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

Familial Partial Lipodystrophy Clinical Trial

— LEAP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05088460
• Other study ID #: R4461-PLD-20100
• Secondary ID: 2021-000138-33
• Status: Completed
• Phase: Phase 2
• Start date: February 28, 2022
• Est. completion date: April 18, 2024

Study information

• Verified date: May 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 18, 2024
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Congenital Abnormalities
• Familial Partial Lipodystrophy
• Lipodystrophy
• Lipodystrophy, Familial Partial

Intervention

Drug:
• REGN4461
Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).
• Matching Placebo
Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).

Locations

Country	Name	City	State
France	ICAN, Institute of Cardiometabolism and Nutrition	Paris
Spain	Complexo Hospitalario Universitario de Santiago-Hospital Médico-Cirúrxico de Conxo	Santiago de Compostela	Galicia
Turkey	Ege University Faculty of Medicine	Izmir	Bornova
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge	UK
United States	University of Michigan	Ann Arbor	Michigan
United States	National Institute of Health	Bethesda	Maryland
United States	Excel Medical Clinical Trials - A Flourish Research Site	Boca Raton	Florida
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change in fasting serum triglyceride (TG)	In patients with elevated baseline fasting TG (fasting TG =200 mg/dL) and with baseline leptin <8.0 ng/mL	Baseline to week 12
Primary	Absolute change in hemoglobin A1c (HbA1c)	In patients with elevated baseline HbA1c (>7.0%) and with baseline leptin <8.0 ng/mL	Baseline to week 12
Secondary	Percent change in fasting serum TG	In patients with elevated baseline fasting TG (>200 mg/dL); Cohort B and Cohorts A+B	Baseline to week 12
Secondary	Absolute change in HbA1c	In patients with elevated baseline HbA1c (>7.0%); Cohort B and Cohorts A+B	Baseline to week 12
Secondary	Percent change in fasting serum TG	Cohorts A and B separately and Cohorts A+B in Study Arm 1	Baseline to week 12
Secondary	Percent change in fasting serum TG	Cohorts A and B separately and Cohorts A+B in Study Arm 1	Week 12 to week 24
Secondary	Percent change in fasting serum TG from baseline to week 12 compared to the percent change between week 12 and week 24	Cohorts A and B separately and Cohorts A+B in Study Arm 1	Week 24
Secondary	Percent change in fasting serum TG	Cohorts A and B separately and Cohorts A+B in Study Arm 2	Baseline to week 24
Secondary	Percent change in fasting serum TG after the first 12 weeks of exposure to REGN4461	Cohorts A and B separately and Cohorts A+B in Study Arm 2	Baseline to week 12
Secondary	Percent change in fasting serum TG after the first 12 weeks of exposure to REGN4461	Cohorts A and B separately and Cohorts A+B in Study Arm 1 Patients must meet stability criteria	Week 12 to week 24
Secondary	Change in HbA1c	Cohorts A and B separately and Cohorts A+B in Study Arm 1	Baseline to week 12
Secondary	Change in HbA1c	Cohorts A and B separately and Cohorts A+B in Study Arm 1	Week 12 to week 24
Secondary	Change in HbA1c from baseline to week 12 compared to change between week 12 and week 24	Cohorts A and B separately and Cohorts A+B in Study Arm 1	Week 24
Secondary	Change in fasting glucose	Cohorts A and B separately and Cohorts A+B in Study Arm 1	Baseline to week 12
Secondary	Change in fasting glucose	Cohorts A and B separately and Cohorts A+B in Study Arm 1	Week 12 to week 24
Secondary	Change in fasting glucose from baseline to week 12 compared to change between week 12 and week 24	Cohorts A and B separately and Cohorts A+B in Study Arm 1	Week 24
Secondary	Change in HbA1c	Cohorts A and B separately and Cohorts A+B in Study Arm 2	Baseline to week 24
Secondary	Change in fasting glucose	Cohorts A and B separately and Cohorts A+B in Study Arm 2	Baseline to week 24
Secondary	Change in HbA1c	Cohorts A and B separately and Cohorts A+B in Study Arm 2	Baseline to week 12
Secondary	Change in HbA1c	Cohorts A and B separately and Cohorts A+B in Study Arm 1 Patients must meet stability criteria	Week 12 to week 24
Secondary	Change in fasting glucose	Cohorts A and B separately and Cohorts A+B in Study Arm 2	Baseline to week 12
Secondary	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	Baseline to week 12
Secondary	Percent change in liver fat (MRI-PDFF) placebo	In patients with baseline liver fat (MRI-PDFF) =8.5%; Cohorts A and B separately and Cohorts A+B	Baseline to week 12
Secondary	Percent change in liver fat (MRI-PDFF) REGN4461 versus placebo	In patients with baseline liver fat (MRI-PDFF) =8.5%; Cohorts A and B separately and Cohorts A+B	Baseline to week 12
Secondary	Percent change in liver fat (MRI-PDFF)	In patients with baseline liver fat (MRI-PDFF) =8.5%; Cohorts A and B separately and Cohorts A+B in Study Arm 1	Baseline to week 12
Secondary	Percent change in liver fat (MRI-PDFF)	In patients with baseline liver fat (MRI-PDFF) =8.5%; Cohorts A and B separately and Cohorts A+B in Study Arm 1	Week 12 to week 24
Secondary	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	Week 24
Secondary	Percent change in liver fat (MRI-PDFF)	In patients with baseline liver fat (MRI-PDFF) =8.5%; Cohorts A and B separately and Cohorts A+B in Study Arm 2	Baseline to week 24
Secondary	Percent change in liver fat (MRI-PDFF)	In patients with baseline liver fat (MRI-PDFF) =8.5%; Cohorts A and B separately and Cohorts A+B in Study Arm 2	Baseline to week 12
Secondary	Change on the daily lipodystrophy hunger questionnaire	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	Baseline to week 12
Secondary	Change on the daily lipodystrophy hunger questionnaire	Cohorts A and B separately and Cohorts A+B	Baseline to week 24
Secondary	Incidence and severity of treatment-emergent adverse events (TEAEs)	Cohorts A and B separately and Cohorts A+B	Up to week 40
Secondary	Concentrations of REGN4461 in serum over time	Cohorts A and B separately and Cohorts A+B	Up to week 40
Secondary	Immunogenicity of REGN4461 over time compared to placebo	Cohorts A and B separately and Cohorts A+B	Up to week 40