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 | 18.0 |
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 |
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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 |
•To assess the efficacy and safety of dose regimens of ALX-0061 administered s.c. in combination with MTX to subjects with active RA despite MTX therapy compared with placebo. |
|
E.2.2 | Secondary objectives of the trial |
•To assess the effects of ALX-0061 on quality of life, PK, PD, and immunogenicity of ALX 0061, and to define the optimal dose regimen for ALX 0061, based on safety and efficacy, for further clinical development. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The main criteria for inclusion include the following:
• Man or woman ≥ 18 years and < 75 years of age at the time of signing the informed consent form.
• Diagnosis of RA (according to the 2010 European League Against Rheumatism [EULAR]/American College of Rheumatology [ACR] classification criteria) for at least 6 months prior to screening, and ACR functional class I-III.
• Treated with and tolerating MTX
• Active RA as defined, for the purpose of this study, by persistent disease activity with at least 6 swollen and 6 tender joints (66/68-joint count), at the time of screening and baseline, and C-reactive protein (CRP) ≥ 1.2 x upper limit of normal (ULN) at screening.
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:
• Have been treated with DMARDs/systemic immunosuppressives other than MTX, during the 4 weeks or 12 weeks for hydroxychloroquine, chloroquine, or leflunomide (except when an adequate wash-out procedure for leflunomide was completed), prior to first administration of study drug.
• Have received approved or investigational biological or targeted synthetic DMARD therapies for RA less than 6 months prior to screening.
• For subjects who received prior rituximab, subjects with an inadequate recovery of B cells should be excluded regardless of when they received rituximab.
• Have a history of toxicity, non-tolerance, primary non-response or inadequate response to a biological therapy, or targeted synthetic DMARDs for RA.
• Have received prior therapy blocking the interleukin-6 (IL-6) pathway at any time.
A complete list of selection criteria can be found in the body of the Clinical Study Protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction of signs and symptoms of RA |
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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) |
- 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
- Pharmacodynamics
- Safety
- Immunogenicity |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 weeks evaluation for secondary endopoints mentioned bove (first 7 bullet points)
PK: 24 weeks
PD, safety and immunogenicity: For the complete duration of the study |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
United States |
|
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
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last visit of the last subject |
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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 | 8 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |