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

Generalized Lipodystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04159415
• Other study ID #: R4461-GLD-1875
• Secondary ID: 2019-000614-11
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 7, 2020
• Est. completion date: October 29, 2024

Study information

• Verified date: February 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 16
• Est. completion date: October 29, 2024
• Est. primary completion date: January 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Generalized Lipodystrophy
• Lipodystrophy

Intervention

Drug:
• Placebo
Intravenous (IV) infusion loading dose or subcutaneous (SC) injection weekly (QW).
• Low-Dose REGN4461
IV infusion loading dose or SC injection QW.
• High-dose REGN4461
IV infusion loading dose or SC injection QW.

Locations

Country	Name	City	State
Peru	Regeneron Research Site	Piura
Russian Federation	Regeneron Research Site	Moscow
Turkey	Regeneron Research Site	Ankara
Turkey	Regeneron Research Site	Diyarbakir
Turkey	Regeneron Research Site	Izmir
United States	Regeneron Research Site	Ann Arbor	Michigan
United States	Regeneron Research Site	Bethesda	Maryland
United States	Regeneron Research Site	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Peru,  Russian Federation,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute change from baseline hemoglobin A1c (HbA1c)	In patients with elevated baseline HBA1c (HbA1c =7%)	Week 8
Primary	Absolute change from baseline fasting glucose	In patients with elevated baseline HBA1c (HbA1c =7%)	Week 8
Primary	Absolute change from baseline weighted mean glucose (WMG)	In patients with elevated baseline HBA1c (HbA1c =7%)	Week 8
Primary	Percent change from baseline fasting triglycerides (TG)	In patients with elevated baseline fasting TG (fasting TG =250 mg/dL)	Week 8
Secondary	Absolute change in composite endpoint comprising absolute change in either HbA1c or percent change in fasting TG	In all patients	Week 8
Secondary	Absolute change in HbA1c from baseline	In all patients	Approximately Week 128
Secondary	Percent change in fasting TG from baseline over time	In all patients	Approximately Week 128
Secondary	Absolute change from baseline in fasting glucose	In all patients	Approximately Week 128
Secondary	Absolute change from baseline in fasting glucose	In patients with elevated baseline HbA1c (HbA1c =7%)	Approximately Week 128
Secondary	Percent change from baseline in fasting TG	In patients with elevated baseline fasting TG (TG =250 mg/dL)	Approximately Week 128
Secondary	Absolute change from baseline in HbA1c over time	In patients with elevated baseline HbA1c (HbA1c =7%)	Approximately Week 128
Secondary	Absolute change from baseline in WMG over time	In all patients	Up to Week 24
Secondary	Absolute change from baseline in WMG over time	In patients with elevated baseline HbA1c (HbA1c =7%)	Up to Week 24
Secondary	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
Secondary	Change from baseline in glucose AUC0-4 during a MMTT	In patients with elevated baseline HbA1c (HbA1c =7%)	At Week 8, 16 and 24
Secondary	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
Secondary	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
Secondary	Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT)	In all patients	At Week 8 and Week 52
Secondary	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
Secondary	Incidence and severity of treatment-emergent adverse events (TEAEs)		Approximately Week 128
Secondary	Concentrations of total REGN4461 in serum over time		Approximately Week 128
Secondary	Incidence of anti-drug antibodies (ADA) to REGN4461 over time		Approximately Week 128
Secondary	Incidence of abnormal weight change		Approximately Week 128
Secondary	Incidence of vital sign abnormalities		Approximately Week 128
Secondary	Incidence of 12-lead electrocardiogram (ECG) abnormalities		Approximately Week 128
Secondary	Incidence of physical examination abnormalities		Approximately Week 128
Secondary	Incidence of laboratory abnormalities		Approximately Week 128
Secondary	Concentrations of total soluble leptin receptor (sLEPR) in serum over time		Approximately Week 128