Generalized Lipodystrophy
Conditions
Keywords
Subcutaneous (SC) adipose tissue, GLD, Berardinelli-Seip Syndrome, Congenital Generalized Lipodystrophy, CGL, Lawrence Syndrome, Acquired Generalized Lipodystrophy, AGL
Brief summary
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
DRUGMibavademab
Administered as per the protocol
DRUGPlacebo
Administered as per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part A will be double blinded; Part B will be open label
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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 \<12 years of age at screening 2. Weighing ≥7 kg at screening 3. No metabolic criteria for study entry is required, as described in the protocol 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin A1c (HbA1c) | Through 36 weeks of exposure to mibavademab | Part A |
| Percent change in fasting Triglycerides (TG) | Through 36 weeks of exposure to mibavademab | Part A |
| Occurrence of Treatment Emergent Adverse Events (TEAEs) | Up to 15 months | Part B |
| Severity of TEAEs | Up to 15 months | Part B |
| Concentrations of total mibavademab in serum | Up to 15 months | Part B |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c compared to placebo | From baseline to week 20 | Part A |
| Change in HbA1c | From baseline to week 52 | Part B |
| Percent change in fasting TG compared to placebo | From baseline to week 20 | Part A |
| Percent change in fasting TG | From baseline to week 52 | Part B |
| Occurrence of HbA1c <7% | At week 20 | Part A |
| Occurrence of HbA1c <6.5% | At week 20 | Part A |
| Occurrence of fasting TG <500 mg/dL | At week 20 | Part A |
| Occurrence of fasting TG <200 mg/dL | At week 20 | Part A |
| Occurrence of fasting TG <150 mg/dL | At week 20 | Part A |
| Percent change in Liver Fat Content (LFC) | From baseline to week 20 | Part A |
| Change in liver volume | From baseline to week 20 | Part A |
| Change in fasting glucose | From baseline to week 20 | Part A |
| Change in total daily insulin dose | From baseline to week 20 | Part A |
| Concentrations of total mibavademab in serum | Through Week 72 | Part A |
| Occurrence of Anti-Drug Antibodies (ADA) to mibavademab | Through Week 72 | Part A |
| Occurrence of ADA to mibavademab | Through Week 60 | Part B |
| Magnitude of ADA to mibavademab | Through Week 72 | Part A |
| Occurrence of TEAEs | Through Week 72 | Part A |
| Severity of TEAEs | Through Week 72 | Part A |
Countries
Brazil, France, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed