Study of efficacy and safety of LNP023 in primary IgA nephropathy patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma 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

25 Jan 2021 → 19 Sep 2025

Decision date (initial)

2024-07-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-511067-29-00

EudraCT number

2020-001049-38

ClinicalTrials.gov

NCT04578834

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others, Therapy, Pharmacodynamic

Main Objective for Interim Analysis:
•To demonstrate superiority of LNP023 vs. placebo in the reduction of proteinuria at 9 months by measuring UPCR sampled from a 24h urine collection.
Main Objective for Final Analysis:
•To demonstrate superiority of LNP023 vs. placebo in slowing IgAN progression measured by the annualized total slope of eGFR decline over 24 months.

Secondary objectives 10

1. For Interim Analysis: To evaluate the effect of LNP023 vs placebo on slowing eGFR decrease as measured by the change from baseline in eGFR.
2. For Interim Analysis: To assess the effect of LNP023 vs placebo on the proportion of study participants reaching proteinuria below 1g/g of UPCR.
3. For Interim Analysis: To evaluate the effect of LNP023 vs placebo on slowing IgAN progression measured by the annualized total slope of eGFR decline over 1 year.
4. For Interim Analysis: To assess the effect of LNP023 vs placebo on the change from baseline to 9 months in fatigue scale measured by the FACIT-Fatigue questionnaire.
5. For Interim Analysis: To evaluate the safety and tolerability of LNP023 compared to placebo.
6. For Final Analysis: To demonstrate the superiority of LNP023 vs placebo on delaying the time to first occurrence of a composite kidney failure endpoint.
7. For Final Analysis: To demonstrate the superiority of LNP023 vs placebo in the reduction of proteinuria at 9 months by measuring UPCR sampled from a 24h urine collection.
8. For Final Analysis: To demonstrate the superiority of LNP023 vs placebo on the proportion of study participants reaching proteinuria below 1g/g of UPCR at 9 months.
9. For Final Analysis: To demonstrate the superiority of LNP023 vs placebo on the change from baseline to 9 months in the fatigue scale measured by FACIT-Fatigue Questionnaire.
10. For Final Analysis: To evaluate the safety and tolerability of LNP023 compared to placebo.

Conditions and MedDRA coding

IgA Nephropathy

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male and female patients ≥ 18 years of age with an eGFR level and biopsy-confirmed IgA nephropathy as follows: •For patients eGFR* ≥ 45ml/min/1.73m2, a qualifying biopsy performed within the last 5 years is required •For patients with eGFR* 30 to <45ml/min/1.73m2, a qualifying biopsy performed within 2 years with < 50% tubulointerstitial fibrosis is required. • For patients with eGFR* 20 to <30ml/min/1.73m2, a qualifying biopsy performed at any time. In all cases, if a historical biopsy is not available, one may be performed during screening. *eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines).
2. Proteinuria due to primary diagnosis of IgA nephropathy as assessed at screening by UPCR ≥1 g/g (113 mg/mmol) sampled from FMV or 24h urine collection, as well as at the completion of the run-in period by UPCR ≥1 g/g (113 mg/mmol) calculated as the (geometric) mean of two 24h urine collections obtained within 14 days of each other at baseline.
3. Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.
4. If not previously vaccinated, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to first study drug administration.
5. All patients must have been on supportive care including stable dose regimen of ACEi or ARB at either the locally approved maximal daily dose or the maximally tolerated dose (per investigators' judgment) for approximately 90 days before first study drug administration. In addition, if patients are taking diuretics or other antihypertensive medication or other background medication for IgAN, the doses should also be stabilized for approximately -90 days prior to the first dosing of study treatment.

Exclusion criteria 6

1. Any secondary IgAN as defined by the investigator; secondary IgAN can be associated with cirrhosis, celiac disease, Human Immunodeficiency Virus (HIV) infection, herpetiformis, seronegative arthritis, small-cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, and inflammatory bowel disease, familial mediterranean fever, etc.
2. Sitting office SBP >140 mmHg or DBP >90 mmHg at the randomization visit.
3. Patients previously treated with immunosuppressive or other immunmodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, hydroxychloroquine, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, or systemic corticosteroids exposure (>7.5 mg/d prednisone/prednisolone equivalent) within 90 days (or 180 days for rituximab) prior to first study drug administration. Participants previously or currently treated with oral budesonide. Participants treated with endothelin (receptor) antagonists within 90 days prior to first study drug administration.
4. Prior use of LNP023 or prior enrollment in any other LNP023 clinical trial where study drug was taken, including matching placebo.
5. History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.
6. Active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study drug administration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary Endpoint for Interim Analysis: •Log-transformed ratio to baseline in UPCR (sampled from 24h urine collection) at 9 months.
2. Primary Endpoint for Final Analysis: •Annualized total eGFR slope estimated over 24 months.

Secondary endpoints 10

1. Secondary Endpoint for Interim Analysis: •Change from baseline in eGFR at 9 months.
2. Secondary Endpoint for Interim Analysis: •Proportion of participants reaching UPCR (sampled from 24h urine collection) <1g/g at 9 months, without receiving CS/IS or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating Kidney Replacement Therapy (KRT).
3. Secondary Endpoint for Interim Analysis: •Annualized total eGFR slope estimated over 12 months.
4. Secondary Endpoint for Interim Analysis: •Change from baseline to 9 months in the fatigue scale measured by the FACIT-Fatigue questionnaire.
5. Secondary Endpoint for Interim Analysis: •Safety endpoints (including adverse events/serious adverse events, safety laboratory parameters, vital signs) collected from baseline to 9 months.
6. Secondary Endpoints for Final Analysis: •Time from randomization to first occurrence of composite kidney failure event, defined as reaching either: - sustained ≥30% decline in eGFR relative to baseline, or - sustained eGFR <15 mL/min/1.73m², or - maintenance dialysis, or - receipt of kidney transplant, or - death from kidney failure.
7. Secondary Endpoints for Final Analysis: •Log-transformed ratio to baseline in UPCR (sampled from 24h urine collection) at 9 months.
8. Secondary Endpoints for Final Analysis: •Proportion of participants reaching UPCR (sampled from 24h urine collection) <1g/g at 9 months without receiving CS/IS, or other newly approved drugs or initiating new background therapy for treatment of IgAN or initiating KRT.
9. Secondary Endpoints for Final Analysis: •Change from baseline to 9 months in the fatigue scale measured by the FACIT-Fatigue questionnaire.
10. Secondary Endpoints for Final Analysis: •Safety endpoints (including adverse events/serious adverse events, safety laboratory parameters, vital signs) collected from baseline to the End of Study (EOS).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 20

Locations

12 EU/EEA countries · 37 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 81 files

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

Application history

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