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)

NCT01350804 | Completed Phase 3 Results DMC

• 2 other identifiers: CAIN457F23092011-000102-21
• Study Type: interventional
• Target: 551
• Locations: 15 countries
• Sites: 117

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; RA; ACR; inflammatory joints

Outcome Measures

Primary Outcomes (1)

• 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.

  week 24

Secondary Outcomes (11)

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

  baseline, week 24

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

  baseline, week 24

• Percentage of Participants Achieving ACR50

  week 24

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

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

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

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

Study Arms (4)

AIN457 10mg/kg - 75 mg

EXPERIMENTAL

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 10mg/kg - 150 mg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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; Biological: Placebo

Abatacept

ACTIVE COMPARATOR

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; Biological: Abatacept

Interventions

AIN457 BIOLOGICAL

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.

Also known as: Secukinumab

AIN457 10mg/kg - 150 mg; AIN457 10mg/kg - 75 mg; Abatacept; Placebo

Placebo BIOLOGICAL

Placebo was given as i.v. at baseline, week 2 and week 4, and then s.c. every 4 weeks starting at week 8.

Placebo

Abatacept BIOLOGICAL

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.

Also known as: Orencia

Abatacept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (117)

Novartis Investigative Site

Anniston, Alabama, 36207-5710, United States

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Vestavia Hills, Alabama, 35216, United States

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Freemont, California, 94538, United States

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Pomona, California, 91767, United States

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Upland, California, 91786, United States

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Van Nuys, California, 91405, United States

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Bridgeport, Connecticut, 06606, United States

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Aventura, Florida, 33180, United States

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Boca Raton, Florida, 33486, United States

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Hialeah, Florida, 33012, United States

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Miami, Florida, 33126, United States

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Orlando, Florida, 32806, United States

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Palm Harbor, Florida, 34684, United States

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Pembroke Pines, Florida, 33026, United States

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Pensacola, Florida, 32514, United States

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Plantation, Florida, 33324, United States

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Sarasota, Florida, 34239, United States

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Tampa, Florida, 33603, United States

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Coeur d'Alene, Idaho, 83814, United States

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Morton Grove, Illinois, 60053, United States

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Springfield, Illinois, 62704, United States

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Wichita, Kansas, 67214, United States

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Bowling Green, Kentucky, 42101, United States

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Lexington, Kentucky, 40615, United States

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Boston, Massachusetts, 02111, United States

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Lansing, Michigan, 48910, United States

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Eagan, Minnesota, 55121, United States

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Kansas City, Missouri, 66160-7330, United States

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Richmond Heights, Missouri, 63117, United States

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Omaha, Nebraska, 68114, United States

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Cincinnati, Ohio, 45219, United States

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Zanesville, Ohio, 43701, United States

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Oklahoma City, Oklahoma, 73103, United States

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Jackson, Tennessee, 38305, United States

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Kingsport, Tennessee, 37660, United States

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Austin, Texas, 78731, United States

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Carrollton, Texas, 75010, United States

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Dallas, Texas, 75204, United States

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Dallas, Texas, 75216, United States

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Houston, Texas, 77034, United States

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Sugar Land, Texas, 77479, United States

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Waco, Texas, 76710, United States

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Spokane, Washington, 99204, United States

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Clarksburg, West Virginia, 26301, United States

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Curitiba, Paraná, 80060-900, Brazil

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Rio de Janeiro, Rio de Janeiro, 22271-100, Brazil

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Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

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São Paulo, São Paulo, 04023-900, Brazil

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São Paulo, São Paulo, 04266-010, Brazil

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São Paulo, São Paulo, 05403-000, Brazil

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Plovdiv, Bulgaria, 4000, Bulgaria

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Plovdiv, Bulgaria, 4002, Bulgaria

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Rousse, Bulgaria, 7000, Bulgaria

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Sevlievo, Bulgaria, Bulgaria

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Sofia, Bulgaria, 1431, Bulgaria

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Sofia, Bulgaria, 1505, Bulgaria

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Sofia, Bulgaria, 1612, Bulgaria

