Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis - Full Text View

Purpose

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).

Condition	Intervention	Phase
Spondyloarthropathies	Biological: CZP 200 mg Q2W Biological: CZP 400 mg Q4W Other: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis

Resource links provided by NLM:

Drug Information available for: Certolizumab pegol

U.S. FDA Resources

Further study details as provided by UCB, Inc.:

Primary Outcome Measures:

Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) response criteria at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
The ASAS20 is defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 following domains:
- Patient's Global Assessment of Disease Activity
- Pain assessment (total spinal pain)
- Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI))
- Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration)
and absence of deterioration in the potential remaining domain (deterioration is defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit).

Secondary Outcome Measures:

Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) response criteria at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
The ASAS20 is defined as an improvement of at least 20 % and absolute improvement of at least 1 unit on a 0 to 10 Numeric Rating Scale (NRS) in at least 3 of the 4 following domains:
- Patient's Global Assessment of Disease Activity
- Pain assessment (total spinal pain)
- Function (represented by Bath Ankylosing Spondylitis Functional Index (BASFI))
- Inflammation (the mean of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6 concerning morning stiffness intensity and duration)
and absence of deterioration in the potential remaining domain (deterioration is defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit).
Change from Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 12 [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
The BASFI assesses physical function in comprising 10 items relating to activities during the past week. Each item ranges from 0 ("Easy") to 10 ("Impossible"). The BASFI is the mean of the 10 scores such that the total score ranges from 0 to 10, with lower scores indicating better physical function.
Change from Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24 [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
The BASFI assesses physical function in comprising 10 items relating to activities during the past week. Each item ranges from 0 ("Easy") to 10 ("Impossible"). The BASFI is the mean of the 10 scores such that the total score ranges from 0 to 10, with lower scores indicating better physical function.
Change from Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 12 [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
The BASDAI is a validated self-reported instrument which consists of six 10 unit horizontal Numerical Rating Scales (NRSs) to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration, respectively) over the last week. The final BASDAI score ranges from 0 to 10, with lower scores indicating lower disease activity.
Change from Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24 [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
The BASDAI is a validated self-reported instrument which consists of six 10 unit horizontal Numerical Rating Scales (NRSs) to measure severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration, respectively) over the last week. The final BASDAI score ranges from 0 to 10, with lower scores indicating lower disease activity.
Change from Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 12 [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
The BASMI characterizes the spinal mobility of subjects with axial SpA and AS. It is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 is calculated for each item based on the measurement. The mean of the sum of the 5 scores provides the BASMI score. The higher the BASMI score the more severe the patient's limitation of movement due to their axial SpA.
Change from Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 24 [ Time Frame: From Baseline to Week 24 ] [ Designated as safety issue: No ]
The BASMI characterizes the spinal mobility of subjects with axial SpA and AS. It is a disease-specific measure consisting of 5 clinical measures to reflect subject axial status: cervical rotation; tragus to wall distance; lateral lumbar flexion; lumbar flexion (modified Schober test); intermalleolar distance. According to the linear definition of the BASMI a score of 0 to 10 is calculated for each item based on the measurement. The mean of the sum of the 5 scores provides the BASMI score. The higher the BASMI score the more severe the patient's limitation of movement due to their axial SpA.
Change from Baseline in the spine Ankylosing Spondylitis spine Magnetic Resonance Imaging (MRI) scoring system for disease activity (ASspiMRI-a) in the Berlin modification at Week 12 [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
The Berlin modification of the ASspiMRI-a is a scoring system with a concentration on Short-Tau-Inversion Recovery (STIR) sequences without other fat saturation techniques. It quantifies changes in 23 Vertebral Units (VU) of the spine. A VU is defined as the region between 2 virtual lines through the middle of each vertebra. Active inflammation is scored by grading the degree of bone marrow edema from 0 to 3 in 1 dimension on 1 or more consecutive slices that represent the highest level of inflammation in a particular VU. Total spine ASspiMRI-a score in the Berlin modification can range from 0 to 69.
Change from Baseline in sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) scores at Week 12 [ Time Frame: From Baseline to Week 12 ] [ Designated as safety issue: No ]
The SPARCC scoring method for lesions found on the Magnetic Resonance Imaging (MRI) is based on an abnormal increased signal on the Short-Tau-Inversion Recovery (STIR) sequence, representing bone marrow edema. Total sacroiliac (SI) joint SPARCC scores can range from 0 to 72.

Enrollment:	325
Study Start Date:	March 2010
Estimated Study Completion Date:	August 2015
Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: CZP 200 mg Q2W 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.	Biological: CZP 200 mg Q2W 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). Other Names: Cimzia CZP Certolizumab Pegol Other: Placebo Matching Placebo to CZP injection.
Experimental: CZP 400 mg Q4W 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.	Biological: CZP 400 mg Q4W 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W). Other Names: Cimzia CZP Certolizumab Pegol Other: Placebo Matching Placebo to CZP injection.
Placebo Comparator: Placebo 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.	Other: Placebo Matching Placebo to CZP injection.
Placebo to CZP 200 mg escape on Week 16 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.	Biological: CZP 200 mg Q2W 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). Other Names: Cimzia CZP Certolizumab Pegol Other: Placebo Matching Placebo to CZP injection.
Placebo to CZP 400 mg escape on Week 16 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.	Biological: CZP 400 mg Q4W 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W). Other Names: Cimzia CZP Certolizumab Pegol Other: Placebo Matching Placebo to CZP injection.
Placebo to CZP 200 mg on Week 24 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.	Biological: CZP 200 mg Q2W 200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W). Other Names: Cimzia CZP Certolizumab Pegol Other: Placebo Matching Placebo to CZP injection.
Placebo to CZP 400 mg on Week 24 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.	Biological: CZP 400 mg Q4W 400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W). Other Names: Cimzia CZP Certolizumab Pegol Other: Placebo Matching Placebo to CZP injection.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01087762

Show 104 Study Locations

Sponsors and Collaborators

UCB BIOSCIENCES GmbH

Investigators

Study Director:

UCB Clinical Trial Call Center

+1 877 822 9493 UCB

More Information

No publications provided

Responsible Party:	UCB, Inc. ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier:	NCT01087762 History of Changes
Other Study ID Numbers:	AS001, 2009-011719-19
Study First Received:	March 15, 2010
Last Updated:	May 2, 2013
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Belgium: Federal Agency for Medicinal Products and Health Products Czech Republic: State Institute for Drug Control France: L’Agence nationale de sécurité du médicament et des produits de santé Germany: Paul-Ehrlich-Institut Hungary: National Institute of Pharmacy Ireland: Irish Medicines Board Italy: Ministry of Health Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Poland: The Central Register of Clinical Trials Spain: Agencia Española de Medicamentos y Productos Sanitarios United Kingdom: Medicines and Healthcare Products Regulatory Agency Brazil: National Health Surveillance Agency Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Mexico: Federal Commission for Sanitary Risks Protection

Keywords provided by UCB, Inc.:

Certolizumab Pegol
Cimzia

Additional relevant MeSH terms:

Spondylarthritis
Spondylarthropathies
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis

Joint Diseases
Bone Diseases, Infectious
Infection
Immunoglobulin Fab Fragments
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013