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NCT05755386PHASE3Recruiting

Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN

Novartis Pharmaceuticals

Start Date

10/2/2023

Completion Date

5/31/2029

Summary

This study is designed as a multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of iptacopan (LNP023) in idiopathic immune complex mediated membranoproliferative glomerulonephritis.

Detailed Description

The purpose of this Phase III study is to evaluate the efficacy and safety of iptacopan compared to placebo (both administered in combination with standard of care) in participants (adults and adolescents aged 12-17 years) with idiopathic IC-MPGN. The study aims to demonstrate a reduction in proteinuria and improvement in estimated glomerular filtration rate (eGFR) in participants treated with iptacopan compared to placebo. Change in patient-reported fatigue will also be evaluated. Alternative complement pathway (AP) dysregulation is believed to underlie the clinical manifestations and progression of IC-MPGN. Upon completion of study treatment, participants will have the option to discontinue iptacopan treatment and enter a 30 day safety follow-up or continue iptacopan treatment by transitioning to an open label extension study (CLNP023B12001B; NCT03955445) and continue iptacopan treatment.

Eligibility Criteria

Age Range: 12 years to 60 years

Inclusion Criteria: * Male and female patients including adults (aged at least 18 years to ≤ 60 years) and adolescents (12 -17 years in non-EU countries at screening and 16-17 years in EU countries at screening). * Diagnosis of idiopathic IC-MPGN as confirmed by kidney biopsy within 12 months prior to screening in adults and within 3 years of screening in adolescents (a biopsy report, review and confirmation by the Investigator is required). If such a biopsy is not available in an adult participant, this must be obtained at screening (performed and assessed locally for adults only). * Prior to randomization, all participants must have been on a maximally recommended or tolerated dose of renin angiotensin system inhibitors (RASi), e.g an ACEi or ARB for at least 90 days (or as according to local guidelines). The doses of other drugs administered to reduce proteinuria and control the disease including mycophenolic acids (MPAs - mycophenolate mofetil or mycophenolate sodium), corticosteroids, SGLT2 inhibitors and mineralocorticoid receptor antagonists should be stable for at least 90 days prior to randomization * UPCR ≥ 1.0 g/g (≥ 113 mg/mmol) sampled from the first morning void urine sample at Day -75 and Day -15 * Estimated GFR (using the chronic kidney disease \[CKD\]-EPI formula for adult participants and modified Schwartz formula for adolescents aged 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 infection prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, the vaccine should be given according to local regulations at least 2 weeks prior to the first administration of study treatment. If the study treatment has to start earlier than 2 weeks post vaccination, prophylactic antibiotic treatment should be initiated in accordance with local standard of care. * 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. Exclusion Criteria: * Participants who have undergone cell or solid organ transplantation, including kidney transplantation. * Participants diagnosed with secondary IC-MPGN including but not limited to any of the following conditions: * Deposition of antigen-antibody immune complexes as a result of any chronic infections, including * Hepatitis C virus (HCV) including HCV-associated mixed cryoglobulinemia, hepatitis B virus (HBV); * Bacterial-endocarditis, infected ventriculo-atrial shunt, visceral abscesses, leprosy, meningococcal meningitis; chronic bacterial infections * Protozoa/other infections- malaria, schistosomiasis, mycoplasma, leishmaniasis, filariasis, histroplasmosis Renal deposition of immune complexes as a result of a systemic autoimmune disease: * Systemic lupus erythematosus (SLE) * Sjögren syndrome * Rheumatoid arthritis * Mixed connective tissue disease Deposition of monoclonal immunoglobulins because of a monoclonal gammopathy due to plasma cell or B cell disorders. Monoclonal gammopathy of undetermined significance (MGUS) confirmed by the measurement of serum free light chains or other investigation as per local standard of care. Fibrillary glomerulonephritis * Rapidly progressive crescentic glomerulonephritis defined as a 50% decline in the eGFR within 3 months with kidney biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli on the most recent biopsy. * Kidney biopsy showing interstitial fibrosis/tubular atrophy (IF/TA) of more than 50%. * Participants with an active systemic bacterial, viral or fungal infection within 14 days prior to study treatment administration or 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., Neisseria meningitidis and Streptococcus pneumoniae. * The use of inhibitors of complement factors (e.g., Factor B, Factor D, complement 3 (C3) inhibitors, anti-Complement 5 (C5) antibodies, C5a receptor antagonists) within 3 months or 5 half-lives prior to the Screening visit. * The use of immunosuppressants (except MPAs), cyclophosphamide or systemic corticosteroids at a dose \>7.5 mg/day (or equivalent for a similar corticosteroid medication) within 90 days of study drug administration. * The use of MPAs is not permitted within 90 days prior to randomization in India, as per the local health authority requirement. * Acute post-infectious glomerulonephritis at screening, based upon the opinion of the investigator. * Body mass index (BMI) \>38 kg/m2 at screening and randomization. Body weight \<35 kg at screening and randomization

