A Study to Evaluate Efficacy and Safety of Obinutuzumab in Patients with Primary Membranous Nephropathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

19 Apr 2021 → ongoing

Decision date (initial)

2024-03-05

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

2023-506525-11-00

EudraCT number

2020-003233-38

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of obinutuzumab compared with tacrolimus on the basis of the proportion of patients who achieve a complete remission (CR) at Week 104

Secondary objectives 5

1. To evaluate the efficacy of obinutuzumab compared with tacrolimus on the basis of: achievement of an overall remission at Week 104; achievement of CR at Week 76; time to treatment failure, meeting escape criteria, or relapse after complete or partial remission; time to a sustained reduction of eGFR>=30% from baseline, mean change in T-score from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue scale at Week 104; duration of CR; change in anti-PLA2R autoantibody titer from baseline to Week 52; mean change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Assessment of Physical Health scale at Week 104
2. To evaluate the safety of obinutuzumab compared with tacrolimus
3. To characterize the pharmacodynamic effects of obinutuzumab in pMN patients
4. To characterize the pharmacokinetics of obinutuzumab in the pMN population
5. To evaluate the immune response to obinutuzumab

Conditions and MedDRA coding

Primary Membranous Nephropathy (pMN)

Study design 5 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Ability to comply with the study protocol, in the investigator's judgment
2. Diagnosis of pMN according to renal biopsy prior to or during screening
3. Screening urinary protein-to-creatinine ratio (UPCR) >= 5 g/g from 24-hour urine collection after best supportive care for >= 3 months prior to screening or screening UPCR >= 4 g/g after best supportive care for >= 6 months prior to screening
4. eGFR >= 40 mL/min/1.73m2 or qualified endogenous creatinine clearance >= 40 mL/min/1.73m2 based on 24-hour urine collection during screening
5. Patients who previously responded to calcineurin inhibitor (CNIs), rituximab, or alkylating agents with either a CR or partial remission and subsequently relapsed are eligible but require discontinuation of CNIs or alkylating agents for >= 6 months and rituximab for >= 9 months prior to screening
6. For patients enrolled in the extended China enrollment phase at China’s sites: current resident of mainland China and of Chinese ancestry

Exclusion criteria 6

1. Uncontrolled blood pressure, in the opinion of the investigator, during 3 months prior to screening
2. Evidence of >= 50% reduction in proteinuria during the previous 6 months prior to randomization
3. Receipt of renal replacement therapy
4. Type 1 or 2 diabetes mellitus
5. Receipt of previous therapies as follows: - Treatment with MMF or oral, intramuscular, or intravenous corticosteroids within 1 month prior to or during screening - Any B-cell depleting therapy such as rituximab, ocrelizumab, or ofatumumab within 9 months prior to or during screening - Treatment with cyclophosphamide or CNI within 6 months prior to or during screening - Treatment with any biologic therapy such as belimumab, ustekinumab, or anifrolumab within 6 months prior to or during screening - Treatment with an inhibitor of Janus-associated kinase, Bruton’s tyrosine kinase, or tyrosine kinase 2, including but not limited to tofacitinib, baricitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib within 3 months prior to or during screening - Treatment with any investigational agent within 28 days of screening or 5 drug-elimination half-lives of the investigational drug, whichever is longer - Receipt of a live vaccine within 28 days prior to screening or during screening
6. Patients with a secondary cause of MN (e.g., hepatitis B, SLE, medications, malignancies)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. The proportion of patients who achieve a CR at Week 104

Secondary endpoints 15

1. 1. The proportion of patients who achieve an overall remission at Week 104
2. 2. The proportion of patients who achieve CR at Week 76
3. 3. Time to treatment failure, meeting escape criteria, or relapse after complete or partial remission
4. 4. Time to a sustained reduction of eGFR >= 30% from baseline
5. 5. Mean change in T-score from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue scale at Week 104
6. 6. Duration of CR
7. 7. Change in anti-PLA2R autoantibody titer from Baseline to Week 52
8. 8. Mean change from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Assessment of Physical Health scale at Week 104
9. 9. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
10. 10. Characterization of adverse events of special interest
11. 11. Change from baseline in targeted vital signs
12. 12. Change from baseline in targeted clinical laboratory test results
13. 13. Serum concentrations of obinutuzumab at specified timepoints
14. 14. Peripheral B-cell counts at specified timepoints
15. 15. Prevalence of anti-drug antibodies (ADAs) to obinutuzumab at baseline and incidence of ADAs during the study

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 4

Locations

4 EU/EEA countries · 18 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 18 files

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

Application history

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