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

NCT05088460 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: R4461-PLD-201002021-000138-33
• Study Type: interventional
• Target: 20
• Locations: 4 countries
• Sites: 8

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

Conditions

Familial Partial Lipodystrophy; Metabolic Abnormalities

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A)

  Percentage change in fasting serum TG was reported for participants with elevated baseline fasting TG (\> 200 mg/dL) and with baseline leptin \< 8.0 ng/mL (Cohort A).

  Baseline to week 12

• Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) (Cohort A)

  Change in HbA1c was reported for participants with elevated baseline HbA1c (\> 7.0%) and with baseline leptin \< 8.0 ng/mL (Cohort A).

  Baseline to week 12

Secondary Outcomes (17)

• Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B)

  Baseline to week 12

• Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B)

  Baseline to week 12

• Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1)

  Baseline, Week 12, Week 24

• Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2)

  Baseline, Week 12, Week 24

• Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1)

  Baseline, Week 12, Week 24

Study Arms (2)

Study Arm 1

EXPERIMENTAL

Randomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks

Drug: REGN4461; Drug: Matching Placebo

Study Arm 2

EXPERIMENTAL

Randomized to receive REGN4461 for 24 weeks

Drug: REGN4461

Interventions

REGN4461 DRUG

Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).

Also known as: mibavademab

Study Arm 1; Study Arm 2

Matching Placebo DRUG

Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).

Study Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (8)

Excel Medical Clinical Trials - A Flourish Research Site

Boca Raton, Florida, 33434, United States

Location

National Institute of Health

Bethesda, Maryland, 20892, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

ICAN, Institute of Cardiometabolism and Nutrition

Paris, 75013, France

Location

Complexo Hospitalario Universitario de Santiago-Hospital Médico-Cirúrxico de Conxo

Santiago de Compostela, Galicia, 15706, Spain

Location

Ege University Faculty of Medicine

Izmir, Bornova, 35100, Turkey (Türkiye)

Location

Related Links

• A Plain Language Summary is available on TrialSummaries.com

MeSH Terms

Conditions

Lipodystrophy, Familial Partial

Condition Hierarchy (Ancestors)

Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipodystrophy; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2021
• First Posted: October 22, 2021
• Study Start: February 28, 2022
• Primary Completion: December 13, 2023
• Study Completion: April 18, 2024
• Last Updated: October 16, 2025
• Results First Posted: July 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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).

Locations

US (5); FR (1); TU (1); ES (1)