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

Phase 2

Completed

Conditions: Generalized Lipodystrophy

Interventions: Drug: Placebo
Drug: Low-Dose REGN4461
Drug: High-dose REGN4461

Registration Number: NCT04159415

Lead Sponsor: Regeneron Pharmaceuticals

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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 & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment A	Placebo	-
Treatment A	Low-Dose REGN4461	-
Treatment A	High-dose REGN4461	-
Treatment B	Placebo	-
Treatment B	Low-Dose REGN4461	-
Treatment B	High-dose REGN4461	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT)	At Week 8, 16 and 24	In all patients
Incidence of Vital Sign Abnormalities	Approximately Week 128
Incidence of 12-lead Electrocardiogram (ECG) Abnormalities	Approximately Week 128
Incidence of Laboratory Abnormalities	Approximately Week 128
Percent Change From Baseline in Fasting TG	Approximately Week 128	In patients with elevated baseline fasting TG (TG ≥250 mg/dL)
Absolute Change in Composite Endpoint Comprising Absolute Change in Either HbA1c or Percent Change in Fasting TG	Week 8	In all patients
Absolute Change in HbA1c From Baseline	Approximately Week 128	In all patients
Percent Change in Fasting TG From Baseline Over Time	Approximately Week 128	In all patients
Absolute Change From Baseline in HbA1c Over Time	Approximately Week 128	In patients with elevated baseline HbA1c (HbA1c ≥7%)
Change From Baseline in Glucose AUC0-4 During a MMTT	At Week 8, 16 and 24	In patients with elevated baseline HbA1c (HbA1c ≥7%)
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 and Severity of Treatment-emergent Adverse Events (TEAEs)	Approximately Week 128
Incidence of Physical Examination Abnormalities	Approximately Week 128
Concentrations of Total Soluble Leptin Receptor (sLEPR) in Serum Over Time	Approximately Week 128