Multicenter Study Evaluating Certolizumab Pegol Compared to Placebo in Subjects With axSpA Without X-ray Evidence of AS

Axial Spondyloarthritis Clinical Trial

— C-AXSPAND  

Official title:

Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Efficacy and Safety of Certolizumab Pegol in Subjects With Active Axial Spondyloarthritis (axSpA) Without X-Ray Evidence of Ankylosing Spondylitis (AS) and Objective Signs of Inflammation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02552212
• Other study ID #: AS0006
• Secondary ID: 2015-001894-41
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: May 2020

Study information

• Verified date: August 2022
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with active Axial Spondyloarthritis without x-ray evidence of Ankylosing Spondylitis and with signs of inflammation will be randomly assigned to receive certolizumab pegol (CZP) 200 mg every two weeks or placebo. The primary objective is to demonstrate the efficacy of CZP in these patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 317
• Est. completion date: May 2020
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• At least 18 years old at the start of Screening Visit

• A documented diagnosis of adult-onset axial SpondyloArthritis (axSpA) and meet the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA

• Subjects must have had back pain for at least 12 months before Screening

• No sacroiliitis defined by Modified New York (mNY) criteria on sacroiliac (SI) x-rays

• Active disease at Screening as defined by

• Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >= 4

• Spinal pain >= 4 on a 0 to 10 Numerical Rating Scale (NRS)

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

Exclusion Criteria:

• Diagnosis of AS or any other Inflammatory Arthritis

• Prior treatment with any experimental biological agents for treatment of Axial SpondyloArthritis (SpA)

• Exposure to more than 1 tumor necrosis factor (TNF)-antagonist or primary failure to TNF antagonist therapy

• History of or current chronic or recurrent infections

• Subjects with known Tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent Tuberculosis (LTB)

• 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

• Axial Spondyloarthritis
• Nonradiographic Axial Spondyloarthritis
• Nr-axSpA
• Spondylarthritis
• Spondylitis

Intervention

Biological:
• Certolizumab Pegol
Active Substance: Certolizumab Pegol Pharmaceutical Form: Prefilled syringe Concentration: 200 mg / ml Route of Administration: Subcutaneous injection

Other:
• Placebo
Active Substance: Placebo Pharmaceutical Form: Prefilled syringe Concentration: 0.9 % saline Route of Administration: Subcutaneous injection

