POSTERITY: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05039619

Collaborator

Genentech, Inc. (Industry)

Enrollment

Locations

Arms

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II, randomized, double-blind, placebo-controlled study is designed to evaluate the safety, efficacy and pharmacokinetics of obinutuzumab in adolescent participants aged 12 to less than 18 with biopsy-confirmed proliferative lupus nephritis (LN).

Condition or Disease	Intervention/Treatment	Phase
Lupus Nephritis	Drug: Obinutuzumab Drug: Placebo Drug: Mycophenolate Mofetil Drug: Acetaminophen/paracetamol Drug: Diphenhydramine hydrochloride (HCl) Drug: Methylprednisolone Drug: Prednisone	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 12, 2022

Anticipated Primary Completion Date :

Mar 28, 2025

Anticipated Study Completion Date :

Mar 13, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	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. Other Names: Gazyva 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.
Placebo Comparator: Placebo Placebo participants will receive obinutuzumab matched placebo 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.

Arm

Intervention/Treatment

Experimental: 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).

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.

Other Names:

Gazyva

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.

Placebo Comparator: Placebo

Placebo participants will receive obinutuzumab matched placebo 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.

Outcome Measures

Primary Outcome Measures

Percentage of Participants who Achieve a Complete Renal Response (CRR) [Week 76]
CRR is defined as achievement of all of the following: Urinary protein-to-creatinine ratio (UPCR) <0.5 Estimated Glomerular Filtration Rate (eGFR) >=85% of baseline No occurrence of intercurrent events

Secondary Outcome Measures

Percentage of Participants Achieving a CRR [Weeks 24 and 52]
Percentage of Participants who Achieve a Partial Renal Response (PRR) [Week 76]
Percentage of Participants Achieving an Overall Response (CRR or PRR) [Weeks 24, 52, and 76]
PRR is defined as: achievement of all of the following: >=50% reduction in urinary protein-to-creatinine ratio (UPCR) from baseline UPCR < 1 (or < 3 if the baseline UPCR was >=3) eGFR >=85% of baseline No occurrence of intercurrent events
Change in UPCR [Baseline to Week 76]
Change in eGFR [Baseline to Week 76]
Time to Onset of CRR over the Course of 76 weeks [Up to Week 76]
Percentage of Participants who Experience Treatment Failure [Week 12 to Week 76]
Change in C3 Complement Levels [Baseline to Week 76]
Change in C4 Complement Levels [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 [Baseline to Week 76]
Serum Concentrations of Obinutuzumab [Baseline to Week 76]
Percentage of Participants Achieving B-cell Depletion via Highly Sensitive Flow Cytometry (HSFC) [Baseline, Weeks 4, 24, 52 and 76]
Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL)-Fatigue Total Score [Baseline to Week 76]
Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) [Baseline to Week 76]
Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores [Baseline to Week 76]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco	San Francisco	California	United States	94117
2	Children's Hospital Colorado, Anchutz Medical Campus	Aurora	Colorado	United States	80045
3	Emory Children's Center	Atlanta	Georgia	United States	20010
4	Indiana University Health University Hospital	Indianapolis	Indiana	United States	46202
5	Louisiana State University	Shreveport	Louisiana	United States	71103
6	Cohen Children's Medical Center of New York; Pediatrics	Queens	New York	United States	11042
7	Cincinnati Childrens Hospital	Cincinnati	Ohio	United States	45229
8	Ser Servicos Especializados Em Reumatologia	Salvador	BA	Brazil	40150-150
9	Universidade Federal de Sao Paulo - UNIFES	Sao Paulo	SP	Brazil	04026-000
10	Hospital das Clinicas - FMUSP	Sao Paulo	SP	Brazil	05403-900
11	Hop Necker Enfants Malades;UIH	Paris		France	75743
12	CHU de Toulouse - Hôpital des Enfants; Nephro - Rhumato - Medecine Interne - Hypertension	Toulouse		France	31000
13	Instituto de Ginecología y Reproducción	Lima		Peru
14	Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadciśnienia Dzieci i Mlodziezy	Gdansk		Poland	80-952
15	Szpital Specjalistyczny dla Dzieci i Doroslych; Oddzial Kliniczny Pediatrii i Nefrologii	Torun		Poland	87-100
16	Saint-Petersburg State; Pediatrics Medical Academy	Saint-Petersburg		Russian Federation	194100
17	Red Cross War Memorial Children's Hospital; Nephrology Unit	Cape Town		South Africa	7700
18	Groote Schuur Hospital; Renal Unit	Cape Town		South Africa	7925
19	Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica	Esplugas DE Llobregat	Barcelona	Spain	08950
20	Hospital Ramon y Cajal ; Servicio de Reumatologia	Madrid		Spain	28034
21	Hospital de La Paz; Unidad de Reumatologia Pediatrica	Madrid		Spain	28046
22	Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica	Valencia		Spain	46026
23	Royal Hospital For Children	Glasgow		United Kingdom	G51 4TF
24	Alder Hey Childrens Hospital	Liverpool		United Kingdom	L12 2AP