A Study to Examine the Effects of the Leptin Receptor (LEPR) Agonist Antibody REGN4461 in Adult Patients With Familial Partial Lipodystrophy (FPLD) (LEAP)

A Study to Examine the Effects of the Leptin Receptor (LEPR) Agonist Antibody REGN4461 in Adult Patients With Familial Partial Lipodystrophy (FPLD)

A Randomized Double-Blind Placebo-Controlled Study of the LEPR Agonist Antibody REGN4461 for the Treatment of Metabolic Abnormalities in Patients With Familial Partial Lipodystrophy

Two cohorts are being studied based on leptin levels. Cohort A is composed of patients with baseline leptin <8.0 ng/mL and Cohort B is composed of patients with baseline leptin 8.0 to ≤20.0 ng/mL The primary objectives will be evaluated for patients in Cohort A only: To evaluate the effect of REGN4461 on fasting triglycerides (TG) in patients with elevated baseline fasting TG To evaluate the effect of REGN4461 on hyperglycemia in patients with elevated baseline Hemoglobin A1c (HbA1c) The following secondary objectives of the study will be evaluated for Cohort B and for the combined set of Cohorts A plus B: To evaluate the effect of REGN4461 on fasting TG levels in patients with hypertriglyceridemia To evaluate the effect of REGN4461 on glycemic control in patients with hyperglycemia The following secondary objectives of the study will be evaluated for Cohorts A and B separately, and for the combined set of Cohorts A plus B: To evaluate the effect of REGN4461 on liver fat in patients with hepatic steatosis To evaluate the effect of REGN4461 on hunger To evaluate safety and tolerability of REGN4461 To characterize the concentration profile of REGN4461 over time To assess immunogenicity to REGN4461

In patients with elevated baseline fasting TG (fasting TG ≥200 mg/dL) and with baseline leptin <8.0 ng/mL

Percent change in fasting serum TG from baseline to week 12 compared to the percent change between week 12 and week 24

Percent change in liver fat magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) REGN4461

In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B in Study Arm 1

In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B in Study Arm 1

Percent change in liver fat (MRI-PDFF) from baseline to week 12 compared to percent change between week 12 and week 24

In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B in Study Arm 1

In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B in Study Arm 2

In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B in Study Arm 2

Cohorts A and B separately and Cohorts A+B Patients will complete the PRO assessments daily. The Hunger questionnaire is self-administered and contains 4 items based on a Likert-like scale, where 0 is not hungry at all and 10 is the hungriest possible

Key Inclusion Criteria: Clinical diagnosis of familial partial lipodystrophy as defined in the protocol Fasting leptin level ≤20.0 ng/ml, as determined during the screening period Presence of significant metabolic abnormalities related to glucose and triglycerides (TGs) as defined in the protocol Stable body weight within the 3 months prior to screening (no gain or loss of >5% current weight) Stable diet during the past 3 months defined as no major change in macronutrient composition (eg, starting or stopping diets such as Atkins, Paleo, Vegetarianism, Veganism) No clinically meaningful change in medication regimen in the 3 months prior to screening as defined in the protocol Key Exclusion Criteria: Treatment with metreleptin within 3 months of the screening visit Patients with a diagnosis of generalized lipodystrophy Patients with a diagnosis of acquired lipodystrophy Pregnant or breastfeeding women NOTE: Other protocol defined inclusion/exclusion criteria apply

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

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

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., Food and Drug Administration (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).