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

Phase 3Not Yet RecruitingNCT07220785

Regeneron Pharmaceuticals28 enrolled

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Generalized Lipodystrophy

Interventions

Eligibility

Sex: ALLMin age: 2 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1\. Diagnosis of congenital or acquired GLD as defined by Multi-Society Practice Guidelines For Part A only: 1. Participants ≥2 years of age at screening 2. 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) 3. Weight ≥15 kg at screening 4. 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: 1. Participants ≥2 and \<12 years of age at screening 2. No metabolic criteria or minimum weight for study entry is required Key Exclusion Criteria: 1. Has a current diagnosis of familial or acquired partial lipodystrophy or autoimmune (Type 1) diabetes mellitus 2. Any malignancy, eg, lymphoma, within the past 1 year, prior to screening visit, as described in the protocol 3. 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 4. History of heart failure hospitalization, diagnosis of a myocardial infarction, stroke, clinically significant arrhythmia, as described in the protocol 5. 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: 1. Treatment with metreleptin within 3 months of the screening visit 2. 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 3. Significant changes to lifestyle and diet, as described in the protocol 4. 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.

Outcomes

Primary Outcomes

Change in Hemoglobin A1c (HbA1c)

Part A

Time frame: Through 36 weeks of exposure to mibavademab

Percent change in fasting Triglycerides (TG)

Part A

Time frame: Through 36 weeks of exposure to mibavademab

Occurrence of Treatment Emergent Adverse Events (TEAEs)

Part B

Time frame: Up to 15 months

Severity of TEAEs

Part B

Time frame: Up to 15 months

Concentrations of total mibavademab in serum

Part B

Time frame: Up to 15 months

Secondary Outcomes

Change in HbA1c compared to placebo

Part A

Time frame: From baseline to week 20

Change in HbA1c compared to placebo

Part A

Time frame: From week 56 to week 64

Change in HbA1c

Part B

Time frame: From baseline to week 52

Percent change in fasting TG compared to placebo

Part A

Time frame: From baseline to week 20

Percent change in fasting TG compared to placebo

Part A

Time frame: From week 56 to week 64

Percent change in fasting TG

Part B

Time frame: From baseline to week 52

Occurrence of HbA1c <7%

Part A

Time frame: At week 20

Occurrence of HbA1c <7%

Part A

Time frame: Through 36 weeks of exposure to mibavademab

Occurrence of HbA1c <6.5%

Part A

Time frame: At week 20

Occurrence of HbA1c <6.5%

Part A

Time frame: Through 36 weeks of exposure to mibavademab

Occurrence of fasting TG <500 mg/dL

Part A

Time frame: At week 20

Occurrence of fasting TG <500 mg/dL

Part A

Time frame: Through 36 weeks of exposure to mibavademab

Occurrence of fasting TG <200 mg/dL

Part A

Time frame: At week 20

Occurrence of fasting TG <200 mg/dL

Part A

Time frame: Through 36 weeks of exposure to mibavademab

Occurrence of fasting TG <150 mg/dL

Part A

Time frame: At week 20

Occurrence of fasting TG <150 mg/dL

Part A

Time frame: Through 36 weeks of exposure to mibavademab

Percent change in Liver Fat Content (LFC)

Part A

Time frame: From baseline to week 20

Percent change in Liver Fat Content (LFC)

Part A

Time frame: From pre-mibavademab exposure to week 56

Change in liver volume

Part A

Time frame: From baseline to week 20

Change in liver volume

Part A

Time frame: From pre-mibavademab exposure to week 56

Change in fasting glucose

Part A

Time frame: From baseline to week 20

Change in fasting glucose

Part A

Time frame: Through 36 weeks of exposure to mibavademab

Change in fasting glucose

Part A

Time frame: From week 56 to week 64

Change in total daily insulin dose

Part A

Time frame: From baseline to week 20

Change in total daily insulin dose

Part A

Time frame: Through 36 weeks of exposure to mibavademab

Change in total daily insulin dose

Part A

Time frame: From week 56 to week 64

Change in total daily insulin dose

Part B

Time frame: From baseline to week 52

Concentrations of total mibavademab in serum

Part A

Time frame: Through Week 72

Occurrence of anti-drug antibodies (ADA) to mibavademab

Part A

Time frame: Through Week 72

Occurrence of ADA to mibavademab

Part B

Time frame: Through Week 60

Titer of ADA to mibavademab

Part A

Time frame: Through Week 72

Titer of ADA to mibavademab

Part B

Time frame: Through Week 60

Occurrence of TEAEs

Part A

Time frame: Through Week 72

Severity of TEAEs

Part A

Time frame: Through Week 72

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts