Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01350804
First received: May 9, 2011
Last updated: May 4, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Rheumatoid Arthritis
Biological: AIN457
Biological: Placebo
Biological: Abatacept
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo- and Active-controlled Study of Secukinumab to Demonstrate the Efficacy at 24 Weeks and to Assess the Safety, Tolerability and Long Term Efficacy up to 1 Year in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Anti-TNFα Agents (CAIN457F2309) and A Four Year Extension Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Rheumatoid Arthritis (CAIN457F2309E1)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20). [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Disease Activity Score Utilizing CRP (DAS28-CRP) [ Time Frame: baseline, week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: baseline, week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving ACR50 [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Achieving ACR20, ACR 50 and ACR 70 - Using Non-responder Imputation [ Time Frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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). The ACR20, ACR50 and ACR70 response results from baseline up to week 52 were based on observed data, i.e. without imputation.

  • Change From Baseline in HAQ-DI - Using Mixed Model Repeated Measures (MMRM) [ Time Frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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. The HAQ-DI results from baseline up to week 52 were based on observed data, i.e. without imputation.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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. The DAS28-CRP results from baseline up to week 52 were based on observed data, i.e. without imputation.

  • Change From Baseline in hsCRP - Observed Data [ Time Frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) - Observed Data [ Time Frame: baseline, weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 ] [ Designated as safety issue: No ]
    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.


Enrollment: 551
Study Start Date: September 2011
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AIN457 10mg/kg - 75 mg
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
Biological: AIN457
AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL-17). AIN457 was given as i.v. (10mg/kg) at baseline, week 2 and week 4, and then s.c. (75 or 150mg) every 4 weeks starting at week 8.
Other Name: Secukinumab
Experimental: AIN457 10mg/kg - 150 mg
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
Biological: AIN457
AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL-17). AIN457 was given as i.v. (10mg/kg) at baseline, week 2 and week 4, and then s.c. (75 or 150mg) every 4 weeks starting at week 8.
Other Name: Secukinumab
Placebo Comparator: Placebo
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.
Biological: AIN457
AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL-17). AIN457 was given as i.v. (10mg/kg) at baseline, week 2 and week 4, and then s.c. (75 or 150mg) every 4 weeks starting at week 8.
Other Name: Secukinumab
Biological: Placebo
Placebo was given as i.v. at baseline, week 2 and week 4, and then s.c. every 4 weeks starting at week 8.
Active Comparator: Abatacept
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).
Biological: AIN457
AIN457 (Secukinumab) is a human monoclonal antibody. Secukinumab binds and reduces the activity of Interleukin 17 (IL-17). AIN457 was given as i.v. (10mg/kg) at baseline, week 2 and week 4, and then s.c. (75 or 150mg) every 4 weeks starting at week 8.
Other Name: Secukinumab
Biological: Abatacept
Abatacept (from 500 to 1000 mg i.v. based on weight) was given as i.v. at baseline, weeks 2 and 4, and then every 4 weeks starting at week 8.
Other Name: Orencia

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01350804

  Show 117 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01350804     History of Changes
Obsolete Identifiers: NCT01640938
Other Study ID Numbers: CAIN457F2309  2011-000102-21 
Study First Received: May 9, 2011
Results First Received: January 26, 2016
Last Updated: May 4, 2016
Health Authority: Bulgaria: Bulgarian Drug Agency
Brazil: National Health Surveillance Agency
Canada: Health Canada
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Germany: Paul-Ehrlich-Institut
Hungary: National Institute of Pharmacy
Mexico: Federal Commission for Sanitary Risks Protection
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Slovakia: State Institute for Drug Control

Keywords provided by Novartis:
Rheumatoid Arthritis
RA
ACR
inflammatory joints

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Abatacept
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 02, 2016