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) (NURTURE 1)

Novartis

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Biological: AIN457; Biological: Abatacept; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01350804

2011-000102-21 (EudraCT Number)

CAIN457F2309

Details and patient eligibility

About

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.

Enrollment: 551 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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551 participants in 4 patient groups, including a placebo group

AIN457 10mg/kg - 75 mg

Experimental group

Description:

Participants received AIN457 i.v. (10 mg/kg) at Baseline (BSL), Weeks 2 and 4 then AIN457 75 mg s.c. at Week 8 and injected every 4 weeks

Treatment:

Biological: AIN457

AIN457 10mg/kg - 150 mg

Experimental group

Description:

Participants received AIN457 i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then AIN457 150 mg s.c. at Week 8 and injected every 4 weeks

Treatment:

Biological: AIN457

Placebo

Placebo Comparator group

Description:

Participants received matching placebo to AIN457 until week 16 or week 24 based on responder status (\>= 20% reduction in tender and swollen joint count). Non-responders were switched to active treatment at week 16. Responders were switched to active treatment at week 24.

Treatment:

Biological: Placebo

Biological: AIN457

Abatacept

Active Comparator group

Description:

Participants received abatacept (from 500 to 1000 mg i.v. based on weight). Participants who did not respond to abatacept at Week 16 were re-randomized 1:1 to AIN457 75mg or 150mg at week 24 (after an 8 week washout period).

Treatment:

Biological: Abatacept

Biological: AIN457