Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy
Study Details
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 2 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment A
|
Drug: Placebo
Intravenous (IV) infusion loading dose or subcutaneous (SC) injection weekly (QW).
Drug: Low-Dose REGN4461
IV infusion loading dose or SC injection QW.
Drug: High-dose REGN4461
IV infusion loading dose or SC injection QW.
|
| Experimental: Treatment B
|
Drug: Placebo
Intravenous (IV) infusion loading dose or subcutaneous (SC) injection weekly (QW).
Drug: Low-Dose REGN4461
IV infusion loading dose or SC injection QW.
Drug: High-dose REGN4461
IV infusion loading dose or SC injection QW.
|
Outcome Measures
Primary Outcome Measures
- Absolute change from baseline hemoglobin A1c (HbA1c) [Week 8]
In patients with elevated baseline HBA1c (HbA1c ≥7%)
- Absolute change from baseline fasting glucose [Week 8]
In patients with elevated baseline HBA1c (HbA1c ≥7%)
- Absolute change from baseline weighted mean glucose (WMG) [Week 8]
In patients with elevated baseline HBA1c (HbA1c ≥7%)
- Percent change from baseline fasting triglycerides (TG) [Week 8]
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 [Week 8]
In all patients
- Absolute change in HbA1c from baseline [Up to Week 52]
In all patients
- Percent change in fasting TG from baseline over time [Up to Week 52]
In all patients
- Absolute change from baseline in fasting glucose [Up to Week 52]
In all patients
- Absolute change from baseline in fasting glucose [Up to Week 52]
In patients with elevated baseline HbA1c (HbA1c ≥7%)
- Percent change from baseline in fasting TG [Up to Week 52]
In patients with elevated baseline fasting TG (TG ≥250 mg/dL)
- Absolute change from baseline in HbA1c over time [Up to Week 52]
In patients with elevated baseline HbA1c (HbA1c ≥7%)
- Absolute change from baseline in WMG over time [Up to Week 24]
In all patients
- Absolute change from baseline in WMG over time [Up to Week 24]
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) [Up to Week 24]
In all patients
- Change from baseline in glucose AUC0-4 during a MMTT [Up to Week 24]
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) [Up to Week 52]
In all patients
- Change from baseline in glucose infusion rate per kilogram body mass during hyperinsulinemia-euglycemic clamp (clamp study) [Up to Week 52]
In patients with elevated baseline HbA1c (HbA1c ≥7%)
- Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT) [Up to Week 52]
In all patients
- Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT) [Up to Week 52]
In patients with elevated baseline HbA1c (HbA1c ≥7%)
- Incidence and severity of treatment-emergent adverse events (TEAEs) [Up to Week 52]
- Concentrations of total REGN4461 in serum over time [Up to Week 52]
- Incidence of anti-drug antibodies (ADA) to REGN4461 over time [Up to Week 52]
- Incidence of abnormal weight change [Up to Week 52]
- Incidence of vital sign abnormalities [Up to Week 52]
- Incidence of 12-lead electrocardiogram (ECG) abnormalities [Up to Week 52]
- Incidence of physical examination abnormalities [Up to Week 52]
- Incidence of laboratory abnormalities [Up to Week 52]
- Concentrations of total soluble leptin receptor (sLEPR) in serum over time [Up to Week 52]
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Regeneron Research Site | Bethesda | Maryland | United States | 20892 |
| 2 | Regeneron Research Site | Ann Arbor | Michigan | United States | 48105 |
| 3 | Regeneron Research Site | Dallas | Texas | United States | 75390 |
| 4 | Regeneron Research Site | Piura | Peru | 2665 | |
| 5 | Regeneron Research Site | Moscow | Russian Federation | 117036 | |
| 6 | Regeneron Research Site | Ankara | Turkey | 06230 | |
| 7 | Regeneron Research Site | Diyarbakir | Turkey | 21808 | |
| 8 | Regeneron Research Site | Izmir | Turkey | 35100 |
Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R4461-GLD-1875
- 2019-000614-11