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

NCT01377012 | Completed Phase 3 Results DMC

• 2 other identifiers: CAIN457F2302/E12011-000275-13
• Study Type: interventional
• Target: 637
• Locations: 16 countries
• Sites: 142

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. 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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; RA; ACR; inflammatory joints

Outcome Measures

Primary Outcomes (2)

• Core Study: Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20) at Week 24

  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

• Extension Phase: Percentage of Patients Achieving a American College of Rheumatology Response ACR20, ACR50 and ACR70

  up to week 260

Secondary Outcomes (8)

• Core Study: Change From Baseline and Week 24 in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)

  Baseline, Week 24

• Core Study: Change From Baseline at Week 24 in Van Der Heijde Total Modified Sharp Score

  Week 24

• Core Study Percentage of Patients Achieving Major Clinical Response (Continuous Six-month Period of ACR70 Response During the 1 Year Period) at Week 52

  52 week

• Extension Phase: Change in Baseline of RA Disease Activity as Measured by Disease Activity Score (DAS28)

  week 260

• Extension Phase: Proportion of Subjects Achieving Low Disease Activity and Good/Moderate European League Against Rheumatism (EULAR) Responses

  up to week 260

Study Arms (3)

AIN457 10mg/kg-75mg

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: Secukinumab (AIN457)

AIN457 10mg/kg-150mg

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: Secukinumab (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: Placebo

Interventions

Secukinumab (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: AIN457

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

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

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 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)

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (142)

Novartis Investigative Site

Mesa, Arizona, 85202, United States

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Paradise Valley, Arizona, 85253, United States

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Peoria, Arizona, 85381, United States

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Little Rock, Arkansas, 72205, United States

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Santa Monica, California, 90404, United States

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Stanford, California, 94305, United States

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Torrance, California, 90502, United States

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Upland, California, 91786, United States

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Hialeah, Florida, 33016, United States

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Largo, Florida, 33773, United States

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Miami, Florida, 33169, 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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South Miami, Florida, 33143, United States

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Tamarac, Florida, 33321, United States

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Tampa, Florida, 33612, United States

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Tampa, Florida, 33614-7118, United States

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Canton, Georgia, 30114, United States

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Bowling Green, Kentucky, 42101, United States

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Wheaton, Maryland, 20902, 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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Las Vegas, Nevada, 89119, United States

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Asheville, North Carolina, 28801, United States

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Charlotte, North Carolina, 28210, United States

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Durham, North Carolina, 27704, United States

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Gallipolis, Ohio, 45631, United States

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Portland, Oregon, 97239, United States

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Pittsburgh, Pennsylvania, 15237, United States

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Columbia, South Carolina, 29204, United States

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Greenville, South Carolina, 29601, United States

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Jackson, Tennessee, 38305, United States

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Johnson City, Tennessee, 37604, United States

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Nashville, Tennessee, 37205, United States

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Dallas, Texas, 75390, United States

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Houston, Texas, 77034, United States

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Houston, Texas, 77074, United States

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Mesquite, Texas, 75150, United States

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Salt Lake City, Utah, 84132, United States

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Buenos Aires, Buenos Aires, C1114AAP, Argentina

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Buenos Aires, Buenos Aires, C1417EYG, Argentina

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Caba, Buenos Aires, C1181ACH, Argentina

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Lanús, Buenos Aires, B8000XAV, Argentina

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Caba, Buenos Aires F.D., C1419AHN, Argentina

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Ciudad Autonoma de Bs As, Ciudad Autonoma de Bs As, C1428AZF, Argentina

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Córdoba, Córdoba Province, X5016KEH, Argentina

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Rosario, Santa Fe Province, S2000CFJ, Argentina

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Rosario, Santa Fe Province, S200BHD, Argentina

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San Miguel de Tucumán, Tucumán Province, 4000, Argentina

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Brussels, 1200, Belgium

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Genk, 3600, Belgium

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Ghent, 9000, Belgium

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Winnipeg, Manitoba, R3A 1M3, Canada

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St. Catharines, Ontario, L2N 7E4, Canada

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Sainte-Foy, Quebec, G1v 3M7, 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, 01010, Guatemala

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Guatemala City, Departamento de Guatemala, 01011, Guatemala

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Guatemala City, Departamento de Guatemala, 01015, Guatemala

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Budapest, 1023, Hungary

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Budapest, 1062, Hungary

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Eger, 3300, Hungary

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Gyula, 5700, Hungary

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Székesfehérvár, H-8000, Hungary

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Szolnok, 5000, Hungary

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Veszprém, H-8200, Hungary

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Hyderabad, Andhra Pradesh, 500004, India

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Bangalore, Karnataka, 560043, India

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Bangalore, Karnataka, 560054, India

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Amravati, Maharashtra, 444606, India

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Mumbai, Maharashtra, 400 053, India

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Pune, Maharashtra, 411 007, India

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New Delhi, National Capital Territory of Delhi, 110 060, India

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Ajmer, Rajasthan, 305 001, India

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Jaipur, Rajasthan, 320013, India

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Secunderabad, Telangana, 500003, India

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Catania, CT, 95100, Italy

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Florence, FI, 50134, Italy

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Pieve di Coriano, MN, 46020, Italy

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Siena, SI, 53100, Italy

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Verona, VR, 37100, Italy

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Nagoya, Aichi-ken, 460-0001, Japan

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Nagoya, Aichi-ken, 466-8560, Japan

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Chiba, Chiba, 260-0801, Japan

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Yotsukaidō, Chiba, 284-0003, Japan

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Fukuoka, Fukuoka, 810-8563, Japan

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Fukuoka, Fukuoka, 813-0017, Japan

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Iizuka, Fukuoka, 820-8505, Japan

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Kitakyushu, Fukuoka, 807-8556, Japan

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Takasaki, Gunma, 370-0053, Japan

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Hiroshima, Hiroshima, 733-0032, Japan

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Sapporo, Hokkaido, 060-0001, Japan

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Sapporo, Hokkaido, 063-0811, Japan

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Kamakura, Kanagawa, 247-8533, Japan

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Kawasaki, Kanagawa, 210-0013, Japan

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Sagamihara, Kanagawa, 228-8522, Japan

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Yokohama, Kanagawa, 231-8682, Japan

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Kumamoto, Kumamoto, 862-0976, Japan

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Taihaku-ku, Miyagi, 982-0032, Japan

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Nagano, Nagano, 380-8582, Japan

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Nagasaki, Nagasaki, 852-8501, Japan

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Sasebo, Nagasaki, 857-1165, Japan

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Kurashiki, Okayama-ken, 710-0016, Japan

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Okayama, Okayama-ken, 700-8511, Japan

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Tsukubo-gun, Okayama-ken, 701-0304, Japan

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Hannan, Osaka, 599-0212, Japan

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Kawachi-Nagano, Osaka, 586-8521, Japan

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Osaka, Osaka, 545-8586, Japan

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Kawagoe, Saitama, 350-1103, Japan

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Tokorozawa, Saitama, 359-1111, Japan

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Fuji, Shizuoka, 417-0045, Japan

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Hamamatsu, Shizuoka, 430-8558, Japan

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Fuchū, Tokyo, 183-8524, Japan

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Itabashi-ku, Tokyo, 174-0071, Japan

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Setagaya-ku, Tokyo, 156-0052, Japan

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Shinjuku-ku, Tokyo, 160-0054, Japan

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Shinjuku-ku, Tokyo, 160-8582, Japan

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Takaoka, Toyama, 933-0874, Japan

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Toyama, Toyama, 930-0138, Japan

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Shimonoseki, Yamaguchi, 752-0976, Japan

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Mexicali, Estado de Baja California, 21100, Mexico

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Mexicali, Estado de Baja California, 21200, 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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Culiacán, Sinaloa, 80000, Mexico

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Panama City, Provincia de Panamá, 0823-01510, Panama

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Panama City, Provincia de Panamá, Panama

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Ponce, 00716, Puerto Rico

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San Juan, 00909, Puerto Rico

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Bangkok, Bangkok, 10400, Thailand

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Bangkok, THA, 10330, Thailand

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Khon Kaen, THA, 40002, Thailand

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Bangkok, 10400, Thailand

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Chiang Mai, 50200, Thailand

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Songkhla, 90110, Thailand

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Ankara, Turkey, 06100, Turkey (Türkiye)

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Leytonstone, London, E11 1NR, United Kingdom

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Cannock, Staffordshire, WS11 2XY, United Kingdom

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Salisbury, SP2 8BJ, United Kingdom

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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

• 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.

  PMID: 29138986 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

secukinumab

Condition Hierarchy (Ancestors)

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

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: June 17, 2011
• First Posted: June 20, 2011
• Study Start: August 30, 2011
• Primary Completion: September 9, 2015
• Study Completion: September 9, 2015
• Last Updated: March 29, 2017
• Results First Posted: March 29, 2017

Record last verified: 2017-02

Locations

CO (3); IT (5); PR (2); TH (6); JP (39); PA (2); CA (3); IN (10); US (39); GU (3); ME (6); TU (1); AR (10); GB (3); HU (7); BE (3)