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
Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A)	Baseline to week 12	Percentage change in fasting serum TG was reported for participants with elevated baseline fasting TG (\> 200 mg/dL) and with baseline leptin \< 8.0 ng/mL (Cohort A).
Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) (Cohort A)	Baseline to week 12	Change in HbA1c was reported for participants with elevated baseline HbA1c (\> 7.0%) and with baseline leptin \< 8.0 ng/mL (Cohort A).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B)	Baseline to week 12	Change in HbA1c was reported for participants with elevated baseline HbA1c (\>7.0%) in Cohort B and Cohorts A + B.
Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2)	Baseline, Week 12, Week 24	Change from baseline in HbA1c was reported for participants in Study Arm 2.
Concentrations of REGN4461 in Serum	Weeks 0, 1, 2, 3, 4, 5, 6, 9, 12, 13, 14, 15, 16, 17, 18, 21, 28, 32 and 36. Weeks 0 and 12 collected pre- and post-dose. All other time points were only pre-dose.
Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1)	Baseline, Week 12, Week 24	Change from baseline in fasting glucose was reported for participants in Study Arm 1.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Up to Day 169
Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B)	Baseline to week 12	Percent change in fasting serum TG was reported for participants with elevated baseline fasting TG (\>200 mg/dL) in Cohort B and Cohorts A + B.
Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2)	Baseline, Week 12, Week 24	Percent change from baseline in MRI-PDFF was reported for participants with baseline liver fat MRI-PDFF ≥8.5% in Study Arm 2.
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score	Baseline, Week 12, Week 24	The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The lowest hunger score asked participants to rate their lowest hunger that day on a scale from 0 to 4, with higher scores indicating higher perceived hunger. A negative change from baseline score indicated a reduction in perceived lowest hunger.
Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1)	Baseline, Week 12, Week 24	Percent change in fasting serum TG was reported for participants in Study Arm 1.
Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2)	Baseline, Week 12, Week 24	Percent change in fasting serum TG was reported for participants in Study Arm 2.
Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1)	Baseline, Week 12, Week 24	Change from baseline in HbA1c was reported for participants in Study Arm 1.
Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2)	Baseline, Week 12, Week 24	Change from baseline in fasting glucose was reported for participants in Study Arm 2.
Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1)	Baseline, Week 12, Week 24	Percent change from baseline in MRI-PDFF was reported for participants with baseline MRI-PDFF ≥8.5% in Study Arm 1.
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score	Baseline, Week 12, Week 24	The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The highest hunger score asked participants to rate their highest hunger that day on a scale from 0 to 4, with higher scores representing the higher perceived hunger. A negative change from baseline indicated a reduction in perceived hunger.
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score	Baseline, Week 12, Week 24	The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The fullness score asked participants to rate how often they felt full after eating that day on a scale from 0 to 4, with higher scores indicating higher feeling of fullness. A negative change from baseline indicated a reduced feeling of fullness.
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score	Baseline, Week 12, Week 24	The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among participants with lipodystrophy. The felt hungry score asked how much time participants felt hunger that day on a scale from 0 to 4, with higher scores indicating more time feeling hungry. A negative change from baseline score indicated a reduction in time spent feeling hungry.
Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Response	Up to Day 281

Trial Locations

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