study (up to week 60)
Secondary	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).	Baseline Up to End Of Study (up to week 60)
Secondary	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).	Baseline Up to End Of Study (up to week 60)
Secondary	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.	Baseline Up to End Of Study (up to week 60)
Secondary	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.	Baseline, Week 18
Secondary	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.	Baseline, Week 18
Secondary	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.	Baseline, Week 18
Secondary	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.	Baseline, Week 18
Secondary	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).	Baseline Up to End Of Study (up to week 60)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	Baseline Up to End Of Study (up to week 60)
Secondary	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.	Baseline Up to End Of Study (up to week 60)
Secondary	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.	Baseline Up to End Of Study (up to week 60)