An Efficacy and Safety Study of Ustekinumab in Participants With Active Nonradiographic Axial Spondyloarthritis

NCT ID: NCT02407223

Last Updated: 2019-03-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 356 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-13
• Study Completion Date: 2017-09-26

Brief Summary

The purpose of this study is to assess the efficacy and safety of ustekinumab in adult participants with active nonradiographic axial spondyloarthritis (nr-AxSpA) measured by the reduction in signs and symptoms of nonradiographic axial spondyloarthritis (nr-AxSpA).

Detailed Description

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of ustekinumab in the treatment of participants with active non-radiographic axial spondylo arthritis. Participants will receive either placebo or ustekinumab 45 or 90 milligram (mg). Participants will primarily be assessed for Assessment of Spondylo Arthritis (ASAS) International Society criteria 20 at Week 24. Safety will be monitored throughout the study.

Conditions

Nonradiographic Axial Spondylitis, Ankylosing

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group 1: Placebo

Participants will receive placebo subcutaneously (SC) at Weeks 0, 4, 16, and 20. At Week 24, all participants (except those who early escaped) will crossover to receive ustekinumab 45 or 90 milligram (mg) SC at Weeks 24 and 28 followed by every 12 weeks up to Week 52. At Week 16, participants in placebo group with \< 10% improvement from baseline in both total back pain and morning stiffness measures at Week 12 and 16 will enter early escape to receive ustekinumab 45 mg or 90 mg at Weeks 16, 20, and 28 followed by every 12 weeks up to Week 52. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and 52 will be re-randomized to receive placebo or ustekinumab every 12 weeks up to Week 88. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or 52 will continue with ustekinumab every 12 weeks up to Week 88. NOTE: Intervention Description should have no more than 800 characters.

Group Type: PLACEBO_COMPARATOR

Group 1: Placebo

Intervention Type: DRUG

Participants will receive placebo SC at Weeks 0, 4, 16, and 20. At Week 24, all participants (except those who early escaped) will crossover to receive ustekinumab 45 or 90 mg SC at Weeks 24 and 28 followed by every 12 weeks up to Week 52. At Week 16, participants in placebo group with \< 10% improvement from baseline in both total back pain and morning stiffness measures at Week 12 and 16 will enter early escape to receive ustekinumab 45 mg or 90 mg at Weeks 16, 20, and 28 followed by every 12 weeks up to Week 52. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and 52 will be re-randomized to receive placebo or ustekinumab every 12 weeks up to Week 88. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or 52 will continue with ustekinumab every 12 weeks up to Week 88.

Group 2: Ustekinumab 45 milligram (mg)

Participants will receive ustekinumab 45 mg subcutaneously at Weeks 0 and 4, followed by every 12 weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and Week 52 will be re-randomized to receive either placebo or ustekinumab 45 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or Week 52 will continue receiving ustekinumab 45 mg every 12 weeks through Week 88.

Group Type: EXPERIMENTAL

Group 2: Ustekinumab 45 mg

Intervention Type: DRUG

Participants will receive ustekinumab 45 mg subcutaneously at Weeks 0 and 4, followed by every 12 weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and Week 52 will be re-randomized to receive either placebo or ustekinumab 45 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or Week 52 will continue receiving ustekinumab 45 mg every 12 weeks through Week 88.

Group 3: Ustekinumab 90 mg

Participants will receive ustekinumab 90 mg subcutaneously at Weeks 0 and 4, followed by every four weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and Week 52 will receive either placebo or ustekinumab 90 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or Week 52 will continue receiving ustekinumab 90 mg every 12 weeks through Week 88.

Group Type: EXPERIMENTAL

Group 3: Ustekinumab 90 mg

Intervention Type: DRUG

Participants will receive ustekinumab 90 mg subcutaneously at Weeks 0 and 4, followed by every four weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and Week 52 will receive either placebo or ustekinumab 90 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or Week 52 will continue receiving ustekinumab 90 mg every 12 weeks through Week 88.

Interventions

Group 1: Placebo

Participants will receive placebo SC at Weeks 0, 4, 16, and 20. At Week 24, all participants (except those who early escaped) will crossover to receive ustekinumab 45 or 90 mg SC at Weeks 24 and 28 followed by every 12 weeks up to Week 52. At Week 16, participants in placebo group with \< 10% improvement from baseline in both total back pain and morning stiffness measures at Week 12 and 16 will enter early escape to receive ustekinumab 45 mg or 90 mg at Weeks 16, 20, and 28 followed by every 12 weeks up to Week 52. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and 52 will be re-randomized to receive placebo or ustekinumab every 12 weeks up to Week 88. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or 52 will continue with ustekinumab every 12 weeks up to Week 88.

Intervention Type: DRUG

Group 2: Ustekinumab 45 mg

Participants will receive ustekinumab 45 mg subcutaneously at Weeks 0 and 4, followed by every 12 weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and Week 52 will be re-randomized to receive either placebo or ustekinumab 45 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or Week 52 will continue receiving ustekinumab 45 mg every 12 weeks through Week 88.

