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

Phase 2RecruitingNCT05039619

Hoffmann-La Roche40 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Lupus Nephritis

Interventions

ObinutuzumabDRUG

Obinutuzumab will be administered by IV infusion at a dose of 1000 mg on Day 1, Day 14, Week 24, Week 26 and Week 52.

Eligibility

Sex: ALLMin age: 5 YearsMax age: 17 Years

Medical Language ↔ Plain English

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

Locations (42)

Loma Linda University health

Loma Linda, California, United States

RECRUITING

UCSF Benioff Childrens Hospital

San Francisco, California, United States

RECRUITING

Children's Hospital Colorado, Anchutz Medical Campus

Aurora, Colorado, United States

RECRUITING

Emory Children's Center

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Percentage of Participants who Achieve a Complete Renal Response (CRR) (AP)

CRR is defined as achievement of all of the following: * Urinary protein-to-creatinine ratio (UPCR) \<0.5 g/g * Estimated Glomerular Filtration Rate (eGFR) \>=85% of baseline * No occurrence of intercurrent events

Time frame: Week 76

Percentage of Participants with Adverse Events (PP)

Time frame: Baseline to Week 76

Secondary Outcomes

Percentage of Participants Achieving a CRR (AP)

Time frame: Weeks 24 and 52

Percentage of Participants who Achieve CRR with Successful Prednisone Taper (AP)

Time frame: Week 76

Percentage of Participants who Achieve a PRR (AP)

Time frame: Week 76

Percentage of Participants Achieving an Overall Response (CRR or PRR) (AP)

PRR is defined as: achievement of all of the following: * \>=50% reduction in urinary protein-to-creatinine ratio (UPCR) from baseline * UPCR \< 1 g/g (or \< 3 g/g if the baseline UPCR was \>=3 g/g) * eGFR \>=85% of baseline * No occurrence of intercurrent events

Time frame: Weeks 24, 52, and 76

Change in UPCR (AP)

Time frame: Baseline to Week 76

Change in eGFR (AP)

Time frame: Baseline to Week 76

Time to Onset of CRR over the Course of 76 weeks (AP)

Time frame: Up to Week 76

Percentage of Participants who Experience Treatment Failure (AP)

Time frame: Week 12 to Week 76

Change in anti-dsDNA titers (AP)

Time frame: Baseline to Week 76

Change in C3 Complement Levels (AP)

Time frame: Baseline to Week 76

Change in C4 Complement Levels (AP)

Time frame: Baseline to Week 76

Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 (AP)

Time frame: Baseline to Week 76

Serum Concentrations of Obinutuzumab (AP)

Time frame: Baseline to Week 76

Percentage of Participants Achieving B-cell Depletion (AP)

Time frame: Baseline, Weeks 4, 24, 52 and 76

Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL)-Fatigue Total Score (AP)

Time frame: Baseline to Week 76

Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AP)

Time frame: Baseline to Week 76

Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores (AP)

Time frame: Baseline to Week 76

Percentage of Participants with Anti-drug Antibodies (ADA) (AP)

Time frame: Weeks 0, 24, 52 and 76

Relationship Between ADA Status and Percentage of Participants Achieving a CRR (AP)

Time frame: Weeks 24, 52 and 76

Percentage of Participants Achieving a CRR (PP)

Time frame: Week 76

Percentage of Participants Achieving an Overall Response (PP)

PRR is defined as achievement of all of the following: * \>=50% reduction in UPCR from baseline * UPCR \< 1 g/g (or \< 3 g/g if the baseline UPCR was \>=3 g/g) * eGFR \>=85% of baseline * No occurrence of intercurrent events

Time frame: Week 76

Percentage of Participants who Achieve CRR with Successful Prednisone Taper (PP)

Time frame: Week 76

Change in eGFR (PP)

Time frame: Baseline to Week 76

Percentage of Participants Achieving B-cell Depletion (PP)

Time frame: Baseline, Weeks 4, 24, 52 and 76

Percentage of Participants with ADAs (PP)

Time frame: Weeks 0, 24, 52 and 76

Change in anti-dsDNA titers (PP)

Time frame: Baseline to Week 76

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

Overview

Conditions

Interventions

Eligibility

Locations (42)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts