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Trial record 2 of 3 for:    regeneron | Lipodystrophy

A Study to Examine the Effects of the Leptin Receptor (LEPR) Agonist Antibody REGN4461 in Adult Patients With Familial Partial Lipodystrophy (FPLD) (LEAP)

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ClinicalTrials.gov Identifier: NCT05088460
Recruitment Status : Recruiting
First Posted : October 22, 2021
Last Update Posted : October 31, 2022
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

Two cohorts are being studied based on leptin levels. Cohort A is composed of patients with baseline leptin <8.0 ng/mL and Cohort B is composed of patients with baseline leptin 8.0 to ≤20.0 ng/mL

The primary objectives will be evaluated for patients in Cohort A only:

  • To evaluate the effect of REGN4461 on fasting triglycerides (TG) in patients with elevated baseline fasting TG
  • To evaluate the effect of REGN4461 on hyperglycemia in patients with elevated baseline Hemoglobin A1c (HbA1c)

The following secondary objectives of the study will be evaluated for Cohort B and for the combined set of Cohorts A plus B:

  • To evaluate the effect of REGN4461 on fasting TG levels in patients with hypertriglyceridemia
  • To evaluate the effect of REGN4461 on glycemic control in patients with hyperglycemia

The following secondary objectives of the study will be evaluated for Cohorts A and B separately, and for the combined set of Cohorts A plus B:

  • To evaluate the effect of REGN4461 on liver fat in patients with hepatic steatosis
  • To evaluate the effect of REGN4461 on hunger
  • To evaluate safety and tolerability of REGN4461
  • To characterize the concentration profile of REGN4461 over time
  • To assess immunogenicity to REGN4461

Condition or disease Intervention/treatment Phase
Familial Partial Lipodystrophy Metabolic Abnormalities Drug: REGN4461 Drug: Matching Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind Placebo-Controlled Study of the LEPR Agonist Antibody REGN4461 for the Treatment of Metabolic Abnormalities in Patients With Familial Partial Lipodystrophy
Actual Study Start Date : February 28, 2022
Estimated Primary Completion Date : July 5, 2023
Estimated Study Completion Date : February 6, 2024


Arm Intervention/treatment
Experimental: Study Arm 1
Randomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks
Drug: REGN4461
Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).

Drug: Matching Placebo
Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).

Experimental: Study Arm 2
Randomized to receive REGN4461 for 24 weeks
Drug: REGN4461
Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).




Primary Outcome Measures :
  1. Percent change in fasting serum triglyceride (TG) [ Time Frame: Baseline to week 12 ]
    In patients with elevated baseline fasting TG (fasting TG ≥200 mg/dL) and with baseline leptin <8.0 ng/mL

  2. Absolute change in hemoglobin A1c (HbA1c) [ Time Frame: Baseline to week 12 ]
    In patients with elevated baseline HbA1c (>7.0%) and with baseline leptin <8.0 ng/mL


Secondary Outcome Measures :
  1. Percent change in fasting serum TG [ Time Frame: Baseline to week 12 ]

    In patients with elevated baseline fasting TG (>200 mg/dL)

    Cohort B and Cohorts A+B


  2. Absolute change in HbA1c [ Time Frame: Baseline to week 12 ]

    In patients with elevated baseline HbA1c (>7.0%)

    Cohort B and Cohorts A+B


  3. Percent change in fasting serum TG [ Time Frame: Baseline to week 12 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1

  4. Percent change in fasting serum TG [ Time Frame: Week 12 to week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1

  5. Percent change in fasting serum TG from baseline to week 12 compared to the percent change between week 12 and week 24 [ Time Frame: Week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1

  6. Percent change in fasting serum TG [ Time Frame: Baseline to week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 2

  7. Percent change in fasting serum TG after the first 12 weeks of exposure to REGN4461 [ Time Frame: Baseline to week 12 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 2

  8. Percent change in fasting serum TG after the first 12 weeks of exposure to REGN4461 [ Time Frame: Week 12 to week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1 Patients must meet stability criteria

  9. Change in HbA1c [ Time Frame: Baseline to week 12 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1

  10. Change in HbA1c [ Time Frame: Week 12 to week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1

  11. Change in HbA1c from baseline to week 12 compared to change between week 12 and week 24 [ Time Frame: Week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1

  12. Change in fasting glucose [ Time Frame: Baseline to week 12 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1

  13. Change in fasting glucose [ Time Frame: Week 12 to week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1

  14. Change in fasting glucose from baseline to week 12 compared to change between week 12 and week 24 [ Time Frame: Week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1

  15. Change in HbA1c [ Time Frame: Baseline to week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 2

  16. Change in fasting glucose [ Time Frame: Baseline to week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 2

  17. Change in HbA1c [ Time Frame: Baseline to week 12 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 2

  18. Change in HbA1c [ Time Frame: Week 12 to week 24 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 1 Patients must meet stability criteria

  19. Change in fasting glucose [ Time Frame: Baseline to week 12 ]
    Cohorts A and B separately and Cohorts A+B in Study Arm 2

  20. Percent change in liver fat magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) REGN4461 [ Time Frame: Baseline to week 12 ]

