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A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Participants With Childhood Onset Idiopathic Nephrotic Syndrome (INShore)

Primary Purpose

Childhood Idiopathic Nephrotic Syndrome

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Obinutuzumab
MMF
Prednisone
Methylprednisolone
Acetaminophen/ Paracetamol
Diphenhydramine Hydrochloride
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Childhood Idiopathic Nephrotic Syndrome

Eligibility Criteria

2 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of frequently relapsing nephrotic syndrome (FRNS) or steroid dependent nephrotic syndrome (SDNS) before the age of 18 years Must be in complete remission defined by the absence of edema, UPCR <= 0.2 g/g at screening and have three consecutive daily urine dipstick readings of trace or negative for protein within the week prior to randomization Must have had at least one relapse in the 6 months prior to screening, after discontinuation of or while receiving oral corticosteroids and/or immunosuppressive therapy to prevent relapses Participants having received cyclophosphamide in the 6 months prior to randomization must have experienced at least 1 relapse subsequent to cyclophosphamide discontinuation Estimated glomerular filtration rate (eGFR) within normal range for age For females of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraception, during the treatment period and for 18 months after the final dose of obinutuzumab and for 6 weeks after the final dose of MMF For males: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm during the treatment period and for 90 days after the final dose of MMF Exclusion Criteria: Secondary nephrotic syndrome History of steroid resistant nephrotic syndrome History of genetic defects known to directly cause nephrotic syndrome Treatment with other immunosuppressive medications to prevent relapse, other than MMF or oral corticosteroids within 2 months prior to randomization Pregnancy or breastfeeding or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab, or within 6 weeks after the final dose of MMF Females of childbearing potential, including those who have had a tubal ligation, must have a negative serum pregnancy test result within 28 days prior to initiation of study treatment and a negative urine pregnancy test at Day 1, prior to randomization History of organ or bone marrow transplant Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug Intolerance or contraindication to study therapies Participants demonstrating prior treatment failure to MMF as defined by two or more relapses in any 6-month period of time while receiving MMF for at least a 6-month duration Participants in the judgment of the investigator likely to require systemic corticosteroids for reasons other than idiopathic nephrotic syndrome during the study Active infection of any kind 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 human immunodeficiency virus (HIV) infection and other severe Immunodeficiency blood disorders History of progressive multifocal leukoencephalopathy History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ within the past 5 years Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening High risk for clinically significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions Evidence of any significant or uncontrolled concomitant disease that, in the investigator's judgment, would preclude participant's participation, including but not limited to nervous system, respiratory, cardiac, hepatic, endocrine, malignant, or gastrointestinal disorders Currently active alcohol or drug abuse or history of alcohol or drug abuse

Sites / Locations

  • Lucile Packard Children's Hospital - StanfordRecruiting
  • Memorial Healthcare SystemRecruiting
  • Children's Healthcare of Atlanta Center for Advanced PediatricsRecruiting
  • Children's Mercy HospitalRecruiting
  • Hackensack University Medical CenterRecruiting
  • UNC Hospitals Outpatient Center at EastowneRecruiting
  • University of Utah - Primary Children's Hospital - PPDSRecruiting
  • University of Virginia Health SystemRecruiting
  • Hôpital Universitaire des Enfants Reine FabiolaRecruiting
  • UZ GentRecruiting
  • Chu ToulouseRecruiting
  • Hopital Femme Mere EnfantsRecruiting
  • Hopital Henri MondorRecruiting
  • CHU Montpellier- Hopital Arnaud de VIlleneuveRecruiting
  • Hopital Necker - Enfants MaladesRecruiting
  • Hopital Robert DebreRecruiting
  • Hokkaido University HospitalRecruiting
  • Hyogo prefectural Kobe Children's HospitalRecruiting
  • Kobe University HospitalRecruiting
  • Yokohama City University Medical CenterRecruiting
  • Kitasato University HospitalRecruiting
  • Dokkyo Medical University HospitalRecruiting
  • Shiga University Of Medical Science HospitalRecruiting
  • National Center for Child Health and DevelopmentRecruiting
  • Tokyo Metropolitan Children's Medical CenterRecruiting
  • Uniwersytecki Szpital Kliniczny w BialymstokuRecruiting
  • In-VIVO Osrodek Badan KlinicznychRecruiting
  • Uniwersyteckie Centrum KliniczneRecruiting
  • Dzieciecy Szpital Kliniczny UCK WUMRecruiting
  • Hospital Universitario Marques de ValdecillaRecruiting
  • Hospital Universitario CrucesRecruiting
  • Hospital Sant Joan de Deu - PINRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Obinutuzumab (Group A)

MMF (Group B)

Arm Description

Participants in Group A will receive obinutuzumab 1000 milligrams (mg) (or 20 mg/ kilogram [kg] for participants <45 kg) administered by intravenous (IV) infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26).

Participants in Group B will receive oral MMF 600 mg/m^2 twice a day (BID) (target 1200 mg/m2/day in divided doses, maximum 2 g/day) to Week 52.

Outcomes

Primary Outcome Measures

Percentage of Participants with Sustained Complete Remission at 1 year

Secondary Outcome Measures

Overall Relapse-free Survival (RFS)
Probability of RFS at Week 52
Cumulative Corticosteroid Dose
Number of Relapses
Percentage of Participants Experiencing Edema Associated Relapse
Percentage of Participants with Sustained Complete Remission
This outcome measure will be assessed at primary analysis
Mean Change in "General Fatigue" Domain of Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale Total Score
Mean Change in "Physical Functioning" Domain of PedsQL Quality of Life Inventory
Mean Change in Cure Glomerulonephropathy (CureGN) Edema Scale
Percentage of Participants with Adverse Events (AEs)
Serum Concentrations of Obinutuzumab
Percentage of Participants Achieving B Cell Depletion Highly Sensitive Flow Cytometry (HSFC)
Total Peripheral B Cell and B Cell Subsets (e.g., Memory B Cells) Counts and Change from Baseline

