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

Lupus Nephritis Clinical Trial

— POSTERITY  

Official title:

A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescent Patients With Active Class III or IV Lupus Nephritis, Including an Evaluation of Open Label Safety and PK in a Cohort of Pediatric Patients (Aged 5 to < 12)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05039619
• Other study ID #: WA42985
• Secondary ID: 2021-000097-2920
• Status: Recruiting
• Phase: Phase 2
• Start date: May 12, 2022
• Est. completion date: March 13, 2029

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: WA42985 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global.rochegenentechtrials[@]roche.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: March 13, 2029
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

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.
• Placebo
Placebo matching obinutuzumab will be administered by IV on Day 1, Day 14, Week 24, Week 26 and Week 52.
• 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.
• Acetaminophen/paracetamol
Acetaminophen 1000 mg will be administered as pre-medication prior to infusions.
• Diphenhydramine hydrochloride (HCl)
Diphenhydramine HCl 50 mg will be administered as pre-medication prior to infusions.
• Methylprednisolone
Methylprednisolone 80 mg IV will be administered as pre-medication prior to infusions.
• 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.

Locations

Country	Name	City	State
Brazil	Ser Servicos Especializados Em Reumatologia	Salvador	BA
Brazil	Hospital das Clinicas - FMUSP	Sao Paulo	SP
Brazil	Universidade Federal de Sao Paulo - UNIFES	Sao Paulo	SP
Canada	The Hospital for Sick Children	Toronto	Ontario
France	CH de Bicêtre; Pediatrie Generale	Le Kremlin Bicêtre
France	Hop Necker Enfants Malades;UIH	Paris
France	Hôpital Robert Debré; Nephrologie pediatrique	Paris
France	CHU de Toulouse - Hôpital des Enfants; Nephro - Rhumato - Medecine Interne - Hypertension	Toulouse
Italy	IRCCS G. Gaslini; U.O. Nefrologia, Dialisi e Trapianto	Genova	Liguria
Italy	Clinica Pediatrica II De Marchi	Milano	Lombardia
Italy	Ospedale Pediatrico Bambino Gesu; U.O. Di Nefrologia E Dialisi	Roma	Lazio
Mexico	CREA Hospital Mexico Americano; Clinica Pediatrica de Reumatologia y Enfermedades Autoinmunes	Guadalajara	Jalisco
Mexico	Clinstile S.A de C.V.	Mexico City	Mexico CITY (federal District)
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria	Monterrey	Nuevo LEON
Peru	Instituto de Ginecología y Reproducción	Lima
Peru	Clinica El Golf	San Isidro
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadci?nienia Dzieci i Mlodziezy	Gdansk
Poland	Szpital Specjalistyczny dla Dzieci i Doroslych; Oddzial Kliniczny Pediatrii i Nefrologii	Torun
Russian Federation	Saint-Petersburg State; Pediatrics Medical Academy	St-peterburg	Sankt Petersburg
South Africa	Groote Schuur Hospital; Renal Unit	Cape Town
South Africa	Red Cross War Memorial Children?s Hospital; Nephrology Unit	Cape Town
Spain	Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica	Esplugas DE Llobregat	Barcelona
Spain	Hospital de La Paz; Unidad de Reumatologia Pediatrica	Madrid
Spain	Hospital Ramon y Cajal ; Servicio de Reumatologia	Madrid
Spain	Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica	Valencia
United Kingdom	Royal Hospital For Children	Glasgow
United Kingdom	Alder Hey Childrens Hospital	Liverpool
United Kingdom	Great Ormond Street Hospital for Children	London
United States	Emory Children's Center	Atlanta	Georgia
United States	Children's Hospital Colorado, Anchutz Medical Campus	Aurora	Colorado
United States	Cincinnati Childrens Hospital	Cincinnati	Ohio
United States	Texas Arthritis Center	El Paso	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Indiana University Health University Hospital	Indianapolis	Indiana
United States	Loma Linda University health	Loma Linda	California
United States	Chldren's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Cohen Children's Medical Center of New York; Pediatrics	Queens	New York
United States	University of California San Francisco	San Francisco	California
United States	Louisiana State University	Shreveport	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  France,  Italy,  Mexico,  Peru,  Poland,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Week 76
Primary	Percentage of Participants with Adverse Events (PP)		Baseline to Week 76
Secondary	Percentage of Participants Achieving a CRR (AP)		Weeks 24 and 52
Secondary	Percentage of Participants who Achieve CRR with Successful Prednisone Taper (AP)		Week 76
Secondary	Percentage of Participants who Achieve a PRR (AP)		Week 76
Secondary	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	Weeks 24, 52, and 76
Secondary	Change in UPCR (AP)		Baseline to Week 76
Secondary	Change in eGFR (AP)		Baseline to Week 76
Secondary	Time to Onset of CRR over the Course of 76 weeks (AP)		Up to Week 76
Secondary	Percentage of Participants who Experience Treatment Failure (AP)		Week 12 to Week 76
Secondary	Change in anti-dsDNA titers (AP)		Baseline to Week 76
Secondary	Change in C3 Complement Levels (AP)		Baseline to Week 76
Secondary	Change in C4 Complement Levels (AP)		Baseline to Week 76
Secondary	Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 (AP)		Baseline to Week 76
Secondary	Serum Concentrations of Obinutuzumab (AP)		Baseline to Week 76
Secondary	Percentage of Participants Achieving B-cell Depletion (AP)		Baseline, Weeks 4, 24, 52 and 76
Secondary	Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL)-Fatigue Total Score (AP)		Baseline to Week 76
Secondary	Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AP)		Baseline to Week 76
Secondary	Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores (AP)		Baseline to Week 76
Secondary	Percentage of Participants with Anti-drug Antibodies (ADA) (AP)		Weeks 0, 24, 52 and 76
Secondary	Relationship Between ADA Status and Percentage of Participants Achieving a CRR (AP)		Weeks 24, 52 and 76
Secondary	Percentage of Participants Achieving a CRR (PP)		Week 76
Secondary	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	Week 76
Secondary	Percentage of Participants who Achieve CRR with Successful Prednisone Taper (PP)		Week 76
Secondary	Change in eGFR (PP)		Baseline to Week 76
Secondary	Percentage of Participants Achieving B-cell Depletion (PP)		Baseline, Weeks 4, 24, 52 and 76
Secondary	Percentage of Participants with ADAs (PP)		Weeks 0, 24, 52 and 76
Secondary	Change in anti-dsDNA titers (PP)		Baseline to Week 76