A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis and the Safety and PK of Obinutuzumab in Pediatric Participants (POSTERITY)

Roche

Status and phase: Enrolling; Phase 2

Conditions: Lupus Nephritis

Treatments: Drug: Acetaminophen/paracetamol; Drug: Prednisone; Drug: Methylprednisolone; Drug: Diphenhydramine hydrochloride (HCl); Drug: Mycophenolate Mofetil; Drug: Placebo; Drug: Obinutuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05039619

2021-000097-29 (EudraCT Number)

2023-505825-15-00 (Other Identifier)

WA42985

Details and patient eligibility

About

This phase II, randomized, double-blind, placebo-controlled study is designed to evaluate the safety, efficacy and pharmacokinetics (PK) of obinutuzumab in adolescent participants (AP) aged 12 to less than 18 with biopsy-confirmed proliferative lupus nephritis (LN). It will also evaluate open label safety and PK of obinutuzumab in pediatric participants (PP), aged 5 to <12 with LN.

Enrollment: 40 estimated patients

Sex: All

Ages: 5 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants who are age 12 to <18 years at the time of randomization
• Participants who are age 5 to <12 years (younger participant cohort) at the time of randomization once recruitment is open. (Investigators will be notified by the Sponsor when recruitment is open to this younger population)
• International Society of Nephrology and the Renal Pathology Society (ISN/RPS) 2003 Class III or IV active LN demonstrated on renal biopsy performed in the 12 months prior to or during screening
• Class V disease may be present in addition to Class III or IV LN, but participants with isolated Class V disease are not eligible
• Diagnosis of SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria
• Significant proteinuria defined by a UPCR above > 0.5 based on a first-morning void (FMV) collection at screening
• During the 12 months prior to or during screening, all participants must have received at least one dose of pulse-range IV methylprednisolone (typically 30 mg/kg, maximum of 1000 mg per dose) or equivalent for the treatment of the current episode of active LN.

Exclusion criteria

• Severe, active central nervous system (CNS) SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia
• Sclerosis in >50% of glomeruli on renal biopsy
• Purely chronic Class III(c) or Class IV(c) disease on renal biopsy, defined as the absence of any active lesions
• Presence of rapidly progressive glomerulonephritis
• Pure Class V LN
• Intolerance or contraindication to study therapies
• Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV anti-infective medications within 4 weeks prior to screening, or completion of oral anti-infectives within 2 weeks prior to randomization
• History of or currently active primary or secondary immunodeficiency, including known history of HIV infection and other severe Immunodeficiency blood disorders
• History of serious recurrent or chronic infection
• History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ (except basal cell carcinoma and squamous cell carcinoma of the skin that have been excised and cured) within the past 5 years
• Significant or uncontrolled concomitant medical disease which, in the investigator's opinion, would preclude participant participation
• Currently active alcohol or drug abuse or history of alcohol or drug abuse

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 3 patient groups, including a placebo group

Blinded Obinutuzumab

Experimental group

Description:

Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).

Treatment:

Drug: Obinutuzumab

Drug: Mycophenolate Mofetil

Drug: Methylprednisolone

Drug: Diphenhydramine hydrochloride (HCl)

Drug: Prednisone

Drug: Acetaminophen/paracetamol

Placebo

Placebo Comparator group

Description:

Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.

Treatment:

Drug: Mycophenolate Mofetil

Drug: Placebo

Drug: Methylprednisolone

Drug: Diphenhydramine hydrochloride (HCl)

Drug: Prednisone

Drug: Acetaminophen/paracetamol

Open-Label Obinutuzumab

Experimental group

Description:

Younger participants aged 5 to \<12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.

Treatment:

Drug: Obinutuzumab

Drug: Mycophenolate Mofetil

Drug: Methylprednisolone

Drug: Diphenhydramine hydrochloride (HCl)

Drug: Prednisone

Drug: Acetaminophen/paracetamol