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

NCT04817618 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CLNP023B123012020-004589-21
• Study Type: interventional
• Target: 98
• Locations: 19 countries
• Sites: 87

Brief 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.

Conditions

C3G

Keywords

LNP023; iptacopan; C3G; UPCR; eGFR; proteinuria; Quality of life

Outcome Measures

Primary Outcomes (4)

• Adult cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)

  To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months of treatment.

  6 months (double-blind)

• Adolescent cohort: Log-transformed ratio to baseline in UPCR (sampled from a 24-hour urine collection)

  To evaluate the effect of iptacopan on proteinuria at 6 months.

  6 months (double-blind)

• Change from baseline in log-transformed UPCR at the 12-month visit (both study treatment arms).

  To evaluate the effect of iptacopan on proteinuria at 12 months.

  12 months (double-blind and open-label)

• Change in log-transformed UPCR from the 6-month visit to the 12-month visit in the placebo arm

  To evaluate the effect of iptacopan on proteinuria at 12 months.

  From month 6 to month 12 (open-label)

Secondary Outcomes (14)

• Change from baseline in eGFR.

  6 months (double-blind)

• Proportion of participants who meet the criteria for achieving a composite renal endpoint

  6 months (double-blind)

• Adult cohort: Change from baseline in disease total activity score in a renal biopsy.

  6 months (double-blind)

• Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.

  6 months (double-blind)

• Number of participants with abnormal clinically significant vital signs, ECGs and safety laboratory measurements

  6 months (double-blind)

Study Arms (2)

iptacopan 200mg

EXPERIMENTAL

iptacopan 200 mg b.i.d.

Drug: iptacopan

Placebo to iptacopan 200mg

PLACEBO COMPARATOR

Placebo to iptacopan 200mg b.i.d.

Drug: Placebo

Interventions

Placebo DRUG

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

Placebo to iptacopan 200mg

iptacopan DRUG

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

Also known as: LNP023

iptacopan 200mg

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (87)

