Active axial spondyloarthritis (AxSpa) MedDRA version: 19.0 Level: PT Classification code 10071400 Term: Axial spondyloarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Cimzia
Product Name: Certolizumab pegol
Product Code: CDP870
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CERTOLIZUMAB PEGOL
CAS Number: 428863-50-7
Concentration unit:
Sponsors
UCB BIOSCIENCES GmbH
Eligibility
Sex/Gender
All
Inclusion 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 by the parent(s) or legal representative. 2. Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, or medication intake according to the judgment of the Investigator. 3. Subject is at least 18 years old and not older than 45 years at the start of 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 (including 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 after the last dose of study treatment for at least 10 weeks (or - for participating countries of the European Union - 5 months in accordance with the Summary of Product Characteristics [SmPC]) or longer, if required by local regulations after the last dose of study treatment. Male subjects must agree to ensure that also their female partner(s) use adequate contraception during the study and for at least 10 weeks (or - for participating countries of the European Union - 5 months in accordance with the SmPC) or longer, if required by local regulations after the subject receives their last dose of study treatment. 5. Subjects must have a documented diagnosis of adult-onset axSpA with at least 3 months' symptom duration as defined by the specified ASAS criteria (according to Appendix 18.1) and symptom duration of less than 5 years prior to the participation of this study. 6. Subjects must have active disease at Screening as defined by the study protocol 7. 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 750 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Subject has previously participated in this study or has been assigned to treatment in a study of the medication under investigation in this study. 2.Subject has participated in another study of an IMP (or a medical device) within the previous 3 months (or five 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 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. 6. Subjects must not have fibromyalgia or total spinal ankylosis or any other inflammatory arthritis. 7.Subjects must not have a secondary, noninflammatory condition that is symptomatic enough to interfere with evaluation of the effect of study medication on the subject's primary diagnosis of axSpA. 8.Subjects must not have used medications as detailed in the protocol. 9.Subjects must not have received any nonbiological therapy for axSpA not listed above within or outside a clinical study in the 3 months or within 5 half-lives prior to the Baseline Visit (whichever is longer). 10.Subjects must not have received any experimental biological agents. 11.Subjects must not have received previous treatment with a PEGylated compound that resulted in a severe hypersensitivity reaction or an anaphylactic reaction. 12.Subjects may not have been exposed to more than 1 TNF antagonist prior to the Baseline Visit and may not be a primary failure to TNF antagonist therapy. 13.Female subjects who are breastfeeding or pregnant. 14.Subjects with a history of chronic or recurrent infections recent serious or life-threatening infection within the 6 months prior to the Baseline Visit. 15.Subjects with a history of herpes zoster infection within 6 months prior to the Baseline Visit. 16. Subjects with known TB infection are excluded. 17.Subjects with current acute or chronic viral hepatitis B or C or with HIV infection. 18.Subjects with current or a history of active infection with histoplasma, coccidiodes, paracoccidioides, pneumocystis, nontuberculous mycobacteria, blastomyces, or aspergillus. 19.Subjects must not have had a history of an infected joint prosthesis.20.Subjects receiving any live vaccination within the 8 weeks prior to Baseline. 21.Subjects who have a high risk of infection. 22.Subjects with a history of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease. 23.Current malignancy or a history of malignancy. 24.Subjects with Class III or IV congestive heart failure as per the NYHA 1964 criteria. 25.Subjects with a history of or suspected demyelinating disease of the central nervous system. 26.Subjects who have had major surgery within 8 weeks prior to Screening or have planned surgery within 6 months of the Screening Visit. 27.Subjects with current or history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, or neurological disease, as determined by the Investigator. 28. Subjects with significant laboratory abnormalities as specified in the protocol. 29.Subjects with any other condition that would make the subject unsuitable for inclusion in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the percentage of subjects who do not experience a flare on CZP 200mg Q2W (full dose) or 200mg Q4W (half-dose) as compared to placebo (CZP withdrawal) during Part B.;Secondary Objective: The secondary objectives are to: -Evaluate the percentage of subjects achieving sustained remission at the end of Part A -For subjects randomized into Part B: 1. Evaluate the time to flare and other measures of signs and symptoms 2. Compare the percentage of subjects who do not experience a flare between CZP full-dose and half-dose 3. Evaluate the efficacy of re-initiation of treatment with the CZP full-dose in subjects who experience a flare following a withdrawal or dose reduction of CZP -Assess safety and tolerability of CZP -Evaluate inflammatory changes over time as assessed by MRI;Primary end point(s): The percentage of subjects in Part B who do not experience a flare.;Timepoint(s) of evaluation of this end point: For the time to flare endpoint, the rules as described above for the primary endpoint will be applied to account for missing data when determining whether or not a subject experienced a flare. Subjects who discontinue the study without meeting the criteria for flare will be censored at the time of their last study visit. Subjects who complete the study without meeting the criteria for flare will be censored at their Week 96 visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): A) Secondary efficacy variables for subjects entering Part A -Percentage of subjects achieving sustained remission at Week 48 -ASDAS disease activity (Ankylosing Spondylitis Disease Activity Score-Inactive Disease [ASDAS-ID], Ankylosing Spondylitis Disease Activity Score Moderate Disease [ASDAS-MD], Ankylosing Spondylitis Disease Activity Score-High Disease activity [ASDAS-HD], and Ankylosing Spondylitis Disease Activity Score-very High Disease activity [ASDAS-vHD]) and clinical improvement (Ankylosing Spondylitis Disease Activity Score-Clinically Important Improvement [ASDAS-CII], Ankylosing Spondylitis Disease Activity Score-Major Improvement [ASDAS-MI]) at Week 48 B) Secondary efficacy variables for subjects entering Part B -Time to flare -ASDAS disease activity (ASDAS ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and clinical improvement (ASDAS-CII, ASDAS MI) at Week 96 -ASAS20, ASAS40, ASAS5/6, and ASAS PR response at Week 96 -Change from Baseline in ASDAS, BASDAI, BASFI, and BASMI at Week 96 -BASDAI50 response at Week 96 -Change from Baseline in sacroiliac SPARCC and spine ASspIMRI-a in the Berlin modification scores at Week 96 C) Secondary efficacy variables for subjects who experience a flare in Part B (These will be evaluated at 12 weeks after escape and at Week 96, or a later timepoint, if applicable. The minimum full-dose treatment for the escapers is 12 weeks and could extend beyond the Week 96 visit.) -ASDAS disease activity (ASDAS-ID, ASDAS-MD, ASDAS-HD, and ASDAS-vHD) and clinical improvement (ASDAS-CII, ASDAS MI) -ASAS20, ASAS40, ASAS5/6, and ASAS PR response -Change from Baseline in ASDAS, BASDAI, BASFI, BASMI, and MRI;Timepoint(s) of evaluation of this end point: Selected continuous secondary efficacy variables will be analyzed using MMRM methods (see Section 14.3.2.2 for details). Missing data for binary response secondary efficacy variables will be handled using NRI. Secondary variables related to MRI will be analyze | — |
Countries
Belgium, Bulgaria, Czech Republic, France, Germany, Hungary, Netherlands, Poland, Romania, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactCT Registries & Results Disclosure
UCB BIOSCIENCES GmbH
Outcome results
None listed