Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy

Regeneron Pharmaceuticals16 enrolled

Overview

The primary objectives of the study are to estimate the effects of REGN4461 on glycemic parameters in the subset of patients with elevated baseline hemoglobin A1c levels (HbA1c ≥7%) and to estimate the effects of REGN4461 on fasting triglyceride levels in the subset of patients with elevated baseline fasting triglycerides (TG ≥250 mg/dL). The secondary objectives are to estimate the effects of REGN4461 on a composite endpoint of changes in either HbA1c or fasting TG for all patients, estimate the effects of 3 dose levels of REGN4461 on glycemic parameters and fasting TG, to estimate the effects of REGN4461 on insulin sensitivity, to evaluate the safety and tolerability of REGN4461 and to evaluate the pharmacokinetics (PK) and immunogenicity of REGN4461.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Generalized Lipodystrophy

Interventions

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Diagnosis of congenital or acquired generalized lipodystrophy (GLD), as defined in the protocol * Presence of one or both of the following metabolic abnormalities at screening: 1. HbA1c ≥ 7% OR 2. Fasting TG ≥250 mg/dL * Generally stable diet (based on patient's recall) and medication regimen (that optimizes treatment for their metabolic disease) for at least 3 months prior to the screening visit Key Exclusion Criteria: * Treatment with metreleptin within 1 month of the screening visit * Treatment with over-the-counter or prescription medications for weight loss within 3 months prior to the screening visit * Treatment with oral glucocorticoids \>7.5 mg prednisone equivalents per day within 3 months prior to screening visit or plans to begin treatment with oral glucocorticoids \>7.5 mg prednisone equivalents per day during the study period * History of Human Immunodeficiency Virus (HIV) or HIV seropositivity at screening visit * Uncontrolled infection with hepatitis B or hepatitis C infection, or known active tuberculosis at screening * Participation in any clinical research study evaluating an Investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit. * Pregnant or breast-feeding women NOTE: Other protocol defined inclusion/exclusion criteria apply.

Locations (8)

Regeneron Research Site

Bethesda, Maryland, United States

Regeneron Research Site

Ann Arbor, Michigan, United States

Regeneron Research Site

Dallas, Texas, United States

Regeneron Research Site

Piura, Peru

Regeneron Research Site

Moscow, Russia

Regeneron Research Site

Ankara, Turkey (Türkiye)

Regeneron Research Site

Diyarbakır, Turkey (Türkiye)

Regeneron Research Site

Izmir, Turkey (Türkiye)

Outcomes

Primary Outcomes

Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8

Absolute change from baseline in HbA1c for subgroup of participants with baseline HbA1c ≥7% reported

Time frame: Baseline, Week 8

Absolute Change From Baseline in Fasting Glucose at Week 8

Absolute change from baseline in fasting glucose for subgroup of participants with baseline HbA1c ≥7% reported

Time frame: Baseline, Week 8

Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8

Absolute change from baseline in WMG for subgroup of participants with baseline HbA1c ≥7% reported

Time frame: Baseline, Week 8

Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8

Percent change from baseline in participants with elevated baseline fasting TG (fasting TG ≥250 mg/dL) reported

Time frame: Baseline, Week 8

Secondary Outcomes

Absolute Change From Baseline in HbA1c and Fasting TG Composite Endpoint at Week 8

The composite score is calculated for each individual participant using baseline and Week 8 measurements of HbA1c and fasting TG. For each participant, a Z-score is calculated separately for HbA1c and fasting TG, rescaling the change from baseline based on the standard deviation of the baseline value for all participants, as a way of standardizing the change value. The composite score uses one or both of the calculated Z-scores depending on which parameters were abnormal at baseline. If both, then the participant's composite is the average of the two parameter Z-scores. At the participant level, a Z-score of zero for either parameter indicates no change in that metabolic parameter, but a composite Z-score of zero can also reflect offsetting changes in metabolic parameters. A negative Z-score would be interpreted as an overall improvement in metabolic function, but a negative Z-score can also result from a decrease in one parameter not being canceled by an increase in the other.

Time frame: Baseline, Week 8

Absolute Change From Baseline in Fasting Glucose

Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52

Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7%

Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52

Percent Change From Baseline in Fasting TG

Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52

Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL

Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52

Absolute Change From Baseline in HbA1c

Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52

Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7%

Time frame: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52

Absolute Change From Baseline in Weighted Mean Glucose (WMG)

Time frame: Baseline, Weeks 16 and 24

Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7%

Time frame: Baseline, Weeks 16 and 24

Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT)

Time frame: Baseline, Weeks 8, 16, 24

Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7%

Time frame: Baseline, Weeks 8, 16, 24

Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp

Time frame: Baseline, Weeks 8 and 52

Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7%

Time frame: Baseline, Weeks 8 and 52

Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT)

Time frame: Baseline, Weeks 8 and 52

Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7%

Time frame: Baseline, Weeks 8 and 52

Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)

Time frame: From first dose of DBTP study treatment through last dose of OLTP 5 study treatment plus 16 weeks (approximately 120 weeks)

Concentrations of Total REGN4461 in Serum Over Time

Time frame: Weeks 0 (post-dose), 8, 16 (post-dose), 36, 52; OLTP 5 Weeks 4, 12, 24, 52

Number of Participants With Anti-drug Antibodies (ADA) to REGN4461

Time frame: Approximately Week 128