Intervention Type: DRUG

Group 3: Ustekinumab 90 mg

Participants will receive ustekinumab 90 mg subcutaneously at Weeks 0 and 4, followed by every four weeks through Week 52. At Weeks 20 and 24, participants will receive placebo subcutaneously to maintain the blind. At Week 52, participants who achieved inactive disease by ASDAS (ESR) \<1.3 at both Week 40 and Week 52 will receive either placebo or ustekinumab 90 mg every 12 weeks in a blinded fashion. At Week 52, participants who did not achieve inactive disease by ASDAS (ESR) \<1.3 at Week 40 or Week 52 will continue receiving ustekinumab 90 mg every 12 weeks through Week 88.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants must be classified as having nonradiographic axial spondyloarthritis (nr-AxSpA) based on 2009 Assessment of SpondyloArthritis International Society (ASAS) criteria
• Must have an age at nr-AxSpA onset of <= 45 years
• Must have at screening or active inflammation on magnetic resonance imaging (MRI) as evidenced by the central readers and no radiographic sacroiliitis that fulfills the 1984 modified New York Criteria
• Must have symptoms of active disease at screening and at baseline, as evidenced by both a BASDAI score of >= 4 and a visual analogue scale (VAS) score for total back pain of more than or equal to (>=) 4, each on a scale of 0 to 10

Exclusion Criteria

• Have radiographic sacroiliitis fulfilling the 1984 modified New York Criteria
• Have other inflammatory diseases that might confound the evaluations of benefit from the ustekinumab therapy
• Have received any systemic immunosuppressives or disease-modifying anti-rheumatic drug (DMARDs) other than methotrexate (MTX), sulfasalazine (SSZ), or hydroxychloroquine (HCQ) within 4 weeks prior to first administration of study agent
• Have received epidural, intra-articular, intramuscular (IM), or intravenous (IV) corticosteroids, including adrenocorticotropic hormone during the 4 weeks prior to first administration of study agent
• Have received prior biologic therapy other than anti-TNFα
• Have received more than 1 prior anti-TNFα agent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Buenos Aires, , Argentina

Ciudad de Buenos Aires, , Argentina

Ciudad de La Plata, , Argentina

Ciudad de San Miguel de Tucuman, , Argentina

Córdoba, , Argentina

Geelong, , Australia

Hobart, , Australia

Kogarah, , Australia

Queensland, , Australia

Woodville South, , Australia

Woolloongabba, , Australia

Genk, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Liège, , Belgium

Merksem, , Belgium

Brno, , Czechia

Bruntál, , Czechia

Kladno, , Czechia

Ostrava, , Czechia

Pardubice, , Czechia

Prague, , Czechia

Uherské Hradiště, , Czechia

Zlín, , Czechia

Boulogne-Billancourt, , France

Chambray-lès-Tours, , France

Échirolles, , France

Montpellier, Herault, , France

Paris, , France

Toulouse, , France

Bad Nauheim, , Germany

Berlin, , Germany

Cologne, , Germany

Hamburg, , Germany

Hanover, , Germany

Herne, , Germany

Olsberg, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Esztergom, , Hungary

Kistarcsa, , Hungary

Nyíregyháza, , Hungary

Székesfehérvár, , Hungary

Szolnok, , Hungary

Veszprém, , Hungary

Chihuahua City, , Mexico

Culiacán, , Mexico

Guadalajara, , Mexico

México, , Mexico

Bydgoszcz, , Poland

Szczecin, , Poland

Torun, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Chelyabinsk, , Russia

Chita, , Russia

Kemerovo, , Russia

Kirov, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Orenburg, , Russia

Petrozavodsk, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Stavropol, , Russia

Ulyanovsk, , Russia

Zelenograd, , Russia

Gwangju, , South Korea

Incheon, , South Korea

Seoul, , South Korea

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Tainan City, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Lviv, , Ukraine

Odesa, , Ukraine

Ternopil, , Ukraine

Vinnytsia, , Ukraine

Zaporizhzhya, , Ukraine

Bath, , United Kingdom

Leeds, , United Kingdom

Leytonstone, , United Kingdom

London, , United Kingdom

Norwich, , United Kingdom

Staffordshire, , United Kingdom

Torquay, , United Kingdom

Countries

Argentina; Australia; Belgium; Czechia; France; Germany; Hungary; Mexico; Poland; Russia; South Korea; Taiwan; Ukraine; United Kingdom

References

Deodhar A, Gensler LS, Sieper J, Clark M, Calderon C, Wang Y, Zhou Y, Leu JH, Campbell K, Sweet K, Harrison DD, Hsia EC, van der Heijde D. Three Multicenter, Randomized, Double-Blind, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Ustekinumab in Axial Spondyloarthritis. Arthritis Rheumatol. 2019 Feb;71(2):258-270. doi: 10.1002/art.40728. Epub 2018 Dec 29.

Reference Type: DERIVED

PMID: 30225992 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CNTO1275AKS3003

Identifier Type: OTHER

Identifier Source: secondary_id

2015-000289-67

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR106995

Identifier Type: -

Identifier Source: org_study_id