A Study of Zigakibart in Adults With IgA Nephropathy

NCT ID: NCT05852938

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 383 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-06
• Study Completion Date: 2028-06-07

Brief Summary

Safety and Efficacy of BION-1301 in Adults with IgA Nephropathy

Detailed Description

Approximately 330 participants with eGFR ≥ 30 mL/min/1.73m^2 and with biopsy-proven IgAN will be randomized to receive 600 mg Q2W BION-1301 or a matched placebo for 104 weeks. An additional exploratory cohort, not included in the primary analysis, will be comprised of approximately 20 participants (10 participants per arm) with biopsy-confirmed IgAN and eGFR of ≥ 20 to < 30 mL/min/1.73 m^2. The exploratory cohort will be randomized using the same schema as the primary cohort.

The primary objective of the study is to evaluate the effect of BION-1301 versus placebo on proteinuria in adults with IgA nephropathy.

Participants will have assessments of safety and efficacy for up to 2.5 years (134 weeks). To facilitate study participation over this time period, other visits may be remote (away from study site) for participants who elect to self-administer the study drug.

Conditions

IgA Nephropathy; Immunoglobulin A Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

BION-1301

600mg subcutaneous administration every 2 weeks for 104 weeks

Group Type: EXPERIMENTAL

BION-1301

Intervention Type: DRUG

BION-1301 Pre-Filled Syringe (PFS) 600mg subcutaneous administration every 2 weeks for 104 weeks.

Placebo

subcutaneous administration every 2 weeks for 104 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo - PFS subcutaneous administration every 2 weeks for 104 weeks.

Interventions

BION-1301

BION-1301 Pre-Filled Syringe (PFS) 600mg subcutaneous administration every 2 weeks for 104 weeks.

Intervention Type: DRUG

Placebo

Placebo - PFS subcutaneous administration every 2 weeks for 104 weeks.

Intervention Type: DRUG

Other Intervention Names

Zigakibart

Eligibility Criteria

Inclusion Criteria

• Male and female participants aged ≥ 18 years at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures.
• Biopsy-proven IgAN diagnosed within the past 10 years prior to Screening, that, in the opinion of the Investigator, is not due to secondary causes. A pseudonymized copy of the report must be available for review by the Sponsor or designee prior to randomization. If biopsy report within 10 years is not available, re-biopsy may be permitted upon discussion with the Sponsor.
• eGFR ≥ 30 mL/min/1.73m^2 at Screening based on the 2021 CKD-EPI equation.
• Total urine protein ≥ 1.0 g/day or UPCR ≥ 0.7 g/g (700 mg/g), as measured from an adequate 24-hour urine collection at Screening by a central laboratory.
• Stable on a maximally tolerated dose of angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin II receptor blockers (ARB) for at least 12 weeks prior to Screening unless intolerant to ACEi and ARB. May also be on a stable and well tolerated dose of sodium glucose cotransporter-2 inhibitors (SGLT2i), endothelin receptor antagonists (ERAs) and/or mineralocorticoid receptor antagonists (MRAs) for at least 12 weeks prior to Screening for the treatment of IgAN. Subjects are expected to stay on a stable dose of ACEi, ARB, SGLT2i, ERAs, and/or MRAs for the duration of the study.
• Screening weight of 45 to 150 kg.
• Men and women of childbearing potential (WOCBP; per Clinical Trials Facilitation and Coordination Group [CTFG] 2020) must agree to follow protocol-specified contraception guidance from Screening through approximately 5 half-lives (24 weeks) after the final dose of study drug. Use of hormonal contraceptive agents must have been initiated > 1 month prior to first dose of study drug.
• Provide written informed consent and be willing to comply with study visits and procedures.

Exclusion Criteria

• Secondary forms of IgAN as determined by the Investigator, in the setting of systemic disorders, infections, autoimmune disorders or neoplasias.
• Diagnosis of IgA Vasculitis.
• Current or history of nephrotic syndrome.
• Average blood pressure > 150/90 mm Hg (systolic/diastolic) from 3 readings obtained at the initial Screening visit. If blood pressure is too high, the 3 readings may be repeated once within the Screening period if clinically appropriate as per the Investigator.
• Clinical suspicion of IgAN with rapidly progressive glomerulonephritis (RPGN) based on KDIGO guidelines
• Chronic Kidney Disease, either clinically suspected or based on biopsy, resulting from any condition or another glomerulopathy/podocytopathy other than IgAN.
• History of Type 1 Diabetes.
• Participants with Type 2 diabetes are excluded if any of the following are present:

• Screening HbA1c (glycated hemoglobin) of > 8%.
• Evidence of diabetic changes on kidney biopsy, performed for any reason.
• History of diabetic microvascular disease (retinopathy, neuropathy, nephropathy) and/or macrovascular disease (atherosclerotic heart disease, peripheral vascular disease, cerebrovascular disease).
• Unstable anti-diabetic regimen:
• Prior exposure to any therapy directed against APRIL.
• History of a previous severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis, including a history of allergy or hypersensitivity to any component of BION-1301, or history of severe hypersensitivity reaction to any monoclonal antibody.
• Received an investigational new drug within 28 days or 5 half-lives, whichever is longer, prior to Screening.
• Received systemic corticosteroid therapy including budesonide (Tarpeyo/Kinpeygo) for > 14 days within 12 weeks prior to Screening.
• Use of systemic immunosuppressant medications.
• Any confirmed or suspected immunosuppressive or immune-deficient state, including but not limited to common variable immunodeficiency (CVID), HIV infection or asplenia, history of bone marrow or organ transplantation with exception of corneal transplants.
• Current severe infection requiring antimicrobials or history of recurrent, severe, infections as determined by the Investigator.
• Positive serology test for hepatitis A virus IgM antibodies (anti-HAV IgM), hepatitis B surface antigen (HBsAg), detectable hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) antibodies (participants who completed treatment and are persistently antibody be allowed), or antibodies to HIV-1 and/or HIV-2 at Screening.
• Received a live vaccination within 12 weeks prior to Screening or plan to have a live vaccination within 6 months after the last dose of study drug.
• History of malignancy unless cancer free for at least 5 years or non-melanoma skin cancer that was completely resected. A participant with curatively treated cervical carcinoma in situ is eligible for the study. Participants with low-risk prostate cancer (i.e., Gleason score < 7 and prostate specific antigen < 10 ng/mL) are allowed.
• Pregnancy or breastfeeding or intent to become pregnant or to donate sperm during the study period and until 24 weeks after last dose.
• History or evidence of any other clinically significant disorder, condition, disease, or laboratory finding that, in the Investigator's assessment, would place the participant at unacceptable risk, limit compliance with study requirements, or confound interpretation of study results.
• IgG levels < 6 g/L at Screening.
• Participation in another interventional trial with an investigational agent/device is prohibited during the course of this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Tainan, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Bornova, İzmir, Turkey (Türkiye)

Novartis Investigative Site

İzmit, Kocaeli, Turkey (Türkiye)

Novartis Investigative Site

Antalya, , Turkey (Türkiye)

Novartis Investigative Site

Kayseri, , Turkey (Türkiye)

Novartis Investigative Site

Brampton, Ontario, Canada

Novartis Investigative Site

East York, Ontario, Canada

Novartis Investigative Site

London, Ontario, Canada

University of Alabama at Birmingham: The Kirklin Clinic

Birmingham, Alabama, United States

Nephrology Consultants, LLC

Huntsville, Alabama, United States

Novartis Investigative Site

Toronto, Ontario, Canada

University of California, San Francisco

San Francisco, California, United States

Valiance Clinical Research

South Gate, California, United States

University of Colorado Hospital

Aurora, Colorado, United States

Denver Nephrology Research Division

Denver, Colorado, United States

Vida Medical Centers - Pembroke Pines

Pembroke Pines, Florida, United States

NorthShore University HealthSystem

Evanston, Illinois, United States

Nephrology Associales of Northern Illinois and Indiana

Hinsdale, Illinois, United States

Nephrology Associates of Northern Illinois and Indiana - 7836 W Jefferson Blvd

Fort Wayne, Indiana, United States

University Of Iowa Hospitals And Clinics

Iowa City, Iowa, United States

Intermed Consultants

Edina, Minnesota, United States

Capital District Renal Physicians

Clifton Park, New York, United States

Nephrology Associates PC - Flushing

Flushing, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

University of Cincinnati College of Medicine - 231 Albert Sabin Way

Cincinnati, Ohio, United States

Cleveland Clinic-9500 Euclid Ave

Cleveland, Ohio, United States

OHSU - Oregon Clinical and Translational Research Institute

Portland, Oregon, United States

Northeast Clinical Research Center, LLC

Bethlehem, Pennsylvania, United States

Columbia Nephrology Associates , P.A. - Columbia

Columbia, South Carolina, United States

Knoxville Kidney Center, PLLC - Frenova F1

Knoxville, Tennessee, United States

Dallas Renal Group - 1411 N Beckley Ave

Dallas, Texas, United States

Dallas Renal Group - Waxachie - 2460 N. I-35

Dallas, Texas, United States

DaVita Clinical Research

El Paso, Texas, United States

University of Texas MD Anderson Cancer Center-1155 Pressler

Houston, Texas, United States

East Texas Nephrology Associates

Lufkin, Texas, United States

Nephrology Associates of Northern Virginia-8501 Arlington Blvd

Fairfax, Virginia, United States

Swedish Center for Comprehensive Care

Seattle, Washington, United States

Novartis Investigative Site

La Plata, Buenos Aires, Argentina

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Catamarca, Catamarca Province, Argentina

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Barracas, Ciudad Autónoma de BuenosAires, Argentina

Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

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Santa Fe, Santa Fe Province, Argentina

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Buenos Aires, , Argentina

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Gosford, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Liverpool, New South Wales, Australia

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Penrith, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Cairns North, Queensland, Australia

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Box Hill, Victoria, Australia

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St Albans, Victoria, Australia

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Bonheiden, Antwerpen, Belgium

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Ghent, Oost-Vlaanderen, Belgium

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Roeselare, West-Vlaanderen, Belgium

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Liège, , Belgium

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Lodelinsart, , Belgium

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Woluwe-Saint-Lambert, , Belgium

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Santana, Amapá, Brazil

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Belo Horizonte, Minas Gerais, Brazil

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Maringá, Paraná, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Joinville, Santa Catarina, Brazil

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São Bernardo do Campo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, , Brazil

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Vancouver, British Columbia, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Hefei, Anhui, China

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Beijing, Beijing Municipality, China

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Foshan, Guangdong, China

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Guangzhou, Guangdong, China

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Guangzhou, Guangdong, China

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Shenzhen, Guangdong, China

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Nanning, Guangxi, China

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Guiyang, Guizhou, China

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Wuhan, Hubei, China

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Nanjing, Jiangsu, China

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Nantong, Jiangsu, China

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Wuxi, Jiangsu, China

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Nanchang, Jiangxi, China

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Jinan, Shandong, China

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Qingdao, Shandong, China

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Shanghai, Shanghai Municipality, China

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Taiyuan, Shanxi, China

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Taiyuan, Shanxi, China

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Chengdu, Sichuan, China

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Ürümqi, Xinjiang, China

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Wulumuji, Xinjiang, China

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Hangzhou, Zhejiang, China

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Taizhou, Zhejiang, China

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Zagreb, City of Zagreb, Croatia

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Biškupec Zelinski, , Croatia

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Rijeka, , Croatia

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Vinkovci, , Croatia

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Prague, Praha, Hlavní Mesto, Czechia

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Nîmes, Gard, France

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Lille, Nord, France

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Lyon, Rhône, France

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Grenoble, , France

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Paris, , France

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Paris, , France

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Augsburg, Bavaria, Germany

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Hanover, Lower Saxony, Germany

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Hanover, Lower Saxony, Germany

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Mainz, Rhineland-Palatinate, Germany

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Trier, Rhineland-Palatinate, Germany

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Magdeburg, Saxony-Anhalt, Germany

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Jena, Thuringia, Germany

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Essen, , Germany

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Pátrai, Achaïa, Greece

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Athens, Attica, Greece

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Kalamaria, Thessaloniki, Greece

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Heralkion, , Greece

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Ioannina, , Greece

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Ioannina, , Greece

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Thessaloniki, , Greece

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Hyderabad, Andhra Pradesh, India

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Chandigarh, Chandigarh, India

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Faridabad, Haryana, India

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Bengaluru, Karnataka, India

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Trivandrum, Kerala, India

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Jaipur, Rajasthan, India

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Jaipur, Rajasthan, India

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Vellore, Tamil Nadu, India

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Lucknow, Uttar Pradesh, India

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Kolkata, West Bengal, India

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Dehradun, , India

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Beersheba, Southern District, Israel

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Holon, Tel Aviv, Israel

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Ramat Gan, Tel Aviv, Israel

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Be’er Ya‘aqov, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Bari, Apulia, Italy

