Study to Demonstrate the Efficacy, Safety and Tolerability of an Intravenous Regimen of Secukinumab Compared to Placebo in Subjects With Active axSpA

NCT04156620 | Completed Phase 3 Results FDA Drug

• 1 other identifier: CAIN457P12301
• Study Type: interventional
• Target: 527
• Locations: 18 countries
• Sites: 102

Brief Summary

The purpose of this global study was to demonstrate the efficacy, safety, and tolerability of an intravenous (i.v.) regimen of secukinumab compared to placebo in participants with active ankylosing spondylitis (AS) or non-radiographic axial spondyloarthritis (nr-axSpA ) at Week 16 despite current or previous non-steroidal anti inflammatory drugs (NSAID), disease-modifying antirheumatic drugs (DMARD) and/or anti Tumor Necrosis Factor (TNF) therapy. In addition, to further support efficacy and safety of an i.v. regimen, data was collected for up to 52 weeks of treatment.

Conditions

Ankylosing Spondylitis

Keywords

Active axSpA; Axial spondyloarthritis; non-radiographic-axSpA; nr-axSpA; ankylosing spondylitis; AS; inflammatory back pain; sacroiliitis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved an ASAS40 (Assessment of SpondyloArthritis International Society Criteria)

  ASAS40 is ≥ 40% and an absolute improvement from baseline of ≥20 units (range 0-100) in ≥ 3 of the following 4 domains: back pain \[10 cm visual analogue scale (VAS)\], patient global assessment of disease activity (10 cm VAS), physical function (BASFI; range 0-100) and inflammation (mean score of items 5 and 6 of the BASDAI; both 10 cm VAS) without any worsening in the remaining domain. ASAS consists of 6 domains (4 main and 2 additional): 1. Patient's global assessment measured on a visual analog scale (VAS); 2. Patient's assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the BAS Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the BAS Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant).

  Baseline to Week 16

Secondary Outcomes (11)

• Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) Major Improvement

  Baseline to Week 16

• The Change From Baseline in Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

  Baseline to Week 16

• Percentage of Participants Who Achieved an ASAS 5/6 (Assessment of Spondylarthritis International Society Criteria)

  Baseline to Week 16

• The Change From Baseline in Total Bath Ankylosing Spondylitis Functional Index (BASFI)

  Baseline to Week 16

• The Change From Baseline in Short Form-36 Physical Component Summary (SF-36 PCS)

  Baseline to Week 16

Study Arms (2)

Secukinumab

EXPERIMENTAL

Secukinumab intravenous (i.v.) regimen

Drug: Secukinumab

Placebo

PLACEBO COMPARATOR

Placebo intravenous (i.v.) regimen

Drug: Placebo

Interventions

Secukinumab DRUG

The subjects will receive secukinumab 6 mg/kg i.v. at randomization (Baseline (BSL) visit), followed by the administration of secukinumab 3 mg/kg i.v. every four weeks starting at Week 4 through Week 48 (exposure through Week 52)

Also known as: AIN457

Secukinumab

Placebo DRUG

The subjects will receive i.v. placebo at randomization (BSL visit), Weeks 4, 8, and 12 , followed by the administration of secukinumab 3 mg/kg i.v. at Week 16 and every four weeks through Week 48 (exposure through Week 52)

Placebo

Eligibility Criteria

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

You may qualify if:

• Subject must be able to understand and communicate with the investigator, comply with the requirements of the study. and must give written, signed and dated informed consent before any study assessment is performed
• Male and non-pregnant, non-lactating female patients ≥ 18 years of age
• Diagnosis of axSpA according to ASAS criteria
• Inflammatory back pain for at least 6 months
• Onset before 45 years of age
• For subjects with AS: Diagnosis of AS with prior documented radiologic evidence (x-ray or radiologist's report) fulfilling the Modified New York criteria for AS
• For subjects with nr-axSpA:
• X-ray of SIJ negative (centrally read) for AS by Modified NY criteria AND
• Sacroiliitis on MRI (centrally read) with ≥ 1 SpA feature OR HLA-B-27 positive with ≥2 SpA features AND
• Objective signs of inflammation at screening, evident by either MRI with SIJ inflammation (centrally read) AND / OR hsCRP \> ULN (as defined by the central lab)
• Active axial SpA assessed by BASDAI ≥4 cm (0-10 cm) at Baseline
• Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at Baseline
• Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at Baseline
• Subjects should have had inadequate response or failure to respond to at least 2 NSAIDs at an approved dose for a minimum of 4 weeks in total and a minimum of 2 weeks for each NSAID prior to randomization, or less than 4 weeks if therapy had to be withdrawn due to intolerance, toxicity or contraindications
• Subjects who are regularly taking NSAIDs (including COX-1 or COX-2 inhibitors) as part of their AS or nr-axSpA therapy are required to be on a stable dose for at least 2 weeks before randomization

You may not qualify if:

• Subjects with total ankylosis of the spine
• Chest x-ray or MRI with evidence of ongoing infectious or malignant process obtained within 3 months of screening and evaluated by a qualified physician
• Subjects taking moderate and high potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
• Presence of significant medical problems which at investigator's discretion, will prevent the subject from participating in the study, including but not limited to the following: Subjects with severely reduced kidney function (estimated glomerular filtration rate (eGFR) \<29 ml/min/1.73m2), history of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.5 mg/dl (132.6 μmol/L)
• Any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before Randomization
• Underlying conditions (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy
• Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol
• Active systemic infections during the last two weeks (exception: common cold) prior to randomization or any infection that reoccurs on a regular basis
• History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by either a positive purified protein derivative (PPD) skin test (the size of induration will be measured after 48-72 hours, and a positive result is defined as an induration of ≥ 5 mm or according to local practice/guidelines) or a positive QuantiFERON TB-Gold test as indicated in the assessment schedule in Table 8-1. Subjects with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment according to local country guidelines must have been initiated
• Past medical history of infection with HIV or hepatitis B prior to randomization or active infection or on treatment for Hepatitis C at randomization
• History of lymphoproliferative disease or any known malignancy, or history of malignancy of any organ system treated or untreated within the past 5 years, regardless of whether there is evidence of local recurrence or metastases (except for skin Bowen's disease, or basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed)
• Use or planned use of prohibited concomitant medication (see Section 6.2.2)
• Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins)
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
• History or evidence of ongoing alcohol or drug abuse, within the last six months before randomization

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (102)

Novartis Investigative Site

Irvine, California, 92604, United States

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Novartis Investigative Site

La Mesa, California, 91942, United States

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San Leandro, California, 94578, United States

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Novartis Investigative Site

Upland, California, 91786, United States

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Ocoee, Florida, 34761, United States

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Plantation, Florida, 33324, United States

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Winter Park, Florida, 32789, United States

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Bowling Green, Kentucky, 42101, United States

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Cumberland, Maryland, 21740, United States

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Grand Blanc, Michigan, 48439, United States

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Lincoln, Nebraska, 68516, United States

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Potsdam, New York, 13676, United States

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Greensboro, North Carolina, 27408, United States

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Middleburg Heights, Ohio, 44130, United States

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Portland, Oregon, 97239, United States

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Duncansville, Pennsylvania, 16635, United States

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Columbia, South Carolina, 29204, United States

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Jackson, Tennessee, 38305, United States

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Memphis, Tennessee, 38119, United States

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Katy, Texas, 77494, United States

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Spring, Texas, 77382, United States

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The Woodlands, Texas, 77380, United States

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Everett, Washington, 98208, United States

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Spokane, Washington, 99204, United States

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Novartis Investigative Site

Beckley, West Virginia, 25801, United States

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Brussels, 1070, Belgium

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Leuven, 3000, Belgium

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Vitória, Espírito Santo, 29055 450, Brazil

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Salvador, Estado de Bahia, 40150 150, Brazil

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Juiz de Fora, Minas Gerais, 36010 570, Brazil

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São Paulo, São Paulo, 01244-030, Brazil

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Rio de Janeiro, 20241-180, Brazil

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Novartis Investigative Site

São José do Rio Preto, 15090 000, Brazil

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Pleven, 5800, Bulgaria

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Plovdiv, 4000, Bulgaria

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Plovdiv, 4002, Bulgaria

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Sofia, 1413, Bulgaria

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Sofia, 1431, Bulgaria

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Novartis Investigative Site

Barranquilla, Atlántico, 080002, Colombia

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Bucaramanga, Santander Department, 0001, Colombia

