Clinical trial NCT03955445: Long-term Efficacy, Safety and Tolerability of Iptacopan in C3G or IC-MPGN
Official title: An Open-label, Non-randomized Extension Study to Evaluate the Long-term Efficacy, Safety and Tolerability of Iptacopan (LNP023) in C3 Glomerulopathy or Idiopathic Immune-complex-membranoproliferative Glomerulonephritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: C3 Glomerulopathy
Immune-complex-membranoproliferative Glomerulonephritis
Keywords: C3G
C3 glomerulopathy
C3GN
C3 glomerulonephritis
DDD
dense deposit disease
iptacopan
LNP023
IC-MPGN
idiopathic immune-complex- membranoproliferative glomerulonephritis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-05-20
Enrollment: 225
Sex: ALL
Minimum age (years): 12
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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".

Eligibility criteria: 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

Primary outcomes:
measure: CLNP023X2202 Cohort A-native C3G: Number of participants who achieve the composite renal endpoint
timeFrame: 9-month visit
measure: CLNP023X2202 Cohort B - kidney transplant and recurrent C3G: Change from baseline in the C3 Deposit Score
timeFrame: 6 - to 9- month visit
measure: Number of AEs of special interest for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
measure: Number of participants with study drug discontinuation due to an AE (or any safety issue) for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
measure: Number of participants with abnormal clinically significant vital signs,ECGs, and safety laboratory measurements for participants from CLNP023X2202, CLNP023B12301 and CLNP023B12302
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
Secondary outcomes:
measure: CLNP023X2202: Number of participants who achieve the 2-component composite renal endpoint
timeFrame: 9-month visit
measure: CLNP023X2202: Change from baseline in log-transformed urine protein/creatinine ratio (UPCR)
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
measure: CLNP023X2202: Change from baseline in log-transformed urine albumin/creatinine ratio (UACR)
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
measure: CLNP023X2202: Change from baseline in serum creatinine concentration
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
measure: CLNP023X2202: Change from baseline in estimated glomerular filtration rate (eGFR)
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
measure: CLNP023X2202: Status of C3G disease progression
timeFrame: 6 to 9 month visit
measure: CLNP023X2202: Log-transformed ratio to baseline in serum C3
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
measure: CLNP023X2202: Number of participants who achieve the composite renal endpoint
timeFrame: Up to 66 months
measure: CLNP023X2202: Plasma LNP023 concentration up to 12 months at trough
timeFrame: 3-months, 6-months, 9-months and 12-months visits
measure: CLNP023B12301 and CLNP023B12302: Change from initiation of iptacopan treatment in the core study in log-transformed UPCR over time.
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
measure: CLNP023B12301 and CLNP023B12302: Change from initiation of iptacopan treatment in the core study in eGFR over time.
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
measure: CLNP023B12301 and CLNP023B12302: Number of participants who achieve a 2-component composite renal endpoint
timeFrame: Participants are expected to continue on study for a minimum of 60 months and a maximum of 84 months
Other outcomes:
Locations:
city: Lawrenceville
country: United States
facility: Georgia Nephrology Research Inst
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: New York
country: United States
facility: Col Uni Med Center New York Presby
state: New York
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Montpellier 5
country: France
facility: Novartis Investigative Site
city: Paris 15
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Petach-Tikva
country: Israel
facility: Novartis Investigative Site
city: Ranica
country: Italy
facility: Novartis Investigative Site
state: BG
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Asahikawa
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Takatsuki
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Ohtsu
country: Japan
facility: Novartis Investigative Site
state: Shiga
city: Niigata
country: Japan
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
state: Zuid Holland
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Talas Kayseri
country: Turkey
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: