LEAP: A Study to Examine the Effects of the Leptin Receptor (LEPR) Agonist Antibody REGN4461 in Adult Patients With Familial Partial Lipodystrophy (FPLD)
Study Details
Study Description
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:
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To evaluate the effect of REGN4461 on fasting triglycerides (TG) in patients with elevated baseline fasting TG
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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:
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To evaluate the effect of REGN4461 on fasting TG levels in patients with hypertriglyceridemia
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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:
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To evaluate the effect of REGN4461 on liver fat in patients with hepatic steatosis
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To evaluate the effect of REGN4461 on hunger
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To evaluate safety and tolerability of REGN4461
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To characterize the concentration profile of REGN4461 over time
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To assess immunogenicity to REGN4461
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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).
|
Outcome Measures
Primary Outcome Measures
- Percent change in fasting serum triglyceride (TG) [Baseline to week 12]
In patients with elevated baseline fasting TG (fasting TG ≥200 mg/dL) and with baseline leptin <8.0 ng/mL
- Absolute change in hemoglobin A1c (HbA1c) [Baseline to week 12]
In patients with elevated baseline HbA1c (>7.0%) and with baseline leptin <8.0 ng/mL
Secondary Outcome Measures
- Percent change in fasting serum TG [Baseline to week 12]
In patients with elevated baseline fasting TG (>200 mg/dL) Cohort B and Cohorts A+B
- Absolute change in HbA1c [Baseline to week 12]
In patients with elevated baseline HbA1c (>7.0%) Cohort B and Cohorts A+B
- Percent change in fasting serum TG [Baseline to week 12]
Cohorts A and B separately and Cohorts A+B in Study Arm 1
- Percent change in fasting serum TG [Week 12 to week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 1
- Percent change in fasting serum TG from baseline to week 12 compared to the percent change between week 12 and week 24 [Week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 1
- Percent change in fasting serum TG [Baseline to week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 2
- Percent change in fasting serum TG after the first 12 weeks of exposure to REGN4461 [Baseline to week 12]
Cohorts A and B separately and Cohorts A+B in Study Arm 2
- Percent change in fasting serum TG after the first 12 weeks of exposure to REGN4461 [Week 12 to week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 1 Patients must meet stability criteria
- Change in HbA1c [Baseline to week 12]
Cohorts A and B separately and Cohorts A+B in Study Arm 1
- Change in HbA1c [Week 12 to week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 1
- Change in HbA1c from baseline to week 12 compared to change between week 12 and week 24 [Week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 1
- Change in fasting glucose [Baseline to week 12]
Cohorts A and B separately and Cohorts A+B in Study Arm 1
- Change in fasting glucose [Week 12 to week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 1
- Change in fasting glucose from baseline to week 12 compared to change between week 12 and week 24 [Week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 1
- Change in HbA1c [Baseline to week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 2
- Change in fasting glucose [Baseline to week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 2
- Change in HbA1c [Baseline to week 12]
Cohorts A and B separately and Cohorts A+B in Study Arm 2
- Change in HbA1c [Week 12 to week 24]
Cohorts A and B separately and Cohorts A+B in Study Arm 1 Patients must meet stability criteria
- Change in fasting glucose [Baseline to week 12]
Cohorts A and B separately and Cohorts A+B in Study Arm 2
- Percent change in liver fat magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) REGN4461 [Baseline to week 12]
In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B
- Percent change in liver fat (MRI-PDFF) placebo [Baseline to week 12]
In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B
- Percent change in liver fat (MRI-PDFF) REGN4461 versus placebo [Baseline to week 12]
In patients with baseline liver fat (MRI-PDFF) ≥8.5% Cohorts A and B separately and Cohorts A+B
- Percent change in liver fat (MRI-PDFF) [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
- Percent change in liver fat (MRI-PDFF) [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
- Percent change in liver fat (MRI-PDFF) from baseline to week 12 compared to percent change between week 12 and week 24 [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
- Percent change in liver fat (MRI-PDFF) [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
- Percent change in liver fat (MRI-PDFF) [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
- Change on the daily lipodystrophy hunger questionnaire [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
- Change on the daily lipodystrophy hunger questionnaire [Baseline to week 24]
Cohorts A and B separately and Cohorts A+B
- Incidence and severity of treatment-emergent adverse events (TEAEs) [Up to week 40]
Cohorts A and B separately and Cohorts A+B
- Concentrations of REGN4461 in serum over time [Up to week 40]
Cohorts A and B separately and Cohorts A+B
- Immunogenicity of REGN4461 over time compared to placebo [Up to week 40]
Cohorts A and B separately and Cohorts A+B
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Clinical diagnosis of familial partial lipodystrophy as defined in the protocol
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Fasting leptin level ≤20.0 ng/ml, as determined during the screening period
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Presence of significant metabolic abnormalities related to glucose and triglycerides (TGs) as defined in the protocol
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Stable body weight within the 3 months prior to screening (no gain or loss of >5% current weight)
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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)
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No clinically meaningful change in medication regimen in the 3 months prior to screening as defined in the protocol
Key Exclusion Criteria:
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Treatment with metreleptin within 3 months of the screening visit
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Patients with a diagnosis of generalized lipodystrophy
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Patients with a diagnosis of acquired lipodystrophy
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Pregnant or breastfeeding women
NOTE: Other protocol defined inclusion/exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institute of Health | Bethesda | Maryland | United States | 20892 |
| 2 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 3 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15213 |
| 4 | UT Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 5 | ICAN, Institute of Cardiometabolism and Nutrition | Paris | France | 75013 | |
| 6 | Complexo Hospitalario Universitario de Santiago-Hospital Médico-Cirúrxico de Conxo | Santiago de Compostela | Galicia | Spain | 15706 |
| 7 | Ege University Faculty of Medicine | 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-PLD-20100
- 2021-000138-33