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] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 objective of this study is to assess the long-term safety of CDP6038 dosed at 120mg q2w while treating the signs and symptoms of active RA in subjects who have previously failed TNFα blocker therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the long-term efficacy of CDP6038, its plasma levels, and immunogenic profile.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects completing RA0056 are eligible to participate in this study, if all of the following criteria are met: 1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject. 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 completed the RA0056 study (Week 12 Visit). 4. Subject must have maintained their stable dose (and route) of MTX between 12.5 to 25mg/week in RA0056, and plan to maintain this same dose and route of administration for at least 12 weeks. Subjects may have been dosed with 10 to ≤12.5mg weekly if they have documented reasons for toxicity. 5. 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 is not considered an acceptable method of contraception for this study. Female subjects of childbearing potential must agree to use 2 methods of adequate contraception during the study and for 6 months (24 weeks) after their last CDP6038 dose. Male subjects must agree to ensure that they or their female partner(s) use adequate contraception during the study and for 12 weeks after the subject receives their last dose of CDP6038. |
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E.4 | Principal exclusion criteria |
Subjects are not permitted to enroll in the study if any of the following criteria is met: 1. Subject has an ongoing SAE from the RA0056 study. 2. Female subject of childbearing potential has a positive pregnancy test at Week 12 in RA0056 or plans to become pregnant during the study or within 6 months (24 weeks) following their last dose of IMP. 3. Subject has evidence of active or latent tuberculosis (TB). 4. Subject is receiving any biologic response modifier or synthetic DMARD other than MTX. 5. Subject has an alcohol consumption of more than 1 unit per day. One unit equals 1 glass of beer or lager (~330mL), a glass of wine (125mL), or a measure of spirits/hard liquor (25mL). 6. Subject has planned surgery during the first 12 weeks of the study. 7. Subject with any other condition in RA0056 (eg, clinically significant laboratory values, frequent AEs or SAEs, or infection SAEs) which in the Investigator’s or Sponsor’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) |
Safety variables • AEs • Vital signs • Chest x-rays • Electrocardiograms (ECG) • Laboratory parameters
Pharmacokinetic variables • PK of CDP6038 following repeat dose administration • Anti-CDP6038 antibodies
Efficacy variables • Change from Baseline (Week 0 of RA0056) in the DAS28(CRP) at Weeks 12, 24, 48, and 96 • ACR20/50/70 improvement criteria response rates (from Baseline at Week 0 of RA0056) at Weeks 24, 48, and 96 • Percentage of subjects with DAS28(CRP) <2.6 and with DAS28(CRP) ≤3.2 at Weeks 12, 24, 48, and 96 • Change from Baseline (Week 0 of RA0056) in CDAI and SDAI at Weeks 48, and 96
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs – assessed every 2 weeks throughout the study Vital signs – assessed every 2 weeks throughout the study Chest x-rays – assessed at Week 48 and completion Electrocardiograms (ECG) – assessed at Weeks 4, 12, 24, 48 and completion Laboratory parameters – assessed at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48 and q8w thereafter to study completion |
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E.5.2 | Secondary end point(s) |
Efficacy variables include: Change from Baseline (Week 0 of RA0056) in the DAS28(CRP) ACR20/50/70 improvement criteria response rates (from Baseline at Week 0 of RA0056) Percentage of subjects with DAS28(CRP) <2.6 and with DAS28(CRP) ≤3.2 Change from Baseline (Week 0 of RA0056) in CDAI and SDAI PK and antibodies. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy variables include: Change from Baseline (Week 0 of RA0056) in the DAS28(CRP) at Weeks 12, 24, and 48 ACR20/50/70 improvement criteria response rates (from Baseline at Week 0 of RA0056) at Weeks 24, and 48 Percentage of subjects with DAS28(CRP) <2.6 and with DAS28(CRP) ≤ 3.2 at Weeks 12, 24, and 48 Change from Baseline (Week 0 of RA0056) in CDAI and SDAI at Week 48 PK and antibodies: Weeks 4, 8, 12, 16, 24, 32, 48, and 72 |
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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 | Yes |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open Label Follow-Up Study |
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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 | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | No |
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 |
Belgium |
United Kingdom |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |