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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02438787
First received: May 6, 2015
Last updated: August 11, 2017
Last verified: August 2017
  Purpose
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.

Condition Intervention Phase
Axial Spondyloarthritis Drug: Placebo Drug: Ustekinumab 45 mg Drug: Ustekinumab 90 mg Drug: Golimumab 50 mg Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF(Alpha) Refractory Subjects With Active Radiographic Axial Spondyloarthritis

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Percentage of Participants Achieving an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 24 [ Time Frame: Week 24 ]
    ASAS 40 is defined as a greater than or equal to (>=) 40 percent (%) improvement in 3 of 4 domains: Patient global; Total back pain; Function (Bath Ankylosing Spondylitis Functional Index [BASFI]); Inflammation (average of the last 2 questions of the BASDAI concerning morning stiffness), with an absolute improvement of at least 2 on a 0 to 10 scale, and no deterioration at all in the remaining domain.


Secondary Outcome Measures:
  • Percentage of Participants Achieving an ASAS 20 Response at Week 24 [ Time Frame: Week 24 ]
    ASAS 20 is an improvement of >= 20% from baseline and absolute improvement from baseline of at least 1 on a 0 to 10 scale in at least 3 of the following 4 domains: Patient global; Total back pain; Function (Bath Ankylosing Spondylitis Functional Index [BASFI]); Inflammation (average of the last 2 questions of the BASDAI concerning morning stiffness) and absence of deterioration from baseline (>=20% and worsening of at least 1 on a 0 to 10 scale) in the potential remaining domain.

  • Percentage of Participants who Achieve at Least 50% Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 [ Time Frame: Week 24 ]
    BASDAI is defined as participant self-assessment using a visual analog scale (VAS; 0 to 10) on the following criteria: A. Fatigue; B. Spinal pain; C. Peripheral joint pain/swelling; D. Enthesitis; E. Intensity of morning stiffness; F. Duration of morning stiffness. The BASDAI = 0.2 (A + B + C + D + 0.5[E + F]).

  • Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 [ Time Frame: Baseline and Week 24 ]
    The BASFI is a participant's self-assessment represented as a mean (VAS; 0 to 10) of 10 questions, 8 of which relate to the participant's functional anatomy and 2 of which relate to a participant's ability to cope with everyday life. An increase along the scale indicates a worsening condition.

  • Percentage of Participants who Achieve Ankylosing Spondylitis Disease Activity Score (ASDAS) (CRP) Inactive Disease at Week 24 [ Time Frame: Week 24 ]
    The ASAS has developed a disease activity score (DAS) for use in AS, the Ankylosing Spondylitis Disease Activity Score (ASDAS). ASDAS (CRP) = 0.121 x Total back pain + 0.058 x Duration of morning stiffness + 0.110 x Patient global assessment + 0.073 x Peripheral joint pain/ swelling + 0.579 x Log (C-reactive protein [CRP]+1). Inactive disease is defined as an ASDAS (CRP) score less than (<) 1.3.


Enrollment: 315
Actual Study Start Date: July 31, 2015
Estimated Study Completion Date: August 16, 2017
Estimated Primary Completion Date: August 16, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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.
Drug: Placebo
Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16 in Group 1.
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.
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.
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.
Experimental: 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.
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.
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.
Experimental: 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.
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.
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02438787

  Show 153 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02438787     History of Changes
Other Study ID Numbers: CR107099
CNTO1275AKS3002 ( Other Identifier: Janssen Research & Development, LLC )
2015-000288-16 ( EudraCT Number )
Study First Received: May 6, 2015
Last Updated: August 11, 2017

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Ankylosing Spondylitis
Ustekinumab
Golimumab
STELARA

Additional relevant MeSH terms:
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases
Ustekinumab
Antibodies, Monoclonal
Dermatologic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 22, 2017