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

Regeneron Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Metabolic Abnormalities; Familial Partial Lipodystrophy

Treatments: Drug: REGN4461; Drug: Matching Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05088460

R4461-PLD-20100

2021-000138-33 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

20 participants in 2 patient groups

Study Arm 1

Experimental group

Description:

Randomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks

Treatment:

Drug: Matching Placebo

Drug: REGN4461

Study Arm 2

Experimental group

Description:

Randomized to receive REGN4461 for 24 weeks

Treatment:

Drug: REGN4461