Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis

Spondyloarthropathies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01087762
• Other study ID #: AS001
• Secondary ID: 2009-011719-19
• Status: Completed
• Phase: Phase 3
• Start date: March 2010
• Est. completion date: August 2015

Study information

• Verified date: November 2016
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 325
• Est. completion date: August 2015
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Spondylarthritis
• Spondylarthropathies
• Spondyloarthropathies

Intervention

Biological:
• CZP 200 mg Q2W
200 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 2 weeks (Q2W).
• CZP 400 mg Q4W
400 mg subcutaneous (sc) injection of Certolizumab Pegol (CZP) every 4 weeks (Q4W).

Other:
• Placebo
Matching Placebo to CZP injection.

Locations

Country	Name	City	State
Argentina	700	Buenos Aires
Argentina	701	Buenos Aires
Argentina	704	Buenos Aires
Argentina	705	Cordoba
Argentina	709	La Plata
Argentina	706	Rosario
Argentina	710	San Juan
Argentina	702	San Miguel de Tucuman
Argentina	708	San Miguel de Tucuman
Belgium	153	Brussels
Belgium	152	Gent
Belgium	151	Liege
Brazil	760	Campinas
Brazil	750	Curitiba
Brazil	761	Goiânia
Brazil	756	Sao Paulo
Canada	902	Sainte Foy	Quebec
Canada	900	St. John's	Newfoundland and Labrador
Canada	907	Victoria	British Columbia
Canada	910	Windsor	Ontario
Canada	903	Winnipeg	Manitoba
Czechia	504	Brno
Czechia	501	Hlucin
Czechia	500	Pardubice
Czechia	502	Praha 2
Czechia	505	Terezin
Czechia	503	Zlin
France	200	Boulogne-Billan Court
France	201	Lille
France	205	Limoges
France	206	Montpellier
France	204	Paris
France	202	Tours
Germany	257	Berlin
Germany	258	Berlin
Germany	255	Freiburg
Germany	254	Hamburg
Germany	250	Herne
Germany	253	Leipzig
Germany	260	München
Germany	263	München
Germany	256	Ratingen
Hungary	303	Budapest
Hungary	305	Budapest
Hungary	302	Debrecen
Hungary	306	Miskolc
Hungary	300	Veszprém
Italy	352	Ancona
Italy	351	Firenze
Italy	350	Pisa
Mexico	802	Cuernavaca
Mexico	801	Monterrey
Netherlands	401	Maastricht
Netherlands	400	Rotterdam
Poland	458	Bialystok
Poland	452	Dabrowka
Poland	455	Elblag
Poland	459	Gdanks
Poland	457	Krakow
Poland	450	Lublin
Poland	454	Poznan
Poland	453	Torun
Poland	456	Warszawa
Poland	462	Warszawa
Spain	550	Mérida
Spain	554	Santander
Spain	552	Santiago de Compostela
Spain	553	Sevilla
United Kingdom	605	Barnsley
United Kingdom	600	Leeds
United Kingdom	602	London
United Kingdom	601	Salford
United States	963	Asheville	North Carolina
United States	957	Aventura	Florida
United States	961	Birmingham	Alabama
United States	985	Brooklyn	New York
United States	977	Cleveland	Ohio
United States	975	Dallas	Texas
United States	972	Duncansville	Pennsylvania
United States	969	Eagan	Minnesota
United States	965	Florissant	Missouri
United States	984	Flowood	Mississippi
United States	962	Fort Lauderdale	Florida
United States	964	Hagerstown	Maryland
United States	978	Houston	Texas
United States	983	Houston	Texas
United States	974	La Jolla	California
United States	973	Los Angeles	California
United States	951	Middleburg Heights	Ohio
United States	970	Oklahoma City	Oklahoma
United States	959	Orange Park	Florida
United States	966	Palm Desert	California
United States	954	Peoria	Arizona
United States	990	Pinellas Park	Florida
United States	982	Portland	Oregon
United States	950	Saint Louis	Missouri
United States	981	Salt Lake City	Utah
United States	967	San Antonio	Texas
United States	952	San Diego	California
United States	971	Scottsdale	Arizona
United States	968	Seattle	Washington
United States	987	Tucson	Arizona
United States	953	Tuscaloosa	Alabama
United States	958	Vero Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
UCB BIOSCIENCES GmbH

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Mexico,  Netherlands,  Poland,  Spain,  United Kingdom, 

References & Publications (1)

Landewé R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, Reveille JD, Rudwaleit M, van der Heijde D, Stach C, Hoepken B, Fichtner A, Coteur G, de Longueville M, Sieper J. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloar — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) Response Criteria at Week 12	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).	Week 12
Secondary	Assessment in Axial Spondyloarthritis International Society 20 % (ASAS20) Response Criteria at Week 24	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).	Week 24
Secondary	Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 12	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. A negative value in BASFI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.	From Baseline to Week 12
Secondary	Change From Baseline in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24	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. A negative value in BASFI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.	From Baseline to Week 24
Secondary	Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 12	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. A negative value in BASDAI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.	From Baseline to Week 12
Secondary	Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24	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. A negative value in BASDAI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.	From Baseline to Week 24
Secondary	Change From Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 12	The BASMI characterizes the spinal mobility of subjects with axial Spondyloarthritis (SpA) and Ankylosing Spondylitis (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. A negative value in BASMI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.	From Baseline to Week 12
Secondary	Change From Baseline in the Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 24	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. A negative value in BASMI change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.	From Baseline to Week 24
Secondary	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	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 with higher scores indicating higher disease activity. A negative value in total spine ASspiMRI-a score change from Baseline indicates an improvement from Baseline. The higher the negative value the higher the reduction of inflammation.	From Baseline to Week 12
Secondary	Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 12	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 score can range from 0 to 72 with higher scores indicating higher joint inflammation. A negative value in SPARCC change from Baseline indicates an improvement from Baseline. The higher the negative value the higher the reduction of inflammation.	From Baseline to Week 12

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