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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	5 Years - 17 Years
Gender	All

More Inclusion & Exclusion Criteria

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 Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05039619
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Hoffmann-La Roche
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Clinical Trials
Principal Investigator Affiliation	Hoffmann-La Roche
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Brazil, Canada, France, Italy, Mexico, Peru, Poland, Russian Federation, South Africa, Spain, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Lupus Nephritis

Arms & Interventions

Arms

Experimental: Blinded Obinutuzumab

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).

Placebo Comparator: Placebo

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

Experimental: Open-Label Obinutuzumab

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

Interventions

Drug: - Obinutuzumab

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.

Drug: - Placebo

Placebo matching obinutuzumab will be administered by IV on Day 1, Day 14, Week 24, Week 26 and Week 52.

Drug: - Mycophenolate Mofetil

Mycophenolate Mofetil (MMF) will be taken by home administration orally at a target dose of 1200 mg/m^2/day to a maximum of 2.5g/day from baseline (Day 1) onwards.

Drug: - Acetaminophen/paracetamol

Acetaminophen 1000 mg will be administered as pre-medication prior to infusions.

Drug: - Diphenhydramine hydrochloride (HCl)

Diphenhydramine HCl 50 mg will be administered as pre-medication prior to infusions.

Drug: - Methylprednisolone

Methylprednisolone 80 mg IV will be administered as pre-medication prior to infusions.

Drug: - Prednisone

Oral prednisone or equivalent corticosteroid will be taken by home administration daily to a maximum dose of 60mg/day followed by a guided taper to 5mg/day or less by Week 24.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Loma Linda University health, Loma Linda, California

Status

Recruiting

Address

Loma Linda University health

Loma Linda, California, 92354

Site Contact

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