E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of the study are to demonstrate the efficacy of CZP administered sc at the dose of 200mg every 2 weeks or 400mg every 4 weeks after loading with 400mg at Weeks 0, 2, and 4 on the signs and symptoms of active PsA and on the inhibition of progression of structural damage in adults with active PsA. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess the effects on safety and tolerability and to demonstrate the effects of CZP on:
• Health outcomes
• Psoriatic skin disease in the subgroup of affected subjects (>3% BSA) at Baseline
• Dactylitis
• Enthesitis
• Axial involvement in subgroup of affected subjects (BASDAI ≥4) at Baseline |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject must be at least 18 years old at the Screening Visit.
2. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent is signed and dated by the subject or designee/witness.
3. Subject is considered reliable, willing, and capable of adhering to the protocol, visit schedule, and medication intake according to the judgment of the Investigator.
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, or 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 longer as per local requirement) after the last dose of study treatment. Male subjects must agree to ensure that they or their female partner(s) use adequate contraception during the study and for at least 10 weeks (or longer as per local requirement) after the subject receives their last dose of study treatment.
5. Subject must have a diagnosis of adult onset PsA of at least 6 months’ duration as defined by the CASPAR criteria (see Appendix 17.1).
6. Subject must have active psoriatic skin lesions or a documented history of PSO.
7. Subject must have active arthritis as defined in the protocol.
8. Subjects must have failed 1 or more disease modifying antirheumatic drug (DMARDs).
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E.4 | Principal exclusion criteria |
Subject:
1. has previously participated in this study or has previously received CZP treatment in or outside of another clinical study.
2. has participated in another study of a medication or a medical device under investigation within the last 3 months or is currently participating in another study of a medication or medical device under investigation.
3. has history of chronic alcohol abuse or drug abuse within the last year.
4. has any medical or psychiatric condition that, in the opinion of the Investigator, can jeopardize or would compromise the subject’s ability to participate in this study.
5. has a known hypersensitivity to any components of CZP, placebo or with a history of an adverse reaction to polyethylene glycol (PEG).
6. must not have a diagnosis of any other inflammatory arthritis.
7. must not have a secondary, noninflammatory condition 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 PsA.
8. must not have used medications in the manner as detailed by the exclusion criteria in the protocol.
9. must not have received any nonbiological therapy for PsA not listed in section "Prior medications exclusion" of the protocol within or outside a clinical study in the 3 months or within 5 half lives prior to Baseline (whichever is longer).
10. must not have received experimental biological agents other than those listed in Table 6:1 and Table 6:2 of the protocol.
11. must not have received previous treatment with a PEGylated compound that resulted in a severe hypersensitivity reaction or an anaphylactic reaction.
12. may not have been exposed to more than 1 TNF antagonist prior to the Baseline Visit and may not be a primary failure to any TNF antagonist therapy (as defined in the protocol).
13. may not have been exposed to more than 2 previous biological response modifiers for PsA or PSO.
14. Female who are breastfeeding, pregnant, or plan to become pregnant during the study or within 3 months following the last dose of investigational product.
15. with a history of chronic or recurrent infections (more than 3 episodes requiring antibiotics/antivirals during the preceding year), recent serious or life threatening infection within the 6 months prior to the Baseline Visit (including herpes zoster), hospitalization for any infection in the last 6 months, or any current sign or symptom that may indicate an infection.
16. with known TB disease, high risk of acquiring TB infection, or latent TB infection, as defined in the protocol.
17. with concurrent acute or chronic viral hepatitis B or C or with known human immunodeficiency virus infection (HIV).
18. with known history of or current clinically active infection with Histoplasma, Coccidiodes, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, Blastomyces, or Aspergillus.
19. with a history of an infected joint prosthesis at any time with that prosthesis still in situ.
20. receiving any live (includes attenuated) vaccination within the 8 weeks prior to Baseline.
21. with a high risk of infection in the Investigator’s opinion.
22. with a history of a lymphoproliferative disorder including lymphoma or current signs and symptoms suggestive of lymphoproliferative disease.
23. with concurrent malignancy or a history of malignancy (subjects with less than 3 excised basal cell carcinomas or with cervical carcinoma in situ successfully surgically treated more than 5 years prior to Screening may be included).
24. with class III or IV congestive heart failure as per the New York Heart Association 1964 criteria.
25. with a history of, or suspected, demyelinating disease of the central nervous system.
26. having had major surgery (including joint surgery) within the 8 weeks prior to Screening, or having planned surgery within 6 months after entering the study.
27. with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, or neurological disease.
28. with clinically significant laboratory abnormalities (as defined in the protocol).
29. with any other condition which, in the Investigator’s judgment, would make the subject unsuitable for inclusion in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy variables:
(1) ACR20 response at Week 12
(2) change from Baseline in mTSS at Week 24
Pharmacokinetic and pharmacodynamic variables:
- Certolizumab pegol plasma concentrations at periods defined in the protocol.
- Anti-certolizumab pegol antibodies at periods defined in the protocol.
- Biomarker and cytokine levels may be analyzed for exploratory research using selected samples collected for measurement of CZP plasma concentration as defined in the protocol.
Safety variables:
- adverse events
- serious adverse events,
- vital signs,
- physical examination
- signs and symptoms of latent or active tuberculosis
- measurements of laboratory parameters (hematology, biochemistry and urinalysis)
- pregnancy testing |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key secondary efficacy variables:
(1) ACR20 response at Week 24
(2) Change from Baseline in HAQ-DI at Week 24
(3) Change from Baseline in mTSS at Week 48
(4) PASI75 response at Week 24 in the subgroup of subjects with PSO
involving at least 3% BSA at Baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
(1) Week 24
(2) Week 24
(3) Week 48
(4) Week 24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
from week 24 to 48: no placebo, dose-blind for subjects/investigators and from week 48: open-label |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Canada |
European Union |
Mexico |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of the last visit of the last subject in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |