A Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF(Alpha) Refractory Participants With Active Radiographic Axial Spondyloarthritis

NCT ID: NCT02438787

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 315 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2017-08-31

Brief Summary

The purpose of this study is to assess the efficacy of ustekinumab, in adult anti-TNF(alpha) refractory participants with active radiographic axial spondyloarthritis (AxSpA), 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 52), and Safety Follow-up (up to 12 weeks). 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 64 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 52. 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

Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16 in Group 1.

Ustekinumab 45 mg

Intervention Type: DRUG

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 52 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 52 in Group 2.

Ustekinumab 90 mg

Intervention Type: DRUG

Ustekinumab 90 mg SC injection at Weeks 24 and 28 followed by q12w dosing, with the last administration of study agent at Week 52 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 52 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 Group 1, 2 and 3.

Group 2 (ustekinumab 45 mg)

Ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52. 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

Ustekinumab 45 mg

Intervention Type: DRUG

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 52 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 52 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 Group 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 52. 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

Ustekinumab 90 mg

Intervention Type: DRUG

Ustekinumab 90 mg SC injection at Weeks 24 and 28 followed by q12w dosing, with the last administration of study agent at Week 52 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 52 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 Group 1, 2 and 3.

Interventions

Placebo

Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16 in Group 1.

Intervention Type: DRUG

Ustekinumab 45 mg

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 52 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 52 in Group 2.

Intervention Type: DRUG

Ustekinumab 90 mg

Ustekinumab 90 mg SC injection at Weeks 24 and 28 followed by q12w dosing, with the last administration of study agent at Week 52 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 52 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 Group 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 Bath Ankylosing Spondylitis Disease Activity Index (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
• Refractory by either lack of benefit or documented intolerance to 1 and no more than 1 anti-TNF(alpha) agent
• Inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) over a 4-week period in total with maximal doses of NSAID(s), or is unable to receive a full 4 weeks of maximal NSAID therapy because of intolerance, toxicity, or contraindications to NSAIDs.
• Participants with complete ankylosis of the spine are permitted to be included in the study, but will be limited to approximately 10 percent (%) of the study population

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 have received infliximab or infliximab biosimilar, within 12 weeks of the first study agent administration; have received adalimumab, adalimumab biosimilar, or certolizumab pegol within 6 weeks of the first study agent administration; have received etanercept or etanercept biosimilar within 6 weeks of the first study agent administration
• Participants who have ever received golimumab
• 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 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 leflunomide, chloroquine, azathioprine, cyclosporine, mycophenolate mofetil, gold, and penicillamine

• 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

Glendale, Arizona, United States

Peoria, Arizona, United States

Phoenix, Arizona, United States

Fremont, California, United States

St. Petersburg, Florida, United States

Tampa, Florida, United States

Boise, Idaho, United States

Chicago, Illinois, United States

Monroe, Louisiana, United States

Eagan, Minnesota, United States

Orchard Park, New York, United States

Portland, Oregon, United States

Duncansville, Pennsylvania, United States

Wyomissing, Pennsylvania, United States

Jackson, Tennessee, United States

Austin, Texas, United States

Mesquite, Texas, United States

Arlington, Virginia, United States

Seattle, Washington, United States

Buenos Aires, , Argentina

Ciudad de Buenos Aires, , Argentina

Ciudad de La Plata, , Argentina

Ciudad de San Miguel de Tucuman, , Argentina

Córdoba, , Argentina

Brussels, , Belgium

Genk, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Liège, , Belgium

Merksem (Antwerp), , Belgium

Campinas, , Brazil

Curitiba, , Brazil

Goiânia, , Brazil

Juiz de Fora, , Brazil

Porto Alegre, , Brazil

Rio de Janeiro, , Brazil

Santo André, , Brazil

São Paulo, , Brazil

Burgas, , Bulgaria

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Rousse, , Bulgaria

Sofia, , Bulgaria

Victoria, British Columbia, Canada

St. John's, Newfoundland and Labrador, Canada

Toronto, Ontario, Canada

Windsor, Ontario, Canada

Québec, Quebec, Canada

Bruntál, , Czechia

Pardubice, , Czechia

Prague, , Czechia

Uherské Hradiště, , Czechia

Zlín, , Czechia

Boulogne-Billancourt, , France

Chambray-lès-Tours, , France

Échirolles, , France

Montpellier, , France

Orléans, , France

Paris, , France

Rouen, , France

Toulouse, , France

Bad Neuheim, , Germany

Berlin, , Germany

Cologne, , Germany

Gommern, , Germany

Hamburg, , Germany

Herne, , Germany

Olsberg, , Germany

Ratingen, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Eger, , Hungary

Kistarcsa, , Hungary

Nyíregyháza, , Hungary

Székesfehérvár, , Hungary

Szolnok, , Hungary

Veszprém, , Hungary

Culiacán, , Mexico

Guadalajara, , Mexico

Mexico City, , Mexico

Bialystok, , Poland

Bydgoszcz, , Poland

Elblag, , Poland

Nadarzyn, , Poland

Szczecin, , Poland

Torun, , Poland

Warsaw, , Poland

Almada, , Portugal

Lisbon, , Portugal

Porto, , Portugal

Belgorod, , Russia

Chelyabinsk, , Russia

Chita, , Russia

Kazan', , Russia

Kemerovo, , Russia

Khanty-Mansiysk, , Russia

Kursk, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Omsk, , Russia

Orenburg, , Russia

Petrozavodsk, , Russia

Pyatigorsk, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Ufa, , Russia

Zelenograd, , Russia

Daegu, , South Korea

Daejeon, , South Korea

Gwangju, , South Korea

Jeonju, , South Korea

Seoul, , South Korea

Suwon, , South Korea

A Coruña, , Spain

Barcelona, , Spain

Bilbao, , Spain

Córdoba, , Spain

L'Hospitalet de Llobregat, , Spain

Madrid, , Spain

Málaga, , Spain

Sabadell, , Spain

Santiago de Compostela, , Spain

Seville, , Spain

Valencia, , Spain

Changhua, , Taiwan

Hualien City, , Taiwan

Kaohsiung City, , Taiwan

Taichung, , Taiwan

Tainan City, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Cherkasy, , Ukraine

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Lviv, , Ukraine

Odesa, , Ukraine

Poltava, , Ukraine

Ternopil, , Ukraine

Uzhhorod, , Ukraine

Vinnytsia, , Ukraine

Zaporizhzhya, , Ukraine

Bath, , United Kingdom

Leytonstone, , United Kingdom

London, , United Kingdom

Peterborough, , United Kingdom

Stoke-on-Trent, , United Kingdom

Upton, , United Kingdom

Countries

United States; Argentina; Belgium; Brazil; Bulgaria; Canada; Czechia; France; Germany; Hungary; Mexico; Poland; Portugal; Russia; South Korea; Spain; Taiwan; Ukraine; United Kingdom

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

CNTO1275AKS3002

Identifier Type: OTHER

Identifier Source: secondary_id

2015-000288-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR107099

Identifier Type: -

Identifier Source: org_study_id