    In patients with baseline liver fat (MRI-PDFF) ≥8.5%

    Cohorts A and B separately and Cohorts A+B


  21. Percent change in liver fat (MRI-PDFF) placebo [ Time Frame: Baseline to week 12 ]

    In patients with baseline liver fat (MRI-PDFF) ≥8.5%

    Cohorts A and B separately and Cohorts A+B


  22. Percent change in liver fat (MRI-PDFF) REGN4461 versus placebo [ Time Frame: Baseline to week 12 ]

    In patients with baseline liver fat (MRI-PDFF) ≥8.5%

    Cohorts A and B separately and Cohorts A+B


  23. Percent change in liver fat (MRI-PDFF) [ Time Frame: Baseline to week 12 ]

    In patients with baseline liver fat (MRI-PDFF) ≥8.5%

    Cohorts A and B separately and Cohorts A+B in Study Arm 1


  24. Percent change in liver fat (MRI-PDFF) [ Time Frame: Week 12 to week 24 ]

    In patients with baseline liver fat (MRI-PDFF) ≥8.5%

    Cohorts A and B separately and Cohorts A+B in Study Arm 1


  25. Percent change in liver fat (MRI-PDFF) from baseline to week 12 compared to percent change between week 12 and week 24 [ Time Frame: Week 24 ]

    In patients with baseline liver fat (MRI-PDFF) ≥8.5%

    Cohorts A and B separately and Cohorts A+B in Study Arm 1


  26. Percent change in liver fat (MRI-PDFF) [ Time Frame: Baseline to week 24 ]

    In patients with baseline liver fat (MRI-PDFF) ≥8.5%

    Cohorts A and B separately and Cohorts A+B in Study Arm 2


  27. Percent change in liver fat (MRI-PDFF) [ Time Frame: Baseline to week 12 ]

    In patients with baseline liver fat (MRI-PDFF) ≥8.5%

    Cohorts A and B separately and Cohorts A+B in Study Arm 2


  28. Change on the daily lipodystrophy hunger questionnaire [ Time Frame: Baseline to week 12 ]

    Cohorts A and B separately and Cohorts A+B

    Patients will complete the PRO assessments daily. The Hunger questionnaire is self-administered and contains 4 items based on a Likert-like scale, where 0 is not hungry at all and 10 is the hungriest possible


  29. Change on the daily lipodystrophy hunger questionnaire [ Time Frame: Baseline to week 24 ]
    Cohorts A and B separately and Cohorts A+B

  30. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to week 40 ]
    Cohorts A and B separately and Cohorts A+B

  31. Concentrations of REGN4461 in serum over time [ Time Frame: Up to week 40 ]
    Cohorts A and B separately and Cohorts A+B

  32. Immunogenicity of REGN4461 over time compared to placebo [ Time Frame: Up to week 40 ]
    Cohorts A and B separately and Cohorts A+B



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Clinical diagnosis of familial partial lipodystrophy as defined in the protocol
  • Fasting leptin level ≤20.0 ng/ml, as determined during the screening period
  • Presence of significant metabolic abnormalities related to glucose and triglycerides (TGs) as defined in the protocol
  • Stable body weight within the 3 months prior to screening (no gain or loss of >5% current weight)
  • Stable diet during the past 3 months defined as no major change in macronutrient composition (eg, starting or stopping diets such as Atkins, Paleo, Vegetarianism, Veganism)
  • No clinically meaningful change in medication regimen in the 3 months prior to screening as defined in the protocol

Key Exclusion Criteria:

  • Treatment with metreleptin within 3 months of the screening visit
  • Patients with a diagnosis of generalized lipodystrophy
  • Patients with a diagnosis of acquired lipodystrophy
  • Pregnant or breastfeeding 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): NCT05088460


Contacts
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Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
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United States, Maryland
National Institute of Health Recruiting
Bethesda, Maryland, United States, 20892
Contact: Rebecca Brown, MD    301-496-4686    brownrebecca@mail.nih.gov   
Contact: Michelle Ashmus    910-409-3636    Michelle.ashmus@nih.gov   
Principal Investigator: Rebecca Brown, Md         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Erin Kershaw, MD    412-370-2961    kershawee@upmc.edu   
Contact: Shari Reynolds Reynolds    412-383-0570    reynoldssl2@upmc.edu   
Principal Investigator: Erin Kershaw, MD         
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
France
ICAN, Institute of Cardiometabolism and Nutrition Recruiting
Paris, France, 75013
Contact: Camille Vatier, MD       camille.vatier@aphp.fr   
Contact: Corinne Vigouroux       corinne.vigouroux@aphp.fr   
Principal Investigator: Camille Vatier, MD         
Spain
Complexo Hospitalario Universitario de Santiago-Hospital Médico-Cirúrxico de Conxo Recruiting
Santiago de Compostela, Galicia, Spain, 15706
Turkey
Ege University Faculty of Medicine Recruiting
Izmir, Turkey, 35100
Contact: Ilgin Yildrim Simsir    +905325126917    ilginyilrimsimsir78@gmail.com   
Principal Investigator: Ilgin Yildrim Simsir, MD         
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: NCT05088460    
Other Study ID Numbers: R4461-PLD-20100
2021-000138-33 ( EudraCT Number )
First Posted: October 22, 2021    Key Record Dates
Last Update Posted: October 31, 2022
Last Verified: July 2022
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., Food and Drug Administration (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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Congenital Abnormalities
Lipodystrophy, Familial Partial
Lipodystrophy
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Laminopathies
Genetic Diseases, Inborn