E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Active Systemic Lupus Erythematosus |
|
E.1.1.1 | Medical condition in easily understood language |
Systemic Lupus Erythematosus |
|
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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025139 |
E.1.2 | Term | Lupus erythematosus systemic |
E.1.2 | System Organ Class | 100000004859 |
|
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 different dose regimens of ALX-0061 administered subcutaneously (s.c.) to subjects with moderate to severe active, seropositive SLE compared to placebo. |
|
E.2.2 | Secondary objectives of the trial |
To assess the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, flare rate, steroid reduction and health-related quality of life, with different dose regimens of ALX-0061. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female adults ≥ 18 years and < 65 years of age.
2. Have a diagnosis of SLE for at least 6 months prior to screening and fulfill the 1997 ACR or 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria.
3. Have moderate to severe active SLE.
5. Have seropositive disease at screening.
6. Subject must be at least on one or more of the treatments for SLE as defined in the protocol.
Others as defined in the protocol. |
|
E.4 | Principal exclusion criteria |
1. Have an A score on the revised BILAG-2004 other than in the mucocutaneous and/or musculoskeletal system at screening and at baseline for the organ systems that can be clinically assessed.
2. Have a systemic inflammatory disease other than SLE.
3. Clinically significant infection treated or needing treatment.
4. Any active or recurrent viral infection that based on the Investigator´s clinical assessment makes the subject unsuitable for the study.
5. Have a history of, or current, class III or IV congestive heart failure.
6. Have received prior therapy blocking the IL-6 pathway.
Others as defined in the protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of subjects who achieved a response at Week 24 according to the composite mBICLA (BILAG-based Combined Lupus Assessment) score. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1) Change in SLE disease activity as measured by change in: composite (m)BICLA, mSRI (modified Systemic lupus erythematosus responder index), standard SRI, (m)SRI with more stringent (m)SLEDAI-cut-offs: SRI-5, SRI-6, SRI-7, SRI-8, mSLEDAI-2K, standard SLEDAI 2K, BILAG2004, physician's global assessment
2) The change from baseline in patient's global assessment over time.
3) The change from baseline in renal parameters
4) The number of patients with treatment failures
5) The number of patients with a reduction in flare rate
6) The change from baseline in corticosteroids use
7) The change from baseline in the physical and mental component scores of SF-36
8) Change from baseline in joints count over time
9) The change from baseline of Cutaneous lupus erythematosus disease area and severity index (CLASI)
10) The determination of ALX-0061 in blood samples
11) The determination of biomarkers in blood samples
12) The determination of anti-ALX-0061 antibodies in blood samples
13) The incidence of adverse events and serious adverse events.
14) The change from baseline in clinical laboratory parameters. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) From screening to Week 48
2) Week 48
3) Week 48
4) Week 24 and Week 48
5) Week 24 and Week 48
6) Week 24 and Week 48
7) Week 24 and Week 48
8) Week 48
9) Week 12, Week 24 and Week 48
10) Week 48
11) Week 60
12) Week 60
13) Week 60
14) From screening to week 60 |
|
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 | 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 | 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.8.2.4 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Chile |
Czech Republic |
Germany |
Hungary |
Korea, Republic of |
Mexico |
Peru |
Philippines |
Poland |
Portugal |
Russian Federation |
Serbia |
Spain |
Taiwan |
Ukraine |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 28 |