A Study to Evaluate the Efficacy and Safety of Sefaxersen, an Antisense Inhibitor of Complement Factor B, in Patients with Primary IgA Nephropathy at High Risk of Progression

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] - Male Urogenital Diseases [C12], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

16 Nov 2023 → ongoing

Decision date (initial)

2023-10-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann La Roche

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To evaluate the efficacy of Sefaxersen compared with placebo on the basis of change in proteinuria, as measured by the urine protein-to-creatinine ratio (UPCR) change at Week 37 from baseline from a 24-hour collection

Secondary objectives 5

1. To evaluate the efficacy of Sefaxersen compared with placebo on the basis of change in estimated glomerular filtration rate (eGFR) at Week 105 from baseline. eGFR will be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation
2. To evaluate the efficacy of Sefaxersen compared with placebo on the basis of time to the composite kidney failure endpoint
3. To evaluate the level of fatigue in participants treated with Sefaxersen compared with placebo on the basis of change in fatigue at Week 105 compared with baseline
4. To evaluate the safety of Sefaxersen compared with placebo
5. To characterize the Sefaxersen pharmacokinetic (PK) profile

Conditions and MedDRA coding

Primary Immunoglobulin A (IgA) Nephropathy

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Primary IgA nephropathy (IgAN), as evidenced by a kidney biopsy performed within 10 years prior to or during screening, without known secondary cause.
2. Treatment with maximum tolerated doses of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for at least 90 days immediately prior to screening, and without an intent to modify the dose during the study, except for interruptions due to illness (not greater than 7 consecutive days) ), unless the potential participant is intolerant to these medications
3. UPCR ≥ 1 g/g or urine protein excretion ≥ 1 g/day (with UPCR ≥ 0.8 g/g), all measured from a 24-hour urine collection during screening
4. eGFR ≥ 20 mL/min/1.73 m2, as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation
5. Vaccination against Neisseria meningitidis < 3 years prior to initiation of study treatment and against Streptococcus pneumoniae. Vaccination against Haemophilus influenzae according to national vaccination recommendations for patients receiving complement inhibitors
6. Agree to use protocol defined methods of contraception by female participants and no contraception requirements for male participants

Exclusion criteria 6

1. Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of Sefaxersen
2. Histopathologic or other evidence of another autoimmune glomerular disease
3. Systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg
4. Previous treatment with Sefaxersen
5. History of malignancy within <5 years prior to screening
6. Hemoglobin A1c ≥ 6.5% or a clinical diagnosis of diabetes mellitus of any type

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in proteinuria, as measured by the UPCR change at Week 37 from baseline from a 24-hour collection

Secondary endpoints 5

1. Change in eGFR at Week 105 from baseline. eGFR will be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation
2. Time to the composite kidney failure endpoint, defined as receipt of kidney transplantation, need for kidney replacement therapy, a sustained decline in eGFR of ≥ 30% from baseline, or a sustained eGFR < 15 mL/min/1.73m2 over at least 4 weeks (both eGFR criteria requiretwo consecutive central laboratory eGFR values meeting criteria ≥ 4 weeks apart), whichever occurs first, without the receipt of other immunosuppressive or background therapies for the treatment of IgAN
3. Change in fatigue at Week 105 compared with baseline, as assessed through the use of the Functional Assessment of Chronic Illness Therapy−Fatigue Scale
4. Incidence and severity of treatment-emergent adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 grading scale
5. Plasma concentrations of Sefaxersen conjugated and/or unconjugated equivalent at specified timepoints

Investigational products

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

Test 1

Placebo 1

Auxiliary 2

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 Town

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 5

Locations

7 EU/EEA countries · 41 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 109 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