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NCT04817618PHASE3Recruiting

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

Novartis Pharmaceuticals

Start Date

7/28/2021

Completion Date

1/29/2027

Summary

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

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.

Eligibility Criteria

Age Range: 12 years to 60 years

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.

Interventions

DRUG

Placebo

DRUG

iptacopan

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Conditions

C3G

Locations

Childrens Hospital Colorado

Aurora, Colorado 80045

United States

Nicklaus Childrens Hospital

Miami, Florida 33155

United States

Georgia Nephrology Research Inst

Lawrenceville, Georgia 30046

United States

IN University School of Med

Indianapolis, Indiana 46202-5111

United States

University of Iowa Health Care

Iowa City, Iowa 52242-1091

United States

University of Iowa Health Care

Iowa City, Iowa 52242

United States

Johns Hopkins Hospital

Baltimore, Maryland 21287

United States

Brigham and Womens Hosp Harvard Med School

Boston, Massachusetts 02115

United States

Hackensack Uni Medical Center

Hackensack, New Jersey 07601

United States

Albany Medical Center

Albany, New York 12208

United States

Col Uni Med Center New York Presby

New York, New York 10032

United States

Baylor Scott and White Research

Temple, Texas 76502

United States

University of Wisconsin

Madison, Wisconsin 53792

United States

Novartis Investigative Site

Córdoba, Córdoba Province X5016KET

Argentina

Novartis Investigative Site

Buenos Aires, W3400ABH

Argentina

Novartis Investigative Site

CABA, C1181ACH

Argentina

Novartis Investigative Site

Edegem, 2650

Belgium

Novartis Investigative Site

Leuven, 3000

Belgium

Novartis Investigative Site

Belo Horizonte, Minas Gerais 30150-221

Brazil

Novartis Investigative Site

Recife, Pernambuco 50740-900

Brazil

Novartis Investigative Site

Passo Fundo, Rio Grande do Sul 99010-260

Brazil

Novartis Investigative Site

Joinville, Santa Catarina 89227-680

Brazil

Novartis Investigative Site

Santo André, São Paulo 09090-790

Brazil

Novartis Investigative Site

São Paulo, São Paulo 04038-002

Brazil

Novartis Investigative Site

São Paulo, São Paulo 05403 000

Brazil

Novartis Investigative Site

Salvador, 40323-010

Brazil

Novartis Investigative Site

London, Ontario N6A 5W9

Canada

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Toronto, Ontario M5G 2C4

Canada

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Montreal, Quebec H3T 1C5

Canada

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Guangzhou, Guangdong 510080

China

Novartis Investigative Site

Wuhan, Hubei 430022

China

Novartis Investigative Site

Beijing, 100034

China

Novartis Investigative Site

Beijing, 100730

China

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Shanghai, 200040

China

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Prague, 128 08

Czechia

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Lille, 59037

France

Novartis Investigative Site

Marseille, 13005

France

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Montpellier, 34295

France

Novartis Investigative Site

Paris, 75015

France

Novartis Investigative Site

Paris, 75019

France

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Cologne, North Rhine-Westphalia 50937

Germany

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Aachen, 52074

Germany

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Erlangen, 91054

Germany

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Essen, 45147

Germany

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Hamburg, 20246

Germany

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Hanover, 30625

Germany

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Heidelberg, 69120

Germany

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Mainz, 55131

Germany

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Athens, 115 27

Greece

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Heraklion Crete., 715 00

Greece

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Thessaloniki, 546 42

Greece

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Thessaloniki, 546 42

Greece

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New Delhi, National Capital Territory of Delhi 110017

India

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New Delhi, National Capital Territory of Delhi 110029

India

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Hyderabad, Telangana 500058

India

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Lucknow, Uttar Pradesh 226014

India

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Dehradun, Uttarakhand 248001

India

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Petah Tikva, 4920235

Israel

Novartis Investigative Site

Petah Tikva, 4941492

Israel

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Ranica, BG 24020

Italy

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Milan, MI 20122

Italy

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Roma, RM 00165

Italy

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Nagoya, Aichi-ken 4668560

Japan

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Asahikawa, Hokkaido 0788510

Japan

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Sapporo, Hokkaido 0608543

Japan

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Takatsuki, Osaka 5691192

Japan

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Ohtsu, Shiga 5202192

Japan

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Niigata, 9518520

Japan

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Nijmegen, Gelderland 6500HB

Netherlands

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Leiden, South Holland 2333 ZA

Netherlands

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Barcelona, Catalonia 08025

Spain

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Port de Sagunt, Valencia 46520

Spain

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Barcelona, 08035

Spain

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Madrid, 28041

Spain

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Málaga, 29010

Spain

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Seville, 41009

Spain

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Bern, 3010

Switzerland

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Lausanne, 1011

Switzerland

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Istanbul, Fatih 34093

Turkey (Türkiye)

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Istanbul, Fatih 34098

Turkey (Türkiye)

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Kayseri, Melikgazi 38039

Turkey (Türkiye)

Novartis Investigative Site

Ankara, Yenimahalle 06500

Turkey (Türkiye)

Novartis Investigative Site

Ankara, Yenimahalle 06500

Turkey (Türkiye)

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Glasgow, Scotland G51 4TF

United Kingdom

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Newcastle upon Tyne, Tyne and Wear NE1 4LP

United Kingdom

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London, W12 0HS

United Kingdom

Novartis Investigative Site

London, WC1N 3JH

United Kingdom