Clinical trial NCT04159415: Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Generalized Lipodystrophy
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-11-12
Enrollment: 16
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Absolute Change From Baseline in Hemoglobin A1c (HbA1c) at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in Fasting Glucose at Week 8
timeFrame: Baseline, Week 8
measure: Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8
timeFrame: Baseline, Week 8
measure: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Absolute Change in Composite Endpoint Comprising Absolute Change in Either HbA1c or Percent Change in Fasting TG
timeFrame: Week 8
measure: Absolute Change in HbA1c From Baseline
timeFrame: Approximately Week 128
measure: Percent Change in Fasting TG From Baseline Over Time
timeFrame: Approximately Week 128
measure: Percent Change From Baseline in Fasting TG
timeFrame: Approximately Week 128
measure: Absolute Change From Baseline in HbA1c Over Time
timeFrame: Approximately Week 128
measure: Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT)
timeFrame: At Week 8, 16 and 24
measure: Change From Baseline in Glucose AUC0-4 During a MMTT
timeFrame: At Week 8, 16 and 24
measure: Incidence and Severity of Treatment-emergent Adverse Events (TEAEs)
timeFrame: Approximately Week 128
measure: Concentrations of Total REGN4461 in Serum Over Time
timeFrame: Approximately Week 128
measure: Incidence of Anti-drug Antibodies (ADA) to REGN4461 Over Time
timeFrame: Approximately Week 128
measure: Incidence of Abnormal Weight Change
timeFrame: Approximately Week 128
measure: Incidence of Vital Sign Abnormalities
timeFrame: Approximately Week 128
measure: Incidence of 12-lead Electrocardiogram (ECG) Abnormalities
timeFrame: Approximately Week 128
measure: Incidence of Physical Examination Abnormalities
timeFrame: Approximately Week 128
measure: Incidence of Laboratory Abnormalities
timeFrame: Approximately Week 128
measure: Concentrations of Total Soluble Leptin Receptor (sLEPR) in Serum Over Time
timeFrame: Approximately Week 128
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Regeneron Research Site
state: Maryland
city: Ann Arbor
country: United States
facility: Regeneron Research Site
state: Michigan
city: Dallas
country: United States
facility: Regeneron Research Site
state: Texas
city: Piura
country: Peru
facility: Regeneron Research Site
city: Moscow
country: Russian Federation
facility: Regeneron Research Site
city: Ankara
country: Turkey
facility: Regeneron Research Site
city: Diyarbakir
country: Turkey
facility: Regeneron Research Site
city: Izmir
country: Turkey
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: