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

Primary Purpose

Generalized Lipodystrophy

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Low-Dose REGN4461
High-dose REGN4461
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Generalized Lipodystrophy

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Regeneron Research Site
  • Regeneron Research Site
  • Regeneron Research Site
  • Regeneron Research Site
  • Regeneron Research Site
  • Regeneron Research Site
  • Regeneron Research Site
  • Regeneron Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Treatment A

Treatment B

Arm Description

Outcomes

Primary Outcome Measures

Absolute change from baseline hemoglobin A1c (HbA1c)
In patients with elevated baseline HBA1c (HbA1c ≥7%)
Absolute change from baseline fasting glucose
In patients with elevated baseline HBA1c (HbA1c ≥7%)
Absolute change from baseline weighted mean glucose (WMG)
In patients with elevated baseline HBA1c (HbA1c ≥7%)
Percent change from baseline fasting triglycerides (TG)
In patients with elevated baseline fasting TG (fasting TG ≥250 mg/dL)

Secondary Outcome Measures

Absolute change in composite endpoint comprising absolute change in either HbA1c or percent change in fasting TG
In all patients
Absolute change in HbA1c from baseline
In all patients
Percent change in fasting TG from baseline over time
In all patients
Absolute change from baseline in fasting glucose
In all patients
Absolute change from baseline in fasting glucose
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Percent change from baseline in fasting TG
In patients with elevated baseline fasting TG (TG ≥250 mg/dL)
Absolute change from baseline in HbA1c over time
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Absolute change from baseline in WMG over time
In all patients
Absolute change from baseline in WMG over time
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Change from baseline in glucose area under the concentration-time curve (AUC0-4) during a mixed meal tolerance test (MMTT)
In all patients
Change from baseline in glucose AUC0-4 during a MMTT
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Change from baseline in glucose infusion rate per kilogram body mass during hyperinsulinemia-euglycemic clamp (clamp study)
In all patients
Change from baseline in glucose infusion rate per kilogram body mass during hyperinsulinemia-euglycemic clamp (clamp study)
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT)
In all patients
Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT)
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Incidence and severity of treatment-emergent adverse events (TEAEs)
Concentrations of total REGN4461 in serum over time
Incidence of anti-drug antibodies (ADA) to REGN4461 over time
Incidence of abnormal weight change
Incidence of vital sign abnormalities
Incidence of 12-lead electrocardiogram (ECG) abnormalities
Incidence of physical examination abnormalities
Incidence of laboratory abnormalities
Concentrations of total soluble leptin receptor (sLEPR) in serum over time

Full Information

First Posted
November 7, 2019
Last Updated
January 4, 2023
Sponsor
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04159415
Brief Title
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

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 7, 2020 (Actual)
Primary Completion Date
January 5, 2022 (Actual)
Study Completion Date
August 6, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Generalized Lipodystrophy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double Blind
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment A
Arm Type
Experimental
Arm Title
Treatment B
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intravenous (IV) infusion loading dose or subcutaneous (SC) injection weekly (QW).
Intervention Type
Drug
Intervention Name(s)
Low-Dose REGN4461
Intervention Description
IV infusion loading dose or SC injection QW.
Intervention Type
Drug
Intervention Name(s)
High-dose REGN4461
Intervention Description
IV infusion loading dose or SC injection QW.
Primary Outcome Measure Information:
Title
Absolute change from baseline hemoglobin A1c (HbA1c)
Description
In patients with elevated baseline HBA1c (HbA1c ≥7%)
Time Frame
Week 8
Title
Absolute change from baseline fasting glucose
Description
In patients with elevated baseline HBA1c (HbA1c ≥7%)
Time Frame
Week 8
Title
Absolute change from baseline weighted mean glucose (WMG)
Description
In patients with elevated baseline HBA1c (HbA1c ≥7%)
Time Frame
Week 8
Title
Percent change from baseline fasting triglycerides (TG)
Description
In patients with elevated baseline fasting TG (fasting TG ≥250 mg/dL)
Time Frame
Week 8
Secondary Outcome Measure Information:
Title
Absolute change in composite endpoint comprising absolute change in either HbA1c or percent change in fasting TG
Description
In all patients
Time Frame
Week 8
Title
Absolute change in HbA1c from baseline
Description
In all patients
Time Frame
Approximately Week 128
Title
Percent change in fasting TG from baseline over time
Description
In all patients
Time Frame
Approximately Week 128
Title
Absolute change from baseline in fasting glucose
Description
In all patients
Time Frame
Approximately Week 128
Title
Absolute change from baseline in fasting glucose
Description
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Time Frame
Approximately Week 128
Title
Percent change from baseline in fasting TG
Description
In patients with elevated baseline fasting TG (TG ≥250 mg/dL)
Time Frame
Approximately Week 128
Title
Absolute change from baseline in HbA1c over time
Description
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Time Frame
Approximately Week 128
Title
Absolute change from baseline in WMG over time
Description
In all patients
Time Frame
Up to Week 24
Title
Absolute change from baseline in WMG over time
Description
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Time Frame
Up to Week 24
Title
Change from baseline in glucose area under the concentration-time curve (AUC0-4) during a mixed meal tolerance test (MMTT)
Description
In all patients
Time Frame
At Week 8, 16 and 24
Title
Change from baseline in glucose AUC0-4 during a MMTT
Description
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Time Frame
At Week 8, 16 and 24
Title
Change from baseline in glucose infusion rate per kilogram body mass during hyperinsulinemia-euglycemic clamp (clamp study)
Description
In all patients
Time Frame
At Week 8 and Week 52
Title
Change from baseline in glucose infusion rate per kilogram body mass during hyperinsulinemia-euglycemic clamp (clamp study)
Description
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Time Frame
At Week 8 and Week 52
Title
Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT)
Description
In all patients
Time Frame
At Week 8 and Week 52
Title
Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT)
Description
In patients with elevated baseline HbA1c (HbA1c ≥7%)
Time Frame
At Week 8 and Week 52
Title
Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame
Approximately Week 128
Title
Concentrations of total REGN4461 in serum over time
Time Frame
Approximately Week 128
Title
Incidence of anti-drug antibodies (ADA) to REGN4461 over time
Time Frame
Approximately Week 128
Title
Incidence of abnormal weight change
Time Frame
Approximately Week 128
Title
Incidence of vital sign abnormalities
Time Frame
Approximately Week 128
Title
Incidence of 12-lead electrocardiogram (ECG) abnormalities
Time Frame
Approximately Week 128
Title
Incidence of physical examination abnormalities
Time Frame
Approximately Week 128
Title
Incidence of laboratory abnormalities
Time Frame
Approximately Week 128
Title
Concentrations of total soluble leptin receptor (sLEPR) in serum over time
Time Frame
Approximately Week 128

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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: HbA1c ≥ 7% OR 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Regeneron Research Site
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Regeneron Research Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Regeneron Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Regeneron Research Site
City
Piura
ZIP/Postal Code
2665
Country
Peru
Facility Name
Regeneron Research Site
City
Moscow
ZIP/Postal Code
117036
Country
Russian Federation
Facility Name
Regeneron Research Site
City
Ankara
ZIP/Postal Code
06230
Country
Turkey
Facility Name
Regeneron Research Site
City
Diyarbakir
ZIP/Postal Code
21808
Country
Turkey
Facility Name
Regeneron Research Site
City
Izmir
ZIP/Postal Code
35100
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All individual patient data (IPD) that underlie publicly available results will be considered for sharing
IPD Sharing Time Frame
Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
IPD Sharing Access Criteria
Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
IPD Sharing URL
https://vivli.org/

Learn more about this trial

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

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