| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Classification code | 10039073 |
|
| 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 |
| To compare the efficacy of two dose regimens of liquid formulation certolizumab pegol in combination with MTX to MTX alone in treating the signs and symptoms of patients with active rheumatoid arthritis. |
|
| E.2.2 | Secondary objectives of the trial |
To assess two dose regimens of certolizumab pegol in combination with MTX and MTX alone in:
The safety and tolerability of certolizumab pegol in patients with active RA.
The prevention of joint damage in patients with active RA.
Health Outcomes Measures in patients with active RA.
Improving physical function in patients with active RA.
To characterize the pharmacokinetic profile and immunogenicity of two dose regimens of liquid formulation certolizumab pegol in combination with methotrexate. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Patients must be at least 18 years old at the screening visit.
2. Patients must have a clear chest X–ray within three months prior to the Baseline visit (negative for TB).
3. Female patients of childbearing potential must have a negative serum pregnancy test at the screening visit and negative urine testing immediately before every certolizumab pegol administration. Females must be surgically sterile, postmenopausal for at least 2 years prior to screening visit, must have undergone tubal ligation or be using an acceptable method of birth control for the duration of the study and for 12 weeks after the last dose of certolizumab pegol. Oral contraceptives must be stable for at least 28 days prior to screening visit. Abstinence is not an acceptable method of contraception for the study.
4. Patients must have a diagnosis of adult–onset RA of at least six months duration but not longer than fifteen years as defined by the 1987 American College of Rheumatology classification criteria.
5. Patients must have active RA disease as defined by:
≥9 tender joints at Screening and Baseline.
≥9 swollen joints at Screening and Baseline.
and fulfilling 1 of the following 2 criteria during the screening period:
a) ≥30 mm/hour ESR (Westergren),
or
b) CRP >15 mg/L.
6. Patients must have received treatment with MTX (with or without folic acid) for at least 6 months prior to the Baseline visit. The dose of MTX and route of administration must have been stable for at least 2 months prior to the baseline visit. The minimum stable dose of MTX allowed is 10 mg weekly.
7. Patients must be willing to complete an X–ray of the hands and feet 24 weeks after randomization even if they are no longer receiving study treatment in the present study, provided they have not withdrawn their informed consent.
8. Patients must be able to understand the information provided to them and to give written Informed Consent. |
|
| E.4 | Principal exclusion criteria |
RA Disease–Related Exclusions:
1. Patients must not have a diagnosis of any other inflammatory arthritis (e.g., psoriatic arthritis or ankylosing spondylitis).
2. Patients must not have a secondary, non–inflammatory type of arthritis (e.g. OA or fibromyalgia) that in the Investigator’s opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the patient’s primary diagnosis of RA.
3. Patients must not have a history of an infected joint prosthesis at any time with that prosthesis still in situ. Concomitant medication exclusions
4. Patients must be free of prohibited medication as detailed on page 33 & 34 of the protocol.
Previous clinical trials and previous biological therapy exclusion:
5. Patients must not have received any experimental non–biological therapy, within or outside a clinical trial in the three months prior to Baseline visit.
6. Patients must not have received any biological therapy for RA within six months prior to Baseline visit, except for etanercept and anakinra where a three month washout prior to baseline visit is acceptable.
7. Patients must not have received previous treatment with a biological therapy for RA that resulted in a severe hypersensitivity reaction or an anaphylactic reaction.
8. Patients who failed to respond to previous treatment with an anti–TNF drug are excluded. Patients who initially responded to a previous treatment with an anti-TNF drug but who later discontinued that drug due to loss of efficacy or other reasons may be included.
Medical History Exclusion:
9. Female patients who are breast feeding, pregnant, or plan to become pregnant during the trial or for three months following last dose of study drug.
10. Patients with a history of chronic infection, recent serious or life–threatening infection within 6 months (including herpes zoster), or any current sign or symptom that may indicate an infection.
11. Patients with a history of tuberculosis or positive chest X–ray for tuberculosis or positive (defined as positive induration per local medical practice) PPD skin test. Patients with a positive PPD skin test associated with previous vaccination where there is no clinical or radiographic suspicion of TB may be enrolled at the discretion of the Investigator. Consideration should be given to the fact that a positive PPD skin test with prior vaccination does not exclude latent TB.
12. Patients at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections and patients who are permanently bed ridden or wheelchair bound).
13. Patients with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease at any time.
14. Patients with a known positive hepatitis B surface antigen test and/or hepatitis C antibody test result.
15. Patients with known human immunodeficiency virus (HIV) infection.
16. Patients receiving any vaccination (live or attenuated) within eight weeks prior to Baseline. (However, influenza and pneumococcal vaccines are allowed).
17. Patients with an active malignancy of any type or a history of malignancy (except basal cell carcinoma of the skin that has been excised prior to study start).
18. Patients with a history of blood dyscrasias.
19. Patients with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral diseasewhich would interfere with the patient’s participation in the trial.
20. Patients with class III or IV congestive heart failure New York Heart Association (NYHA) 1964.
21. Patients with a history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis).
22. Patients with a history of an adverse reaction to PEG or a protein medicinal product.
23. Patients with any other condition (e.g. clinically significant laboratory values) which in the Investigator’s judgment would make the patient unsuitable for inclusion in the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary endpoint and analysis:
The primary efficacy variable is the ACR20 responder rate at Week 24 (Visit 17). The study will be declared successful for the treatment of signs and symptoms objective if at least one of the two dose comparisons to placebo is statistically significant for the ACR20 endpoint.
Treatment comparisons versus placebo for the two certolizumab pegol dose groups will be performed using logistic regression with factors for treatment and country. Statistical tests will be performed two–tailed at the 2.5% level of significance. |
|
| 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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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 | No |
| 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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
|
| The end of study is defined as the date of final Clinical Study Report. At this time, interactions between the Sponsor and the Investigator(s) with possible impact on subject’s data have ended. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
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