Generalized Lipodystrophy
Conditions
Keywords
Congenital or acquired generalized lipodystrophy, Leptin deficiency, Loss of subcutaneous tissue, Nutritional deprivation, Severe metabolic derangements, Severe diabetes mellitus, Hypertriglyceridemia, Berardinelli-Seip Syndrome, Lawrence Syndrome, Severe Insulin Resistance
Brief summary
This study is researching an experimental drug called mibavademab. The study is focused on participants with GLD who have been on metreleptin treatment for at least 6 months with no change in dose for the last 3 months. The aim of the study is to see how safe and tolerable mibavademab is when switching from treatment with metreleptin. The study is looking at several other research questions, including: * What side effects may happen from taking mibavademab * How much mibavademab is in the blood at different times * Whether the body makes antibodies against mibavademab (which could make mibavademab less effective or could lead to side effects)
Interventions
DRUGmibavademab
Administered by intravenous (IV) infusion followed by subcutaneous (SC) injection
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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 2. Treatment with metreleptin for ≥6 months at time of screening at a stable dose, defined as no change in dose within the last 3 months prior to screening 3. Generally stable diet (based on participant's recall) and stable medication regimen for diabetes and/or dyslipidemia (in addition to metreleptin), for the last 3 months prior to screening 4. Willing and able to comply with clinic visits and study-related procedures. Participants who are unable/unwilling to self-inject, but are willing to have a capable caregiver inject, are considered eligible 5. Willing and able to provide, or have the treating physician provide, values of HbA1c and fasting triglycerides from at least 6 months prior to screening, as defined in the protocol Key
Exclusion criteria
1. Treatment with over-the-counter or prescription medications for weight loss within 3 months prior to the screening visit 2. Current chronic treatment with high-dose corticosteroids, as defined in the protocol 3. Any malignancy, eg, lymphoma, within the past 1 year, prior to screening visit except for fully treated basal cell or squamous epithelial cell carcinomas of the skin or carcinoma in situ of the cervix or anus 4. Estimated glomerular filtration rate (GFR) of \<30 mL/min/1.73 m\^2 based on chronic kidney disease epidemiology collaboration (CKD-EPI)/Schwartz equation at screening. Assessment can be repeated once 5. History of heart failure hospitalization, diagnosis of a myocardial infarction, stroke, clinically significant arrhythmia, transient ischemic attack, unstable angina, percutaneous or surgical revascularization procedure, or intracardiac device placement within 3 months before the screening visit, as defined in the protocol 6. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the participant by their participation in the study, as defined in the protocol NOTE: Other protocol-defined inclusion /
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | Up to week 68 |
| Severity of TEAEs | Up to week 68 |
Secondary
| Measure | Time frame |
|---|---|
| Change in Hemoglobin A1c (HbA1c) | Baseline, week 20 and week 52 |
| Occurrence of HbA1c <7% | Week 20 and week 52 |
| Occurrence of HbA1c <6.5% | Week 20 and week 52 |
| Occurrence of requiring therapy with insulin in participants treated with mibavademab | Week 20 and week 52 |
| Change in total insulin dose | Baseline, week 20 and week 52 |
| Change in fasting plasma glucose | Baseline, week 20 and week 52 |
| Percent change in fasting triglycerides | Baseline, week 20 and week 52 |
| Occurrence of fasting triglycerides <500 mg/dL in participants treated with mibavademab | Baseline, week 20 and week 52 |
| Occurrence of fasting triglycerides <200 mg/dL in participants treated with mibavademab | Baseline, week 20 and week 52 |
| Occurrence of fasting triglycerides <150 mg/dL in participants treated with mibavademab | Baseline, week 20 and week 52 |
| Concentrations of total mibavademab in serum | Up to week 68 |
| Incidence of anti-drug antibodies (ADAs) to mibavademab | Up to week 68 |
| Titer of ADAs to mibavademab | Up to week 68 |
| Incidence of neutralizing antibodies (Nabs) to mibavademab | Up to week 68 |
Countries
United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed