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: Active, not recruiting
• Conditions: Generalized Lipodystrophy
• Intervention / Treatment: Drug: Placebo; Drug: Low-Dose REGN4461; Drug: High-dose REGN4461

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

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Peru
  • Piura, Peru, 2665
    • Regeneron Research Site
• Russian Federation
  • Moscow, Russian Federation, 117036
    • Regeneron Research Site
• Turkey
  • Ankara, Turkey, 06230
    • Regeneron Research Site
  • Diyarbakir, Turkey, 21808
    • Regeneron Research Site
  • Izmir, Turkey, 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 hemoglobin A1c (HbA1c)	In patients with elevated baseline HBA1c (HbA1c ≥7%)	Week 8
Absolute change from baseline fasting glucose	In patients with elevated baseline HBA1c (HbA1c ≥7%)	Week 8
Absolute change from baseline weighted mean glucose (WMG)	In patients with elevated baseline HBA1c (HbA1c ≥7%)	Week 8
Percent change from baseline fasting triglycerides (TG)	In patients with elevated baseline fasting TG (fasting TG ≥250 mg/dL)	Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in composite endpoint comprising absolute change in either HbA1c or percent change in fasting TG	In all patients	Week 8
Absolute change in HbA1c from baseline	In all patients	Approximately Week 128
Percent change in fasting TG from baseline over time	In all patients	Approximately Week 128
Absolute change from baseline in fasting glucose	In all patients	Approximately Week 128
Absolute change from baseline in fasting glucose	In patients with elevated baseline HbA1c (HbA1c ≥7%)	Approximately Week 128
Percent change from baseline in fasting TG	In patients with elevated baseline fasting TG (TG ≥250 mg/dL)	Approximately Week 128
Absolute change from baseline in HbA1c over time	In patients with elevated baseline HbA1c (HbA1c ≥7%)	Approximately Week 128
Absolute change from baseline in WMG over time	In all patients	Up to Week 24
Absolute change from baseline in WMG over time	In patients with elevated baseline HbA1c (HbA1c ≥7%)	Up to Week 24
Change from baseline in glucose area under the concentration-time curve (AUC0-4) during a mixed meal tolerance test (MMTT)	In all patients	At Week 8, 16 and 24
Change from baseline in glucose AUC0-4 during a MMTT	In patients with elevated baseline HbA1c (HbA1c ≥7%)	At Week 8, 16 and 24
Change from baseline in glucose infusion rate per kilogram body mass during hyperinsulinemia-euglycemic clamp (clamp study)	In all patients	At Week 8 and Week 52
Change from baseline in glucose infusion rate per kilogram body mass during hyperinsulinemia-euglycemic clamp (clamp study)	In patients with elevated baseline HbA1c (HbA1c ≥7%)	At Week 8 and Week 52
Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT)	In all patients	At Week 8 and Week 52
Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT)	In patients with elevated baseline HbA1c (HbA1c ≥7%)	At Week 8 and Week 52
Incidence and severity of treatment-emergent adverse events (TEAEs)		Approximately Week 128
Concentrations of total REGN4461 in serum over time		Approximately Week 128
Incidence of anti-drug antibodies (ADA) to REGN4461 over time		Approximately Week 128
Incidence of abnormal weight change		Approximately Week 128
Incidence of vital sign abnormalities		Approximately Week 128
Incidence of 12-lead electrocardiogram (ECG) abnormalities		Approximately Week 128
Incidence of physical examination abnormalities		Approximately Week 128
Incidence of laboratory abnormalities		Approximately Week 128
Concentrations of total soluble leptin receptor (sLEPR) in serum over time		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 (Estimated): October 29, 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): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Skin Diseases, Metabolic; 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