Efficacy and Safety of Mibavademab in Adult and Pediatric Patients With Generalized Lipodystrophy

Official title

A Two-Part, Randomized, Placebo-Controlled Phase 3 Study of the Efficacy, Safety, and Pharmacokinetics of Mibavademab in Patients With Generalized Lipodystrophy (LAGO)

Overview

This study is researching a new drug called mibavademab (called "study drug"). The study involves participants with a condition called Generalized Lipodystrophy (GLD). The aim of the study is to see how well mibavademab works and what side effects it has. Researchers will also look at how much mibavademab is in the body at different times. This is a 2-part study: Part A is an efficacy study in pediatric and adult participants, Part B is a safety and pharmacokinetic study in pediatric participants. The study is researching several other questions, including: * How mibavademab affects the amount of sugar in the blood * How mibavademab affects the amount of fat (triglycerides) in the blood * How mibavademab affects the amount of fat that has built up in the liver * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Interventions

• Drug Mibavademab
  Administered as per the protocol
• Drug Placebo
  Administered as per the protocol

Primary outcome measures

• Change in Hemoglobin A1c (HbA1c) [Time frame: Through 36 weeks of exposure to mibavademab]
• Percent change in fasting Triglycerides (TG) [Time frame: Through 36 weeks of exposure to mibavademab]
• Occurrence of Treatment Emergent Adverse Events (TEAEs) [Time frame: Up to 15 months]
• Severity of TEAEs [Time frame: Up to 15 months]
• Concentrations of total mibavademab in serum [Time frame: Up to 15 months]

Secondary outcome measures (12)

• Change in HbA1c compared to placebo [Time frame: From baseline to week 20]
• Change in HbA1c compared to placebo [Time frame: From week 56 to week 64]
• Change in HbA1c [Time frame: From baseline to week 52]
• Percent change in fasting TG compared to placebo [Time frame: From baseline to week 20]
• Percent change in fasting TG compared to placebo [Time frame: From week 56 to week 64]
• Percent change in fasting TG [Time frame: From baseline to week 52]
• Occurrence of HbA1c <7% [Time frame: At week 20]
• Occurrence of HbA1c <7% [Time frame: Through 36 weeks of exposure to mibavademab]
• Occurrence of HbA1c <6.5% [Time frame: At week 20]
• Occurrence of HbA1c <6.5% [Time frame: Through 36 weeks of exposure to mibavademab]
• Occurrence of fasting TG <500 mg/dL [Time frame: At week 20]
• Occurrence of fasting TG <500 mg/dL [Time frame: Through 36 weeks of exposure to mibavademab]

Eligibility criteria

Inclusion criteria

1\. Diagnosis of congenital or acquired GLD as defined by Multi-Society Practice Guidelines

For Part A only:

• Participants ≥2 years of age at screening
• At least one of the below criteria are fulfilled during screening (measurements can be repeated once during screening period)

• HbA1c ≥7%
• Fasting TG ≥500 mg/dL
• Fasting TG value of ≥300 mg/dL and the presence of another complication of GLD consistent with leptin deficiency (history of diabetes mellitus, hyperphagia, Metabolic Associated Fatty Liver Disease (MAFLD), polycystic ovary syndrome, etc)
• Weight ≥15 kg at screening
• Willing and able to provide, or have the treating physician provide, values of HbA1c and fasting TG from at least 6 months prior to screening, as described in the protocol

For Part B only:

• Participants <12 years of age at screening
• Weighing ≥7 kg at screening
• No metabolic criteria for study entry is required, as described in the protocol

Exclusion criteria

• Has a current diagnosis of familial or acquired partial lipodystrophy or autoimmune (Type 1) diabetes mellitus
• Any malignancy, eg, lymphoma, within the past 1 year, prior to screening visit, as described in the protocol
• eGFR of <30 mL/min/1.73 m2 based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine or Schwartz equation, as applicable, at screening. Assessment can be repeated once
• History of heart failure hospitalization, diagnosis of a myocardial infarction, stroke, clinically significant arrhythmia, as described in the protocol
• Treatment with over-the-counter or prescription medications with the intention of weight loss within 3 months prior to the screening visit

For Part A only:

• Treatment with metreleptin within 3 months of the screening visit
• Addition or discontinuation of prescription medications or over-the-counter supplements for diabetes and/or dyslipidemia within 3 months prior to the start of the screening period, or changes in the use of these medications, as described in the protocol
• Significant changes to lifestyle and diet, as described in the protocol
• Current chronic treatment with high-dose corticosteroids, defined as use of higher than physiologic doses, as described in the protocol

NOTE: Other protocol defined inclusion/exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• University of Michigan — Ann Arbor
• UT Southwestern Medical Center — Dallas

France · 2 centers

• Hopital Universitaire Robert-Debre — Paris
• Assistance Publique-Hopitaux de Paris (AP-HP) — Paris

Identifiers

NCT: NCT07220785 · R4461-GLD-2285 · 2024-519879-25-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