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

• ClinicalTrials.gov Identifier: NCT04159415
• Recruitment Status: Active, not recruiting
• First Posted: November 12, 2019
• Last Update Posted: May 21, 2020
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

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
Generalized Lipodystrophy	Drug: Placebo; Drug: Low-Dose REGN4461; Drug: High-dose REGN4461	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double Blind
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy
• Actual Study Start Date: January 7, 2020
• Estimated Primary Completion Date: May 31, 2021
• Estimated Study Completion Date: August 22, 2022

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 :

1. Absolute change from baseline hemoglobin A1c (HbA1c) [ Time Frame: Week 8 ]
   In patients with elevated baseline HBA1c (HbA1c ≥7%)
2. Absolute change from baseline fasting glucose [ Time Frame: Week 8 ]
   In patients with elevated baseline HBA1c (HbA1c ≥7%)
3. Absolute change from baseline weighted mean glucose (WMG) [ Time Frame: Week 8 ]
   In patients with elevated baseline HBA1c (HbA1c ≥7%)
4. Percent change from baseline fasting triglycerides (TG) [ Time Frame: Week 8 ]
   In patients with elevated baseline fasting TG (fasting TG ≥250 mg/dL)

Secondary Outcome Measures :

1. Absolute change in composite endpoint comprising absolute change in either HbA1c or percent change in fasting TG [ Time Frame: Week 8 ]
   In all patients
2. Absolute change in HbA1c from baseline [ Time Frame: Up to Week 52 ]
   In all patients
3. Percent change in fasting TG from baseline over time [ Time Frame: Up to Week 52 ]
   In all patients
4. Absolute change from baseline in fasting glucose [ Time Frame: Up to Week 52 ]
   In all patients
5. Absolute change from baseline in fasting glucose [ Time Frame: Up to Week 52 ]
   In patients with elevated baseline HbA1c (HbA1c ≥7%)
6. Percent change from baseline in fasting TG [ Time Frame: Up to Week 52 ]
   In patients with elevated baseline fasting TG (TG ≥250 mg/dL)
7. Absolute change from baseline in HbA1c over time [ Time Frame: Up to Week 52 ]
   In patients with elevated baseline HbA1c (HbA1c ≥7%)
8. Absolute change from baseline in WMG over time [ Time Frame: Up to Week 24 ]
   In all patients
9. Absolute change from baseline in WMG over time [ Time Frame: Up to Week 24 ]
   In patients with elevated baseline HbA1c (HbA1c ≥7%)
10. Change from baseline in glucose area under the concentration-time curve (AUC0-4) during a mixed meal tolerance test (MMTT) [ Time Frame: Up to Week 24 ]
    In all patients
11. Change from baseline in glucose AUC0-4 during a MMTT [ Time Frame: Up to Week 24 ]
    In patients with elevated baseline HbA1c (HbA1c ≥7%)
12. Change from baseline in glucose infusion rate per kilogram body mass during hyperinsulinemia-euglycemic clamp (clamp study) [ Time Frame: Up to Week 52 ]
    In all patients
13. Change from baseline in glucose infusion rate per kilogram body mass during hyperinsulinemia-euglycemic clamp (clamp study) [ Time Frame: Up to Week 52 ]
    In patients with elevated baseline HbA1c (HbA1c ≥7%)
14. Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT) [ Time Frame: Up to Week 52 ]
    In all patients
15. Change from baseline in glucose clearance rate (kITT) during insulin-tolerance test (ITT) [ Time Frame: Up to Week 52 ]
    In patients with elevated baseline HbA1c (HbA1c ≥7%)
16. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to Week 52 ]
17. Concentrations of total REGN4461 in serum over time [ Time Frame: Up to Week 52 ]
18. Incidence of anti-drug antibodies (ADA) to REGN4461 over time [ Time Frame: Up to Week 52 ]
19. Incidence of abnormal weight change [ Time Frame: Up to Week 52 ]
20. Incidence of vital sign abnormalities [ Time Frame: Up to Week 52 ]
21. Incidence of 12-lead electrocardiogram (ECG) abnormalities [ Time Frame: Up to Week 52 ]
22. Incidence of physical examination abnormalities [ Time Frame: Up to Week 52 ]
23. Incidence of laboratory abnormalities [ Time Frame: Up to Week 52 ]
24. Concentrations of total soluble leptin receptor (sLEPR) in serum over time [ Time Frame: Up to Week 52 ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Clinical diagnosis of congenital or acquired generalized lipodystrophy (GLD)

• 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
• 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

United States, Michigan

Regeneron Research Facility

Ann Arbor, Michigan, United States, 48105

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04159415
• Other Study ID Numbers: R4461-GLD-1875; 2019-000614-11 ( EudraCT Number )
• First Posted: November 12, 2019
• Last Update Posted: May 21, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All individual patient data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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.
• 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).
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lipodystrophy, Congenital Generalized; Lipodystrophy; Skin Diseases, Metabolic; Skin Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn