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

NCT04159415 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: R4461-GLD-18752019-000614-11
• Study Type: interventional
• Target: 16
• Locations: 4 countries
• Sites: 8

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 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.

Conditions

Generalized Lipodystrophy

Outcome Measures

Primary Outcomes (4)

• Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8

  Absolute change from baseline in HbA1c for subgroup of participants with baseline HbA1c ≥7% reported

  Baseline, Week 8

• Absolute Change From Baseline in Fasting Glucose at Week 8

  Absolute change from baseline in fasting glucose for subgroup of participants with baseline HbA1c ≥7% reported

  Baseline, Week 8

• Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8

  Absolute change from baseline in WMG for subgroup of participants with baseline HbA1c ≥7% reported

  Baseline, Week 8

• Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8

  Percent change from baseline in participants with elevated baseline fasting TG (fasting TG ≥250 mg/dL) reported

  Baseline, Week 8

Secondary Outcomes (18)

• Absolute Change From Baseline in HbA1c and Fasting TG Composite Endpoint at Week 8

  Baseline, Week 8

• Absolute Change From Baseline in Fasting Glucose

  Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52

• Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7%

  Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52

• Percent Change From Baseline in Fasting TG

  Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52

• Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL

  Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52

Study Arms (2)

Treatment A

EXPERIMENTAL

Drug: Placebo; Drug: Low-Dose REGN4461; Drug: High-dose REGN4461

Treatment B

EXPERIMENTAL

Drug: Placebo; Drug: Low-Dose REGN4461; Drug: High-dose REGN4461

Interventions

Placebo DRUG

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

Treatment A; Treatment B

Low-Dose REGN4461 DRUG

IV infusion loading dose or SC injection QW.

Also known as: mibavademab

Treatment A; Treatment B

High-dose REGN4461 DRUG

IV infusion loading dose or SC injection QW.

Also known as: mibavademab

Treatment A; Treatment B

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (8)

Regeneron Research Site

Bethesda, Maryland, 20892, United States

Location

Regeneron Research Site

Ann Arbor, Michigan, 48105, United States

Location

Regeneron Research Site

Dallas, Texas, 75390, United States

Location

Regeneron Research Site

Piura, 2665, Peru

Location

Regeneron Research Site

Moscow, 117036, Russia

Location

Regeneron Research Site

Ankara, 06230, Turkey (Türkiye)

Location

Regeneron Research Site

Diyarbakır, 21808, Turkey (Türkiye)

Location

Regeneron Research Site

Izmir, 35100, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Lipodystrophy, Congenital Generalized

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipodystrophy; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; 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
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 12, 2019
• Study Start: January 7, 2020
• Primary Completion: January 5, 2022
• Study Completion: September 24, 2024
• Last Updated: November 17, 2025
• Results First Posted: February 25, 2025

Record last verified: 2025-10

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., 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

RU (1); TU (3); US (3); PE (1)