Efficacy at 24 Weeks and Safety, Tolerability and Long Term Efficacy up to 2 Years of Secukinumab (AIN457) in Patients With Active Rheumatoid Arthritis and an Inadequate Response to Anti-TNFα Agents

NCT ID: NCT01377012

Last Updated: 2017-03-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

637 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-30

Study Completion Date

2015-09-09

Brief Summary

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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. The core study was completed. However, the extension study was terminated early (unrelated to safety) due to the results of study AIN457F2309, which indicated the efficacy of AIN457 was not comparable to the currently available RA treatment, abatacept, thus leading to closing of the AIN457 RA program.

Detailed Description

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CAIN457F2302 (Core Study): Completed Sep 9 2015

CAIN457F2302E1 (Extension study): terminated early May 26 2015, ((unrelated to safety) due to the results of study AIN457F2309, which indicated the efficacy of AIN457 was not comparable to the currently available RA treatment, abatacept, thus leading to closing of the AIN457 RA program.

Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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AIN457 10mg/kg-75mg

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

Group Type EXPERIMENTAL

Secukinumab (AIN457)

Intervention Type 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.

AIN457 10mg/kg-150mg

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

Group Type EXPERIMENTAL

Secukinumab (AIN457)

Intervention Type 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.

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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.

Interventions

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Secukinumab (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.

Intervention Type 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.

Intervention Type BIOLOGICAL

Other Intervention Names

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AIN457

Eligibility Criteria

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Inclusion Criteria

* Male or non-pregnant, non-lactating female patients
* Presence of RA classified by American College of Rheumatology (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 (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 mm/1st hr
* 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 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 Japan only: 6 to 25 mg/week)

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 including but not limited to anti-CD20, investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Mesa, Arizona, United States

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Paradise Valley, Arizona, United States

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Peoria, Arizona, United States

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Little Rock, Arkansas, United States

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Santa Monica, California, United States

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Stanford, California, United States

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Torrance, California, United States

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Upland, California, United States

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Hialeah, Florida, United States

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Largo, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Palm Harbor, Florida, United States

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South Miami, Florida, United States

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Tamarac, Florida, United States

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Tampa, Florida, United States

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Tampa, Florida, United States

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Canton, Georgia, United States

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Bowling Green, Kentucky, United States

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Wheaton, Maryland, United States

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Eagan, Minnesota, United States

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Kansas City, Missouri, United States

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Las Vegas, Nevada, United States

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Asheville, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Gallipolis, Ohio, United States

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Portland, Oregon, United States

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Pittsburgh, Pennsylvania, United States

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Columbia, South Carolina, United States

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Greenville, South Carolina, United States

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Jackson, Tennessee, United States

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Johnson City, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Mesquite, Texas, United States

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Salt Lake City, Utah, United States

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Buenos Aires, Buenos Aires, Argentina

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Buenos Aires, Buenos Aires, Argentina

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Caba, Buenos Aires, Argentina

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Lanús, Buenos Aires, Argentina

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Caba, Buenos Aires F.D., Argentina

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Ciudad Autonoma de Bs As, Ciudad Autonoma de Bs As, Argentina

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Córdoba, Córdoba Province, Argentina

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Rosario, Santa Fe Province, Argentina

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Rosario, Santa Fe Province, Argentina

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San Miguel de Tucumán, Tucumán Province, Argentina

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Brussels, , Belgium

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Genk, , Belgium

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Ghent, , Belgium

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Winnipeg, Manitoba, Canada

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St. Catharines, Ontario, Canada

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Sainte-Foy, Quebec, Canada

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Bucaramanga, Colombia, Colombia

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Bogotá, , Colombia

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Medellín, , Colombia

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Guatemala City, Departamento de Guatemala, Guatemala

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Guatemala City, Departamento de Guatemala, Guatemala

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Guatemala City, Departamento de Guatemala, Guatemala

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Budapest, , Hungary

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Budapest, , Hungary

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Eger, , Hungary

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Gyula, , Hungary

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Székesfehérvár, , Hungary

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Szolnok, , Hungary

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Veszprém, , Hungary

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Hyderabad, Andhra Pradesh, India

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Bangalore, Karnataka, India

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Bangalore, Karnataka, India

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Amravati, Maharashtra, India

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Mumbai, Maharashtra, India

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Pune, Maharashtra, India

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New Delhi, National Capital Territory of Delhi, India

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Ajmer, Rajasthan, India

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Jaipur, Rajasthan, India

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Secunderabad, Telangana, India

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Catania, CT, Italy

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Florence, FI, Italy

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Pieve di Coriano, MN, Italy

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Siena, SI, Italy

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Verona, VR, Italy

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Nagoya, Aichi-ken, Japan

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Nagoya, Aichi-ken, Japan

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Chiba, Chiba, Japan

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Yotsukaidō, Chiba, Japan

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Fukuoka, Fukuoka, Japan

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Fukuoka, Fukuoka, Japan

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Iizuka, Fukuoka, Japan

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Kitakyushu, Fukuoka, Japan

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Takasaki, Gunma, Japan

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Hiroshima, Hiroshima, Japan

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Sapporo, Hokkaido, Japan

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Sapporo, Hokkaido, Japan

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Kamakura, Kanagawa, Japan

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Kawasaki, Kanagawa, Japan

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Sagamihara, Kanagawa, Japan

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Yokohama, Kanagawa, Japan

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Kumamoto, Kumamoto, Japan

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Taihaku-ku, Miyagi, Japan

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Nagano, Nagano, Japan

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Nagasaki, Nagasaki, Japan

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Sasebo, Nagasaki, Japan

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Kurashiki, Okayama-ken, Japan

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Okayama, Okayama-ken, Japan

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Tsukubo-gun, Okayama-ken, Japan

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Hannan, Osaka, Japan

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Kawachi-Nagano, Osaka, Japan

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Osaka, Osaka, Japan

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Kawagoe, Saitama, Japan

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Tokorozawa, Saitama, Japan

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Fuji, Shizuoka, Japan

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Hamamatsu, Shizuoka, Japan

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Fuchū, Tokyo, Japan

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Itabashi-ku, Tokyo, Japan

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Setagaya-ku, Tokyo, Japan

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Shinjuku-ku, Tokyo, Japan

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Shinjuku-ku, Tokyo, Japan

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Takaoka, Toyama, Japan

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Toyama, Toyama, Japan

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Shimonoseki, Yamaguchi, Japan

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Mexicali, Estado de Baja California, Mexico

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Mexicali, Estado de Baja California, Mexico

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Guadalajara, Jalisco, Mexico

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Mexico City, Mexico City, Mexico

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Mexico City, Mexico City, Mexico

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Culiacán, Sinaloa, Mexico

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Panama City, Provincia de Panamá, Panama

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Panama City, Provincia de Panamá, Panama

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Ponce, , Puerto Rico

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San Juan, , Puerto Rico

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Bangkok, Bangkok, Thailand

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Bangkok, THA, Thailand

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Khon Kaen, THA, Thailand

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Bangkok, , Thailand

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Chiang Mai, , Thailand

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Songkhla, , Thailand

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Ankara, Turkey, Turkey (Türkiye)

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Leytonstone, London, United Kingdom

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Cannock, Staffordshire, United Kingdom

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Salisbury, , United Kingdom

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Countries

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United States Argentina Belgium Canada Colombia Guatemala Hungary India Italy Japan Mexico Panama Puerto Rico Thailand Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 31087226 (View on PubMed)

Tahir H, Deodhar A, Genovese M, Takeuchi T, Aelion J, Van den Bosch F, Haemmerle S, Richards HB. Secukinumab in Active Rheumatoid Arthritis after Anti-TNFalpha Therapy: A Randomized, Double-Blind Placebo-Controlled Phase 3 Study. Rheumatol Ther. 2017 Dec;4(2):475-488. doi: 10.1007/s40744-017-0086-y. Epub 2017 Nov 14.

Reference Type DERIVED
PMID: 29138986 (View on PubMed)

Other Identifiers

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2011-000275-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAIN457F2302/E1

Identifier Type: -

Identifier Source: org_study_id

NCT01901900

Identifier Type: -

Identifier Source: nct_alias

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