Long-term Efficacy, Safety and Tolerability of Iptacopan in C3G or IC-MPGN

Phase 3RecruitingNCT03955445

Novartis Pharmaceuticals225 enrolled

Overview

This is an open-label extension study to evaluate the long-term efficacy, safety and tolerability of iptacopan in subjects with C3 glomerulopathy or idiopathic immune-complex-membranoproliferative glomerulonephritis

The primary purpose of this extension study is to collect long-term efficacy, safety and tolerability data in eligible participants receiving open-label iptacopan after completing treatment in the C3G Phase 2 proof of concept study CLNP023X2202. The primary (at 9 months) and longer-term (\>9 months) efficacy and safety data of iptacopan collected from CLNP023X2202 participants will be used to support health authority submissions. This umbrella protocol will also allow: * continued access to iptacopan to patients enrolled in the ongoing Phase 3 programs (C3G and IC-MPGN) * C3G study (CLNP023B12301): adults and adolescents * IC-MPGN study (CLNP023B12302): adults and adolescents * provision of additional efficacy and safety information following longer-term treatment in C3G and IC-MPGN populations to support health authority submissions. Efficacy and safety assessments at the 9 month visit of this extension study in combination with data from CLNP023X2202 (baseline plus 3 months of treatment) allowed evaluation of the effects of iptacopan on potential endpoint(s) at 12 months of iptacopan treatment in C3G participants. The enrollment of C3G and IC-MPGN participants (adults and adolescents) from Phase 3 studies, CLNP023B12301 and CLNP023B12302, permits longer-term evaluation of the persistence of effects observed after iptacopan treatment. These longer term efficacy and safety assessments may be compared to historical/concurrent control data available from relevant real world databases in C3G or IC-MPGN patients and used as supportive information for registration purposes. This extension study is expected to continue until the drug product becomes commercially available and accessible (anticipated to be up to approximately 168 months from the first patient first visit date), or the benefit-risk profile is no longer positive, or the program is discontinued for business or strategic reasons. "Baseline" refers to the Day 1 visit (pre-dose) of CLNP023X2202, CLNP023B12301 or CLNP023B12302, whereas the Day 1 visit for this C3G/IC-MPGN extension study (CLNP023B12001B) is identified as "Extension Day 1".

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

225

Conditions

C3 Glomerulopathy Immune-complex-membranoproliferative Glomerulonephritis

Interventions

LNP023DRUG

LNP023 capsules

Eligibility

Sex: ALLMin age: 12 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: \- Patients must have completed the treatment period of the CLNP023X2202, CLNP023B12301 or CLNP023B12302 study on study drug Exclusion Criteria: * Severe concurrent co-morbidities, e.g. advanced cardiac disease (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 LNP023 or complying with the requirements of the study * 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. * History or current diagnosis of ECG abnormalities indicating significant risk of safety for subjects * History of HIV or any other immunodeficiency disease Other protocol-defined inclusion/exclusion criteria may apply

Locations (48)

Outcomes

Primary Outcomes

CLNP023X2202 Cohort A-native C3G: Number of participants who achieve the composite renal endpoint

A participant meets the requirements of the composite renal endpoint if they satisfy the following criteria at the 9-month visit in CLNP023B12001B: (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 and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., ≥ the lower limit of normal (LLN)). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as not meeting the endpoint.

Time frame: 9-month visit

CLNP023X2202 Cohort B - kidney transplant and recurrent C3G: Change from baseline in the C3 Deposit Score

Change from baseline in the C3 Deposit Score (based on immunofluorescence microscopy) compared to baseline in the CLNP023X2202 study.

Time frame: 6 - to 9- month visit

Number of AEs of special interest for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302

Number of participants with AEs of special interest will be collected to evaluate the long-term safety and tolerability of iptacopan in participants.

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

Number of participants with study drug discontinuation due to an AE (or any safety issue) for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302

Number of participants with study drug discontinuation due to an AE to evaluate the long-term safety and tolerability of iptacopan in participants.

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

Number of participants with abnormal clinically significant vital signs,ECGs, and safety laboratory measurements for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302

Central Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682 novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Childrens Hospital Colorado

Aurora, Colorado, United States

RECRUITING

Georgia Nephrology Research Inst

Lawrenceville, Georgia, United States

RECRUITING

University of Iowa Health Care

Iowa City, Iowa, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

RECRUITING

Col Uni Med Center New York Presby

New York, New York, United States

RECRUITING

Novartis Investigative Site

CABA, Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

Buenos Aires, Argentina

RECRUITING

Novartis Investigative Site

Belo Horizonte, Minas Gerais, Brazil

RECRUITING

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, Brazil

RECRUITING

Novartis Investigative Site

Botucatu, São Paulo, Brazil

RECRUITING

...and 38 more locations

Secondary Outcomes

CLNP023X2202: Number of participants who achieve the 2-component composite renal endpoint

A participant is defined as achieving the composite renal endpoint if they meet the following criteria at the 9-month visit in CLNP023B12001B: (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. Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a not meeting the composite renal endpoint.

Time frame: 9-month visit

CLNP023X2202: Change from baseline in log-transformed urine protein/creatinine ratio (UPCR)

Long-term effect of LNP023 on renal function in C3G subjects by assessing the change from baseline in log-transformed urine protein/creatinine ratio (UPCR)

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

CLNP023X2202: Change from baseline in log-transformed urine albumin/creatinine ratio (UACR)

Long-term effect of LNP023 on renal function in C3G subjects by assessing the change from baseline in log-transformed urine albumin/creatinine ratio (UACR)

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

CLNP023X2202: Change from baseline in serum creatinine concentration

Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in serum creatinine compared to CLNP023X2202 baseline

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

CLNP023X2202: Change from baseline in estimated glomerular filtration rate (eGFR)

Long-term effect of LNP023 on renal function in C3G subjects by assessing the change in eGFR compared to CLNP023X2202 baseline

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

CLNP023X2202: Status of C3G disease progression

Describe the status of C3G disease progression based on glomerular histopathology in a renal biopsy at 6 to 9 months from entry to the study compared to those obtained prior to treatment in the CLNP023X2202 study

Time frame: 6 to 9 month visit

CLNP023X2202: Log-transformed ratio to baseline in serum C3

Long-term effect of LNP023 on C3 by evaluating the Log-transformed ratio to baseline in serum C3

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

CLNP023X2202: Number of participants who achieve the composite renal endpoint

A participant is defined as achieving the composite renal endpoint if they meet the following criteria at times \>9 months in CLNP023B12001B: (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 and (3) either a ≥50% increase in C3 compared to baseline or an increase to ≥90 mg/dL (i.e., LLN). Initiation of treatment with eculizumab or any other complement pathway modifying agent automatically designates the participant as a not meeting the composite renal endpoint.

Time frame: Up to 66 months

CLNP023X2202: Plasma LNP023 concentration up to 12 months at trough

Measurement of LNP023 plasma concentration to evaluate the pharmacokinetics of iptacopan in participants with prolonged treatment

Time frame: 3-months, 6-months, 9-months and 12-months visits

CLNP023B12301 and CLNP023B12302: Change from initiation of iptacopan treatment in the core study in log-transformed UPCR over time.

Change from initiation of iptacopan treatment in the core study in log-transformed UPCR will be assessed to evaluate the long-term effect of iptacopan on proteinuria

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

CLNP023B12301 and CLNP023B12302: Change from initiation of iptacopan treatment in the core study in eGFR over time.

Change from initiation of iptacopan treatment in the core study in eGFR over time will be assessed to evaluate the long-term effect of iptacopan on eGFR

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months

CLNP023B12301 and CLNP023B12302: Number of participants who achieve a 2-component composite renal endpoint

A participant is defined as meeting the requirements of the composite renal endpoint if they satisfy the eGFR (a stable or improved eGFR, i.e., ≤15% reduction in eGFR compared to the initiation of iptacopan treatment in the core study) and UPCR (≥50% reduction in UPCR compared to the initiation of iptacopan treatment in the core study) criteria assessed at a visit. Initiation of any complement pathway modifying agent or initiation/intensification of corticosteroid or immunosuppressant therapy, or renal replacement therapy automatically designates the participant as not having met the endpoint. The rate will be evaluated over time.

Time frame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months