Study to Evaluate Maintenance of Sustained Remission of axSpA With CZP Compared to Placebo (C-OPTIMISE)

UCB

Status and phase: Completed; Phase 3

Conditions: Axial Spondyloarthrithis; Ankylosing Spondylitis

Treatments: Biological: Certolizumab Pegol; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02505542

2015-000339-34 (EudraCT Number)

AS0005

Details and patient eligibility

About

Patients receive study drug for one year (Part A). If, after the initial run-in phase, a sustained remission is reached they will be randomly split into one of three dose groups for another year (Part B). The maintenance of the sustained remission will be analyzed.

Enrollment: 736 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented diagnosis of adult-onset axial SpondyloArthritis (axSpA) with at least 3 months' symptom duration and meet the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA and symptom duration of less than 5 years prior to the participation of this study

• Active disease at Screening as defined by

  • Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.1
  • Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4
  • Spinal pain > 4 on a 0 to 10 Numerical Rating Scale (NRS) (from BASDAI Item 2)
  • for modified New York (mNY) -negative subjects only: C-reactive Protein (CRP) > upper limit of normal (ULN) and/or current evidence for sacroiliitis on the Screening Magnetic Resonance Imaging (MRI)

• Inadequate response to, or contraindication to, or intolerant to at least 2 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

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 primary failure to TNF antagonist therapy
• 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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736 participants in 7 patient groups, including a placebo group

Open-label Certolizumab Pegol

Other group

Description:

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 to Week 48 (Part A). Subjects in sustained remission at Week 48 are eligible for randomization into Part B.

Treatment:

Biological: Certolizumab Pegol

Double-blind Certolizumab Pegol 200 mg Q2W

Experimental group

Description:

Certolizumab Pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.

Treatment:

Biological: Certolizumab Pegol

Double-blind Certolizumab Pegol 200 mg Q4W

Experimental group

Description:

Certolizumab Pegol (CZP) 200 mg subcutaneous (sc) every 4 weeks (Q4W) from Week 48 onwards. At visits where CZP is not received, subjects receive one injection of Placebo to maintain the study blind.

Treatment:

Biological: Certolizumab Pegol

Other: Placebo

Placebo

Placebo Comparator group

Description:

One placebo injection is administered every 2 weeks from Week 48 onwards.

Treatment:

Other: Placebo

Placebo to CZP 200 mg Q2W escape

Other group

Description:

Subjects randomized to Placebo who meet flare criteria receive CZP 400 mg subcutaneous (sc) every 2 weeks (Q2W) for the first 3 visits after flare has been confirmed. After that, CZP 200 mg is given every 2 weeks in open-label fashion.

Treatment:

Biological: Certolizumab Pegol

Other: Placebo

CZP 200 mg Q4W to CZP 200 mg Q2W escape

Other group

Description:

Subjects randomized to CZP 200 mg Q4W who meet flare criteria receive CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, subjects receive one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.

Treatment:

Biological: Certolizumab Pegol

Other: Placebo

CZP 200 mg Q2W to CZP 200 mg Q2W escape

Other group

Description:

Subjects randomized to CZP 200 mg Q2W who meet flare criteria receive CZP 200 mg subcutaneous (sc) every 2 weeks (Q2W) for all visits after flare has been confirmed. At the first 3 visits after flare has been confirmed, subjects receive one injection of 200 mg CZP and one injection of Placebo to maintain the study blind.

Treatment:

Biological: Certolizumab Pegol

Other: Placebo