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Foggia, Apulia, Italy

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Napoli, Campania, Italy

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Modena, Emilia-Romagna, Italy

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Trieste, Friuli Venezia Giulia, Italy

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Pavia, Lombardy, Italy

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Ranica, Lombardy, Italy

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Kasugai-Shi, Aiti, Japan

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Toyoake-shi, Aiti, Japan

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Urayasu-Shi, Chiba, Japan

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Sapporo, Hokkaidô, Japan

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Kitakyushu, Hukuoka, Japan

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Yokohama, Kanagawa, Japan

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Kashihara, Nara, Japan

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Nara, Nara, Japan

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Osaka, Osaka, Japan

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Bunkyo-Ku, Tokyo, Japan

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Hachioji-Shi, Tokyo, Japan

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Minato-Ku, Tokyo, Japan

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Shinjuku-Ku, Tokyo, Japan

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Chiba, , Japan

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Niigata, , Japan

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Okayama, , Japan

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Tokyo, , Japan

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Yufu-Shi, Ôita, Japan

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Kuantan, Pahang, Malaysia

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Sibu, Sarawak, Malaysia

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Kajang, Selangor, Malaysia

Novartis Investigative Site

Kuala Lumpur, WilayahPersekutuan KualaLumpur, Malaysia

Novartis Investigative Site

Kuala Lumpur, WilayahPersekutuan KualaLumpur, Malaysia

Novartis Investigative Site

Chihuahua, Chiapas, Mexico

Novartis Investigative Site

Barrio Belisario Domínguez Secc, Mexico City, Mexico

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Oaxaca, Mexico City, Mexico

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Aguascalientes, , Mexico

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Chihuahua City, , Mexico

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Monterrey, , Mexico

Novartis Investigative Site

Dongan-Gu, Anyang-Si, Gyeonggido, South Korea

Novartis Investigative Site

Guri-si, Gyeonggido, South Korea

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Uijeongbu-si, Gyeonggido, South Korea

Novartis Investigative Site

Jongno-gu, Seoul Teugbyeolsi, South Korea

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Seodaemun-gu, Seoul Teugbyeolsi, South Korea

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Seongbuk-Gu, Seoul Teugbyeolsi, South Korea

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Cheonan, , South Korea

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Daejeon, , South Korea

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Seoul, , South Korea

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Manises, Valencia, Spain

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Barcelona, , Spain

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Girona, , Spain

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Lleida, , Spain

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Lugo, , Spain

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Madrid, , Spain

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Madrid, , Spain

Novartis Investigative Site

Seville, , Spain

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Keelung, Keelung, Taiwan

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Changhua County, , Taiwan

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Hsinchu, , Taiwan

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Hualien City, , Taiwan

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Kaohsiung City, , Taiwan

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Bristol, Bristol, City of, United Kingdom

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Brighton, East Sussex, United Kingdom

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Salford, Lancashire, United Kingdom

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Leicester, Leicestershire, United Kingdom

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London, London, City of, United Kingdom

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Nottingham, Nottinghamshire, United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; China; Croatia; Czechia; France; Germany; Greece; India; Israel; Italy; Japan; Malaysia; Mexico; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

References

Kooienga L, Lo J, Lee EY, Kim SG, Thomas H, Workeneh B, Agha I, Song Y, Smith W, van Eenennaam H, Van Elsas A, Dulos J, Barratt J. Zigakibart demonstrates clinical safety and efficacy in a Phase 1/2 trial of healthy volunteers and patients with IgA nephropathy. Kidney Int. 2025 Sep;108(3):445-454. doi: 10.1016/j.kint.2025.05.006. Epub 2025 Jun 5.

Reference Type: DERIVED

PMID: 40482854 (View on PubMed)

Ahmad SB, Jefferson JA. Targeting B Cells and Plasma Cells in Glomerular Disease. J Am Soc Nephrol. 2025 Jun 4;36(9):1844-1857. doi: 10.1681/ASN.0000000772.

Reference Type: DERIVED

PMID: 40465397 (View on PubMed)

Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.pub3.

Reference Type: DERIVED

PMID: 38299639 (View on PubMed)

Other Identifiers

CHK02-02

Identifier Type: OTHER

Identifier Source: secondary_id

CFUB523A12301

Identifier Type: -

Identifier Source: org_study_id