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

NCT ID: NCT02437162

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 347 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-03
• Study Completion Date: 2017-09-06

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.

Detailed Description

This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect) study. The study consists of 3 phases; Screening (up to 8 weeks), Treatment phase: placebo-controlled (Week 0 to 24) and active treatment (Week 24 to Week 100), and Safety Follow-up (12 weeks after last dose). Participants will be randomly assigned to 1 of 3 treatment groups: placebo, ustekinumab 45 mg and ustekinumab 90 mg. The total duration of study will be up to 112 weeks. Participants will be primarily assessed for Assessment of SpondyloArthritis International Society (ASAS) 40 response at Week 24. Participants' safety will be monitored throughout the trial.

Conditions

Axial Spondyloarthritis

Study Design

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

Study Groups

Group 1 (Placebo)

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Ustekinumab 45 mg

Intervention Type: 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.

Ustekinumab 90 mg

Intervention Type: 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.

Golimumab 50 mg

Intervention Type: 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 2 (Ustekinumab 45 mg)

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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.

Ustekinumab 45 mg

Intervention Type: 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.

Golimumab 50 mg

Intervention Type: 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 3 (Ustekinumab 90 mg)

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: 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.

Ustekinumab 90 mg

Intervention Type: 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.

Golimumab 50 mg

Intervention Type: 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.

Interventions

Placebo

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.

Intervention Type: DRUG

Ustekinumab 45 mg

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.

Intervention Type: DRUG

Ustekinumab 90 mg

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.

Intervention Type: DRUG

Golimumab 50 mg

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 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

Peoria, Arizona, United States

St. Petersburg, Florida, United States

Tampa, Florida, United States

Chicago, Illinois, United States

Eagan, Minnesota, United States

Duncansville, Pennsylvania, United States

Wyomissing, Pennsylvania, United States

Jackson, Tennessee, United States

Austin, Texas, United States

Mesquite, Texas, United States

Seattle, Washington, United States

Brno, , Czechia

Bruntál, , Czechia

Kladno, , Czechia

Ostrava, , Czechia

Pardubice, , Czechia

Prague, , Czechia

Uherské Hradiště, , Czechia

Zlín, , Czechia

Bydgoszcz, , Poland

Szczecin, , Poland

Torun, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Chelyabinsk, , Russia

Chita, , Russia

Ivanovo, , Russia

Kemerovo, , Russia

Kirov, , Russia

Kursk, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Orenburg, , Russia

Petrozavodsk, , Russia

Pyatigorsk, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Stavropol, , Russia

Ufa, , Russia

Ulyanovsk, , Russia

Daegu, , South Korea

Daejeon, , South Korea

Gwangju, , South Korea

Seoul, , South Korea

Suwon, , South Korea

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Tainan City, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Lviv, , Ukraine

Odesa, , Ukraine

Ternopil, , Ukraine

Vinnytsia, , Ukraine

Zaporizhzhya, , Ukraine

Countries

United States; Czechia; Poland; Russia; South Korea; Taiwan; Ukraine

References

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.

Reference Type: DERIVED

PMID: 36995469 (View on PubMed)

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

CNTO1275AKS3001

Identifier Type: OTHER

Identifier Source: secondary_id

2014-003679-48

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR107098

Identifier Type: -

Identifier Source: org_study_id