Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy

A Randomized, Double-Blind, Placebo-Controlled Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy

The primary objectives of the study are to estimate the effects of REGN4461 on glycemic parameters in the subset of patients with elevated baseline hemoglobin A1c levels (HbA1c ≥7%) and to estimate the effects of REGN4461 on fasting triglyceride levels in the subset of patients with elevated baseline fasting triglycerides (TG ≥250 mg/dL).

The secondary objectives are to estimate the effects of REGN4461 on a composite endpoint of changes in either HbA1c or fasting TG for all patients, estimate the effects of 3 dose levels of REGN4461 on glycemic parameters and fasting TG, to estimate the effects of REGN4461 on insulin sensitivity, to evaluate the safety and tolerability of REGN4461 and to evaluate the pharmacokinetics (PK) and immunogenicity of REGN4461.

Study Overview

• Status: Completed
• Conditions: Generalized Lipodystrophy
• Intervention / Treatment: Drug: Placebo; Drug: Low-Dose REGN4461; Drug: High-dose REGN4461

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Peru
  • Piura, Peru, 2665
    • Regeneron Research Site
• Russia
  • Moscow, Russia, 117036
    • Regeneron Research Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Regeneron Research Site
  • Diyarbakır, Turkey (Türkiye), 21808
    • Regeneron Research Site
  • Izmir, Turkey (Türkiye), 35100
    • Regeneron Research Site
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Regeneron Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Regeneron Research Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Regeneron Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Diagnosis of congenital or acquired generalized lipodystrophy (GLD), as defined in the protocol

• Presence of one or both of the following metabolic abnormalities at screening:

  1. HbA1c ≥ 7% OR
  2. Fasting TG ≥250 mg/dL
• Generally stable diet (based on patient's recall) and medication regimen (that optimizes treatment for their metabolic disease) for at least 3 months prior to the screening visit

Key Exclusion Criteria:

• Treatment with metreleptin within 1 month of the screening visit
• Treatment with over-the-counter or prescription medications for weight loss within 3 months prior to the screening visit
• Treatment with oral glucocorticoids >7.5 mg prednisone equivalents per day within 3 months prior to screening visit or plans to begin treatment with oral glucocorticoids >7.5 mg prednisone equivalents per day during the study period
• History of Human Immunodeficiency Virus (HIV) or HIV seropositivity at screening visit
• Uncontrolled infection with hepatitis B or hepatitis C infection, or known active tuberculosis at screening
• Participation in any clinical research study evaluating an Investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit.
• Pregnant or breast-feeding women

NOTE: Other protocol defined inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment B	Drug: Placebo; Intravenous (IV) infusion loading dose or subcutaneous (SC) injection weekly (QW).; Drug: Low-Dose REGN4461; IV infusion loading dose or SC injection QW.; Other Names: mibavademab; Drug: High-dose REGN4461; IV infusion loading dose or SC injection QW.; Other Names: mibavademab
Experimental: Treatment A	Drug: Placebo; Intravenous (IV) infusion loading dose or subcutaneous (SC) injection weekly (QW).; Drug: Low-Dose REGN4461; IV infusion loading dose or SC injection QW.; Other Names: mibavademab; Drug: High-dose REGN4461; IV infusion loading dose or SC injection QW.; Other Names: mibavademab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in Fasting Glucose at Week 8	Absolute change from baseline in fasting glucose for subgroup of participants with baseline HbA1c ≥7% reported	Baseline, Week 8
Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8	Absolute change from baseline in WMG for subgroup of participants with baseline HbA1c ≥7% reported	Baseline, Week 8
Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8	Percent change from baseline in participants with elevated baseline fasting TG (fasting TG ≥250 mg/dL) reported	Baseline, Week 8
Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8	Absolute change from baseline in HbA1c for subgroup of participants with baseline HbA1c ≥7% reported	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in HbA1c and Fasting TG Composite Endpoint at Week 8	The composite score is calculated for each individual participant using baseline and Week 8 measurements of HbA1c and fasting TG. For each participant, a Z-score is calculated separately for HbA1c and fasting TG, rescaling the change from baseline based on the standard deviation of the baseline value for all participants, as a way of standardizing the change value. The composite score uses one or both of the calculated Z-scores depending on which parameters were abnormal at baseline. If both, then the participant's composite is the average of the two parameter Z-scores. At the participant level, a Z-score of zero for either parameter indicates no change in that metabolic parameter, but a composite Z-score of zero can also reflect offsetting changes in metabolic parameters. A negative Z-score would be interpreted as an overall improvement in metabolic function, but a negative Z-score can also result from a decrease in one parameter not being canceled by an increase in the other.	Baseline, Week 8
Absolute Change From Baseline in Fasting Glucose		Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7%		Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Percent Change From Baseline in Fasting TG		Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL		Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Absolute Change From Baseline in HbA1c		Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52
Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7%		Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52
Absolute Change From Baseline in Weighted Mean Glucose (WMG)		Baseline, Weeks 16 and 24
Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7%		Baseline, Weeks 16 and 24
Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT)		Baseline, Weeks 8, 16, 24
Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7%		Baseline, Weeks 8, 16, 24
Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp		Baseline, Weeks 8 and 52
Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7%		Baseline, Weeks 8 and 52
Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT)		Baseline, Weeks 8 and 52
Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7%		Baseline, Weeks 8 and 52
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)		From first dose of DBTP study treatment through last dose of OLTP 5 study treatment plus 16 weeks (approximately 120 weeks)
Concentrations of Total REGN4461 in Serum Over Time		Weeks 0 (post-dose), 8, 16 (post-dose), 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Number of Participants With Anti-drug Antibodies (ADA) to REGN4461		Approximately Week 128

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2020
• Primary Completion (Actual): January 5, 2022
• Study Completion (Actual): September 24, 2024

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 7, 2019
• First Posted (Actual): November 12, 2019

Study Record Updates

• Last Update Posted (Estimated): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Skin Diseases; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Skin Diseases, Metabolic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Lipodystrophy; Lipodystrophy, Congenital Generalized
• Other Study ID Numbers: R4461-GLD-1875; 2019-000614-11 (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: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data 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, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• 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