A Study of the Safety of Mibavademab in Pediatric and Adult Participants Switching From Metreleptin to Mibavademab for the Treatment of Generalized Lipodystrophy (GLD)

A Single-Arm, Open-Label, Safety Study in Patients With Generalized Lipodystrophy Switching From Metreleptin to Mibavademab, A Leptin Receptor Agonist Antibody

This study is researching an experimental drug called mibavademab. The study is focused on participants with GLD who have been on metreleptin treatment for at least 6 months with no change in dose for the last 3 months.

The aim of the study is to see how safe and tolerable mibavademab is when switching from treatment with metreleptin.

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Generalized Lipodystrophy
• Intervention / Treatment: Drug: mibavademab

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Diagnosis of congenital or acquired GLD as defined by Multi-Society Practice Guidelines
2. Treatment with metreleptin for ≥6 months at time of screening at a stable dose, defined as no change in dose within the last 3 months prior to screening
3. Generally stable diet (based on participant's recall) and stable medication regimen for diabetes and/or dyslipidemia (in addition to metreleptin), for the last 3 months prior to screening
4. Willing and able to comply with clinic visits and study-related procedures. Participants who are unable/unwilling to self-inject, but are willing to have a capable caregiver inject, are considered eligible
5. Willing and able to provide, or have the treating physician provide, values of HbA1c and fasting triglycerides from at least 6 months prior to screening, as defined in the protocol

Key Exclusion Criteria:

1. Treatment with over-the-counter or prescription medications for weight loss within 3 months prior to the screening visit
2. Current chronic treatment with high-dose corticosteroids, as defined in the protocol
3. Any malignancy, eg, lymphoma, within the past 1 year, prior to screening visit except for fully treated basal cell or squamous epithelial cell carcinomas of the skin or carcinoma in situ of the cervix or anus
4. Estimated glomerular filtration rate (GFR) of <30 mL/min/1.73 m^2 based on chronic kidney disease epidemiology collaboration (CKD-EPI)/Schwartz equation at screening. Assessment can be repeated once
5. History of heart failure hospitalization, diagnosis of a myocardial infarction, stroke, clinically significant arrhythmia, transient ischemic attack, unstable angina, percutaneous or surgical revascularization procedure, or intracardiac device placement within 3 months before the screening visit, as defined in the protocol
6. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the participant by their participation in the study, as defined in the protocol

NOTE: Other protocol-defined inclusion / exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mibavademab; Patients switching from at least 6 months of therapy with metreleptin to mibavademab.	Drug: mibavademab; Administered by intravenous (IV) infusion followed by subcutaneous (SC) injection; Other Names: REGN4461

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Up to week 68
Severity of TEAEs	Up to week 68

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Hemoglobin A1c (HbA1c)	Baseline, week 20 and week 52
Occurrence of HbA1c <7%	Week 20 and week 52
Occurrence of HbA1c <6.5%	Week 20 and week 52
Occurrence of requiring therapy with insulin in participants treated with mibavademab	Week 20 and week 52
Change in total insulin dose	Baseline, week 20 and week 52
Change in fasting plasma glucose	Baseline, week 20 and week 52
Percent change in fasting triglycerides	Baseline, week 20 and week 52
Occurrence of fasting triglycerides <500 mg/dL in participants treated with mibavademab	Baseline, week 20 and week 52
Occurrence of fasting triglycerides <200 mg/dL in participants treated with mibavademab	Baseline, week 20 and week 52
Occurrence of fasting triglycerides <150 mg/dL in participants treated with mibavademab	Baseline, week 20 and week 52
Concentrations of total mibavademab in serum	Up to week 68
Incidence of anti-drug antibodies (ADAs) to mibavademab	Up to week 68
Titer of ADAs to mibavademab	Up to week 68
Incidence of neutralizing antibodies (Nabs) to mibavademab	Up to week 68

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2024
• Primary Completion (Estimated): July 14, 2026
• Study Completion (Estimated): November 3, 2026

Study Registration Dates

• First Submitted: August 7, 2024
• First Submitted That Met QC Criteria: August 7, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Severe Insulin Resistance; Hypertriglyceridemia; Congenital or acquired generalized lipodystrophy; Leptin deficiency; Loss of subcutaneous tissue; Nutritional deprivation; Severe metabolic derangements; Severe diabetes mellitus; Berardinelli-Seip Syndrome; Lawrence Syndrome
• Additional Relevant MeSH Terms: Laminopathies; Endocrine System Diseases; Nutrition Disorders; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Skin Diseases; Hyperinsulinism; Overweight; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Obesity; Skin Diseases, Metabolic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Signs and Symptoms; Lipodystrophy; Diabetes Mellitus; Insulin Resistance; Obesity, Morbid; Hypertriglyceridemia; Lipodystrophy, Familial Partial; Lipodystrophy, Congenital Generalized
• Other Study ID Numbers: R4461-GLD-2284; 2024-513202-54-00 (Ctis: EU CT Number); 2026-000121-16 (EudraCT 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 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