NCT02407223

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).

Trial Health

68
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
356

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jul 2015

Geographic Reach
14 countries

90 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 30, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 2, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

July 13, 2015

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 26, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 26, 2017

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

March 13, 2019

Completed
Last Updated

March 13, 2019

Status Verified

February 1, 2019

Enrollment Period

2.2 years

First QC Date

March 30, 2015

Results QC Date

September 26, 2018

Last Update Submit

March 11, 2019

Conditions

Keywords

Nonradiographic Axial Spondylitis, AnkylosingUstekinumab

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants Who Achieved Assessment of SpondyloArthritis International Society (ASAS) 20 Response at Week 24

    ASAS 20 defined as improvement of greater than or equal to (\>=) 20 % from baseline and absolute improvement from baseline of 1 on a 0 to 10 centimeter(cm) scale in at least 3 of following 4 domains: Patient's global assessment of disease activity (0 to 10 cm; 0=very well,10=very poor), total back pain (0 to 10 cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 to participant's ability to cope with everyday life), Inflammation (0 to 10 cm;0=none,10=very severe); absence of deterioration (\>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in remaining domain. ASAS20 response based on imputed data using treatment failure (consider non-responders at and after treatment failure),early escape rules (consider non-responder at Week 20 and 24),non-responder\[NRI\] (missing responses at post baseline visit imputed as non-responder).

    Week 24

Secondary Outcomes (11)

  • Percentage of Participants Who Achieved an ASAS 40 Response at Week 24

    Week 24

  • Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24

    Week 24

  • Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24

    Baseline, Week 24

  • Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive Protein (CRP) Inactive Disease (<1.3) at Week 24

    Week 24

  • Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24

    Baseline, Week 4, 8, 12, 16, 20 and 24

  • +6 more secondary outcomes

Study Arms (3)

Group 1: Placebo

PLACEBO COMPARATOR

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.

Drug: Group 1: Placebo

Group 2: Ustekinumab 45 milligram (mg)

EXPERIMENTAL

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.

Drug: Group 2: Ustekinumab 45 mg

Group 3: Ustekinumab 90 mg

EXPERIMENTAL

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.

Drug: Group 3: Ustekinumab 90 mg

Interventions

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 1: Placebo

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 2: Ustekinumab 45 milligram (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 3: Ustekinumab 90 mg

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (90)

Unknown Facility

Buenos Aires, Argentina

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Ciudad de Buenos Aires, Argentina

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Ciudad de La Plata, Argentina

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Ciudad de San Miguel de Tucuman, Argentina

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Córdoba, Argentina

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Geelong, Australia

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Hobart, Australia

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Kogarah, Australia

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Queensland, Australia

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Woodville South, Australia

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Woolloongabba, Australia

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Genk, Belgium

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Ghent, Belgium

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Leuven, Belgium

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Liège, Belgium

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Merksem, Belgium

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Brno, Czechia

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Bruntál, Czechia

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Kladno, Czechia

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Ostrava, Czechia

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Pardubice, Czechia

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Prague, Czechia

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Uherské Hradiště, Czechia

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Zlín, Czechia

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Boulogne-Billancourt, France

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Chambray-lès-Tours, France

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Échirolles, France

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Montpellier, Herault, France

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Paris, France

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Toulouse, France

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Bad Nauheim, Germany

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Berlin, Germany

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Cologne, Germany

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Hamburg, Germany

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Hanover, Germany

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Herne, Germany

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Olsberg, Germany

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Budapest, Hungary

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Debrecen, Hungary

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Esztergom, Hungary

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Kistarcsa, Hungary

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Nyíregyháza, Hungary

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Székesfehérvár, Hungary

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Szolnok, Hungary

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Veszprém, Hungary

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Chihuahua City, Mexico

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Culiacán, Mexico

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Guadalajara, Mexico

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México, Mexico

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Bydgoszcz, Poland

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Szczecin, Poland

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Torun, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Chelyabinsk, Russia

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Chita, Russia

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Kemerovo, Russia

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Kirov, Russia

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Moscow, Russia

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Novosibirsk, Russia

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Orenburg, Russia

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Petrozavodsk, Russia

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Saint Petersburg, Russia

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Saratov, Russia

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Stavropol, Russia

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Ulyanovsk, Russia

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Zelenograd, Russia

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Gwangju, South Korea

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Incheon, South Korea

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Seoul, South Korea

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Kaohsiung City, Taiwan

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Taichung, Taiwan

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Tainan, Taiwan

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Taipei, Taiwan

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Taoyuan District, Taiwan

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Ivano-Frankivsk, Ukraine

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Kharkiv, Ukraine

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Kyiv, Ukraine

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Lviv, Ukraine

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Odesa, Ukraine

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Ternopil, Ukraine

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Vinnytsia, Ukraine

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Zaporizhzhya, Ukraine

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Bath, United Kingdom

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Leeds, United Kingdom

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Leytonstone, United Kingdom

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London, United Kingdom

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Norwich, United Kingdom

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Staffordshire, United Kingdom

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Torquay, United Kingdom

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Related Publications (1)

  • 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.

Limitations and Caveats

The study was discontinued before it was fully enrolled, therefore, the interpretation of the efficacy data is limited.

Results Point of Contact

Title
Scientific Director
Organization
Janssen Research & Development, LLC

Study Officials

  • Janssen Research & Development, LLC Clinical Trial

    Janssen Research & Development, LLC

    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
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 30, 2015

First Posted

April 2, 2015

Study Start

July 13, 2015

Primary Completion

September 26, 2017

Study Completion

September 26, 2017

Last Updated

March 13, 2019

Results First Posted

March 13, 2019

Record last verified: 2019-02

Locations