Dose Escalation Study With Bispecific Antibodies in Adult Participants With Lupus Nephritis

A Dose Escalation Study Investigating Bispecific Antibody Therapy in Patients With Lupus Nephritis

This study is researching a particular group of experimental drugs administered for a short period in the treatment of participants with Lupus Nephritis (LN).

The main aim of the current study is to see how safe and tolerable the study drugs are in a long-term follow-up.

This is a main study, called an umbrella study, which includes several independent smaller sub-studies. Each of these smaller main sub-studies tests different drugs at the same time, all aimed at treating LN.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis (LN)
• Intervention / Treatment: Drug: Vonsetamig; Drug: Odronextamab

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• France
  • New Aquitaine
    • Bordeaux, New Aquitaine, France, 33076
      • Recruiting
      • Centre Hospitalier Universitaire (CHU) Bordeaux
• Germany
  • Mainz, Germany, 55131
    • Recruiting
    • University Medical Center of the Johannes Gutenberg-University Mainz
  • Bavaria
    • Regensburg, Bavaria, Germany, D-93053
      • Recruiting
      • University Hospital Regensburg
• South Korea
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Gyeonggi-do
    • Anyang-si, Gyeonggi-do, South Korea, 14068
      • Recruiting
      • Hallym University Sacred Heart Hospital
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital Gregorio Marañón
  • Málaga, Spain, 290090
    • Recruiting
    • Hospital Regional Universitario de Malaga
  • Andalusia
    • Seville, Andalusia, Spain, 41013
      • Recruiting
      • Hospital Universitario Virgen del Rocio
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
• Taiwan
  • Changhua, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital
  • Taichung, Taiwan, 40705
    • Recruiting
    • Taichung General Veterans Hospital
  • Taipei, Taiwan, 112
    • Recruiting
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 106
    • Recruiting
    • National Taiwan University Hospital
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Key General Inclusion Criteria:

1. Diagnosis of Systemic Lupus Erythematosus (SLE) and LN, as described in the protocol
2. Participant must have refractory or relapsed disease, as described in the protocol

Key General Exclusion Criteria:

1. History of or active severe or unstable lupus-associated neuropsychiatric disease that is likely to require acute or emergent medical treatment or hospitalization
2. Active overlap syndrome with mixed connective tissue disease or systemic sclerosis within 12 months prior to screening or during screening
3. Catastrophic or severe antiphospholipid syndrome within 12 months prior to screening or during screening

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Arm 1: Vonsetamig	Drug: Vonsetamig; Administered as per the protocol; Other Names: REGN5459
Experimental: Experimental Arm 2: Odronextamab	Drug: Odronextamab; Administered as per the protocol; Other Names: REGN1979

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of Dose Limiting Toxicities (DLT)	Up to 56 days
Occurrence of Treatment Emergent Adverse Events (TEAEs)	Through week 76
Severity of TEAEs	Through week 76

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative total exposure to corticosteroids		At 76 weeks
Absolute values of urine Protein-Creatinine Ratio (uPCR)		Through week 76
Percent change from baseline of uPCR		Through week 76
Absolute values of estimated Glomerular Filtration Rate (eGFR) serum creatinine		Through week 76
Percent change from baseline of eGFR serum creatinine		Through week 76
Absolute values of blood B-cell counts and other immune cell populations	T cells and Natural Killer (NK) cells	Through week 76
Change from baseline of blood B-cell counts and other immune cell populations	T cells and NK cells	Through week 76
Absolute values of double-stranded DNA (dsDNA) antibodies		Through week 76
Percent change from baseline of dsDNA antibodies		Through week 76
Absolute values of anti-Smith antibodies		Through week 76
Percent change from baseline of anti-Smith antibodies		Through week 76
Absolute values of anti-C1q antibodies		Through week 76
Percent change from baseline of anti-C1q antibodies		Through week 76
Absolute values of other autoantibodies	anti-nucleosome	Through week 76
Percent change from baseline of other autoantibodies	anti-nucleosome	Through week 76
Absolute values of Complement Factor C3 (C3) circulating factors		Through week 76
Percent change from baseline of C3 circulating factors		Through week 76
Absolute values of Complement Factor C4 (C4) circulating factors		Through week 76
Percent change from baseline of C4 circulating factors		Through week 76
Absolute values of serum levels of Immunoglobulin A (IgA)		Through week 76
Percent change from baseline of serum levels of IgA		Through week 76
Absolute values of serum levels of Immunoglobulin G (IgG)		Through week 76
Percent change from baseline of serum levels of IgG		Through week 76
Proportion of participants no longer receiving a corticosteroid		At 6 months
Concentrations of vonsetamig in serum		Through week 76
Concentrations of odronextamab in serum		Through week 76
Occurence of Anti-Drug Antibodies (ADAs) to vonsetamig		Through week 76
Occurence of ADAs to odronextamab		Through week 76
Magnitude of ADAs to vonsetamig		Through week 76
Magnitude of ADAs to odronextamab		Through week 76

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2025
• Primary Completion (Estimated): September 9, 2029
• Study Completion (Estimated): September 9, 2029

Study Registration Dates

• First Submitted: May 8, 2025
• First Submitted That Met QC Criteria: May 8, 2025
• First Posted (Actual): May 16, 2025

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Systemic Lupus Erythematosus (SLE); Bispecific Antibodies (bsAb); Double-stranded DNA (dsDNA); LN class III or IV
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis
• Other Study ID Numbers: R5459-1979-LN-2459; 2024-518288-37-00 (Ctis: EUCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No