Full Information

First Posted
November 4, 2022
Last Updated
October 17, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT05627557
Brief Title
A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Participants With Childhood Onset Idiopathic Nephrotic Syndrome
Acronym
INShore
Official Title
A Phase III, International, Multicenter, Randomised Open Label Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Patients With Childhood Onset Idiopathic Nephrotic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 29, 2023 (Actual)
Primary Completion Date
August 15, 2026 (Anticipated)
Study Completion Date
August 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This open-label, randomized multicenter study is to assess the efficacy, safety, and pharmacokinetics (PK)/pharmacodynamics (PD) of obinutuzumab compared with mycophenolate mofetil (MMF) in children and young adults (aged >= 2-25 years) with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Childhood Idiopathic Nephrotic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Obinutuzumab (Group A)
Arm Type
Experimental
Arm Description
Participants in Group A will receive obinutuzumab 1000 milligrams (mg) (or 20 mg/ kilogram [kg] for participants <45 kg) administered by intravenous (IV) infusion on Days 1, 15, 168 (Week 24), and 182 (Week 26).
Arm Title
MMF (Group B)
Arm Type
Active Comparator
Arm Description
Participants in Group B will receive oral MMF 600 mg/m^2 twice a day (BID) (target 1200 mg/m2/day in divided doses, maximum 2 g/day) to Week 52.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Intervention Description
Obinutuzumab will be administered as per schedule specified in the respective arm.
Intervention Type
Drug
Intervention Name(s)
MMF
Intervention Description
MMF will be administered as per schedule specified in the respective arm.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Non-Investigational Medicinal Product
Intervention Description
Participants taking prednisone or equivalent at randomization will follow a guided tapering schedule to reach the goal of 0mg/day by Weeks 4-6 (and no later than Week 8 following randomization and continue without prednisone through Week 52.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Other Intervention Name(s)
Non-Investigational Medicinal Product
Intervention Description
Methylprednisolone 80 mg (or 1.5 mg/kg if </=45 kg) IV will be administered as premedication prior to infusions.
Intervention Type
Drug
Intervention Name(s)
Acetaminophen/ Paracetamol
Other Intervention Name(s)
Non-Investigational Medicinal Product
Intervention Description
Acetaminophen 15 mg/kg (maximum dose 1000 mg) will be administered PO as premedication prior to infusions.
Intervention Type
Drug
Intervention Name(s)
Diphenhydramine Hydrochloride
Other Intervention Name(s)
Non-Investigational Medicinal Product
Intervention Description
Diphenhydramine HCl 0.5-1 mg/kg (maximum dose 50 mg) will be administered PO or IV as premedication prior to infusions.
Primary Outcome Measure Information:
Title
Percentage of Participants with Sustained Complete Remission at 1 year
Time Frame
At Week 52
Secondary Outcome Measure Information:
Title
Overall Relapse-free Survival (RFS)
Time Frame
At Week 52
Title
Probability of RFS at Week 52
Time Frame
At Week 52
Title
Cumulative Corticosteroid Dose
Time Frame
At Week 52
Title
Number of Relapses
Time Frame
At Week 52
Title
Percentage of Participants Experiencing Edema Associated Relapse
Time Frame
At Week 52
Title
Percentage of Participants with Sustained Complete Remission
Description
This outcome measure will be assessed at primary analysis
Time Frame
Week 52 to Week 76
Title
Mean Change in "General Fatigue" Domain of Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale Total Score
Time Frame
Baseline to Week 52
Title
Mean Change in "Physical Functioning" Domain of PedsQL Quality of Life Inventory
Time Frame
Baseline to Week 52
Title
Mean Change in Cure Glomerulonephropathy (CureGN) Edema Scale
Time Frame
Baseline to Week 52
Title
Percentage of Participants with Adverse Events (AEs)
Time Frame
Baseline to Week 52
Title
Serum Concentrations of Obinutuzumab
Time Frame
At Days 1, 15 28, 84, 168, 182, 224, 364, and at Early Study Discontinuation Visit (unscheduled visit at the time of discontinuation from study, any time between Day 1 and Day 364)
Title
Percentage of Participants Achieving B Cell Depletion Highly Sensitive Flow Cytometry (HSFC)
Time Frame
At Days 1, 15, 28, 84, 168, 224, 364, and at Early Study Discontinuation Visit (unscheduled visit at the time of discontinuation from study, any time between Day 1 and Day 364)
Title
Total Peripheral B Cell and B Cell Subsets (e.g., Memory B Cells) Counts and Change from Baseline
Time Frame
At Days 1, 15, 28, 84, 168, 224, 364, and at Early Study Discontinuation Visit (unscheduled visit at the time of discontinuation from study, any time between Day 1 and Day 364)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of frequently relapsing nephrotic syndrome (FRNS) or steroid dependent nephrotic syndrome (SDNS) before the age of 18 years Must be in complete remission defined by the absence of edema, UPCR <= 0.2 g/g at screening and have three consecutive daily urine dipstick readings of trace or negative for protein within the week prior to randomization Must have had at least one relapse in the 6 months prior to screening, after discontinuation of or while receiving oral corticosteroids and/or immunosuppressive therapy to prevent relapses Participants having received cyclophosphamide in the 6 months prior to randomization must have experienced at least 1 relapse subsequent to cyclophosphamide discontinuation Estimated glomerular filtration rate (eGFR) within normal range for age For females of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraception, during the treatment period and for 18 months after the final dose of obinutuzumab and for 6 weeks after the final dose of MMF For males: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm during the treatment period and for 90 days after the final dose of