Locations

Country	Name	City	State
Australia	As0006 208	Camperdown
Australia	As0006 210	Coffs Harbour
Australia	As0006 204	Footscray
Australia	As0006 201	Malvern East
Australia	As0006 209	Maroochydore
Australia	As0006 205	South Hobart
Australia	As0006 202	Victoria Park
Bulgaria	As0006 302	Plovdiv
Bulgaria	As0006 305	Plovdiv
Bulgaria	As0006 304	Ruse
Bulgaria	As0006 306	Sevlievo
Bulgaria	As0006 300	Sofia
Bulgaria	As0006 307	Sofia
Bulgaria	As0006 309	Sofia
Bulgaria	As0006 308	Varna
Canada	As0006 152	Edmonton
Canada	As0006 150	Victoria
Czechia	As0006 326	Hlucín
Czechia	As0006 324	Hustopece
Czechia	As0006 327	Olomouc
Czechia	As0006 320	Ostrava
Czechia	As0006 322	Pardubice
Czechia	As0006 323	Praha
Czechia	As0006 329	Praha
Czechia	As0006 330	Praha
Czechia	As0006 328	Praha 2
Czechia	As0006 333	Príbor
Czechia	As0006 332	Rychnov Nad Knežnou
Czechia	As0006 331	Zlín
Hungary	As0006 365	Balatonfüred
Hungary	As0006 362	Budapest
Hungary	As0006 363	Budapest
Hungary	As0006 361	Szekesfehervar
Poland	As0006 406	Bydgoszcz
Poland	As0006 400	Elblag
Poland	As0006 401	Kraków
Poland	As0006 402	Kraków
Poland	As0006 411	Lublin
Poland	As0006 403	Poznan
Poland	As0006 404	Poznan
Poland	As0006 405	Torun
Poland	As0006 407	Warszawa
Poland	As0006 408	Warszawa
Poland	As0006 409	Warszawa
Poland	As0006 410	Warszawa
Poland	As0006 413	Wroclaw
Poland	As0006 414	Wroclaw
Russian Federation	As0006 461	Chelyabinsk
Russian Federation	As0006 453	Ivanovo
Russian Federation	As0006 450	Kazan
Russian Federation	As0006 451	Kazan
Russian Federation	As0006 458	Kemerovo
Russian Federation	As0006 455	Moscow
Russian Federation	As0006 466	Moscow
Russian Federation	As0006 462	Orenburg
Russian Federation	As0006 452	Ryazan'
Russian Federation	As0006 459	Saint Petersburg
Russian Federation	As0006 463	Saint Petersburg
Russian Federation	As0006 464	Saint Petersburg
Russian Federation	As0006 467	Saint Petersburg
Russian Federation	As0006 465	Samara
Russian Federation	As0006 454	Saratov
Russian Federation	As0006 460	Smolensk
Russian Federation	As0006 456	Tolyatti
Russian Federation	As0006 457	Yaroslavl
Taiwan	As0006 232	Hualien City
Taiwan	As0006 230	Taichung City
Taiwan	As0006 233	Taichung City
Taiwan	As0006 231	Taipei
United States	As0006 148	Atlanta	Georgia
United States	As0006 155	Beverly Hills	California
United States	As0006 125	Birmingham	Alabama
United States	As0006 127	Boston	Massachusetts
United States	As0006 114	Brooklyn	New York
United States	As0006 118	Charlotte	North Carolina
United States	As0006 102	Cumberland	Maryland
United States	As0006 141	Cumberland	Maryland
United States	As0006 117	Daytona Beach	Florida
United States	As0006 116	DeBary	Florida
United States	As0006 108	Duncansville	Pennsylvania
United States	As0006 110	Eagan	Minnesota
United States	As0006 124	Fort Lauderdale	Florida
United States	As0006 137	Idaho Falls	Idaho
United States	As0006 158	Manitowoc	Wisconsin
United States	As0006 160	New Haven	Connecticut
United States	As0006 133	New Port Richey	Florida
United States	As0006 149	Oklahoma City	Oklahoma
United States	As0006 113	Onalaska	Wisconsin
United States	As0006 156	Orangeburg	South Carolina
United States	As0006 101	Palm Desert	California
United States	As0006 144	Philadelphia	Pennsylvania
United States	As0006 138	Plantation	Florida
United States	As0006 105	Portland	Oregon
United States	As0006 123	Rochester	Minnesota
United States	As0006 103	Saint Louis	Missouri
United States	As0006 107	Salt Lake City	Utah
United States	As0006 143	San Francisco	California
United States	As0006 120	Scottsdale	Arizona
United States	As0006 104	Seattle	Washington
United States	As0006 134	Tampa	Florida
United States	As0006 115	Tucson	Arizona
United States	As0006 106	Vero Beach	Florida
United States	As0006 111	Wheaton	Maryland
United States	As0006 147	Worcester	Massachusetts
United States	As0006 129	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
UCB BIOSCIENCES GmbH

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Hungary,  Poland,  Russian Federation,  Taiwan, 

References & Publications (2)

Robinson PC, Maksymowych WP, Gensler LS, Hall S, Rudwaleit M, Hoepken B, Bauer L, Kumke T, Kim M, de Peyrecave N, Deodhar A. Certolizumab Pegol Efficacy in Patients With Non-Radiographic Axial Spondyloarthritis Stratified by Baseline MRI and C-Reactive Pr — View Citation

van der Heijde D, Gensler LS, Maksymowych WP, Landewé R, Rudwaleit M, Bauer L, Kumke T, Kim M, Auteri SE, Hoepken B, Deodhar A. Long-term safety and clinical outcomes of certolizumab pegol treatment in patients with active non-radiographic axial spondyloa — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52	This variable was considered as primary in all countries except for Canada (and any other country where applicable or where requested by Regulatory Authorities) where it was considered as secondary variable.; ASDAS-MI was achieved when there was a reduction (improvement) >= 2.0 in the ASDAS relative to Baseline, or when the lowest possible ASDAS score (0.6) was reached.; The ASDAS was calculated as the sum of the following components: 0.121 × Back pain (BASDAI Q2 result) 0.058 × Duration of morning stiffness (BASDAI Q6 result) 0.110 × Patient's Global Assessment of Disease Activity (PGADA) 0.073 × Peripheral pain/swelling (BASDAI Q3 result) 0.579 × (natural logarithm [ln] of the (CRP [mg/L] + 1)) Back pain, PGADA, duration of morning stiffness, peripheral pain/swelling and fatigue were all assessed on a numerical scale (0 to 10 units, where 0 is "not active" and 10 is "very active").	Week 52
Primary	Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12	This variable was considered as primary for Canada (and any other country where applicable or where requested by Regulatory Authorities) and as secondary variable in all other countries.; The ASAS40 response was defined as relative improvements of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is "not active" and 10 is "very active" in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.	Week 12
Primary	Certolizumab Pegol Plasma Concentration at Baseline	Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL).	Baseline (Week 0)
Primary	Certolizumab Pegol Plasma Concentration at Week 1	Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.	Week 1
Primary	Certolizumab Pegol Plasma Concentration at Week 2	Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.	Week 2
Primary	Certolizumab Pegol Plasma Concentration at Week 4	Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.	Week 4
Primary	Certolizumab Pegol Plasma Concentration at Week 12	Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.	Week 12
Primary	Certolizumab Pegol Plasma Concentration at Week 24	Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.	Week 24
Primary	Certolizumab Pegol Plasma Concentration at Week 36	Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.	Week 36
Primary	Certolizumab Pegol Plasma Concentration at Week 52	Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.	Week 52
Primary	Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit	Certolizumab pegol plasma concentration was measured at the Follow-Up Visit, in µg/mL.; Follow-Up Visit was defined as 8 weeks after Week 52 or Withdrawal (WD) visit for subjects not participating in the Safety Follow-Up Extension (SFE) Period.	Follow-up Visit (up to Week 60)
Secondary	Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52	The ASAS40 response was defined as relative improvements of at least 40% and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS), where 0 is "not active" and 10 is "very active" in at least 3 of the 4 domains: Patient's Global Assessment of Disease Activity (PGADA), Pain assessment (total spinal pain NRS scores), Function (Bath Ankylosing Spondylitis Functional Index (BASFI)), Inflammation (mean of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) questions 5 and 6 concerning morning stiffness intensity and duration) and no worsening at all in the remaining domain.	Week 52
Secondary	Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)	The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 12
Secondary	Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI)	The BASFI is a validated disease-specific instrument for assessing physical function. The BASFI comprises 10 items relating to the past week. The BASFI is the mean of the 10 scores such that the total score ranges from 0 (Easy) to 10 (Impossible), with lower scores indicating better physical function. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 52
Secondary	Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)	The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 12
Secondary	Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)	The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales to measure the disease activity of ankylosing spondylitis (AS) from the subject's perspective. It measures the severity of fatigue, spinal and peripheral joint pain and swelling, enthesitis, and morning stiffness (both severity and duration) over the last week. The final BASDAI scores ranges from 0 (not active) to 10 (very active), with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 52
Secondary	Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score	The Spondyloarthritis Research Consortium of Canada (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. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 12
Secondary	Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52	The number of subjects who did not have relevant changes to background medications during the study treatment period.; A subject is without relevant changes to background medication if they do not have: the addition of a new disease-modifying antirheumatic drug (DMARD) or the change from one DMAR to another; the addition of an nonsteroidal anti-inflammatory drug (NSAID) or the change from one NSAID to another; an increased dose of chronic corticosteroids; the addition of a new chronic analgesic medication or increased dose in chronic analgesic medication; and they complete double-blind study treatment to Week 52.	From Baseline to Week 52
Secondary	Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 52
Secondary	Change From Baseline in ASQoL at Week 1	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 1
Secondary	Change From Baseline in ASQoL at Week 2	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 2
Secondary	Change From Baseline in ASQoL at Week 4	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 4
Secondary	Change From Baseline in ASQoL at Week 12	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 12
Secondary	Change From Baseline in ASQoL at Week 24	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 24
Secondary	Change From Baseline in ASQoL at Week 36	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 36
Secondary	Change From Baseline in ASQoL at Week 48	The ASQoL score ranged from 0 to 18 with higher score indicating worse Health-Related Quality of Life (HRQoL) and 0 indicating good HRQoL. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 48
Secondary	Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52	The nocturnal spinal pain experienced by subjects due to AS was measured by following question 'How much pain of your spine due to spondylitis do you have at night?'. The NRS ranged from 0 to 10, where 0 represented 'no pain' and 10 represented 'most severe pain'. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Baseline to Week 52
Secondary	Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52	The number of subjects with AU or new AU flares during the study treatment period.	Throughout the study conduct (up to Week 52)
Secondary	Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Secondary	Percentage of Subjects With Serious Adverse Events (SAEs) During the Study	A serious adverse event (SAE) is any untoward medical occurrence that at any dose: Results in death; Is life-threatening; Requires in patient hospitalization or prolongation of existing hospitalization; Is a congenital anomaly or birth defect; Is an infection that requires treatment parenteral antibiotics; Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above.	From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)
Secondary	Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study	An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From Baseline up to the End of Safety Follow-up Extension Period (up to Week 156)

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