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

A Multicenter, Open-label (Part A) Followed by a Randomized, Double-blind, Parallel-group, Placebo Controlled Study (Part B) to Evaluate Maintenance of Remission in Subjects With Active Axial Spondyloarthritis (axSpA) Receiving Either Certolizumab Pegol 200 mg Q2W or 200 mg Q4W as Compared to Placebo

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.

Study Overview

• Status: Completed
• Conditions: Ankylosing Spondylitis; Axial Spondyloarthrithis
• Intervention / Treatment: Biological: Certolizumab Pegol; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 736
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Genk, Belgium
    • As0005 1006
  • Gent, Belgium
    • As0005 1001
  • Merksem, Belgium
    • As0005 1004
  • Mons, Belgium
    • As0005 1003
• Bulgaria
  • Pleven, Bulgaria
    • As0005 1109
  • Plovdiv, Bulgaria
    • As0005 1103
  • Plovdiv, Bulgaria
    • As0005 1106
  • Ruse, Bulgaria
    • As0005 1111
  • Sevlievo, Bulgaria
    • As0005 1110
  • Sofia, Bulgaria
    • As0005 1101
  • Sofia, Bulgaria
    • As0005 1108
• Czechia
  • Brno, Czechia
    • As0005 1308
  • Bruntal, Czechia
    • As0005 1309
  • Kladno, Czechia
    • As0005 1301
  • Ostrava, Czechia
    • As0005 1307
  • Pardubice, Czechia
    • As0005 1303
  • Praha 11, Czechia
    • As0005 1305
  • Praha 2, Czechia
    • As0005 1306
  • Praha 3, Czechia
    • As0005 1314
  • Praha 4, Czechia
    • As0005 1302
  • Praha 5, Czechia
    • As0005 1310
  • Praha 5, Czechia
    • As0005 1311
  • Uherske Hradiste, Czechia
    • As0005 1313
  • Zlin, Czechia
    • As0005 1304
• France
  • Montpellier, France
    • As0005 1504
  • Orleans, France
    • As0005 1505
  • Paris, France
    • As0005 1501
  • Tours Cedex 9, France
    • As0005 1503
• Germany
  • Berlin, Germany
    • As0005 1406
  • Berlin, Germany
    • As0005 1408
  • Berlin, Germany
    • As0005 1410
  • Berlin, Germany
    • As0005 1412
  • Bochum, Germany
    • As0005 1413
  • Erlangen, Germany
    • As0005 1405
  • Frankfurt am Main, Germany
    • As0005 1404
  • Hamburg, Germany
    • As0005 1402
  • Herne, Germany
    • As0006 1409
  • Koeln, Germany
    • As0005 1407
  • Leipzig, Germany
    • As0005 1403
• Hungary
  • Budapest, Hungary
    • As0005 1705
  • Budapest, Hungary
    • As0005 1710
  • Debrecen, Hungary
    • As0005 1704
  • Miskolc, Hungary
    • As0005 1706
  • Nyiregyhaza, Hungary
    • As0005 1711
  • Szeged, Hungary
    • As0005 1707
  • Szentes, Hungary
    • As0005 1702
  • Szombathely, Hungary
    • As0005 1703
  • Veszprem, Hungary
    • As0005 1701
• Netherlands
  • Amsterdam, Netherlands
    • As0005 2502
  • Rotterdam, Netherlands
    • As0005 2503
  • Sneek, Netherlands
    • As0005 2501
• Poland
  • Bialystok, Poland
    • As0005 1806
  • Bydgoszcz, Poland
    • As0005 1805
  • Elblag, Poland
    • As0005 1801
  • Elblag, Poland
    • As0005 1802
  • Krakow, Poland
    • As0005 1812
  • Lodz, Poland
    • As0005 1808
  • Lodz, Poland
    • As0005 1814
  • Lublin, Poland
    • As0005 1803
  • Ostrowiec Swietokrzyski, Poland
    • As0005 1816
  • Poznan, Poland
    • As0005 1809
  • Poznan, Poland
    • As0005 1813
  • Torun, Poland
    • As0005 1807
  • Warszawa, Poland
    • As0005 1804
  • Warszawa, Poland
    • As0005 1811
  • Warszawa, Poland
    • As0005 1815
• Romania
  • Braila, Romania
    • As0005 1904
  • Brasov, Romania
    • As0005 1912
  • Bucuresti, Romania
    • As0005 1902
  • Bucuresti, Romania
    • As0005 1903
  • Bucuresti, Romania
    • As0005 1913
  • Cluj-Napoca, Romania
    • As0005 1907
  • Iasi, Romania
    • As0005 1910
  • Târgu-Mureş, Romania
    • As0005 1911
• Spain
  • Cordoba, Spain
    • As0005 2403
  • Getafe, Spain
    • As0005 2404
  • Madrid, Spain
    • As0005 2401
  • Sevilla, Spain
    • As0005 2402
• Taiwan
  • Kaohsiung, Taiwan
    • As0005 2205
  • Taichung, Taiwan
    • As0005 2201
  • Taichung, Taiwan
    • As0005 2202
  • Taipei, Taiwan
    • As0005 2203
  • Taipei, Taiwan
    • As0005 2204
  • Taipei, Taiwan
    • As0005 2206
• Turkey
  • Ankara, Turkey
    • As0005 2101
  • Edirne, Turkey
    • As0005 2103
  • Gaziantep, Turkey
    • As0005 2102
  • Istanbul, Turkey
    • As0005 2105
  • Istanbul, Turkey
    • As0005 2106
  • Izmir, Turkey
    • As0005 2104
• United Kingdom
  • Leeds, United Kingdom
    • As0005 1603
  • Norwich, United Kingdom
    • As0005 1601
• United States
  • Arizona
    • Glendale, Arizona, United States, 85304
      • As0005 2313
    • Mesa, Arizona, United States, 85202
      • As0005 2316
    • Phoenix, Arizona, United States, 85037
      • As0005 2314
    • Sun City, Arizona, United States, 85351
      • As0005 2317
  • California
    • Palm Desert, California, United States, 92260
      • As0005 2307
    • San Francisco, California, United States, 94143
      • As0005 2310
    • Upland, California, United States, 91786
      • As0005 2305
  • Colorado
    • Denver, Colorado, United States, 80230
      • As0005 2308
  • Florida
    • Brandon, Florida, United States, 33511
      • As0005 2302
  • Maryland
    • Hagerstown, Maryland, United States, 21742
      • As0005 2321
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • As0005 2312
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73101
      • As0005 2323
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • As0005 2311
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • As0005 2315
  • Texas
    • Austin, Texas, United States, 78731
      • As0005 2303
    • Dallas, Texas, United States, 75231
      • As0005 2318

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Open-label Certolizumab Pegol; 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.	Biological: Certolizumab Pegol; Active substance: Certolizumab Pegol; Pharmaceutical form: Prefilled syringe; Concentration: 200 mg / ml; Route of Administration: Subcutaneous injection; Other Names: Cimzia; CDP870
EXPERIMENTAL: Double-blind Certolizumab Pegol 200 mg Q2W; Certolizumab Pegol (CZP) 200 mg subcutaneous (sc) every 2 weeks (Q2W) from Week 48 onwards.	Biological: Certolizumab Pegol; Active substance: Certolizumab Pegol; Pharmaceutical form: Prefilled syringe; Concentration: 200 mg / ml; Route of Administration: Subcutaneous injection; Other Names: Cimzia; CDP870
EXPERIMENTAL: Double-blind Certolizumab Pegol 200 mg Q4W; 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.	Biological: Certolizumab Pegol; Active substance: Certolizumab Pegol; Pharmaceutical form: Prefilled syringe; Concentration: 200 mg / ml; Route of Administration: Subcutaneous injection; Other Names: Cimzia; CDP870; Other: Placebo; Active substance: Placebo; Pharmaceutical form: Prefilled syringe; Concentration: 0.9 % Saline; Route of Administration: Subcutaneous injection
PLACEBO_COMPARATOR: Placebo; One placebo injection is administered every 2 weeks from Week 48 onwards.	Other: Placebo; Active substance: Placebo; Pharmaceutical form: Prefilled syringe; Concentration: 0.9 % Saline; Route of Administration: Subcutaneous injection
OTHER: Placebo to CZP 200 mg Q2W escape; 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.	Biological: Certolizumab Pegol; Active substance: Certolizumab Pegol; Pharmaceutical form: Prefilled syringe; Concentration: 200 mg / ml; Route of Administration: Subcutaneous injection; Other Names: Cimzia; CDP870; Other: Placebo; Active substance: Placebo; Pharmaceutical form: Prefilled syringe; Concentration: 0.9 % Saline; Route of Administration: Subcutaneous injection
OTHER: CZP 200 mg Q4W to CZP 200 mg Q2W escape; 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.	Biological: Certolizumab Pegol; Active substance: Certolizumab Pegol; Pharmaceutical form: Prefilled syringe; Concentration: 200 mg / ml; Route of Administration: Subcutaneous injection; Other Names: Cimzia; CDP870; Other: Placebo; Active substance: Placebo; Pharmaceutical form: Prefilled syringe; Concentration: 0.9 % Saline; Route of Administration: Subcutaneous injection
OTHER: CZP 200 mg Q2W to CZP 200 mg Q2W escape; 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.	Biological: Certolizumab Pegol; Active substance: Certolizumab Pegol; Pharmaceutical form: Prefilled syringe; Concentration: 200 mg / ml; Route of Administration: Subcutaneous injection; Other Names: Cimzia; CDP870; Other: Placebo; Active substance: Placebo; Pharmaceutical form: Prefilled syringe; Concentration: 0.9 % Saline; Route of Administration: Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in Part B Who Did Not Experienced a Flare	A participant was considered to have experienced a flare if the participant had an Ankylosing spondylitis disease activity score (ASDAS) greater or equal to (≥) 2.1 at 2 consecutive visits or an ASDAS greater than (>) 3.5 at any visit during Part B up until Week 96. A participant qualified for Part B only if he achieved sustained remission after 48 weeks of Open-Label certolizumab pegol (CZP) treatment. Sustained remission was achieved when a participant had an ASDAS less than (<) 1.3 at Week 32 or Week 36 (if ASDAS < 1.3 at Week 32, it must have been < 2.1 at Week 36; if ASDAS < 2.1 at Week 32, it must have been < 1.3 at Week 36) and an ASDAS < 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods.	From Week 48 to Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Sustained Remission at Week 48 in Part A	Sustained remission was achieved when a participant had an ASDAS less than (<) 1.3 at Week 32 or Week 36 (if ASDAS < 1.3 at Week 32, it must have been < 2.1 at Week 36; if ASDAS < 2.1 at Week 32, it must have been < 1.3 at Week 36) and an ASDAS < 1.3 at Week 48. Missing data were handled using non-response imputation (NRI) methods.	Week 48
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 48 in Part A	The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). Disease activity was measured by categorical response variables: ASDAS-Inactive Disease (ASDAS-ID): ASDAS < 1.3; ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, < 2.1; ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5; ASDAS-very High Disease activity (ASDAS-vHD): ASDAS > 3.5 Missing data were handled using last observation carried forward (LOCF) methods.	Week 48
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 48 in Part A	The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). ASDAS improvement was measured by binary response variables: ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline; ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods.	Week 48
Time to Flare in Part B	For those who met the criteria for flare (see primary efficacy variable), the time to flare was the length in days from randomization in Part B until the visit at which the criteria for flare were met. Participants who discontinued the study without meeting the criteria for flare were counted as experiencing a flare at the time of their last study visit. The time to flare was analyzed using Kaplan-Meier methods. If Kaplan-Meier Estimate was NA for all estimates then more than 75 % failed to meet the flare condition. Missing data were handled using non-response imputation (NRI) methods.	From Week 48 to Week 96
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Week 96 in Part B	The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). Disease activity was measured by categorical response variables: ASDAS-Inactive Disease (ASDAS-ID): ASDAS < 1.3; ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, < 2.1; ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5; ASDAS-very High Disease activity (ASDAS-vHD): ASDAS > 3.5	Week 96
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Week 96 in Part B	The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). ASDAS improvement was measured by binary response variables: ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline; ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline Missing data were handled using non-response imputation (NRI) methods.	Week 96
Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Week 96 in Part B	The ASAS20 response was 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 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 absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20 % and an absolute worsening of at least 1 unit]. Missing data were handled using non-response imputation (NRI) methods.	Week 96
Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Week 96 in Part B	The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) 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. Missing data were handled using non-response imputation (NRI) methods.	Week 96
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Week 96 in Part B	The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP). Missing data were handled using non-response imputation (NRI) methods.	Week 96
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Week 96 in Part B	The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20. Missing data were handled using non-response imputation (NRI) methods.	Week 96
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 96 in Part B	The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as "below the limit of quantification" (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Week 48 to Week 96
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 96 in Part B	The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) 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 to 10, with lower scores indicating lower disease activity. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Week 48 to Week 96
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 96 in Part B	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 Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Week 48 to Week 96
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 96 in Part B	The BASMI 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 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Week 48 to Week 96
Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response Criteria Response at Week 96 in Part B	The BASDAI50 response was defined as an improvement of at least 50 % in the BASDAI score relative to Baseline. Missing data were handled using non-response imputation (NRI) methods.	Week 96
Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Week 96 in Part B	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. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Week 48 to Week 96
Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Disease Activity (ASspIMRI-a) in the Berlin Modification Score at Week 96 in Part B	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. Active inflammation was 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. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From Week 48 to Week 96
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Disease Activity Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B	The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). Disease activity was measured by categorical response variables: ASDAS-Inactive Disease (ASDAS-ID): ASDAS < 1.3; ASDAS-Moderate Disease (ASDAS-MD): ASDAS ≥ 1.3, < 2.1; ASDAS-High Disease activity (ASDAS-HD): ASDAS ≥ 2.1, ≤ 3.5; ASDAS-very High Disease activity (ASDAS-vHD): ASDAS > 3.5	Escape Week 12
Percentage of Participants in Ankylosing Spondylitis Disease Activity Score (ASDAS) Clinical Improvement Categories at Escape Week 12 for Participants Who Experienced a Flare in Part B	The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). ASDAS improvement was measured by binary response variables: ASDAS-CII: ASDAS reduction (improvement) of ≥ 1.1 relative to Baseline; ASDAS-MI: ASDAS reduction (improvement) of ≥ 2.0 relative to Baseline	Escape Week 12
Percentage of Participants With Axial SpondyloArthritis International Society 20 % Response Criteria (ASAS20) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B	The ASAS20 response was 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 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 absence of deterioration in the potential remaining domain [deterioration was defined as a relative worsening of at least 20% and an absolute worsening of at least 1 unit].	Escape Week 12
Percentage of Participants With Axial SpondyloArthritis International Society 40 % Response Criteria (ASAS40) Response at Escape Week 12 for Participants Who Experienced a Flare in Part B	The ASAS40 response was defined as a relative improvement of at least 40 % and absolute improvement of at least 2 units on a 0 to 10 Numeric Rating Scale (NRS) 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.	Escape Week 12
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) 5/6 Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B	The ASAS 5/6 response was defined as achieving at least 20 % improvement in 5 of 6 domains, including the 4 domains defined for ASAS20 as well as spinal mobility (lateral spinal flexion) and C-reactive Protein (CRP).	Escape Week 12
Percentage of Participants With Axial SpondyloArthritis International Society (ASAS) Partial Remission (PR) Response Criteria Response at Escape Week 12 for Participants Who Experienced a Flare in Part B	The ASAS partial remission (PR) response was defined as a score of ≤ 2 units on a 0 to 10 unit scale in all 4 domains listed for ASAS20.	Escape Week 12
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Escape Week 12 for Participants Who Experienced a Flare in Part B	The ASDAS was calculated as the sum of the following components: 0.121 x Back pain (BASDAI Q2 result) 0.058 x Duration of morning stiffness (BASDAI Q6 result) 0.110 x PGADA (Patient's Global Assessment of Disease Activity) 0.073 x 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). There is a minimum score of 0.636 for the total ASDAS score, but no defined upper score. Based on the formula even in the situation that the CRP is normal, any value below 4 is recorded as "below the limit of quantification" (BLQ) and a value of BLQ/2=2 was prespecified. This assumption is triggering the lowest possible value of 0.636. The change from Part B Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From time of flare to Escape Week 12
Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Escape Week 12 for Participants Who Experienced a Flare in Part B	The BASDAI is a validated self-reported instrument, which consists of six 10 unit horizontal Numeric Rating Scales (NRS) 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 to 10, with lower scores indicating lower disease activity. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From time of flare to Escape Week 12
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Escape Week 12 for Participants Who Experienced a Flare in Part B	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 flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From time of flare to Escape Week 12
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Escape Week 12 for Participants Who Experienced a Flare in Part B	The BASMI 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 was calculated for each item based on the measurement. The mean of the sum of the 5 scores provided the total BASMI score, ranging from 0 to 10. The higher the BASMI score the more severe the patient's limitation of movement due to their axial spondyloarthritis (axSpA). The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From time of flare to Escape Week 12
Change From Baseline in Sacroiliac Spondyloarthritis Research Consortium of Canada (SPARCC) Score at Escape Week 12 for Participants Who Experienced a Flare in Part B	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. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From time of flare to Escape Week 12
Change From Baseline in Spine Ankylosing Spondylitis Spine Magnetic Resonance Imaging Score for Activity (ASspIMRI-a) in the Berlin Modification Score at Escape Week 12 for Participants Who Experienced a Flare in Part B	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. Active inflammation was 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. The change from flare Baseline is calculated, a negative value indicating improvement and a positive value worsening.	From time of flare to Escape Week 12
Certolizumab Pegol (CZP) Plasma Concentration During the Study	CZP plasma concentration was measured in micrograms per milliliter (μg/mL). Blood sample measurements that were deemed to be below the level of quantification, were set to half the lower level of quantification (LLOQ) for analysis purposes. Summary statistics were only displayed if at least two-thirds of the values were above the LLOQ and if n was greater or equal to (>=) 4. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the PK of these patients. The CZP plasma concentration of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP.	From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
Percentage of Participants With Positive Anti-certolizumab Pegol-antibody Levels in Plasma During the Study	Treatment emergent ADAb status positive was defined as either baseline ADAb negative subjects having at least one ADAb confirmed positive sample post baseline or baseline ADAb positive subjects with at least one post baseline sample with >= minimum significant ratio (MSR) increase from baseline on CZP treatment. Once determined positive, the highest titer during Part A and Part B (including Escape and Safety Follow up) was used to categorize the subject. The primary purpose of the study was to evaluate treatment options for axSpA patients after being in sustained remission. Hence, one of the objectives was to evaluate the immunogenicity of these patients. The ADAb titer of the patients that did not reach sustained remission were therefore not analysed, and the Pharmacokinetic Set A as described in the protocol was removed from the SAP.	From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
Percentage of Participants With at Least One Adverse Event (AE) During Part A of the Study	An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	From Screening Period (Week -5 to Week -1) until Week 48
Percentage of Participants With at Least One Adverse Event (AE) During Part B of the Study	An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. For subjects with flare in Part B and do escape to CZP full-dose therapy, only TEAEs with an onset date prior to the start date of escape CZP full-dose therapy were included.	From Week 0 until the Safety Follow-up Visit (10 weeks after the last dose of study medication)
Percentage of Participants With at Least One Adverse Event (AE) and Who Experienced a Flare During Part B of the Study	An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. For subjects with flare in Part B and do escape to CZP full-dose therapy, only TEAEs with an onset date after or on the start date of escape CZP full-dose therapy were included.	From time of flare to Escape Week 12

Collaborators and Investigators

• Sponsor: UCB BIOSCIENCES GmbH
• Collaborators: Parexel

Publications and helpful links

General Publications

• Landewe RB, van der Heijde D, Dougados M, Baraliakos X, Van den Bosch FE, Gaffney K, Bauer L, Hoepken B, Davies OR, de Peyrecave N, Thomas K, Gensler LS. Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction. Ann Rheum Dis. 2020 Jul;79(7):920-928. doi: 10.1136/annrheumdis-2019-216839. Epub 2020 May 7. Erratum In: Ann Rheum Dis. 2020 Sep;79(9):e120.
• Landewe R, van der Heijde D, Dougados M, Baraliakos X, Van den Bosch F, Gaffney K, Bauer L, Hoepken B, de Peyrecave N, Thomas K, Gensler LS. Induction of Sustained Clinical Remission in Early Axial Spondyloarthritis Following Certolizumab Pegol Treatment: 48-Week Outcomes from C-OPTIMISE. Rheumatol Ther. 2020 Sep;7(3):581-599. doi: 10.1007/s40744-020-00214-7. Epub 2020 Jun 11.

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2015
• Primary Completion (ACTUAL): February 1, 2019
• Study Completion (ACTUAL): April 1, 2019

Study Registration Dates

• First Submitted: July 16, 2015
• First Submitted That Met QC Criteria: July 20, 2015
• First Posted (ESTIMATE): July 22, 2015

Study Record Updates

• Last Update Posted (ACTUAL): December 17, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Arthritis; Certolizumab Pegol; Remission; Ankylosing Spondylitis; Spinal Diseases; Immunosuppressive Agents; Axial Spondyloarthritis; axSpA; Anti TNF-alpha; Spondylarthropathies
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Certolizumab Pegol
• Other Study ID Numbers: AS0005; 2015-000339-34 (EUDRACT_NUMBER)