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St. John's, Newfoundland and Labrador, A1C 5B8, Canada

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Sainte-Foy, Quebec, G1W 4R4, Canada

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Trois-Rivières, Quebec, G8Z 1Y2, Canada

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Bogotá, Cundinamarca, Colombia

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Barranquilla, Colombia

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Bogotá, 110221, Colombia

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Bruntál, Czech Republic, 792 01, Czechia

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Ostrava, Czech Republic, 772 00, Czechia

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Uherské Hradiště, Czech Republic, 686 01, Czechia

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Zlín, Czech Republic, 760 01, Czechia

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Bordeaux, 33076, France

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Cahors, 46005, France

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Montpellier, 34195, France

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Paris, 75014, France

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Toulouse, 31059, France

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Aachen, 52064, Germany

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Berlin, 10117, Germany

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Berlin, 14059, Germany

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Cologne, 50924, Germany

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Cottbus, 03042, Germany

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Erlangen, 91056, Germany

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Essen, 45276, Germany

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Gommern, 39245, Germany

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Hamburg, 22147, Germany

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Hamburg, 22415, Germany

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Leipzig, 04103, Germany

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Magdeburg, 39110, Germany

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Osnabrück, 49074, Germany

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Zerbst, 39261, Germany

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Győr, Hungary, 9023, Hungary

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Budapest, 1023, Hungary

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Budapest, 1062, Hungary

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Gyula, 5700, Hungary

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Szolnok, 5000, Hungary

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Valeggio sul Mincio, (vr), 37067, Italy

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Florence, FI, 50139, Italy

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Genova, GE, 16132, Italy

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Perugia, PG, 06100, Italy

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Siena, SI, 53100, Italy

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Mexicali, Estado de Baja California, 21100, Mexico

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Guadalajara, Jalisco, 44160, Mexico

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Mexico City, Mexico City, 06700, Mexico

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Mexico City, Mexico City, 11850, Mexico

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Monterrey, Nuevo León, 64020, Mexico

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Culiacán, Sinaloa, 80000, Mexico

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Iași, Iaşi, 700195, Romania

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Korolyov, 141060, Russia

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Moscow, 115522, Russia

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Petrozavodsk, 185019, Russia

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Saint Petersburg, 197341, Russia

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Tula, 300053, Russia

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Banská Bystrica, Slovak Republic, 975 17, Slovakia

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Piešťany, Slovakia, 92112, Slovakia

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Málaga, Andalusia, 29010, Spain

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Seville, Andalusia, 41009, Spain

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Sabadell, Barcelona, 08208, Spain

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Santander, Cantabria, 39008, Spain

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A Coruña, Galicia, 15006, Spain

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Santiago de Compostela, Galicia, 15706, Spain

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Madrid, Madrid, 28046, Spain

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Related Publications (2)

• Huang Y, Fan Y, Liu Y, Xie W, Zhang Z. Efficacy and safety of secukinumab in active rheumatoid arthritis with an inadequate response to tumor necrosis factor inhibitors: a meta-analysis of phase III randomized controlled trials. Clin Rheumatol. 2019 Oct;38(10):2765-2776. doi: 10.1007/s10067-019-04595-1. Epub 2019 May 14.

  PMID: 31087226 DERIVED

• Blanco FJ, Moricke R, Dokoupilova E, Codding C, Neal J, Andersson M, Rohrer S, Richards H. Secukinumab in Active Rheumatoid Arthritis: A Phase III Randomized, Double-Blind, Active Comparator- and Placebo-Controlled Study. Arthritis Rheumatol. 2017 Jun;69(6):1144-1153. doi: 10.1002/art.40070. Epub 2017 May 3.

  PMID: 28217871 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

secukinumab; Abatacept

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2011
• First Posted: May 10, 2011
• Study Start: September 1, 2011
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: May 23, 2016
• Results First Posted: May 23, 2016

Record last verified: 2016-05

Locations

CO (3); HU (5); FR (5); BR (6); CZ (4); IT (5); CA (3); ES (7); RO (1); BU (7); SL (2); US (44); DE (14); RU (5); ME (6)