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

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: January 5, 2022

Interventions

  • 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.
  • Drug: High-dose REGN4461
    • IV infusion loading dose or SC injection QW.

Arms, Groups and Cohorts

  • Experimental: Treatment A
  • Experimental: Treatment B

Clinical Trial Outcome Measures

Primary Measures

  • Absolute change from baseline hemoglobin A1c (HbA1c)
    • Time Frame: Week 8
    • In patients with elevated baseline HBA1c (HbA1c ≥7%)
  • Absolute change from baseline fasting glucose
    • Time Frame: Week 8
    • In patients with elevated baseline HBA1c (HbA1c ≥7%)
  • Absolute change from baseline weighted mean glucose (WMG)
    • Time Frame: Week 8
    • In patients with elevated baseline HBA1c (HbA1c ≥7%)
  • Percent change from baseline fasting triglycerides (TG)
    • Time Frame: Week 8
    • In patients with elevated baseline fasting TG (fasting TG ≥250 mg/dL)

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 12 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Regeneron Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Trial Management, Study Director, Regeneron Pharmaceuticals

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