Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy.

NCT ID: NCT04817618

Last Updated: 2025-03-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-28

Study Completion Date

2026-07-04

Brief Summary

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The Primary Completion Date and Study Completion Date have been updated to reflect completion of the adolescent cohort, which has been added to the protocol.

The study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in complement 3 glomerulopathy.

Detailed Description

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The purpose of this study is to evaluate the efficacy and safety of iptacopan compared to placebo and standard of care in patients with native C3G. CLNP023B12301 is a Phase 3 pivotal trial for registration of iptacopan in C3G. The study aims to determine the reduction in UPCR and improvement in eGFR in participants treated with iptacopan compared to placebo, as well as the proportion of participants who achieve a composite renal endpoint consisting of eGFR and UPCR elements. These effects of iptacopan in conjunction with increases in serum C3 levels will provide support for an iptacopan profile that includes stabilization of eGFR, clinically meaningful reductions in proteinuria and inhibition of the complement AP. Kidney biopsies will be performed in adult participants to evaluate histopathological improvements in immunofluorescence and light microscopy that support these functional benefits of iptacopan.

Conditions

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C3G

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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iptacopan 200mg

iptacopan 200 mg b.i.d.

Group Type EXPERIMENTAL

iptacopan

Intervention Type DRUG

iptacopan 200 mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)

Placebo to iptacopan 200mg

Placebo to iptacopan 200mg b.i.d.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo to iptacopan 200mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)

Interventions

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Placebo

Placebo to iptacopan 200mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)

Intervention Type DRUG

iptacopan

iptacopan 200 mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d)

Intervention Type DRUG

Other Intervention Names

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LNP023

Eligibility Criteria

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Inclusion Criteria

* Male and female participants age ≥ 12 and ≤ 60 years at screening.
* Diagnosis of C3G as confirmed by renal biopsy within 12 months prior to enrollment in adults and within 3 years in adolescents.
* Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for at least 90 days. The doses of other antiproteinuric medications including mycophenolic acid, corticosteroids and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization.
* Reduced serum C3 (defined as less than 0.85 x lower limit of the central laboratory normal range) at Screening.
* UPCR ≥ 1.0 g/g sampled from the first morning void urine sample at Day -75 and Day -15.
* Estimated GFR (using the CKD-EPI formula for ages ≥ 18 years and modified Schwartz formula for ages 12 to 17 years) or measured GFR ≥ 30 ml/min/1.73m2 at screening and Day -15.
* Mandatory vaccination against Neisseria meningitidis and Streptococcus pneumoniae prior to the start of study treatment.
* If not previously vaccinated or if a booster is required, vaccination against Haemophilus influenzae infections should be given, if available and according to local regulations, at least 2 weeks prior to the first study treatment administration. If study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated.

Exclusion Criteria

* Participants who have received any cell or organ transplantation, including a kidney transplantation.
* Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with renal biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli.
* Renal biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%
* Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care.
* Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration
* The presence of fever ≥ 38°C (100.4°F) within 7 days prior to study treatment administration.
* A history of recurrent invasive infections caused by encapsulated organisms, e.g., N. meningitidis and S. pneumoniae.
* The use of inhibitors of complement factors (e.g., Factor B, Factor D, C3 inhibitors, anti C5 antibodies, C5a receptor antagonists) within 6 months prior to the Screening visit.
* The use of immunosuppressants (except mycophenolic acids), cyclophosphamide or systemic corticosteroids at a dose \>7.5 mg/day (or equivalent for a similar medication) within 90 days of study drug administration.
* Acute post-infectious glomerulonephritis at screening based upon the opinion of the investigator.
Minimum Eligible Age

12 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Childrens Hospital Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Nicklaus Childrens Hospital

Miami, Florida, United States

Site Status RECRUITING

Georgia Nephrology Research Inst

Lawrenceville, Georgia, United States

Site Status RECRUITING

University of Iowa Health Care

Iowa City, Iowa, United States

Site Status RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status WITHDRAWN

