Synergetic B-cell Immunomodulation in SLE - 2nd Study.

• Register: ClinicalTrials.gov
• Last refreshed on: 16 October 2023
• Main ID: NCT03747159
• Date of registration: 12/10/2018
• Prospective Registration: No
• Primary sponsor: Leiden University Medical Center
• Public title: Synergetic B-cell Immunomodulation in SLE - 2nd Study. SynBioSe-2
• Scientific title: A Randomized Trial to Investigate the Reset of Humoral Autoimmunity by Combining Belimumab With Rituximab in Severe Systemic Lupus Erythematosus
• Date of first enrolment: October 1, 2018
• Target sample size: 70
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03747159
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Netherlands

Contacts

• Name: Dr. Y.K.O. Teng, MD, PhD
• Affiliation: Leiden University Medical Center

• Name: Dr. Y.K.O. Teng, MD, PhD

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Have a clinical diagnosis of SLE according to the SLICC criteria 2012

2. Severe, active SLE disease defined as a situation in which 1 or more of the following
criteria are met:

1. SLEDAI-2K (SLE Disease Activity Index) with 12 or more points

2. 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)

3. high disease activity that requires or warrants induction treatment by switching
to or increasing dosage of oral mycophenolate

3. New, persisting or progressive disease activity despite the use of conventional
maintenance immunosuppressive treatment (e.g. mycophenolate or azathioprine)

4. Positive for relevant SLE-specific autoantibodies defined as a situation in which 1 or
more of the following criteria are met:

1. 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.

2. 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.

5. Female subjects are eligible to enter the study if she is:

- Not pregnant or nursing

- Of non-child-bearing potential (i.e. after hysterectomy, 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%.

Exclusion Criteria:

1. Active pregnancy, as proven by a positive urine beta-HCG test or a positive serum
beta-HCG

2. Significant hypogammaglobulinemia (IgG < 4.0 g/L) or an IgA deficiency (IgA < 0.1 g/L)

3. Immunization with a live vaccine 1 month before screening

4. Active infection at time of screening, as follows:

- Hospitalization for treatment of infection within previous 60 days of day 0 of
the study

- Use of parenteral (intravenous of intramuscular) antibiotics (including
anti-bacterials, anti-virals, anti-fungals or anti-parasitic agents) within
previous 60 days of day 0 of the study

- Serological evidence of viral hepatitis defined as: patients positive for HbsAg
test or HBcAb or a positive hepatitis C antibody not treated with antiviral
medication

5. Have a historically positive HIV test or test positive at screening for HIV

6. Have a history of a primary immunodeficiency

7. Have a neutrophil count of < 1.5x10E9/L

8. Have a significant infection history that in the opinion of the investigator would
make the candidate unsuitable for the study

9. Have a history of an anaphylactic reaction to parenteral administration of contrast
agents, human or murine proteins or monoclonal antibodies

10. Have any other clinically significant abnormal laboratory value in the opinion of the
investigator

11. Have current drugs or alcohol abuse or dependence within 365 days prior to Day 0 of
the study

12. Have an active malignant neoplasm or one in the history of the last 5 years, except
basal cell or squamous cell carcinoma of the skin treated with local resection only or
carcinoma in situ of the uterine cervix treated locally and with no evidence of
metastatic disease for 3 years

13. Have evidence of serious suicide risk including any history of suicidal behavior in
the last 6 months and/or any suicidal ideation in the last 2 months or who, in the
investigator's opinion, poses a significant suicide risk

14. Have any other clinically significant abnormal laboratory value, any intercurrent
significant medical or psychiatric illness that in the opinion of the investigator
would make the candidate unsuitable for the study



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Lupus Erythematosus, Systemic

Intervention(s)

Drug: Belimumab Injection

Primary Outcome(s)

Treatment failure rate [Time Frame: 2 years]

Secondary Outcome(s)

Change of memory B-cell numbers [Time Frame: 28 weeks]

Evaluation of the clinical response by SLEDAI [Time Frame: 2 years]

Sustained change of memory B-cell numbers [Time Frame: 2 years]

Evaluation of the clinical response by the ability to reduce concomitant immunosuppression without flares [Time Frame: 2 years]

Evaluation of the clinical response by the amount of moderate and severe flares. [Time Frame: 2 years]

Sustained change of immune complex-mediated excessive neutrophil extracellular traps (NET) formation [Time Frame: 2 years]

Change of immune complex-mediated excessive neutrophil extracellular traps (NET) formation [Time Frame: 28 weeks]

Evaluation of the clinical response by SLICC [Time Frame: 2 years]

Change of disease relevant auto-antibodies present at baseline, in particular anti-dsDNA [Time Frame: 28 weeks]

Evaluation of the renal response [Time Frame: 2 years]

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Time Frame: 2 years]

Seroconversion of disease relevant auto-antibodies [Time Frame: 2 years]

Evaluation of the clinical response by QoL questionnaires [Time Frame: 2 years]

Sustained change of autoantibody production [Time Frame: 2 years]

Secondary ID(s)

NL65720.058.18

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Dutch Kidney Foundation

GlaxoSmithKline