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

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

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

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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


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.




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 ]


Information from the National Library of Medicine

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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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04159415


Locations
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United States, Michigan
Regeneron Research Facility
Ann Arbor, Michigan, United States, 48105
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
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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    Key Record Dates
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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lipodystrophy, Congenital Generalized
Lipodystrophy
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn