Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy of Secukinumab (AIN457) in Patients With Active Rheumatoid Arthritis (RA) and an Inadequate Response to Anti-Tumor Necrosis Factor α (Anti-TNFα) Agents (CAIN457F2309 and CAIN457F2309E1)

Novartis Pharmaceuticals551 enrolled

Overview

The core and extension studies assessed the safety and efficacy of secukinumab when added to a background therapy in patients with active rheumatoid arthritis who are intolerant to or have had an inadequate response to anti-TNF-α agents. Patients received either secukinumab, placebo or abatacept (active comparator). The core study was completed. However, the extension study was prematurely terminated after the primary endpoint analysis of the core study at week 24 had demonstrated numerically higher efficacy for the active comparator abatacept compared to secukinumab.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

551

Conditions

Rheumatoid Arthritis

Interventions

AIN457

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or non-pregnant, non-lactating female patients * Presence of RA classified by ACR 2010 revised criteria for at least 3 months before screening * At Baseline: Disease activity criteria defined by \>= 6 tender joints out of 68 and \>= 6 swollen joints out of 66 WITH at least 1 of the following at screening: * Anti-Cyclic Citrullinated Peptide (Anti-CCP) antibodies positive OR * Rheumatoid Factor positive AND WITH at least 1 of the following at screening: * High sensitivity C-Reactive Protein (hsCRP) \>= 10 mg/L OR * Erythrocyte Sedimentation Rate (ESR) \>= 28 millimeter (mm)/1st hour * Patients must have been taking at least one anti-TNF-α agent given at an approved dose for at least 3 months before randomization and have experienced an inadequate response to treatment or have been intolerant to at least one administration of an anti-TNF-α agent * Patients must be taking MTX or any other DMARD (but not more than 1 DMARD) for at least 3 months before randomization and have to be on a stable dose at least 4 weeks before randomization (7.5 to 25 mg/week for MTX or other DMARD at maximum tolerated dose) Exclusion Criteria: * Chest x-ray with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician * RA patients functional status class IV according to the ACR 1991 revised criteria * Patients who have ever received biologic immunomodulating agents except for those targeting TNFα * Previous treatment with any cell-depleting therapies Other protocol-defined inclusion/exclusion criteria may apply.

Locations (117)

Novartis Investigative Site

Anniston, Alabama, United States

Novartis Investigative Site

Vestavia Hills, Alabama, United States

Novartis Investigative Site

Freemont, California, United States

Novartis Investigative Site

Pomona, California, United States

Novartis Investigative Site

Upland, California, United States

Outcomes

Primary Outcomes

Percentage of Participants Achieving an 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). The ACR20 response results at week 24 used non-responder imputation.

Time frame: week 24

Secondary Outcomes

Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP)

The DAS28 is a measure of disease activity in RA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient's Global Assessment of Disease Activity. A DAS28 score greater than 5.1 implies active disease, equal to or less than 3.2 low disease activity, and less than 2.6 remission. A negative change from baseline indicates improvement.

Time frame: baseline, week 24

Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)

The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement.

Time frame: baseline, week 24

Percentage of Participants Achieving 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). The ACR50 response results at week 24 used non-responder imputation.

Time frame: week 24

Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation

ACR20, ACR 50 and ACR 70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20%, 50% and/or 70% improvement, respectively, 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, weeks 1, 2, 4, 8, 12, 16, 20 and 24

Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Observed Data

Time frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM)

The HAQ-DI, assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement.

Time frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24

Change From Baseline in HAQ-DI - Observed Data

Time frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Using MMRM

Time frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24

Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) - Observed Data

Time frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52

Change From Baseline in hsCRP - Observed Data

Blood samples were obtained to identify the presence of inflammation, to determine its severity and to monitor response to treatment. A negative change from baseline indicates improvement. The hsCRP results from baseline up to week 52 were based on observed data, i.e. without imputation.

Time frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data

Blood samples were obtained to monitor disease activity and response to treatment. A negative change from baseline indicates improvement. The ESR results from baseline up to week 52 were based on observed data, i.e. without imputation.

Time frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52