Clinical trial NCT05088460: A Study to Examine the Effects of the Leptin Receptor (LEPR) Agonist Antibody REGN4461 in Adult Patients With Familial Partial Lipodystrophy (FPLD)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Familial Partial Lipodystrophy
Metabolic Abnormalities
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-10-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Percent change in fasting serum triglyceride (TG)
timeFrame: Baseline to week 12
measure: Absolute change in hemoglobin A1c (HbA1c)
timeFrame: Baseline to week 12
Secondary outcomes:
measure: Percent change in fasting serum TG
timeFrame: Baseline to week 12
measure: Absolute change in HbA1c
timeFrame: Baseline to week 12
measure: Percent change in fasting serum TG
timeFrame: Baseline to week 12
measure: Percent change in fasting serum TG
timeFrame: Week 12 to week 24
measure: Percent change in fasting serum TG from baseline to week 12 compared to the percent change between week 12 and week 24
timeFrame: Week 24
measure: Percent change in fasting serum TG
timeFrame: Baseline to week 24
measure: Percent change in fasting serum TG after the first 12 weeks of exposure to REGN4461
timeFrame: Baseline to week 12
measure: Percent change in fasting serum TG after the first 12 weeks of exposure to REGN4461
timeFrame: Week 12 to week 24
measure: Change in HbA1c
timeFrame: Baseline to week 12
measure: Change in HbA1c
timeFrame: Week 12 to week 24
measure: Change in HbA1c from baseline to week 12 compared to change between week 12 and week 24
timeFrame: Week 24
measure: Change in fasting glucose
timeFrame: Baseline to week 12
measure: Change in fasting glucose
timeFrame: Week 12 to week 24
measure: Change in fasting glucose from baseline to week 12 compared to change between week 12 and week 24
timeFrame: Week 24
measure: Change in HbA1c
timeFrame: Baseline to week 24
measure: Change in fasting glucose
timeFrame: Baseline to week 24
measure: Change in HbA1c
timeFrame: Baseline to week 12
measure: Change in HbA1c
timeFrame: Week 12 to week 24
measure: Change in fasting glucose
timeFrame: Baseline to week 12
measure: Percent change in liver fat magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) REGN4461
timeFrame: Baseline to week 12
measure: Percent change in liver fat (MRI-PDFF) placebo
timeFrame: Baseline to week 12
measure: Percent change in liver fat (MRI-PDFF) REGN4461 versus placebo
timeFrame: Baseline to week 12
measure: Percent change in liver fat (MRI-PDFF)
timeFrame: Baseline to week 12
measure: Percent change in liver fat (MRI-PDFF)
timeFrame: Week 12 to week 24
measure: Percent change in liver fat (MRI-PDFF) from baseline to week 12 compared to percent change between week 12 and week 24
timeFrame: Week 24
measure: Percent change in liver fat (MRI-PDFF)
timeFrame: Baseline to week 24
measure: Percent change in liver fat (MRI-PDFF)
timeFrame: Baseline to week 12
measure: Change on the daily lipodystrophy hunger questionnaire
timeFrame: Baseline to week 12
measure: Change on the daily lipodystrophy hunger questionnaire
timeFrame: Baseline to week 24
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Up to week 40
measure: Concentrations of REGN4461 in serum over time
timeFrame: Up to week 40
measure: Immunogenicity of REGN4461 over time compared to placebo
timeFrame: Up to week 40
Other outcomes:
Locations:
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials - A Flourish Research Site
state: Florida
city: Bethesda
country: United States
facility: National Institute of Health
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Paris
country: France
facility: ICAN, Institute of Cardiometabolism and Nutrition
city: Santiago de Compostela
country: Spain
facility: Complexo Hospitalario Universitario de Santiago-Hospital Médico-Cirúrxico de Conxo
state: Galicia
city: Izmir
country: Turkey
facility: Ege University Faculty of Medicine
state: Bornova
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: