Rheumatoid ArthritisPhase 3REASSURENCT01377012
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
A Phase 3 study testing Secukinumab (AIN457) in people with Rheumatoid Arthritis, run by Novartis Pharmaceuticals at 142 sites in 16 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Secukinumab (AIN457)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 637 participants
- Where
- 142 sitesin 16 countries
- Study dates
- 30 Aug 2011to 9 Sep 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
142 sites in 16 countries.
142 sites in 16 countries
United States39 sites
Novartis Investigative Site
Asheville, North Carolina, 28801
Novartis Investigative Site
Bowling Green, Kentucky, 42101
Novartis Investigative Site
Canton, Georgia, 30114
Novartis Investigative Site
Charlotte, North Carolina, 28210
Novartis Investigative Site
Columbia, South Carolina, 29204
Novartis Investigative Site
Dallas, Texas, 75390
Novartis Investigative Site
Durham, North Carolina, 27704
Novartis Investigative Site
Eagan, Minnesota, 55121
Novartis Investigative Site
Gallipolis, Ohio, 45631
Novartis Investigative Site
Greenville, South Carolina, 29601
Novartis Investigative Site
Hialeah, Florida, 33016
Novartis Investigative Site
Houston, Texas, 77034
Novartis Investigative Site
Houston, Texas, 77074
Novartis Investigative Site
Jackson, Tennessee, 38305
Novartis Investigative Site
Johnson City, Tennessee, 37604
Novartis Investigative Site
Kansas City, Missouri, 66160-7330
Novartis Investigative Site
Largo, Florida, 33773
Novartis Investigative Site
Las Vegas, Nevada, 89119
Novartis Investigative Site
Little Rock, Arkansas, 72205
Novartis Investigative Site
Mesa, Arizona, 85202
Novartis Investigative Site
Mesquite, Texas, 75150
Novartis Investigative Site
Miami, Florida, 33169
Novartis Investigative Site
Nashville, Tennessee, 37205
Novartis Investigative Site
Orlando, Florida, 32806
Novartis Investigative Site
Palm Harbor, Florida, 34684
Novartis Investigative Site
Paradise Valley, Arizona, 85253
Novartis Investigative Site
Peoria, Arizona, 85381
Novartis Investigative Site
Pittsburgh, Pennsylvania, 15237
Novartis Investigative Site
Portland, Oregon, 97239
Novartis Investigative Site
Salt Lake City, Utah, 84132
Novartis Investigative Site
Santa Monica, California, 90404
Novartis Investigative Site
South Miami, Florida, 33143
Novartis Investigative Site
Stanford, California, 94305
Novartis Investigative Site
Tamarac, Florida, 33321
Novartis Investigative Site
Tampa, Florida, 33612
Novartis Investigative Site
Tampa, Florida, 33614-7118
Novartis Investigative Site
Torrance, California, 90502
Novartis Investigative Site
Upland, California, 91786
Novartis Investigative Site
Wheaton, Maryland, 20902
Japan39 sites
Novartis Investigative Site
Chiba, Chiba, 260-0801
Novartis Investigative Site
Fuchū, Tokyo, 183-8524
Novartis Investigative Site
Fuji, Shizuoka, 417-0045
Novartis Investigative Site
Fukuoka, Fukuoka, 810-8563
Novartis Investigative Site
Fukuoka, Fukuoka, 813-0017
Novartis Investigative Site
Hamamatsu, Shizuoka, 430-8558
Novartis Investigative Site
Hannan, Osaka, 599-0212
Novartis Investigative Site
Hiroshima, Hiroshima, 733-0032
Novartis Investigative Site
Iizuka, Fukuoka, 820-8505
Novartis Investigative Site
Kamakura, Kanagawa, 247-8533
Novartis Investigative Site
Kawachi-Nagano, Osaka, 586-8521
Novartis Investigative Site
Kawagoe, Saitama, 350-1103
Novartis Investigative Site
Kawasaki, Kanagawa, 210-0013
Novartis Investigative Site
Kitakyushu, Fukuoka, 807-8556
Novartis Investigative Site
Kumamoto, Kumamoto, 862-0976
Novartis Investigative Site
Kurashiki, Okayama-ken, 710-0016
Novartis Investigative Site
Nagano, Nagano, 380-8582
Novartis Investigative Site
Nagasaki, Nagasaki, 852-8501
Novartis Investigative Site
Nagoya, Aichi-ken, 460-0001
Novartis Investigative Site
Nagoya, Aichi-ken, 466-8560
Novartis Investigative Site
Okayama, Okayama-ken, 700-8511
Novartis Investigative Site
Osaka, Osaka, 545-8586
Novartis Investigative Site
Sagamihara, Kanagawa, 228-8522
Novartis Investigative Site
Sapporo, Hokkaido, 060-0001
Novartis Investigative Site
Sapporo, Hokkaido, 063-0811
Novartis Investigative Site
Sasebo, Nagasaki, 857-1165
Novartis Investigative Site
Setagaya-ku, Tokyo, 156-0052
Novartis Investigative Site
Shimonoseki, Yamaguchi, 752-0976
Novartis Investigative Site
Shinjuku-ku, Tokyo, 160-0054
Novartis Investigative Site
Shinjuku-ku, Tokyo, 160-8582
Novartis Investigative Site
tabashi City, Tokyo, 174-0071
Novartis Investigative Site
Taihaku-ku, Miyagi, 982-0032
Novartis Investigative Site
Takaoka, Toyama, 933-0874
Novartis Investigative Site
Takasaki, Gunma, 370-0053
Novartis Investigative Site
Tokorozawa, Saitama, 359-1111
Novartis Investigative Site
Toyama, Toyama, 930-0138
Novartis Investigative Site
Tsukubo-gun, Okayama-ken, 701-0304
Novartis Investigative Site
Yokohama, Kanagawa, 231-8682
Novartis Investigative Site
Yotsukaidō, Chiba, 284-0003
Argentina10 sites
Novartis Investigative Site
Buenos Aires, Buenos Aires, C1114AAP
Novartis Investigative Site
Buenos Aires, Buenos Aires, C1417EYG
Novartis Investigative Site
Caba, Buenos Aires, C1181ACH
Novartis Investigative Site
Caba, Buenos Aires F.D., C1419AHN
Novartis Investigative Site
Ciudad Autonoma de Bs As, Ciudad Autonoma de Bs As, C1428AZF
Novartis Investigative Site
Córdoba, Córdoba Province, X5016KEH
Novartis Investigative Site
Lanus, Buenos Aires, B8000XAV
Novartis Investigative Site
Rosario, Santa Fe Province, S2000CFJ
Novartis Investigative Site
Rosario, Santa Fe Province, S200BHD
Novartis Investigative Site
San Miguel de Tucumán, Tucumán Province, 4000
India10 sites
Novartis Investigative Site
Ajmer, Rajasthan, 305 001
Novartis Investigative Site
Amravati, Maharashtra, 444606
Novartis Investigative Site
Bangalore, Karnataka, 560043
Novartis Investigative Site
Bangalore, Karnataka, 560054
Novartis Investigative Site
Hyderabad, Andhra Pradesh, 500004
Novartis Investigative Site
Jaipur, Rajasthan, 320013
Novartis Investigative Site
Mumbai, Maharashtra, 400 053
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110 060
Novartis Investigative Site
Pune, Maharashtra, 411 007
Novartis Investigative Site
Secunderabad, Telangana, 500003
Hungary7 sites
Novartis Investigative Site
Budapest, 1023
Novartis Investigative Site
Budapest, 1062
Novartis Investigative Site
Eger, 3300
Novartis Investigative Site
Gyula, 5700
Novartis Investigative Site
Székesfehérvár, H-8000
Novartis Investigative Site
Szolnok, 5000
Novartis Investigative Site
Veszprém, H-8200
Mexico6 sites
Novartis Investigative Site
Culiacán, Sinaloa, 80000
Novartis Investigative Site
Guadalajara, Jalisco, 44160
Novartis Investigative Site
Mexicali, Estado de Baja California, 21100
Novartis Investigative Site
Mexicali, Estado de Baja California, 21200
Novartis Investigative Site
Mexico City, Mexico City, 06700
Novartis Investigative Site
Mexico City, Mexico City, 11850
Thailand6 sites
Novartis Investigative Site
Bangkok, Bangkok, 10400
Novartis Investigative Site
Bangkok, THA, 10330
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Chiang Mai, 50200
Novartis Investigative Site
Khon Kaen, THA, 40002
Novartis Investigative Site
Songkhla, 90110
Italy5 sites
Novartis Investigative Site
Catania, CT, 95100
Novartis Investigative Site
Florence, FI, 50134
Novartis Investigative Site
Pieve di Coriano, MN, 46020
Novartis Investigative Site
Siena, SI, 53100
Novartis Investigative Site
Verona, VR, 37100
Belgium3 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Genk, 3600
Novartis Investigative Site
Ghent, 9000
Canada3 sites
Novartis Investigative Site
Sainte-Foy, Quebec, G1v 3M7
Novartis Investigative Site
St. Catharines, Ontario, L2N 7E4
Novartis Investigative Site
Winnipeg, Manitoba, R3A 1M3
Colombia3 sites
Novartis Investigative Site
Bogotá
Novartis Investigative Site
Bucaramanga, Colombia
Novartis Investigative Site
Medellín
Guatemala3 sites
Novartis Investigative Site
Guatemala City, Departamento de Guatemala, 01010
Novartis Investigative Site
Guatemala City, Departamento de Guatemala, 01011
Novartis Investigative Site
Guatemala City, Departamento de Guatemala, 01015
United Kingdom3 sites
Novartis Investigative Site
Cannock, Staffordshire, WS11 2XY
Novartis Investigative Site
Leytonstone, London, E11 1NR
Novartis Investigative Site
Salisbury, SP2 8BJ
Panama2 sites
Novartis Investigative Site
Panama City, Provincia de Panamá, 0823-01510
Novartis Investigative Site
Panama City, Provincia de Panamá
Puerto Rico2 sites
Novartis Investigative Site
Ponce, 00716
Novartis Investigative Site
San Juan, 00909
Turkey (Türkiye)1 site
Novartis Investigative Site
Ankara, Turkey, 06100
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Study of Secukinumab to Demonstrate the Efficacy at 24 Weeks and to Assess the Safety, Tolerability and Long Term Efficacy up to 2 Years in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Anti-TNFα Agents (CAIN457F2302) and a Three Year Extension Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Rheumatoid Arthritis (CAIN457F2302E1)
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.
Read the detailed description
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
- Rheumatoid Arthritis
- Being tested
- Secukinumab (AIN457), Placebo
- Keywords
- Rheumatoid Arthritis, RA, ACR, inflammatory joints
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Secukinumab (AIN457)Biological
Also called 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.
PlaceboBiological
Placebo was given as i.v. at baseline, week 2 and week 4, and then s.c. every 4 weeks starting at week 8.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 24
Extension Phase: Percentage of Patients Achieving a American College of Rheumatology Response ACR20, ACR50 and ACR70
Measured: up to week 260
Secondary outcomes (8)
Core Study: Change From Baseline and Week 24 in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)
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.
Measured: Baseline, Week 24
Core Study: Change From Baseline at Week 24 in Van Der Heijde Total Modified Sharp Score
Separate radiographs of each hand/wrist and each foot were taken at basline and Week 24. The radiographs were assessed using the van der Heijde modified Sharp score. The change in the Van der Heijde modified Sharp score is calculated against the baseline value. The total van der Heide modified Sharp score goes from 0 to 448, the bigger the change, the worse it is for the patient.
Measured: 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
The major clinical response is defined as continuous six-month period of ACR70 response during the 1 year period. ACR70 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 70% 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 ACR70 response results at week 24 used non-responder imputation.
Measured: 52 week
Extension Phase: Change in Baseline of RA Disease Activity as Measured by Disease Activity Score (DAS28)
The DAS28 score is a measure of RA disease activity calculated using variables such as swollen joint count, the Erythrocyte Sedimentation Rate (ESR) and patient reported assessment of health.
Using this data, the DAS28 calculation provides a number on a scale from 0-10 indicating the current activity of a patient's RA. A DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 score lower than 2.6.
Measured: week 260
Extension Phase: Proportion of Subjects Achieving Low Disease Activity and Good/Moderate European League Against Rheumatism (EULAR) Responses
Low Disease Activity is defined as DAS28 ≤ 3.2. EULAR good response requires an improvement of > 1.2 in the DAS28 score with a present score of ≤3.2; EULAR moderate response is defined as an improvement of >0.6 to ≤1.2 in DAS28 and a present score of ≤5.1; or an improvement of >1.2 and a present score of >3.2.