Brigham and Womens Hosp Harvard Med School

Boston, Massachusetts, United States

Site Status WITHDRAWN

Albany Medical Center

Albany, New York, United States

Site Status WITHDRAWN

Col Uni Med Center New York Presby

New York, New York, United States

Site Status RECRUITING

Baylor Scott and White Research

Temple, Texas, United States

Site Status WITHDRAWN

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Site Status WITHDRAWN

Novartis Investigative Site

Buenos Aires, , Argentina

Site Status COMPLETED

Novartis Investigative Site

Córdoba, , Argentina

Site Status WITHDRAWN

Novartis Investigative Site

Edegem, , Belgium

Site Status WITHDRAWN

Novartis Investigative Site

Leuven, , Belgium

Site Status WITHDRAWN

Novartis Investigative Site

Belo Horizonte, Minas Gerais, Brazil

Site Status RECRUITING

Novartis Investigative Site

Pernambuco, Recife, Brazil

Site Status RECRUITING

Novartis Investigative Site

Passo Fundo, Rio Grande do Sul, Brazil

Site Status RECRUITING

Novartis Investigative Site

Joinville, Santa Catarina, Brazil

Site Status WITHDRAWN

Novartis Investigative Site

Santo André, São Paulo, Brazil

Site Status RECRUITING

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Site Status RECRUITING

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Salvador, , Brazil

Site Status RECRUITING

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London, Ontario, Canada

Site Status RECRUITING

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Toronto, Ontario, Canada

Site Status WITHDRAWN

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Montreal, Quebec, Canada

Site Status RECRUITING

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Guangzhou, Guangdong, China

Site Status WITHDRAWN

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Beijing, , China

Site Status RECRUITING

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Beijing, , China

Site Status WITHDRAWN

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Shanghai, , China

Site Status COMPLETED

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Wuhan, , China

Site Status WITHDRAWN

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Prague, , Czechia

Site Status COMPLETED

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Lille, , France

Site Status COMPLETED

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Marseille, , France

Site Status WITHDRAWN

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Montpellier, , France

Site Status RECRUITING

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Paris, , France

Site Status COMPLETED

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Paris, , France

Site Status RECRUITING

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Aachen, , Germany

Site Status WITHDRAWN

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Erlangen, , Germany

Site Status COMPLETED

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Essen, , Germany

Site Status COMPLETED

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Hamburg, , Germany

Site Status RECRUITING

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Hanover, , Germany

Site Status WITHDRAWN

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Heidelberg, , Germany

Site Status RECRUITING

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Mainz, , Germany

Site Status RECRUITING

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Athens, , Greece

Site Status RECRUITING

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Heraklion Crete, , Greece

Site Status RECRUITING

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Thessaloniki, , Greece

Site Status WITHDRAWN

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Thessaloniki, , Greece

Site Status RECRUITING

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New Delhi, National Capital Territory of Delhi, India

Site Status RECRUITING

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Hyderabad, Telangana, India

Site Status WITHDRAWN

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Lucknow, Uttar Pradesh, India

Site Status RECRUITING

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Dehradun, Uttarakhand, India

Site Status WITHDRAWN

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New Delhi, , India

Site Status RECRUITING

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Petah Tikva, , Israel

Site Status RECRUITING

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Petah Tikva, , Israel

Site Status RECRUITING

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Ranica, BG, Italy

Site Status RECRUITING

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Milan, MI, Italy

Site Status RECRUITING

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Roma, RM, Italy

Site Status RECRUITING

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Site Status COMPLETED

Novartis Investigative Site

Asahikawa, Hokkaido, Japan

Site Status COMPLETED

Novartis Investigative Site

Sapporo, Hokkaido, Japan

Site Status COMPLETED

Novartis Investigative Site

Takatsuki, Osaka, Japan

Site Status RECRUITING

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Ohtsu, Shiga, Japan

Site Status RECRUITING

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Niigata, , Japan

Site Status COMPLETED

Novartis Investigative Site

Leiden, South Holland, Netherlands

Site Status COMPLETED

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Nijmegen, , Netherlands

Site Status RECRUITING

Novartis Investigative Site

Málaga, Andalusia, Spain

Site Status WITHDRAWN

Novartis Investigative Site

Seville, Andalusia, Spain

Site Status RECRUITING

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status WITHDRAWN

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status WITHDRAWN

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status RECRUITING

Novartis Investigative Site

Port de Sagunt, Valencia, Spain

Site Status WITHDRAWN

Novartis Investigative Site

Madrid, , Spain

Site Status COMPLETED

Novartis Investigative Site

Bern, , Switzerland

Site Status RECRUITING

Novartis Investigative Site

Lausanne, , Switzerland

Site Status WITHDRAWN

Novartis Investigative Site

Istanbul, TUR, Turkey (Türkiye)

Site Status WITHDRAWN

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Novartis Investigative Site

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

Novartis Investigative Site

Talas Kayseri, , Turkey (Türkiye)

Site Status RECRUITING

Novartis Investigative Site

Glasgow, , United Kingdom

Site Status WITHDRAWN

Novartis Investigative Site

London, , United Kingdom

Site Status RECRUITING

Novartis Investigative Site

Newcastle upon Tyne, , United Kingdom

Site Status RECRUITING

Countries

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United States Argentina Belgium Brazil Canada China Czechia France Germany Greece India Israel Italy Japan Netherlands Spain Switzerland Turkey (Türkiye) United Kingdom

Central Contacts

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Novartis Pharmaceuticals

Role: CONTACT

1-888-669-6682

Novartis Pharmaceuticals

Role: CONTACT

+41613241111

Facility Contacts

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Kati Dugan

Role: primary

720-777-1234

Moya Chang

Role: primary

305-661-1515

Role: primary

+1 404 645 7850#3024

Nikki Gerot

Role: primary

319-335-0348

Brianna Ortiz

Role: primary

212-304-5684

References

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Kavanagh D, Bomback AS, Vivarelli M, Nester CM, Remuzzi G, Zhao MH, Wong EKS, Wang Y, Krishnan I, Schuhmann I, Trapani AJ, Webb NJA, Meier M, Israni RK, Smith RJH; APPEAR-C3G investigators. Oral iptacopan therapy in patients with C3 glomerulopathy: a randomised, double-blind, parallel group, multicentre, placebo-controlled, phase 3 study. Lancet. 2025 Oct 11;406(10512):1587-1598. doi: 10.1016/S0140-6736(25)01148-1. Epub 2025 Sep 25.

Reference Type DERIVED
PMID: 41016405 (View on PubMed)

Other Identifiers

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2020-004589-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLNP023B12301

Identifier Type: -

Identifier Source: org_study_id

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