E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
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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 trial is to evaluate the efficacy of atacicept compared to placebo in preventing new flares in subjects with SLE. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of the trial are: - To evaluate the safety and tolerability profile of atacicept in treated subjects with SLE, - To confirm the optimal dose of atacicept for treatment of subjects with SLE, - To gain further information on the effect of atacicept on relevant markers specific to its mechanism of action (MoA) and their correlation to disease activity/progression, - To further characterise the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of atacicept, and - To identify genetic and genomic variations associated with drug response and disease activity/progression. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of SLE satisfying at least 4 out of the 11 ACR criteria at the time of diagnosis, with a disease duration of at least six months. 2. Active SLE with at least one BILAG A or B score at initial screening (excluding a single B due to haematological values) requiring a change in the dose of corticosteroids. 3. Positive antinuclear antibody (ANA) test results (HEp-2 ANA ≥1:80 and/or anti dsDNA ≥30 IU/mL) (subjects will be tested at screening). 4. Male or female ≥18 years of age. 5. Written informed consent, given before any study-related procedure. Subjects must have read and understood the Informed Consent Form, must fully understand the requirements of the study and must be willing to comply with all study visits and assessments. For subjects under the age of legal majority (according to local law), the subject and a legal guardian must read and sign the informed consent. 6. Female subjects must be willing to avoid pregnancy by using an adequate method of contraception for 4 weeks prior to Study Day 1, during the trial and 24 weeks after the last dose of study medication. This requirement does not apply to surgically sterile subjects or to subjects who are post-menopausal for at least 2 years. Adequate contraception is defined as two barrier methods, or one barrier method with a spermicide, or an intrauterine device or use of a female hormonal contraceptive. 7. Women of childbearing potential must have a negative serum pregnancy test at initial screening and at the end of screening before dosing. For the purpose of this study, women of childbearing potential are defined as all female subjects after puberty unless they are post-menopausal for at least 2 years or surgically sterile.
In addition, to be eligible for inclusion into this trial, subjects must fulfil the following criteria at the end of the initial flare treatment period: 8. Improvement of the qualifying BILAG A or B flare to BILAG C or D within 10 weeks after commencing steroid treatment. 9. Use of an appropriate steroid regimen for the qualifying flare during the screening period, with stability of the dose at 7.5 mg of prednisone or equivalent for 2 weeks after improvement to BILAG C or D. 10. No other new BILAG A or B at an assessment performed following confirmation of stable steroid dose.
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E.4 | Principal exclusion criteria |
1. Any condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that constitutes a risk or a contraindication for participation to the study in the opinion of the Investigator or that could interfere with study objectives, conduct or evaluation. 2. Active moderate to severe glomerulonephritis 3. Active central nervous system SLE deemed to be severe or progressive and/or associated with significant cognitive impairment leading to inability to provide informed consent and/or comply with the protocol. 4. Comorbidities requiring systemic corticosteroid therapy (such as asthma or inflammatory bowel disease) and/or preventing engagement in study conduct. 5. Any history of treatment with rituximab, abatacept or belimumab. 6. Introduction of azathioprine, hydroxychloroquine, chloroquine, or methotrexate within 2 months before initial screening or increase in the dose regimen of any of these medications within 2 months before initial screening. 7. Initiation of any immunosuppressive drug within 3 months before initial screening. 8. Participation in any interventional clinical trial within the last 28 days or within 5 half-lives of the investigated compound (whichever is longer) before initial screening. 9. Treatment with cyclophosphamide mycophenolate mofetil or a calcineurin inhibitor within 3 months before initial screening. 10. Treatment with leflunomide, 6-mercaptopurine or thalidomide within 3 months before initial screening. 11. Active infection with herpes zoster or Epstein-Barr virus at initial screening. 12. Positive HIV serology (subjects will be tested at screening). 13. Positive hepatitis B surface antigen (HBsAg) or hepatitis C serology (subjects will be tested at screening). 14. History or presence of tuberculosis infection without documentation of adequate treatment, or treatment that occurred in the past year. Subjects should be evaluated and screened for tuberculosis according to national or local recommendations. 15. Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalisation or treatment with parenteral anti-infectives within 4 weeks of baseline or completion of oral anti-infectives within 2 weeks prior to screening. 16. Diagnosis or family history of Creutzfeldt-Jakob disease (CJD). 17. History or presence of uncontrolled or New York Heart Association (NYHA) class 3 or 4 congestive heart failure. 18. History of cancer, except for adequately treated basal cell carcinoma of the skin, cervical dysplasia or carcinoma in situ of the skin or the cervix. 19. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (AP) level > 2.5 x ULN, or total bilirubin > 1.5 x ULN. 20. Clinically significant abnormality in any haematological test (e.g. haemoglobin < 5.5 mmol/L, WBC < 2.5 x 10^9/L, platelets < 75 x 10^9/L) unless attributable to active SLE. 21. Serum immunoglobulin G below 6 g/L. 22. Clinically significant abnormality on chest X-ray performed within 3 months of initial screening or on ECGs performed at initial screening unless attributable to active SLE. 23. Hypersensitivity to any of the components of the formulated atacicept. 24. Immunisation with live vaccines or Ig treatment within 1 month before Study Day 1. 25. Planned major surgery during the trial period (including follow-up). 26. Active alcohol or drug abuse or history of alcohol or drug abuse in the last 6 months. 27. Breastfeeding or pregnancy. 28. History of any demyelinating disease, such as MS or ON.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint of this trial is the proportion of subjects experiencing a new flare (as defined by a British Isles Lupus Assessment Group [BILAG] score of A or B) during the 52-week treatment period following randomisation. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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
| Information not present in EudraCT |
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 | 50 |
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 |
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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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For administrative and safety reporting purposes, the end of the trial will be defined as the date of the final clinical database lock. This provides for a single and conservative definition across all trial sites. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |