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

Официальное название

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

Обзор

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)

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

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

Франция · 2 центра

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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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