A Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNFα Naive Participants With Active Radiographic Axial Spondyloarthritis

NCT02437162 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: CR107098CNTO1275AKS30012014-003679-48
• Study Type: interventional
• Target: 347
• Locations: 7 countries
• Sites: 57

Brief Summary

The purpose of this study is to assess the efficacy of ustekinumab, in adult participants with active radiographic axial spondyloarthritis (AxSpA), who are naive to anti-TNF alpha agents, as measured by the reduction in signs and symptoms of radiographic AxSpA.

Conditions

Axial Spondyloarthritis

Keywords

Axial Spondyloarthritis; Ustekinumab; Golimumab; Stelara

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Week 24

  ASAS 40 defined as improvement from baseline of greater than or equal to (\>=) 40 percent (%) and absolute improvement from baseline of at least 2 on 0 to 10 centimeter (cm) scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 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 relate to participant's ability to cope with everyday life), Inflammation(0 to 10cm;0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 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 (35)

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

  Week 24

• Percentage of Participants Who Achieved at Least a 50 Percent (%) 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) Total Score at Week 24

  Baseline and Week 24

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

Study Arms (3)

Group 1 (Placebo)

PLACEBO COMPARATOR

Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16. At Week 24 all participants (with the exception of participants who qualified for early escape \[EE\]) will be re-randomized to receive either ustekinumab 45 or 90 milligram (mg) SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing, with the last administration of study agent at Week 100. Participants who meet EE criteria (less than \[\<\] 10 percent \[%\] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52.

Drug: Placebo; Drug: Ustekinumab 45 mg; Drug: Ustekinumab 90 mg; Drug: Golimumab 50 mg

Group 2 (Ustekinumab 45 mg)

EXPERIMENTAL

Ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by every 12 week dosing, with the last administration of study agent at Week 100. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (\<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.

Drug: Placebo; Drug: Ustekinumab 45 mg; Drug: Golimumab 50 mg

Group 3 (Ustekinumab 90 mg)

EXPERIMENTAL

Ustekinumab 90 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 100. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (\<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.

Drug: Placebo; Drug: Ustekinumab 90 mg; Drug: Golimumab 50 mg

Interventions

Placebo DRUG

Participants will receive Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16 in Group 1 and at Week 24 in Group 2 and Group 3.

Group 1 (Placebo); Group 2 (Ustekinumab 45 mg); Group 3 (Ustekinumab 90 mg)

Ustekinumab 45 mg DRUG

Participants will receive Ustekinumab 45 mg SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing, with the last administration of study agent at Week 100 in Group 1. Participants will start with ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 100 in Group 2.

Group 1 (Placebo); Group 2 (Ustekinumab 45 mg)

Ustekinumab 90 mg DRUG

Participants will receive Ustekinumab 90 mg SC injection at Weeks 24 and 28 followed by q12w dosing, with the last administration of study agent at Week 100 in Group 1. Participants will start with ustekinumab 90 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 100 in Group 3.

Group 1 (Placebo); Group 3 (Ustekinumab 90 mg)

Golimumab 50 mg DRUG

Participants who meet EE criteria (less than \[\<\] 10 percent \[%\] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52 in Groups 1, 2 and 3.

Group 1 (Placebo); Group 2 (Ustekinumab 45 mg); Group 3 (Ustekinumab 90 mg)

Eligibility Criteria

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

You may qualify if:

• Participants must have a diagnosis of definite ankylosing spondylitis (AS), as defined by the modified 1984 New York criteria. The radiographic criterion must be confirmed by a central xray reader and at least 1 clinical criterion must be met
• Participants must have symptoms of active disease at screening and at baseline, as evidenced by both a BASDAI score of greater than or equal to (\>=4) and a visual analog scale (VAS) score for total back pain of \>=4, each on a scale of 0 to 10
• Participants with elevated high sensitivity C-reactive protein (hsCRP) level of \>=0.300 milligram per deciliter (mg/dL) at Screening
• If using nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics for AS, must be on a stable dose for at least 2 weeks prior to the first administration of study agent. If currently not using NSAIDs or other analgesics for AS, must not have received NSAIDs or other analgesics for AS for at least 2 weeks prior to the first administration of the study agent
• A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening and a negative urine pregnancy test at Week 0 before randomization

You may not qualify if:

• Participants who have other inflammatory diseases that might confound the evaluations of benefit from the ustekinumab therapy, including but not limited to, rheumatoid arthritis, systemic lupus erythematosus, or Lyme disease
• Participants who are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 5 months after receiving the last administration of study agent
• Participants who have received any prior biologic therapy, including but not limited to anti-TNF alpha agents, tocilizumab, alefacept, efalizumab, natalizumab, abatacept, anakinra, ustekinumab, tidrakizumab or other anti-interleukin (IL) 23 biologics, brodalumab, secukinumab, ixekizumab, and B-cell depleting therapies
• Participants who have received any systemic immunosuppressives or disease-modifying antirheumatic drugs (DMARDs) other than methotrexate (MTX), sulfasalazine (SSZ), or hydroxychloroquine (HCQ) within 4 weeks prior to first administration of study agent. Medications in these categories include, but are not limited to chloroquine, azathioprine, cyclosporine, mycophenolate mofetil, gold, and penicillamine
• Participant who have received leflunomide within 3 months prior to the first administration of study agent (irrespective of undergoing a drug elimination procedure), or have received leflunomide within 12 months prior to the first administration of study agent and have not undergone a drug elimination procedure

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (57)

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Peoria, Arizona, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Eagan, Minnesota, United States

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Duncansville, Pennsylvania, United States

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Wyomissing, Pennsylvania, United States

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Jackson, Tennessee, United States

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Austin, Texas, United States

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Mesquite, Texas, United States

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Seattle, Washington, United States

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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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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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Ivanovo, Russia

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Kemerovo, Russia

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Kirov, Russia

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Kursk, 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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Pyatigorsk, Russia

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Saint Petersburg, Russia

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Saratov, Russia

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Stavropol, Russia

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Ufa, Russia

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Ulyanovsk, Russia

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Daegu, South Korea

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Daejeon, South Korea

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Gwangju, South Korea

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Seoul, South Korea

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Suwon, 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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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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Related Publications (2)

• Kavanaugh A, Baraliakos X, Gao S, Chen W, Sweet K, Chakravarty SD, Song Q, Shawi M, Rahman P. Genetic and Molecular Distinctions Between Axial Psoriatic Arthritis and Radiographic Axial Spondyloarthritis: Post Hoc Analyses from Four Phase 3 Clinical Trials. Adv Ther. 2023 May;40(5):2439-2456. doi: 10.1007/s12325-023-02475-4. Epub 2023 Mar 30.

  PMID: 36995469 DERIVED

• 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.

  PMID: 30225992 DERIVED

MeSH Terms

Conditions

Axial Spondyloarthritis

Interventions

Ustekinumab; golimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated since neither dose achieved the study's primary or major secondary endpoints.

Results Point of Contact

• Title: SENIOR DIRECTOR CLINICAL DEVELOPMENT
• Organization: Johnson&Johnson

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

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: 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: May 5, 2015
• First Posted: May 7, 2015
• Study Start: September 3, 2015
• Primary Completion: March 22, 2017
• Study Completion: September 6, 2017
• Last Updated: April 29, 2025
• Results First Posted: April 23, 2018

Record last verified: 2025-04

Locations

KR (5); UA (7); US (11); RU (16); CZ (8); TW (5); PL (5)