Phase 2
N=16
Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy
Generalized Lipodystrophy
Bottom Line
View on ClinicalTrials.gov: NCT04159415 ↗Enrolled (actual)
16
Serious AEs
12.2%
Results posted
Feb 2025
Primary outcome: Primary: Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8 — -0.1; 0.2 millimoles per mole (mmol/mol)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Placebo (Drug); Low-Dose REGN4461 (Drug); High-dose REGN4461 (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Regeneron Pharmaceuticals
- Primary completion
- Jan 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8 |
-0.1; 0.2 | — |
| PRIMARY Absolute Change From Baseline in Fasting Glucose at Week 8 |
15.5; 53.6 | — |
| PRIMARY Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8 |
-3.7; -3.7 | — |
| PRIMARY Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8 |
-6.0; 11.8 | — |
| SECONDARY Absolute Change From Baseline in HbA1c and Fasting TG Composite Endpoint at Week 8 |
0.0; 0.1 | — |
| SECONDARY Absolute Change From Baseline in Fasting Glucose |
-29.4; -22.0; -68.8; -21.1; -47.6; 12.5 | — |
| SECONDARY Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7% |
-29.4; -26.3; -68.8; -24.5; -47.6; 13.1 | — |
| SECONDARY Percent Change From Baseline in Fasting TG |
-22.5; -50.2; -55.1; -45.7; -40.2; -43.9 | — |
| SECONDARY Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL |
-39.4; -45.4; -62.8; -42.4; -48.6; -44.0 | — |
| SECONDARY Absolute Change From Baseline in HbA1c |
-0.60; -0.50; -2.34; -0.85; -2.56; -0.83 | — |
| SECONDARY Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7% |
-0.60; -0.36; -2.34; -0.77; -2.56; -0.74 | — |
| SECONDARY Absolute Change From Baseline in Weighted Mean Glucose (WMG) |
-10.626; -7.579; -73.634; -49.107 | — |
| SECONDARY Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7% |
-10.626; -4.510; -73.634; -53.797 | — |
| SECONDARY Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT) |
829.3; 1479.3; -5300.7; 3734.1; -18000.6; -5777.7 | — |
| SECONDARY Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7% |
829.3; 3098.2; -5300.7; 5976.4; -18000.6; -5828.2 | — |
| SECONDARY Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp |
0.030; 4.789; 6.256; 4.776 | — |
| SECONDARY Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7% |
0.030; 0.572; 6.256; 3.740 | — |
| SECONDARY Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT) |
0.021; 2.230; 2.311; 0.632 | — |
| SECONDARY Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7% |
0.021; 2.230; 2.311; 0.632 | — |
| SECONDARY Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) |
7; 8; 8; 7; 1; 6 | — |
| SECONDARY Concentrations of Total REGN4461 in Serum Over Time |
0; 49.2; 45.8; 2.51; 2.34; 50.6 | — |
| SECONDARY Number of Participants With Anti-drug Antibodies (ADA) to REGN4461 |
0; 0 | — |
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 3 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.
Eligibility 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.
Data sourced from ClinicalTrials.gov (NCT04159415). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.