Multicenter study evaluating certolizumab pegol compared to placebo in subjects with axSpA without X-ray evidence of AS

• Register: EUCTR
• Last refreshed on: 15 June 2020
• Main ID: EUCTR2015-001894-41-HU
• Date of registration: 19/08/2015
• Prospective Registration: Yes
• Primary sponsor: UCB BIOSCIENCES GmbH
• Public title: Multicenter study evaluating certolizumab pegol compared to placebo in subjects with axSpA without X-ray evidence of AS
• Scientific 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.
• Date of first enrolment: 16/10/2015
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001894-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Bulgaria, Canada, Czech Republic, Hungary, Poland, Russian Federation, Taiwan, United States

Contacts

• Name: Clin Trial Reg & Results Disclosure
• Affiliation: UCB BIOSCIENCES GmbH

• Name: Clin Trial Reg & Results Disclosure
• Affiliation: UCB BIOSCIENCES GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject or legal representative.
2. Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete questionnaires), visit schedule, or medication intake according to the judgment of the Investigator.
3. Subject is at least 18 years old at the Screening visit.
4. Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and spermicide).
Abstinence only is not an acceptable method. Subjects must agree to use adequate contraception during the study and for at least 10 weeks (or [for participating countries of the EU – 5 months in accordance with the Summary of Product Characteristics, SPC] longer if required by local regulations) after the last dose of study treatment. Male subjects must agree to ensure they or their female partner(s) use adequate contraception during the study and for at least 10 weeks (or [for participating countries of the EU - 5 months in accordance with the SPC] longer if required by local regulations) after their last dose of study treatment.
5. Subjects must have a documented diagnosis of adult-onset axSpA and met the ASAS criteria for axSpA (not including family history and good response to NSAIDs; see Appendix 18.1).
6. Subjects must have had back pain for at least 12 months before Screening.
7. Subjects must NOT have sacroiliitis defined by mNY criteria (see Appendix18.2) (bilateral =Grade 2; unilateral =Grade 3) on SI joint x-rays (based on central reading of x-rays, within the last 12 months from Baseline).
8. Subjects must have active disease as defined by each of the following at Screening and Baseline:
- BASDAI score =4
- Spinal pain =4 on a 0 to 10 NRS (from BASDAI item 2)
9. Subjects must have a combination of current evidence of sacroiliitis on the screening MRI as defined by ASAS/OMERACT scoring confirmed via central reading (MRI+) and CRP either >upper limit of normal (ULN) or =ULN (for CRP the ULN is defined as the ULN indicative for inflammatory disease) at Baseline (CRP+ or CRP-), or no evidence of sacroiliitis on the screening MRI (MRI-) and CRP >ULN (CRP+) as follows:
- MRI+/CRP+
- MRI+/CRP-
- MRI-/CRP+
10. Subjects must have had an inadequate response to, have a contraindication to, or have been intolerant to at least 2 NSAIDs. Inadequate response to an NSAID is defined as lack of response to at least 14 days of continuous NSAID therapy at the highest tolerated dose of the administered NSAID.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 290
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1. Subject has previously participated in this study or subject has previously been assigned to treatment in a study of the medication under investigation in this study.
2. Subject has participated in another study of an investigational medicinal product (IMP) (or a medical device) within the previous 3 months (or 5 half-lives, whichever is greater) or is currently participating in another study of an IMP (or a medical device).
3. Subject has history of chronic alcohol abuse or drug abuse within the last year.
4. Subject has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject’s ability to participate in this study.
5. Subject has a known hypersensitivity to any components of the IMP or comparative drugs as stated in this protocol.

Axial SpA-disease-related exclusions
6. Subjects must not have AS or any other inflammatory arthritis (eg, RA, systemic lupus erythematosus, or sarcoidosis).
7. Subject must not have fibromyalgia.
8. Subjects must not have a secondary, noninflammatory condition (eg, osteoarthritis) that in the Investigator’s opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the subject’s primary diagnosis of axSpA.

9. Prior medications exclusions Subjects must not have used the following medications in the manner as detailed by the exclusion criteria in the following table in the study protocol (see Table 7?1).

10- 13. Previous clinical studies and previous biological therapy exclusions- for details, please refer to page 52 of the study protocol.
14-30. Medical History Exclusions- for details, please refer to pages 52-54 of the study protocol.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

ACTIVE AXIAL SPONDYLOARTHRITIS (AXSPA) WITHOUT X-RAY EVIDENCE OF ANKYLOSING SPONDYLITIS (AS) AND OBJECTIVE SIGNS OF INFLAMMATION
MedDRA version: 20.0 Level: LLT Classification code 10076297 Term: Non-radiographic axial spondyloarthritis System Organ Class: 100000004859

Intervention(s)

Trade Name: CIMZIA certolizumab pegol 200 mg/ml solution for injection
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CERTOLIZUMAB PEGOL
CAS Number: 428863-50-7
Current Sponsor code: CDP870
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To demonstrate the efficacy of CZP 200mg Q2W on the signs and symptoms of subjects with active axSpA without x-ray evidence of AS.

Primary end point(s): 1. Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI) response at Week 52
2. Axial SpondyloArthritis International Society 40% response criteria (ASAS40) response at Week 12 (this primary variable is applicable for countries where requested by regulatory authorities)
3. Certolizumab pegol plasma concentration at Baseline
4. Certolizumab pegol plasma concentration at Week 1
5. Certolizumab pegol plasma concentration at Week 2
6. Certolizumab pegol plasma concentration at Week 4
7. Certolizumab pegol plasma concentration at Week 12
8. Certolizumab pegol plasma concentration at Week 24
9. Certolizumab pegol plasma concentration at Week 36
10. Certolizumab pegol plasma concentration at Week 52
11. Certolizumab pegol plasma concentration at Follow-Up Visit

Secondary Objective: To assess efficacy, safety, and tolerability and to
demonstrate the effect of CZP on:
- Health outcomes
- Disease Activity
- SI joint inflammation through MRI
- Changes in concomitant and background medications

Timepoint(s) of evaluation of this end point: 1.; 10. Week 52
2.; 7. Week 12
3. Baseline (Week 0)
4. Week 1
5. Week 2
6. Week 4
8. Week 24
9. Week 36
11. Follow-Up Visit (8 weeks after the Week 52)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Week 52
2.; 4.; 6.; 12.; From Baseline to Week 12
3.; 5.; 7.; 8.; 16.; 17.; From Baseline to Week 52
9. From Baseline to Week 1
10. From Baseline to Week 2
11. From Baseline to Week 4
13. From Baseline to Week 24
14. From Baseline to Week 36
15. From Baseline to Week 48
18.-20. From Baseline until Follow-Up (FU)/Safety Follow-Up Extension (SFE) (up to Week 60/156)

Secondary end point(s): 1. Axial SpondyloArthritis International Society 40% response criteria (ASAS40) at Week 52
2. Change from Baseline to Week 12 in the Bath ankylosing spondylitis functional index (BASFI)
3. Change from Baseline to Week 52 in the Bath ankylosing spondylitis functional index (BASFI)
4. Change from Baseline to Week 12 in the Bath ankylosing spondylitis disease activity index (BASDAI)
5. Change from Baseline to Week 52 in the Bath ankylosing spondylitis disease activity index (BASDAI)
6. Change from Baseline to Week 12 in sacroiliac Spondyloarthritis Research Consortium of Canada (SI-SPARCC) score
7. Relevant changes to background medication from Baseline to Week 52
8. Change from Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 52
9. Change from Baseline in ASQoL at Week 1
10. Change from Baseline in ASQoL at Week 2
11. Change from Baseline in ASQoL at Week 4
12. Change from Baseline in ASQoL at Week 12
13. Change from Baseline in ASQoL at Week 24
14. Change from Baseline in ASQoL at Week 36
15. Change from Baseline in ASQoL at Week 48
16. Change from Baseline in nocturnal spinal pain Numerical Rating Scale (NRS) at Week 52
17. Occurence of anterior uveitis (AU) or new AU flares through Week 52
18. Incidence of treatment-emergent adverse events (TEAEs) during the study
19. Incidence of serious adverse events (SAEs) during the study
20. Adverse events leading to withdrawal from investigational medicinal product (IMP) during the study

Secondary ID(s)

AS0006

NCT02552212

Source(s) of Monetary Support

UCB BIOSCIENCES GmbH

Ethics review

Status: Approved
Approval date: 05/10/2015
Contact: