A study to evaluate the efficacy and safety of frexalimab, brivekimig or rilzabrutinib in participants aged 16 to 75 years with primary focal segmental glomerulosclerosis or minimal change disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

17 Jan 2025 → ongoing

Decision date (initial)

2024-12-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-511775-15-00

WHO UTN

U1111-1301-2676

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacokinetic

To evaluate the efficacy of frexalimab, brivekimig and rilzabrutinib on reduction in proteinuria compared to placebo in participants with primary FSGS/MCD

Secondary objectives 5

1. To evaluate the efficacy of frexalimab, brivekimig and rilzabrutinib on the rate of partial remission compared to placebo in participants with primary FSGS/MCD
2. To evaluate the efficacy of frexalimab, brivekimig and rilzabrutinib on the rate of complete remission (CR) compared to placebo in participants with primary FSGS/MCD
3. To evaluate the safety and tolerability of frexalimab, brivekimig or rilzabrutinib in participants with primary FSGS/MCD
4. To characterize the pharmacokinetics (PK) of frexalimab, brivekimig and rilzabrutinib
5. To evaluate the potential for immunogenicity of frexalimab and brivekimig in participants with primary FSGS/MCD

Conditions and MedDRA coding

Immune system diseases

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Biopsy report indicative of primary FSGS or primary MCD, with supportive clinical presentation per Investigator's judgement.
2. UPCR ≥3 g/g at screening, or ≥ 1.5 g/g in those with eGFR ≥ 60.
3. eGFR ≥45 mL/min/1.73 m^2 at screening.
4. Documented history of UPCR (or 24-hour urine protein) reduction by ≥40% in response to corticosteroid or other immunosuppressive therapy when pre-treatment UPCR was ≥3.5 g/g (or pre-treatment 24-hr urine protein was ≥3.5 g/day if 24-hour urine protein is used).
5. ≤10 mg/day prednisone or equivalent and stable starting at least 1 week prior to randomization.
6. For those on a RAAS inhibitor prior to screening, the dose must be stable ≥4 weeks prior to screening; starting RAAS inhibitors or changing the dose will not be allowed during the double-blind or OLE treatment period.
7. For those on an SGLT2 inhibitor prior to screening, the dose must be stable ≥4 weeks prior to screening; starting SGLT2 inhibitor treatment or changing the dose will not be allowed during the double-blind or OLE treatment periods.
8. Body weight within 45 to 120 kg (inclusive) at screening.

Exclusion criteria 3

1. Genetic or secondary FSGS or MCD. Those with APOL1 risk alleles are eligible.
2. Collapsing variant of FSGS.
3. ESKD requiring dialysis or transplantation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent reduction in urine protein to creatinine ratio (UPCR)

Secondary endpoints 5

1. Percentage of participants achieving FSGS partial remission endpoint
2. Percentage of participants achieving CR
3. Incidence of treatment-emergent adverse events, treatment-emergent serious adverse events (SAEs), treatment-emergent adverse events of special interest (AESIs) and IMP discontinuation due to TEAEs during the study
4. Plasma concentrations of frexalimab and rilzabrutinib and serum concentrations of SAR442970
5. Occurrence of anti-drug antibodies (ADAs) against frexalimab and SAR442970

Investigational products

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

Test 3

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 13

Locations

11 EU/EEA countries · 38 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 122 files

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

Application history

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