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

Janssen (J&J Innovative Medicine)

Status and phase: Terminated; Phase 3

Conditions: Axial Spondyloarthritis

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02437162

CNTO1275AKS3001 (Other Identifier)

2014-003679-48 (EudraCT Number)

CR107098

Details and patient eligibility

About

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.

Full 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.

Enrollment: 347 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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347 participants in 3 patient groups, including a placebo group

Group 1 (Placebo)

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Ustekinumab 90 mg

Drug: Golimumab 50 mg

Drug: Ustekinumab 45 mg

Group 2 (Ustekinumab 45 mg)

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Golimumab 50 mg

Drug: Ustekinumab 45 mg

Group 3 (Ustekinumab 90 mg)

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Ustekinumab 90 mg

Drug: Golimumab 50 mg