A randomized trial to investigate the reset of humoral autoimmunity by combining belimumab with rituximab in severe systemic lupus erythematosus

You may be able to join if

• Adults with the age of 18 years and above
• Have a clinical diagnosis of SLE according to the SLICC criteria 2012
• Severe, active SLE disease, defined as a situation in which 1 or more of the following criteria are met: a. SLEDAI (SLE Disease Activity Index) with 12 or more points b. New or worse SLE-related activity of major organs, i.e.: CNS-SLE (includes NPSLE), vasculitis, nephritis, pericarditis and/or myocarditis, myositis, thrombocytopenia < 60, hemolytic anemia < 4.4mmol/L (=7.0g/dL) c. high disease activity that requires or warrants induction treatment by switching to or increasing dosage of oral mycophenolate
• New, persisting or progressive disease activity despite the use of conventional maintenance immunosuppressive treatment (e.g. mycophenolate or azathioprine)
• Positive for relevant SLE-specific autoantibodies defined as a situation in which 1 or more of the following criteria are met: a. ANA seropositivity, as defined by a positive ANA-titer ≥ 1:80, before and at screening : - Positive test results from 2 independent time points within the study screening period; OR - One positive historical test result and 1 positive result during the screening period. Historical documentation of a positive test of ANA (eg, ANA by HEp-2 titer, ANA by ELISA) must include the date of the test. b. Anti-DNA seropositivity, as defined by a positive anti-dsDNA serum antibody ≥ 30 IU/mL, before and at screening: - Positive test results from 2 independent time points within the study screening period. - One positive historical test result and 1 positive result during the screening period. Historical documentation of a positive test of anti-dsDNA (eg, anti-dsDNA by Farr assay or ELISA) must include the date of the test.
• Female subjects are eligible to enter the study if she is: - Not pregnant or nursing - Of non-child-bearing potential (i.e. after hyseterectomy, postmenopausal, bilateral ovariectomy or documented bilateral tubal ligation or other permanent female sterilization procedure) - in agreement to not become pregnant (if female subjects of childbearing potential) and therefore must be sexually inactive by abstinence or use contraceptive methods with a failure rate of < 1%. 16 Version: 10.0 Date: April 19, 2022 Therefore, these women must have a negative serum pregnancy test at screening, and agree to 1 of the following with respect to the use of effective contraception: • Complete abstinence from intercourse from 2 weeks prior to administration of the 1st dose of study agent until 16 weeks after the last dose of study agent (Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study intervention. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred lifestyle of the participant.) Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception); OR • Consistent and correct use of 1 of the following acceptable methods of birth control for 1 month prior to the start of the study agent, during the study, and 16 weeks after the last dose of study agent: o Oral contraceptive, either combined or progestogen alone o Injectable progestogen o Implants of levonorgestrel or etonogestrel o Estrogenic vaginal ring o Percutaneous contraceptive patches o Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure rate as stated in the product label o Bilateral tubal occlusion (documentation in the CRF based on investigator's /designee’s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records. o Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, “documented” refers to the outcome of the investigator's/designee’s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records. o Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) • These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring subjects understand how to properly use these methods of contraception. • Female subjects using mycophenolate mofetil (MMF) should be made aware that MMF affects the metabolism of oral contraceptives and may reduce their effectiveness. As such, women receiving MMF who are using oral contraceptives for birth control should employ an additional method (e.g., barrier method), resulting in two reliable forms of contraception being used simultaneously before starting study treatments, during therapy, and for 6 weeks after stopping therapy; unless abstinence is the chosen method of contraception