Interventions

DRUG

Placebo

DRUG

iptacopan

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Conditions

IC-MPGN

Locations

Ronald Reagan UCLA Medical Center

Los Angeles, California 90095

United States

Univ Cali Irvine ALS Neuromuscular

Orange, California 92868

United States

UCSF

San Francisco, California 94115

United States

Olive View UCLA Medical Center

Sylmar, California 91342

United States

Childrens Hospital Colorado

Aurora, Colorado 80045

United States

Nicklaus Childrens Hospital

Miami, Florida 33155

United States

Emory University School of Medicine-Winship Cancer Institute

Atlanta, Georgia 30322

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Boston Univ School of Medicine

Boston, Massachusetts 02118

United States

University of Minnesota

Minneapolis, Minnesota 55455

United States

Washington University in St Louis

St Louis, Missouri 63110

United States

University of New Mexico

Albuquerque, New Mexico 87131-0001

United States

Col Uni Med Center New York Presby

New York, New York 10032

United States

University Of Cincinnati

Cincinnati, Ohio 45267

United States

OHSU Dept of Nephrology

Portland, Oregon 97239

United States

Univ of Pennsylvania Medical Center

Philadelphia, Pennsylvania 19104

United States

MUSC Health Lancaster Med Ctr

Lancaster, South Carolina 29720

United States

UT Southwestern Medical Center

Dallas, Texas 75235

United States

Prolato Clinical Research Center

Houston, Texas 77054

United States

Baylor Scott and White Research

Temple, Texas 76502

United States

University of Utah

Salt Lake City, Utah 84113

United States

University of Wisconsin

Madison, Wisconsin 53792

United States

Novartis Investigative Site

CABA, Buenos Aires C1425AGC

Argentina

Novartis Investigative Site

CABA, Buenos Aires C1425EFD

Argentina

Novartis Investigative Site

Córdoba, Córdoba Province X5000

Argentina

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Buenos Aires, W3400ABH

Argentina

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CABA, C1181ACH

Argentina

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Santa Fe, S3000EPV

Argentina

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Fortaleza, Ceará 60430 370

Brazil

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Brasília, Federal District 71635-580

Brazil

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Belo Horizonte, Minas Gerais 30150-221

Brazil

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Recife, Pernambuco 50740-900

Brazil

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Niterói, Rio de Janeiro 24020 096

Brazil

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Rio de Janeiro, Rio de Janeiro 22211-230

Brazil

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Natal, Rio Grande do Norte 59012 300

Brazil

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Porto Alegre, Rio Grande do Sul 90035-074

Brazil

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Botucatu, São Paulo 18618-970

Brazil

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Santo André, São Paulo 09090-790

Brazil

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Sao Jose Rio Preto, São Paulo 15090-000

Brazil

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São Paulo, São Paulo 04038-002

Brazil

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São Paulo, São Paulo 05403 000

Brazil

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São Paulo, São Paulo 05403-000

Brazil

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Salvador, 40323-010

Brazil

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Etobicoke, Ontario M9W 6V1

Canada

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London, Ontario N6A 5W9

Canada

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Toronto, Ontario M5G 2C4

Canada

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Montreal, Quebec H2X 1R9

Canada

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Montreal, Quebec H3T 1C5

Canada

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Prague, 128 08

Czechia

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Aarhus N, 8200

Denmark

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Copenhagen, DK-2100

Denmark

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Marseille, 13005

France

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Montpellier, 34295

France

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Paris, 75015

France

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Rennes, 35033

France

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Toulouse, 31054

France

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Munich, Bavaria 81377

Germany

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Würzburg, Bavaria 97080

Germany

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Dresden, Saxony 01307

Germany

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Jena, Thuringia 07740

Germany

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Berlin, 13353

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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Mainz, 55131

Germany

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Ulm, 89081

Germany

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Athens, 115 27

Greece

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Chaïdári, 124 62

Greece

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Heraklion Crete., 715 00

Greece

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Ioannina, 455 00

Greece

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Pátrai, 265 04

Greece

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Thessaloniki, 54636

Greece

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Thessaloniki, 570 10

Greece

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Bangalore, Karnataka 560004

India

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Nagpur, Maharashtra 440015

India

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Pune, Maharashtra 411011

India

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New Delhi, National Capital Territory of Delhi 110029

India

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Hyderabad, Telangana 500082

India

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Haifa, 3109601

Israel

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Jerusalem, 9103102

Israel

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Petah Tikva, 4920235

Israel

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Bari, BA 70124

Italy

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Ranica, BG 24020

Italy

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Brescia, BS 25123

Italy

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Milan, MI 20122

Italy

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Roma, RM 00165

Italy

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Torino, TO 10126

Italy

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Naples, 80131

Italy

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Toyoake, Aichi-ken 4701192

Japan

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Fuchū, Tokyo 1838561

Japan

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Hachiōji, Tokyo 193-0998

Japan

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Okayama, 7008558

Japan

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Osaka, 558-8558

Japan

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Groningen, 9713 GZ

Netherlands

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Poznan, Greater Poland Voivodeship 60-355

Poland

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Bialystok, 15-540

Poland

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Krakow, 30-688

Poland

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Olsztyn, 10-561

Poland

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Warsaw, 02-006

Poland

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Warsaw, 02-097

Poland

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Wroclaw, 50-417

Poland

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Martin, Slovakia 036 59

Slovakia

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Banská Bystrica, 975 17

Slovakia

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Košice, 041 90

Slovakia

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Seoul, Seoul 03080

South Korea

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Seoul, 03722

South Korea

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Pamplona, Navarre 31008

Spain

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Almería, 04009

Spain

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Barcelona, 08035

Spain

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Barcelona, 08036

Spain

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Madrid, 28040

Spain

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Madrid, 28041

Spain

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Madrid, 280796

Spain

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Salamanca, 37007

Spain

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Bern, 3010

Switzerland

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Lausanne, 1011

Switzerland

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Zurich, 8091

Switzerland

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Kaohsiung City, 81346

Taiwan

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Istanbul, Fatih 34093

Turkey (Türkiye)

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Izmir, Karsiyaka 35575

Turkey (Türkiye)

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Köseköy, Kocaeli 41380

Turkey (Türkiye)

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Kayseri, Melikgazi 38039

Turkey (Türkiye)

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Ankara, Yenimahalle 06500

Turkey (Türkiye)

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Mersin, Yenisehir 33110

Turkey (Türkiye)

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Belfast, BT9 7AB

United Kingdom

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Cardiff, CF14 4XW

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London, NW3 2QG

United Kingdom

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London, WC1N 3JH

United Kingdom

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Manchester, M13 9WL

United Kingdom

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Salford, M6 8HD

United Kingdom

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Ho Chi Minh City, 700000

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