MMF Exclusion Criteria: Secondary nephrotic syndrome History of steroid resistant nephrotic syndrome History of genetic defects known to directly cause nephrotic syndrome Treatment with other immunosuppressive medications to prevent relapse, other than MMF or oral corticosteroids within 2 months prior to randomization Pregnancy or breastfeeding or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab, or within 6 weeks after the final dose of MMF Females of childbearing potential, including those who have had a tubal ligation, must have a negative serum pregnancy test result within 28 days prior to initiation of study treatment and a negative urine pregnancy test at Day 1, prior to randomization History of organ or bone marrow transplant Participation in another therapeutic trial within 30 days of enrollment or 5 half-lives of the investigational drug Intolerance or contraindication to study therapies Participants demonstrating prior treatment failure to MMF as defined by two or more relapses in any 6-month period of time while receiving MMF for at least a 6-month duration Participants in the judgment of the investigator likely to require systemic corticosteroids for reasons other than idiopathic nephrotic syndrome during the study Active infection of any kind 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 human immunodeficiency virus (HIV) infection and other severe Immunodeficiency blood disorders History of progressive multifocal leukoencephalopathy History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ within the past 5 years Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening High risk for clinically significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions Evidence of any significant or uncontrolled concomitant disease that, in the investigator's judgment, would preclude participant's participation, including but not limited to nervous system, respiratory, cardiac, hepatic, endocrine, malignant, or gastrointestinal disorders Currently active alcohol or drug abuse or history of alcohol or drug abuse
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: WA43380 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. and Canada)
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Lucile Packard Children's Hospital - Stanford
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Healthcare System
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Healthcare of Atlanta Center for Advanced Pediatrics
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329-2309
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108-4619
Country
United States
Individual Site Status
Recruiting
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Recruiting
Facility Name
UNC Hospitals Outpatient Center at Eastowne
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514-2286
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Utah - Primary Children's Hospital - PPDS
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113-1103
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Individual Site Status
Recruiting
Facility Name
Hôpital Universitaire des Enfants Reine Fabiola
City
Bruxelles
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Chu Toulouse
City
Bron
ZIP/Postal Code
69500
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Femme Mere Enfants
City
Bron
ZIP/Postal Code
69500
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Henri Mondor
City
Creteil
ZIP/Postal Code
94010
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Montpellier- Hopital Arnaud de VIlleneuve
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Necker - Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Robert Debre
City
Paris
ZIP/Postal Code
75019
Country
France
Individual Site Status
Recruiting
Facility Name
Hokkaido University Hospital
City
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Individual Site Status
Recruiting
Facility Name
Hyogo prefectural Kobe Children's Hospital
City
Hyogoken
ZIP/Postal Code
6500047
Country
Japan
Individual Site Status
Recruiting
Facility Name
Kobe University Hospital
City
Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Individual Site Status
Recruiting
Facility Name
Yokohama City University Medical Center
City
Kanagawa
ZIP/Postal Code
232-0024
Country
Japan
Individual Site Status
Recruiting
Facility Name
Kitasato University Hospital
City
Kanagawa
ZIP/Postal Code
252-0375
Country
Japan
Individual Site Status
Recruiting
Facility Name
Dokkyo Medical University Hospital
City
Mibu-Machi
ZIP/Postal Code
321-0293
Country
Japan
Individual Site Status
Recruiting
Facility Name
Shiga University Of Medical Science Hospital
City
Shiga
ZIP/Postal Code
520-2192
Country
Japan
Individual Site Status
Recruiting
Facility Name
National Center for Child Health and Development
City
Tokyo
ZIP/Postal Code
157-8535
Country
Japan
Individual Site Status
Recruiting
Facility Name
Tokyo Metropolitan Children's Medical Center
City
Tokyo
ZIP/Postal Code
1838561
Country
Japan
Individual Site Status
Recruiting
Facility Name
Uniwersytecki Szpital Kliniczny w Bialymstoku
City
Bia?ystok
ZIP/Postal Code
15-276
Country
Poland
Individual Site Status
Recruiting
Facility Name
In-VIVO Osrodek Badan Klinicznych
City
Bydgoszcz
ZIP/Postal Code
85-048
Country
Poland
Individual Site Status
Recruiting
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdansk
Country
Poland
Individual Site Status
Recruiting
Facility Name
Dzieciecy Szpital Kliniczny UCK WUM
City
Warszawa
ZIP/Postal Code
02-091
Country
Poland
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Marques de Valdecilla
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Cruces
City
Barakaldo
State/Province
Vizcaya
ZIP/Postal Code
48903
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Sant Joan de Deu - PIN
City
Barcelona
ZIP/Postal Code
08950
Country
Spain
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Learn more about this trial

A Study to Evaluate the Efficacy and Safety of Obinutuzumab Versus MMF in Participants With Childhood Onset Idiopathic Nephrotic Syndrome

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