E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid Arthritis (RA) |
|
E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis (RA) |
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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 | 18.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021428 |
E.1.2 | Term | Immune system disorders |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
|
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 evaluate the long-term efficacy and safety of ALX-0061 administered subcutaneously (s.c.) to subjects with active RA. |
|
E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Must have been eligible for one of the preceding Phase IIb studies with
ALX-0061 (study ALX0061-C201 or ALX0061-C202), have been randomized to placebo or one of the ALX-0061 arms (subjects randomized to tocilizumab [TCZ] in study ALX0061-C202 are not eligible), and completed the entire treatment and assessment period of the preceding studies (i.e., 24 weeks for Study ALX0061-C201 and 12 weeks for Study ALX0061-C202).
• Must have reached at least 20% improvement in SJC and/or TJC (66/68 counts) at Week 24 for subjects participating in the preceding Phase IIb ALX0061-C201 study, or at Week 12 for subjects participating in the preceding Phase IIb ALX0061-C202 study.
A complete list of selection criteria can be found in the body of the Clinical Study Protocol. |
|
E.4 | Principal exclusion criteria |
The main criteria for exclusion include the following:
• Received TCZ during the previous Study ALX0061-C202.
• Received any prohibited treatment during the previous Phase IIb
• Diagnosis of or suspicion of a serious infection
• Diagnosis of malignancy or demyelinating disease during the preceding study.
• Any active or recurrent viral infection that based on the Investigator´s clinical assessment make the subject unsuitable for the study.
• Diagnosis of congestive heart failure (CHF) class III or IV, unstable angina pectoris, myocardial infarction, cerebrovascular accident during the preceding study.
• Abnormality in laboratory test results observed at the Week 22 Visit for subjects
participating in the preceding Phase IIb ALX0061-C201 study, or observed at the Week 10 Visit for subjects participating in the preceding Phase IIb ALX0061-C202 study.
A complete list of selection criteria can be found in the body of the Clinical Study Protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- ACR20, ACR50, and ACR70 response over time.
- Disease activity: Disease Activity Score using 28 joint counts (DAS28 using CRP and erythrocyte sedimentation rate [ESR]), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI).
- EULAR DAS28 response (good, moderate, or no response).
- Remission using disease remission parameters: DAS28, SDAI, CDAI, Boolean.
- Health Assessment Questionnaire-Disability Index (HAQ-DI).
- Physical and mental component scores of Short Form Health Survey (SF-36).
- Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue).
Pharmacokinetics:
• Determination of ALX-0061 serum levels.
Safety:
• Safety assessments will include:
- Physical examinations.
- Vital sign measurements
- Clinical laboratory assessments
- Adverse events
Immunogenicity:
• Determination of anti-ALX-0061 antibodies (ADA) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 104 weeks evaluation for secondary endopoints mentioned bove (first 7 bullet points)
Pharmacokinetics: up to 104 weeks
Safety: up to 114 weeks
Immunogenicity: up to 114 weeks |
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E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 56 |
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 |
Argentina |
Belgium |
Bulgaria |
Czech Republic |
Georgia |
Germany |
Hungary |
Macedonia, the former Yugoslav Republic of |
Mexico |
Moldova, Republic of |
Poland |
Romania |
Serbia |
Spain |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
last visit of the last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |