A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Patients with ISN/RPS 2003 Class III or IV Lupus Nephritis
- Conditions
- lupus nephritisMedDRA version: 21.1Level: PTClassification code 10025140Term: Lupus nephritisSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-004034-42-FR
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 252
- Age 18-75 years
- Ability to comply with the study protocol, in the investigator's judgment
- International Society of Nephrology / Renal Pathology Society (ISN/RPS) 2003 Class III or IV LN by renal biopsy performed in the 6 months prior to screening or during screening
- Diagnosis of SLE according to the 2019 European League Against Rheumatism/ American College of Rheumatology (EULAR/ACR) Classification Criteria, which are met by the presence of Class III or IV LN (above) and: Current or past positive antinuclear antibody (ANA), as evidenced by ANA at a titer of >= 1:80 on HEp-2 cells or an equivalent positive ANA test at least once
- Urinary protein-to-creatinine ratio >= 1 on a 24-hour collection at screening
- Receipt of at least one dose of pulse methylprednisolone IV (>= 250 mg) or equivalent for treatment of the current episode of active LN during the 6 months prior to screening or during screening; a maximum of 3 g methylprednisolone IV or equivalent during the 4 weeks prior to screening or during screening is allowed.
- For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, women must remain abstinent or use two methods of contraception, including at least one method with a failure rate of < 1% per year, during study treatment and for 18 months after the final dose of obinutuzumab and 6 weeks after the final dose of mycophenolate mofetil (MMF)
- For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm, with a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 90 days after the final dose of MMF and for 90 days after the final dose of obinutuzumab study drug; With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 90 days after the final dose of MMF and for 12 months after the final dose of obinutuzumab or placebo to avoid exposing the embryo.
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 235
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or placebo or within 6 weeks after the final dose of MMF
- Severe renal impairment, as defined by eGFR < 30 mL/min/1.73 m2 or the need for dialysis or renal transplantation
- Sclerosis in > 50% of glomeruli on renal biopsy
- Presence of rapidly progressive glomerulonephritis
- Receipt of an excluded therapy
- Severe, active central nervous system SLE, including retinitis, poorly-controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia
- High risk for clinically-significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions
- Significant or uncontrolled medical disease which, in the investigators opinion, would preclude patient participation
- HIV and Tuberculosis infection; latent TB after completion of appropriate treatment is not exclusionary.
- Active infection of any kind, excluding fungal infection of the nail beds
- Any major episode of infection that required hospitalization or treatment with IV antibiotics or anti-infectives during the 8 weeks prior to screening or during screening; antibiotics or anti-infectives given in the absence of a major episode of infection are not exclusionary.
- History of serious recurrent or chronic infection
- History of progressive multifocal leukoencephalopathy
- History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the past 5 years
- Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening
- Current alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening or during screening
- Intolerance or contraindication to study therapies
- Laboratory parameters
•AST or ALT > 2.5 × upper limit of normal (ULN)
•Amylase or lipase > 2 × ULN
•Neutrophils < 1.5 × 103/µL
•Positive hepatitis B surface antigen (HBsAg)
•Positive hepatitis C serology
•Hemoglobin < 7 g/dL, unless caused by autoimmune hemolytic anemia resulting from SLE
•Platelet count < 25,000/µL
•Positive serum human chorionic gonadotropin measured at screening
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