Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis

UCB

Status and phase: Completed; Phase 3

Conditions: Spondyloarthropathies

Treatments: Biological: CZP 200 mg Q2W; Other: Placebo; Biological: CZP 400 mg Q4W

Study type: Interventional

Funder types: Industry

Identifiers

NCT01087762

2009-011719-19 (EudraCT Number)

AS001

Details and patient eligibility

About

The study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of two dose regimens of Certolizumab Pegol (CZP) in subjects with active axial Spondyloarthritis (axial SpA).

Enrollment: 325 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented diagnosis of adult-onset axial Spondyloarthritis (SpA) of at least 3 months' duration as defined by the specified Assessment of Spondyloarthritis International Society (ASAS) criteria

• Active disease as defined by:

  • Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4
  • Back pain ≥ 4 on a 0 to 10 Neurobehavioral Rating Scale (NRS) (from BASDAI item 2)
  • C-Reactive Protein (CRP) > ULN (Upper Limit of Normal) and/or current evidence (ie, within the last 3 months from Screening) for Sacroiliitis on Magnetic Resonance Imaging (MRI) as defined by Assessment of Spondyloarthritis International Society (ASAS) criteria

• Intolerance to or inadequate response to at least 1 Nonsteroidal Anti-Inflammatory Drug (NSAID)

Exclusion criteria

• Presence of total Spinal Ankylosis ("bamboo spine")
• Diagnosis of any other Inflammatory Arthritis
• Prior treatment with any experimental biological agents for treatment of Axial Spondyloarthritis (SpA)
• Exposure to more than 1 TNF-antagonist or to more than 2 previous biological agents for Axial Spondyloarthritis (SpA)
• History of or current chronic or recurrent infections
• High risk of infection
• Recent live vaccination
• Concurrent malignancy or a history of malignancy
• Class III or IV congestive heart failure - New York Heart Association (NYHA)
• Demyelinating disease of the central nervous system
• Female subjects who are breastfeeding, pregnant or plan to become pregnant during the study or within 3 months following the last dose of the investigational product
• Subjects with any other condition which, in the investigator's judgment, would make the subject unsuitable for inclusion in the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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325 participants in 7 patient groups, including a placebo group

CZP 200 mg Q2W

Experimental group

Description:

Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards. At every visit, subjects received one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.

Treatment:

Other: Placebo

Biological: CZP 200 mg Q2W

CZP 400 mg Q4W

Experimental group

Description:

Subjects received Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 8 onwards. Subjects received 2 injections of Placebo every 4 weeks in between the 2 injections of 200 mg CZP to maintain the study blind.

Treatment:

Other: Placebo

Biological: CZP 400 mg Q4W

Placebo

Placebo Comparator group

Description:

Matching Placebo to CZP injections from Week 0 to Week 24. Placebo subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16. After 24 weeks, all subjects were randomized to active treatment with CZP 200 mg Q2W or CZP 400 mg Q4W.

Treatment:

Other: Placebo

Placebo to CZP 200 mg escape on Week 16

Other group

Description:

Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 22 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.

Treatment:

Other: Placebo

Biological: CZP 200 mg Q2W

Placebo to CZP 400 mg escape on Week 16

Other group

Description:

Matching Placebo to CZP injections from Week 0 to Week 16. Subjects who did not achieve certain predefined response criteria at both Weeks 14 and 16 left the Placebo group on Week 16 and were treated with three loading doses of CZP 400 mg sc on Weeks 16, 18 and 20, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 24 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.

Treatment:

Other: Placebo

Biological: CZP 400 mg Q4W

Placebo to CZP 200 mg on Week 24

Other group

Description:

Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 30 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.

Treatment:

Other: Placebo

Biological: CZP 200 mg Q2W

Placebo to CZP 400 mg on Week 24

Other group

Description:

Matching Placebo to CZP injections from Week 0 to Week 24. Three loading doses of CZP 400 mg sc were given on Weeks 24, 26 and 28, followed by 400 mg CZP sc every 4 weeks (Q4W) from Week 32 onwards. Additionally, Placebo injections were administered as appropriate in order to maintain the study blind.

Treatment:

Other: Placebo

Biological: CZP 400 mg Q4W