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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

31 Jul 2023 → ongoing

Decision date (initial)

2024-03-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-505140-19-00

EudraCT number

2022-000369-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacodynamic, Pharmacokinetic

1. To evaluate the efficacy of obinutuzumab compared with MMF

Secondary objectives 7

1. 1. To evaluate the efficacy of obinutuzumab compared with MMF
2. 2. To evaluate changes in fatigue of participants treated with obinutuzumab compared with MMF
3. 3. To evaluate changes in the quality of life of participants treated with obinutuzumab compared with MMF
4. 4. To evaluate edema over time
5. 5. To evaluate the safety of obinutuzumab compared with MMF
6. 6. To characterize the obinutuzumab PK profile
7. 7. To characterize obinutuzumab-induced PD changes

Conditions and MedDRA coding

Childhood Idiopathic Nephrotic Syndrome

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001207-PIP05-22

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Diagnosis of frequently relapsing nephrotic syndrome (FRNS) or steroid dependent nephrotic syndrome (SDNS) before the age of 18 years
2. 2. 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
3. 3. 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
4. 4. Participants having received cyclophosphamide in the 6 months prior to randomization must have experienced at least 1 relapse subsequent to cyclophosphamide discontinuation
5. 5. Estimated glomerular filtration rate (eGFR) within normal range for age

Exclusion criteria 6

1. 1. Secondary nephrotic syndrome
2. 2. History of steroid resistant nephrotic syndrome. History of genetic defects known to directly cause nephrotic syndrome
3. 3. Treatment with other immunosuppressive medications to prevent relapse, other than MMF or oral corticosteroids within 2 months prior to randomization
4. 4. 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
5. 5. 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
6. 6. Patients 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Percentage of Participants with Sustained Complete Remission at 1 year

Secondary endpoints 14

1. 1. Overall relapse-free survival (RFS)
2. 2. Probability of RFS at Week 52
3. 3. Cumulative corticosteroid dose
4. 4. Number of relapses
5. 5. Proportion of participants experiencing edema associated relapse during the 52-week treatment period
6. 6. Proportion of patients with sustained complete remission at Week 76
7. 7. Mean change in “General Fatigue” domain of PedsQL-Multidimensional Fatigue scale total score from baseline to Week 52
8. 8. Mean change in “Physical Functioning” domain of PedsQL-Quality of Life Inventory from baseline to Week 52
9. 9. Mean change in CureGN Edema Scale from baseline to Week 52
10. 10. Incidence, nature, and severity of adverse events, with severity determined according to AE intensity (mild, moderate, severe, life-threatening) and NCI CTCAE grading if applicable from baseline to Week 52
11. 11. Incidence of laboratory or vital sign abnormalities from baseline to Week 52
12. 12. Serum concentrations of obinutuzumab at specified timepoints
13. 13. Proportion of participants achieving B-cell depletion (HSFC) at specified timepoints
14. 14. Total peripheral B cell and B cell subsets (e.g., memory B cells) counts and change from baseline at specified timepoints

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 8

Locations

6 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 85 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications