Long-term efficacy, safety and tolerability of LNP023 in C3G or IC-MPGN

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Oct 2019 → ongoing

Decision date (initial)

2024-08-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-509343-27-00

EudraCT number

2018-004253-24

ClinicalTrials.gov

NCT03955445

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others, Pharmacokinetic, Therapy

Participants enrolling from study CLNP023X2202:
• Primary Efficacy Objective (Cohort A - native C3G): To assess the effect of iptacopan on a 3-component composite renal endpoint in C3G participants at the 9-month visit.
• Primary Efficacy Objective (Cohort B - transplanted kidney with recurrent C3G): To assess the effect of iptacopan on C3 deposit score at the 6 to 9 month visit.
• Primary Safety Objective: To evaluate the long-term safety and tolerability of iptacopan in participants with C3G.
Participants enrolling from study CLNP023B12301 or CLNP023B12302:
• Primary Objective: To evaluate the long-term safety and tolerability of iptacopan in participants with C3G or IC-MPGN.

Secondary objectives 9

1. Participants enrolling from study CLNP023X2202: • To characterize the effect of treatment with iptacopan on a 2-component composite renal endpoint at the 9-month visit.
2. Participants enrolling from study CLNP023X2202: • To assess the long-term effect of iptacopan on renal function (eGFR and UPCR) in C3G participants at the 9-month visit.
3. Participants enrolling from study CLNP023X2202: • To assess the effect of iptacopan on proteinuria in C3G participants at the 3-month visit.
4. Participants enrolling from study CLNP023X2202: • To describe the status of C3G disease progression based on glomerular histopathology in a renal biopsy at 6-9 months.
5. Participants enrolling from study CLNP023X2202: • To evaluate the long-term effect of iptacopan on C3 at the 9-month visit.
6. Participants enrolling from study CLNP023X2202: • To evaluate the pharmacokinetics of iptacopan in participants with prolonged treatment.
7. Participants enrolling from study CLNP023B12301 or CLNP023B12302: • To evaluate the long-term effect of iptacopan on proteinuria.
8. Participants enrolling from study CLNP023B12301 or CLNP023B12302: • To evaluate the long-term effect of iptacopan on eGFR.
9. Participants enrolling from study CLNP023B12301 or CLNP023B12302: • To evaluate the long-term effect of iptacopan on a 2-component composite renal endpoint.

Conditions and MedDRA coding

C3 Glomerulopathy or idiopathic immune-complex membranoproliferative glomerulonephritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Participants must have completed the treatment period of the CLNP023X2202, CLNP023B12301 or CLNP023B12302 study on study drug.

Exclusion criteria 4

1. Severe concurrent co-morbidities, e.g., advanced cardiac disease (New York Heart Association (NYHA) class IV), severe pulmonary arterial hypertension (WHO class IV), or any illness or medical condition that in the opinion of the investigator and sponsor is likely to prevent the patient from safely tolerating iptacopan or complying with the requirements of the study.
2. Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to screening, or The presence of fever ≥ 38oC (100.4oF) within 7 days prior to screening.
3. History of human immunodeficiency virus (HIV) or any other immunodeficiency disease.
4. History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Participants from study CLNP023X2202: • Composite renal endpoint met at the 9-month visit if following criteria satisfied: (1) stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR) and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL.
2. Participants from study CLNP023X2202: • Change from baseline in the C3 Deposit Score (based on immunofluorescence microscopy) compared to baseline in the CLNP023X2202 study.
3. Participants from study CLNP023X2202: • Occurrence of clinically significant vital signs (msDBP, msSBP, heart rate), ECGs, and safety laboratory measurements, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue).
4. Participants from studies CLNP023B12301 or CLNP023B12302: • Occurrence of clinically significant vital signs (msDBP, msSBP, heart rate), ECGs, and safety laboratory measurements, as well as adverse events (AEs), AEs of special interest, and study drug discontinuation due to an AE (or any safety issue).

Secondary endpoints 12

1. Participants from study CLNP023X2202: • Composite renal endpoint met at the 9-month visit if following criteria satisfied: (1) a stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), and (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR.
2. Participants from study CLNP023X2202: • Change from baseline in log-transformed urine protein/creatinine ratio (UPCR), change from baseline in log-transformed urine albumin/creatinine ratio (UACR), change from baseline in serum creatinine concentration and change from baseline in estimated glomerular filtration rate (eGFR) at the 9-month visit in CLNP023B12001B.
3. Participants from study CLNP023X2202: • Change from baseline in log-transformed urine protein/creatinine ratio (UPCR) and change from baseline in log-transformed urine albumin/creatinine ratio (UACR), at the 3-month visit in CLNP023B12001B.
4. Participants from study CLNP023X2202: • Disease activity and chronicity scores from a renal biopsy at 6 to 9 months from entry to the CLNP023B12001B study. Biopsies will be compared to those obtained in the CLNP023X2202 study (if available).
5. Participants from study CLNP023X2202: • Log-transformed ratio to baseline in serum C3 at the 9-month visit in CLNP023B12001B.
6. Participants from study CLNP023X2202: • Composite renal endpoint met at times >9 months if following criteria satisfied: (1) stable or improved eGFR compared to the baseline visit in CLNP023X2202 (≤10% reduction in eGFR), (2) either ≥50% reduction compared to the baseline visit in CLNP023X2202 or a reduction to <300 mg/g in UPCR and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL.
7. Participants from study CLNP023X2202: • Change from baseline in log-transformed UPCR, log-transformed UACR, serum creatinine concentration and estimated glomerular filtration rate (eGFR) at times >9 months in CLNP023B12001B. Change in eGFR slope.
8. Participants from study CLNP023X2202: • Log-transformed ratio to baseline in serum C3 at times >9 months in CLNP023B12001B.
9. Participants from study CLNP023X2202: • Determine plasma iptacopan concentration up to 12 months at trough.
10. Participants from studies CLNP023B12301 or CLNP023B12302: • Change from initiation of iptacopan treatment in the core study in log-transformed UPCR over time.
11. Participants from studies CLNP023B12301 or CLNP023B12302: • Change from initiation of iptacopan treatment in the core study in eGFR over time.
12. Participants from studies CLNP023B12301 or CLNP023B12302: • Composite renal endpoint met if following criteria satisfied (1) eGFR (a stable or improved eGFR, i.e., ≤15% reduction in eGFR compared to the initiation of iptacopan treatment in the core study) and (2) UPCR (≥50% reduction in UPCR compared to the initiation of iptacopan treatment in the core study).

Investigational products

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

Test 2

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 19

Locations

7 EU/EEA countries · 34 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 84 files

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

Application history

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