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Nicklaus Childrens Hospital

Miami, Florida, 33155, United States

RECRUITING

Georgia Nephrology Research Inst

Lawrenceville, Georgia, 30046, United States

ACTIVE NOT RECRUITING

IN University School of Med

Indianapolis, Indiana, 46202-5111, United States

WITHDRAWN

University of Iowa Health Care

Iowa City, Iowa, 52242-1091, United States

RECRUITING

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

WITHDRAWN

Brigham and Womens Hosp Harvard Med School

Boston, Massachusetts, 02115, United States

WITHDRAWN

Hackensack Uni Medical Center

Hackensack, New Jersey, 07601, United States

WITHDRAWN

Albany Medical Center

Albany, New York, 12208, United States

WITHDRAWN

Col Uni Med Center New York Presby

New York, New York, 10032, United States

COMPLETED

Baylor Scott and White Research

Temple, Texas, 76502, United States

WITHDRAWN

University of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

Novartis Investigative Site

Córdoba, Córdoba Province, 5000, Argentina

WITHDRAWN

Novartis Investigative Site

Buenos Aires, W3400ABH, Argentina

COMPLETED

Novartis Investigative Site

CABA, C1181ACH, Argentina

WITHDRAWN

Novartis Investigative Site

Edegem, 2650, Belgium

WITHDRAWN

Novartis Investigative Site

Leuven, 3000, Belgium

WITHDRAWN

Novartis Investigative Site

Belo Horizonte, Minas Gerais, 30150-221, Brazil

RECRUITING

Novartis Investigative Site

Recife, Pernambuco, 50740-900, Brazil

RECRUITING

Novartis Investigative Site

Passo Fundo, Rio Grande do Sul, 99010-260, Brazil

RECRUITING

Novartis Investigative Site

Joinville, Santa Catarina, 893227-680, Brazil

WITHDRAWN

Novartis Investigative Site

Santo André, São Paulo, 09090-790, Brazil

WITHDRAWN

Novartis Investigative Site

São Paulo, São Paulo, 04038-002, Brazil

RECRUITING

Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

WITHDRAWN

Novartis Investigative Site

Salvador, 40323-010, Brazil

RECRUITING

Novartis Investigative Site

London, Ontario, N6A 5W9, Canada

COMPLETED

Novartis Investigative Site

Toronto, Ontario, M5G 2C4, Canada

COMPLETED

Novartis Investigative Site

Montreal, Quebec, H3T 1C5, Canada

WITHDRAWN

Novartis Investigative Site

Guangzhou, Guangdong, 510030, China

ACTIVE NOT RECRUITING

Novartis Investigative Site

Wuhan, Hubei, 430022, China

WITHDRAWN

Novartis Investigative Site

Beijing, 100034, China

ACTIVE NOT RECRUITING

Novartis Investigative Site

Beijing, 100730, China

RECRUITING

Novartis Investigative Site

Shanghai, 200040, China

ACTIVE NOT RECRUITING

Novartis Investigative Site

Prague, 128 08, Czechia

COMPLETED

Novartis Investigative Site

Lille, 59037, France

COMPLETED

Novartis Investigative Site

Marseille, 13005, France

WITHDRAWN

Novartis Investigative Site

Montpellier, 34295, France

WITHDRAWN

Novartis Investigative Site

Paris, 75015, France

COMPLETED

Novartis Investigative Site

Paris, 75019, France

WITHDRAWN

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

ACTIVE NOT RECRUITING

Novartis Investigative Site

Aachen, 52074, Germany

WITHDRAWN

Novartis Investigative Site

Erlangen, 91054, Germany

COMPLETED

Novartis Investigative Site

Essen, 45147, Germany

COMPLETED

Novartis Investigative Site

Hamburg, 20246, Germany

COMPLETED

Novartis Investigative Site

Hanover, 30625, Germany

WITHDRAWN

Novartis Investigative Site

Heidelberg, 69120, Germany

ACTIVE NOT RECRUITING

Novartis Investigative Site

Mainz, 55131, Germany

COMPLETED

Novartis Investigative Site

Athens, 115 27, Greece

WITHDRAWN

Novartis Investigative Site

Heraklion Crete., 715 00, Greece

COMPLETED

Novartis Investigative Site

Thessaloniki, 546 42, Greece

COMPLETED

Novartis Investigative Site

Thessaloniki, 546 42, Greece

WITHDRAWN

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110017, India

ACTIVE NOT RECRUITING

Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110029, India

ACTIVE NOT RECRUITING

Novartis Investigative Site

Hyderabad, Telangana, 500058, India

WITHDRAWN

Novartis Investigative Site

Lucknow, Uttar Pradesh, 226014, India

ACTIVE NOT RECRUITING

Novartis Investigative Site

Dehradun, Uttarakhand, 248001, India

WITHDRAWN

Novartis Investigative Site

Petah Tikva, 4920235, Israel

COMPLETED

Novartis Investigative Site

Petah Tikva, 4941492, Israel

COMPLETED

Novartis Investigative Site

Ranica, BG, 24020, Italy

ACTIVE NOT RECRUITING

Novartis Investigative Site

Milan, MI, 20122, Italy

WITHDRAWN

Novartis Investigative Site

Roma, RM, 00165, Italy

ACTIVE NOT RECRUITING

Novartis Investigative Site

Nagoya, Aichi-ken, 4668560, Japan

COMPLETED

Novartis Investigative Site

Asahikawa, Hokkaido, 0788510, Japan

COMPLETED

Novartis Investigative Site

Sapporo, Hokkaido, 0608543, Japan

COMPLETED

Novartis Investigative Site

Takatsuki, Osaka, 5691192, Japan

COMPLETED

Novartis Investigative Site

Ohtsu, Shiga, 5202192, Japan

COMPLETED

Novartis Investigative Site

Niigata, 9518520, Japan

COMPLETED

Novartis Investigative Site

Nijmegen, Gelderland, 6500HB, Netherlands

WITHDRAWN

Novartis Investigative Site

Leiden, South Holland, 2333 ZA, Netherlands

COMPLETED

Novartis Investigative Site

Barcelona, Catalonia, 08025, Spain

WITHDRAWN

Novartis Investigative Site

Port de Sagunt, Valencia, 46520, Spain

WITHDRAWN

Novartis Investigative Site

Barcelona, 08035, Spain

WITHDRAWN

Novartis Investigative Site

Madrid, 28041, Spain

COMPLETED

Novartis Investigative Site

Málaga, 29010, Spain

WITHDRAWN

Novartis Investigative Site

Seville, 41009, Spain

COMPLETED

Novartis Investigative Site

Bern, 3010, Switzerland

ACTIVE NOT RECRUITING

Novartis Investigative Site

Lausanne, 1011, Switzerland

WITHDRAWN

Novartis Investigative Site

Istanbul, Fatih, 34093, Turkey (Türkiye)

WITHDRAWN

Novartis Investigative Site

Istanbul, Fatih, 34098, Turkey (Türkiye)

WITHDRAWN

Novartis Investigative Site

Kayseri, Melikgazi, 38039, Turkey (Türkiye)

COMPLETED

Novartis Investigative Site

Ankara, Yenimahalle, 06500, Turkey (Türkiye)

COMPLETED

Novartis Investigative Site

Ankara, Yenimahalle, 06500, Turkey (Türkiye)

WITHDRAWN

Novartis Investigative Site

Glasgow, Scotland, G51 4TF, United Kingdom

WITHDRAWN

Novartis Investigative Site

Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom

ACTIVE NOT RECRUITING

Novartis Investigative Site

London, W12 0HS, United Kingdom

COMPLETED

Novartis Investigative Site

London, WC1N 3JH, United Kingdom

ACTIVE NOT RECRUITING

Related Publications (1)

• 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.

  PMID: 41016405 DERIVED

MeSH Terms

Conditions

Proteinuria

Interventions

iptacopan

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

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

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2021
• First Posted: March 26, 2021
• Study Start: July 28, 2021
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): January 29, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (13); BE (2); DE (8); IN (5); BR (8); NL (2); CN (5); CA (3); FR (5); AR (3); ES (6); CH (2); TU (5); GB (4); CZ (1); IT (3); GR (4); JP (6); IL (2)