Atacicept phase II/III in Generalized Systemic Lupus Erythematosus (APRIL SLE)
- Conditions
- Systemic Lupus ErythematosusMedDRA version: 14.1Level: PTClassification code 10042945Term: Systemic lupus erythematosusSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
- Registration Number
- EUCTR2007-003698-13-CZ
- Lead Sponsor
- Merck Serono S.A. Geneva. An affiliate of Merck KGaA, Darmstadt, Germany
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 510
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 =16 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
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. Brea
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method