NCT02552212 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2022-08-18

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52

→

outcome · POSTED

Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12

→

outcome · POSTED

Certolizumab Pegol Plasma Concentration at Baseline

→

outcome · POSTED

Certolizumab Pegol Plasma Concentration at Week 1

→

outcome · POSTED

Certolizumab Pegol Plasma Concentration at Week 2

→

outcome · POSTED

Certolizumab Pegol Plasma Concentration at Week 4

→

outcome · POSTED

Certolizumab Pegol Plasma Concentration at Week 12

→

outcome · POSTED

Certolizumab Pegol Plasma Concentration at Week 24

→

outcome · POSTED

Certolizumab Pegol Plasma Concentration at Week 36

→

outcome · POSTED

Certolizumab Pegol Plasma Concentration at Week 52

→

outcome · POSTED

Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit

→

outcome · POSTED

Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52

→

outcome · POSTED

Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)

→

outcome · POSTED

Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI)

→

outcome · POSTED

Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

→

outcome · POSTED

Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

→

outcome · POSTED

Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score

→

outcome · POSTED

Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52

→

outcome · POSTED

Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52

→

outcome · POSTED

Change From Baseline in ASQoL at Week 1

→

outcome · POSTED

Change From Baseline in ASQoL at Week 2

→

outcome · POSTED

Change From Baseline in ASQoL at Week 4

→

outcome · POSTED

Change From Baseline in ASQoL at Week 12

→

outcome · POSTED

Change From Baseline in ASQoL at Week 24

→

outcome · POSTED

Change From Baseline in ASQoL at Week 36

→

outcome · POSTED

Change From Baseline in ASQoL at Week 48

→

outcome · POSTED

Change From Baseline in Nocturnal Spinal Pain Numerical Rating Scale (NRS) at Week 52

→

outcome · POSTED

Number of Subjects With Anterior Uveitis (AU) or New AU Flares Through Week 52

→

outcome · POSTED

Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) During the Study

→

outcome · POSTED

Percentage of Subjects With Serious Adverse Events (SAEs) During the Study

→

outcome · POSTED

Percentage of Subjects With Adverse Events Leading to Withdrawal From Investigational Medicinal Product (IMP) During the Study

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Certolizumab Pegol (CZP) 400 mg subcutaneous (sc) on Weeks 0, 2 and 4, followed by 200 mg CZP sc every 2 weeks (Q2W) from Week 6 onwards.
intervention Names
Biological: Certolizumab Pegol
label
Certolizumab Pegol 200 mg Q2W
type
EXPERIMENTAL
description
Matching placebo to Certolizumab Pegol (CZP) injections are administered every 2 weeks from Week 0 onwards.
intervention Names
Other: Placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Certolizumab Pegol 200 mg Q2W
description
* Active Substance: Certolizumab Pegol * Pharmaceutical Form: Prefilled syringe * Concentration: 200 mg / ml * Route of Administration: Subcutaneous injection
name
Certolizumab Pegol
other Names
Cimzia
CDP870
type
BIOLOGICAL
arm Group Labels
Placebo
description
* Active Substance: Placebo * Pharmaceutical Form: Prefilled syringe * Concentration: 0.9 % saline * Route of Administration: Subcutaneous injection
name
Placebo
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 317
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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").
measure
Percentage of Subjects With Ankylosing Spondylitis Disease Activity Score Major Improvement (ASDAS-MI) Response Criteria Response at Week 52
time Frame
Week 52
description
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.
measure
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 12
time Frame
Week 12
description
Certolizumab pegol plasma concentration was measured at Baseline in micrograms per millilitre (µg/mL).
measure
Certolizumab Pegol Plasma Concentration at Baseline
time Frame
Baseline (Week 0)
description
Certolizumab pegol plasma concentration was measured at Week 1, in µg/mL.
measure
Certolizumab Pegol Plasma Concentration at Week 1
time Frame
Week 1
description
Certolizumab pegol plasma concentration was measured at Week 2, in µg/mL.
measure
Certolizumab Pegol Plasma Concentration at Week 2
time Frame
Week 2
description
Certolizumab pegol plasma concentration was measured at Week 4, in µg/mL.
measure
Certolizumab Pegol Plasma Concentration at Week 4
time Frame
Week 4
description
Certolizumab pegol plasma concentration was measured at Week 12, in µg/mL.
measure
Certolizumab Pegol Plasma Concentration at Week 12
time Frame
Week 12
description
Certolizumab pegol plasma concentration was measured at Week 24, in µg/mL.
measure
Certolizumab Pegol Plasma Concentration at Week 24
time Frame
Week 24
description
Certolizumab pegol plasma concentration was measured at Week 36, in µg/mL.
measure
Certolizumab Pegol Plasma Concentration at Week 36
time Frame
Week 36
description
Certolizumab pegol plasma concentration was measured at Week 52, in µg/mL.
measure
Certolizumab Pegol Plasma Concentration at Week 52
time Frame
Week 52
description
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.
measure
Certolizumab Pegol Plasma Concentration at Follow-Up (FU) Visit
time Frame
Follow-up Visit (up to Week 60)

secondary Outcomes

description
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.
measure
Percentage of Subjects With Axial SpondyloArthritis International Society 40% Response Criteria (ASAS40) Response at Week 52
time Frame
Week 52
description
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.
measure
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
time Frame
From Baseline to Week 12
description
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.
measure
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Functional Index (BASFI)
time Frame
From Baseline to Week 52
description
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.
measure
Change From Baseline to Week 12 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
time Frame
From Baseline to Week 12
description
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.
measure
Change From Baseline to Week 52 in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
time Frame
From Baseline to Week 52
description
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.
measure
Change From Baseline to Week 12 in Sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) Score
time Frame
From Baseline to Week 12
description
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.
measure
Number of Subjects Without Relevant Changes to Background Medication From Baseline to Week 52
time Frame
From Baseline to Week 52
description
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.
measure
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52
time Frame
From Baseline to Week 52
description
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.
measure
Change From Baseline in ASQoL at Week 1
time Frame
From Baseline to Week 1
description
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.
measure
Change From Baseline in ASQoL at Week 2
time Frame
From Baseline to Week 2
description
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.
measure
Change From Baseline in ASQoL at Week 4
time Frame
From Baseline to Week 4
description
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.
measure
Change From Baseline in ASQoL at Week 12
time Frame
From Baseline to Week 12

Full study description

brief 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.

Source references

references

citation
van der Heijde D, Gensler LS, Maksymowych WP, Landewe 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 spondyloarthritis: 3-year results from the phase 3 C-axSpAnd study. RMD Open. 2022 Mar;8(1):e002138. doi: 10.1136/rmdopen-2021-002138.
pmid
35296532
type
RESULT
citation
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 Protein Status: An Analysis From the C-axSpAnd Study. ACR Open Rheumatol. 2022 Sep;4(9):794-801. doi: 10.1002/acr2.11469. Epub 2022 Jun 22.
pmid
35733363
type
RESULT
citation
Maksymowych WP, Kumke T, Auteri SE, Hoepken B, Bauer L, Rudwaleit M. Predictors of long-term clinical response in patients with non-radiographic axial spondyloarthritis receiving certolizumab pegol. Arthritis Res Ther. 2021 Oct 29;23(1):274. doi: 10.1186/s13075-021-02650-4.
pmid
34715908
type
DERIVED
citation
Deodhar A, Gensler LS, Kay J, Maksymowych WP, Haroon N, Landewe R, Rudwaleit M, Hall S, Bauer L, Hoepken B, de Peyrecave N, Kilgallen B, van der Heijde D. A Fifty-Two-Week, Randomized, Placebo-Controlled Trial of Certolizumab Pegol in Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol. 2019 Jul;71(7):1101-1111. doi: 10.1002/art.40866. Epub 2019 May 28.
pmid
30848558
type
DERIVED