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 who achieved ORR (CRR + PRR) at week 50
(3)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 and whose parents were both Japanese
(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 serious 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
-Rapidly progressive glomerulonephritis as determined by the investigator
(4)Central nervous system lupus
(5)Any anti-CD20 antibody therapy within 9 months prior to screening
(6)Calcineurin inhibitors within 4 weeks prior to screening
(7)Cyclophosphamides within 2 months prior to screening
(8)Any biologic therapy other than anti-CD20 antibody within 2 months prior to screening
(9)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
(10)Any live vaccine within 28 days prior to screening
(11)Active infection or history of serious recurrent infection
(12)Patients who have serious infection(hospitalization or treatment with IV antibiotics within 8 weeks prior to screening, etc.)
(13)History of cancer within the past 5 years
(14)Patients who have undergone surgical procedures requiring hospitalization within 4 weeks prior to screening (excluding minor surgical procedures performed under local anesthesia)
(15)History of progressive multifocal leukoencephalopathy (PML)

Related Information

• Primary Sponsor: Tanaka Yoshiya