Measured: up to week 260
Extension Phase: Proportion of Subjects Achieving ACR/(EULAR) Remission
ACR/EULAR remission is defined as SDAI ≤ 3.3, where SDAI is a measure of disease activity in RA based on 28 tender and swollen joint counts, CRP, Physician and Patient's Global Assessments of Disease
Measured: up to week 260
Extension Phase: Changes in Baseline of Quality of Life (Qol) Outcomes Measured by Medical Outcome Short Form SF-36 v2
Short Form Health Survey (SF-36) consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed.
Measured: Baseline, up to week 260
Extension Phase: Immunogenicity Against Secukinumab
Measured: up to week 260
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2011 (estimated)
- Study start30 Aug 2011
- Primary completion9 Sep 2015
- Study completion9 Sep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 637 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01377012
- Sponsor's protocol ID
- CAIN457F2302/E1
- Other IDs
- 2011-000275-13
- Acronym
- REASSURE
- Status last verified
- Feb 2017
- First submitted
- 17 Jun 2011
- Last updated
- 29 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 31087226Tahir 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.
PubMed 29138986
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Study of Secukinumab to Demonstrate the Efficacy at 24 Weeks and to Assess the Safety, Tolerability and Long Term Efficacy up to 2 Years in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Anti-TNFα Agents (CAIN457F2302) and a Three Year Extension Study to Evaluate the Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Rheumatoid Arthritis (CAIN457F2302E1)
- ClinicalTrials.gov ID
- NCT01377012
- Acronym / sponsor ID
- REASSURE / CAIN457F2302/E1
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, RA, ACR, inflammatory joints
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 637 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Aug 2011 (actual)
- Primary completion
- 9 Sep 2015 (actual)
- Study completion
- 9 Sep 2015 (actual)
- First posted
- 20 Jun 2011 (estimated)
- Results
- Posted 29 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AIN457 10mg/kg-75mg | Experimental | Biological: Secukinumab (AIN457)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 |
| AIN457 10mg/kg-150mg | Experimental | Biological: Secukinumab (AIN457)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 |
| Placebo | Placebo comparator | Biological: PlaceboParticipants 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
- High sensitivity C-reactive protein (hsCRP) ≥ 10 mg/L OR Erythrocyte sedimentation rate (ESR) ≥ 28 mm/1st hr
Key exclusion criteria (4 listed)
- 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)
- Other protocol-defined inclusion/exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Secukinumab (AIN457)Also: AIN457AIN457 (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. | Biological | AIN457 10mg/kg-150mg, AIN457 10mg/kg-75mg |
| PlaceboPlacebo was given as i.v. at baseline, week 2 and week 4, and then s.c. every 4 weeks starting at week 8. | Biological | Placebo |
Primary outcome
Core Study: Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20) at Week 24
Time frame: 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.
Extension Phase: Percentage of Patients Achieving a American College of Rheumatology Response ACR20, ACR50 and ACR70
Time frame: up to week 260
8 secondary outcomes
Core Study: Change From Baseline and Week 24 in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI)
Time frame: Baseline, Week 24
Core Study: Change From Baseline at Week 24 in Van Der Heijde Total Modified Sharp Score
Time frame: 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
Time frame: 52 week
Extension Phase: Change in Baseline of RA Disease Activity as Measured by Disease Activity Score (DAS28)
Time frame: week 260
Extension Phase: Proportion of Subjects Achieving Low Disease Activity and Good/Moderate European League Against Rheumatism (EULAR) Responses
Time frame: up to week 260
Extension Phase: Proportion of Subjects Achieving ACR/(EULAR) Remission
Time frame: up to week 260
Extension Phase: Changes in Baseline of Quality of Life (Qol) Outcomes Measured by Medical Outcome Short Form SF-36 v2
Time frame: Baseline, up to week 260
Extension Phase: Immunogenicity Against Secukinumab
Time frame: up to week 260
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31087226Huang 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.
- Derived from this study: PubMed 29138986Tahir 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
142 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Secukinumab (AIN457) in people with Rheumatoid Arthritis, run by Novartis Pharmaceuticals at 142 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 142 sites in United States, Japan, Argentina, India, Hungary and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Core Study: Percentage of Participants Achieving an American College of Rheumatology Response 20 (ACR20) at Week 24 (time frame: Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01377012, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2017.