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

Phase 2

Terminated

Conditions: Familial Partial Lipodystrophy
Metabolic Abnormalities

Interventions: Drug: REGN4461
Drug: Matching Placebo

Registration Number: NCT05088460

Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 20

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Arm 1	Matching Placebo	Randomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks
Study Arm 1	REGN4461	Randomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks
Study Arm 2	REGN4461	Randomized to receive REGN4461 for 24 weeks

Primary Outcome Measures

Name	Time	Method
Absolute change in hemoglobin A1c (HbA1c)	Baseline to week 12	In patients with elevated baseline HbA1c (\>7.0%) and with baseline leptin \<8.0 ng/mL
Percent change in fasting serum triglyceride (TG)	Baseline to week 12	In patients with elevated baseline fasting TG (fasting TG ≥200 mg/dL) and with baseline leptin \<8.0 ng/mL

Secondary Outcome Measures

Name	Time	Method
Percent change in fasting serum TG	Baseline to week 24	Cohorts A and B separately and Cohorts A+B in Study Arm 2
Change in fasting glucose	Baseline to week 12	Cohorts A and B separately and Cohorts A+B in Study Arm 2
Percent change in liver fat (MRI-PDFF) from baseline to week 12 compared to percent change between week 12 and week 24	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
Incidence and severity of treatment-emergent adverse events (TEAEs)	Up to week 40	Cohorts A and B separately and Cohorts A+B
Absolute change in HbA1c	Baseline to week 12	In patients with elevated baseline HbA1c (\>7.0%) Cohort B and Cohorts A+B
Percent change in liver fat (MRI-PDFF)	Baseline to week 12	In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B in Study Arm 2
Percent change in fasting serum TG after the first 12 weeks of exposure to REGN4461	Week 12 to week 24	Cohorts A and B separately and Cohorts A+B in Study Arm 1 Patients must meet stability criteria
Percent change in liver fat (MRI-PDFF) placebo	Baseline to week 12	In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B
Percent change in liver fat (MRI-PDFF) REGN4461 versus placebo	Baseline to week 12	In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B
Percent change in fasting serum TG from baseline to week 12 compared to the percent change between week 12 and week 24	Week 24	Cohorts A and B separately and Cohorts A+B in Study Arm 1
Change in HbA1c	Week 12 to week 24	Cohorts A and B separately and Cohorts A+B in Study Arm 1 Patients must meet stability criteria
Change in fasting glucose from baseline to week 12 compared to change between week 12 and week 24	Week 24	Cohorts A and B separately and Cohorts A+B in Study Arm 1
Percent change in liver fat magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) REGN4461	Baseline to week 12	In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B
Change in HbA1c from baseline to week 12 compared to change between week 12 and week 24	Week 24	Cohorts A and B separately and Cohorts A+B in Study Arm 1
Immunogenicity of REGN4461 over time compared to placebo	Up to week 40	Cohorts A and B separately and Cohorts A+B
Concentrations of REGN4461 in serum over time	Up to week 40	Cohorts A and B separately and Cohorts A+B
Change on the daily lipodystrophy hunger questionnaire	Baseline to week 24	Cohorts A and B separately and Cohorts A+B

Trial Locations

Locations (8): National Institute of Health
🇺🇸
Bethesda, Maryland, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Excel Medical Clinical Trials - A Flourish Research Site
🇺🇸
Boca Raton, Florida, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Complexo Hospitalario Universitario de Santiago-Hospital Médico-Cirúrxico de Conxo
🇪🇸
Santiago de Compostela, Galicia, Spain
ICAN, Institute of Cardiometabolism and Nutrition
🇫🇷
Paris, France
UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Ege University Faculty of Medicine
🇹🇷
Izmir, Bornova, Turkey