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Novartis Investigative Site

Ibagué, Tolima Department, 730006, Colombia

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Novartis Investigative Site

Barranquilla, 080020, Colombia

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Bogotá, 110221, Colombia

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Novartis Investigative Site

Cundinamarca, 111121, Colombia

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Novartis Investigative Site

Ostrava, Czech Republic, 772 00, Czechia

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Novartis Investigative Site

Prague, 128 50, Czechia

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Novartis Investigative Site

Prague, 140 59, Czechia

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Prague, 150 06, Czechia

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Novartis Investigative Site

Uherské Hradiště, 686 01, Czechia

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Novartis Investigative Site

Athens, 115 27, Greece

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Pátrai, 26443, Greece

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Guatemala City, 01009, Guatemala

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Guatemala City, 01010, Guatemala

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Guatemala City, 01011, Guatemala

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Novartis Investigative Site

Surat, Gujarat, 395009, India

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Bangalore, Karnataka, 560 079, India

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Mumbai, Maharashtra, 400 053, India

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Nashik, Maharashtra, 422 101, India

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Hyderabad, Telangana, 500082, India

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New Delhi, 110029, India

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Siena, SI, 53100, Italy

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Verona, VR, 37134, Italy

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Seremban, Negeri Sembilan, 70300, Malaysia

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Ipoh, Perak, 30450, Malaysia

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Kuching, Sarawak, 93586, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Selangor Darul Ehsan, 68100, Malaysia

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Lipa City, Batangas, 4217, Philippines

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Dasmariñas, Cavite, 4114, Philippines

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Manila, 1008, Philippines

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Quezon, 1102, Philippines

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Bialystok, 15-351, Poland

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Krakow, 30 002, Poland

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Sochaczew, 96-500, Poland

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Torun, 87-100, Poland

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Warsaw, 02 637, Poland

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Novartis Investigative Site

Chelyabinsk, 454076, Russia

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Novartis Investigative Site

Kazan', 420064, Russia

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Kemerovo, 650029, Russia

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Kemerovo, 650070, Russia

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Moscow, 115522, Russia

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Novosibirsk, 630047, Russia

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Novosibirsk, 630099, Russia

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Novartis Investigative Site

Petrozavodsk, 185019, Russia

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Novartis Investigative Site

Saint Petersburg, 190068, Russia

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Novartis Investigative Site

Saint Petersburg, 197341, Russia

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Ulyanovsk, 432063, Russia

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Novartis Investigative Site

Yaroslavl, 150003, Russia

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Novartis Investigative Site

Yekaterinburg, 620137, Russia

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Novartis Investigative Site

Gwangju, 61469, South Korea

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Novartis Investigative Site

Seoul, 04763, South Korea

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Novartis Investigative Site

Seoul, 05030, South Korea

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Novartis Investigative Site

Seoul, 05278, South Korea

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Novartis Investigative Site

Danderyd, 182 88, Sweden

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Novartis Investigative Site

Stockholm, 171 76, Sweden

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Novartis Investigative Site

Bangkoknoi, Bangkok, 10700, Thailand

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Novartis Investigative Site

Songkhla, Hat Yai, 90110, Thailand

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Novartis Investigative Site

Khon Kaen, THA, 40002, Thailand

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Novartis Investigative Site

Bangkok, 10400, Thailand

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Novartis Investigative Site

Adana, 01160, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

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Related Links

• Patient Lay Trial Summary

MeSH Terms

Conditions

Spondylitis, Ankylosing; Axial Spondyloarthritis; Non-Radiographic Axial Spondyloarthritis; Sacroiliitis

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

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
• Masking Details: This is a double-blind, randomized treatment trial. Subjects, investigators, investigator staff and persons performing the assessments, will remain blind to the identity of the treatment from the time of randomization until database lock, using the following methods: (1) Randomization data are kept strictly confidential until the time of unblinding and will not be accessible by anyone else involved in the study with the exception of the bioanalyst, (2) the identity of the treatments will be concealed by the use of study treatment in form of vials, filled with secukinumab or placebo that are identical in appearance.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2019
• First Posted: November 7, 2019
• Study Start: December 11, 2019
• Primary Completion: February 17, 2022
• Study Completion: December 20, 2022
• Last Updated: June 18, 2024
• Results First Posted: January 23, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

US (25); PL (5); IT (2); CO (6); GU (3); MY (5); PH (4); BR (6); RU (13); GR (2); BE (2); TU (3); TH (4); BU (5); KR (4); IN (6); CZ (5); SE (2)