A MULTICENTER, PLACEBO-CONTROLLED, RANDOMIZED, DOUBLE-BLIND PHASE III CLINICAL TRIAL OF OBINUTUZUMAB IN PATIENTS WITH ACTIVE LUPUS NEPHRITIS

JRCT ID: jRCT2011210059

Registered date:25/12/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Lupus Nephritis
• Date of first enrollment: 24/06/2022
• Target sample size: 24
• Study type: Interventional
• Intervention(s): Obinutuzumab: Intravenous infusion of 1000 mg of obinutuzumab (genetical recombination) at a time.

Outcome(s)

Primary Outcome

Efficacy
To compare the efficacy of obinutuzumab when combined with standard-of-care therapy consisting of mycophenolate mofetil + oral steroids and placebo when combined with standard-of-care therapy (complete renal response at Week 76 defined as protocol).

Secondary Outcome

Safety, Efficacy, Phamacokinetics, Phamacodynamics, Other
To compare the efficacy of obinutuzumab when combined with standard-of-care therapy and placebo when combined with standard-of-care (i.e., the secondary endpoints).
The main secondary endpoints are:
(1)Proportion of patients who showing improvement in proteinuric at week 76
(2)Proportion of patients achieving CRR with successful corticosteroid component at Week 76
(3)Proportion of patients who achieved ORR (CRR + PRR) at week 50
(4)Proportion of patients who died, failed treatment or developed renal-related events by week 76

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

(1)Patients living in Japan aged 18-75 years
(2)Active Class III or IV or III/IV+V LN (not including Class III(C),IV(C))diagnosed according to ISN/RPS 2003 Classification Criteria by renal biopsy performed in the 6 months prior to ICF or during screening
(3)SLE according to the EULAR/ACR 2019 Classification Criteria, which are met by the presence of Class III or IV LN refer to (2) and positive antinuclear antibody status at the time of screening or in previous examinations
(4)UPCR >= 1 on a 24-hour collection
(5)Patient who receipt of at least one dose of steroid pulse therapy (methylprednisolone >= 250 mg or equivalent) for treatment to active LN within 6 months prior to screening or during screening (until prior to Day 1 obinutuzumab or placebo)
(6)For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use appropriate contraception, and agreement to refrain from ovum donation (18 months after the final dose of obinutuzumab or placebo and 6 weeks after the final dose of MMF)
(7)For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm(90 days after the final dose of MMF)

Exclude criteria

(1)eGFR<30 mL/min/1.73 m2(eGFR creat equation)or Severe renal impairment patient who need for dialysis or renal transplantation
(2)Sclerosis in > 50% of glomeruli
(3)Presence of rapidly progressive glomerulonephritis, defined by any of the following:
-Crescent formation in >= 50% of glomeruli assessed
-Sustained doubling of the serum creatinine reference range within 2 months prior to screening
(4)Rapidly progressive glomerulonephritis as determined by the investigator
(5)Central nervous system lupus
(6)Any biologic agents that deplete B cells or plasma cells (Anti-CD 19 antibody, anti-CD 20 antibody, etc) within 9 months prior to screening or during screening.
(7)Calcineurin inhibitors within 4 weeks prior to screening or during screening
(8)Cyclophosphamides within 2 months prior to screening or during screening
(9)Any biologic therapy (drugs other than B cell or plasma cell depleting drugs that may affect the safety of subjects or evaluation of this study) within 2 months prior to screening or during screening
(10)Oral inhibitors of Janus-associated kinase (JAK), Bruton's tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2) or any investigational agent within 2 months prior to screening or during screening
(11)Any live vaccine within 27 days prior to screening or during screening

Related Information

• Primary Sponsor: Tanaka Yoshiya