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Efficacy and Safety of Mibavademab in Adult and Pediatric Patients With Generalized Lipodystrophy 3상 28 소아
This is a 2-part study: Part A is an efficacy study in pediatric and adult pa...
더 보기A Two-Part, Randomized, Placebo-Controlled Phase 3 Study of the Efficacy, Safety, and Pharmacokinetics of Mibavademab in Patients With Generalized Lipodystrophy
- R4461-GLD-2285
- 2024-519879-25-00 (등록 식별자) (EUCT Number)
GLD
Berardinelli-Seip Syndrome
Congenital Generalized Lipodystrophy
CGL
Lawrence Syndrome
Acquired Generalized Lipodystrophy
AGL
| 참가자 그룹/시험군 | 개입/치료 |
|---|---|
실험적Part A: Arm A | Mibavademab Administered as per the protocol |
실험적Part A: Arm B | Mibavademab Administered as per the protocol 위약 Administered as per the protocol |
실험적Part A: Arm C | Mibavademab Administered as per the protocol |
위약 대조군Part A: Arm D | 위약 Administered as per the protocol |
실험적Part B | Mibavademab Administered as per the protocol |
| 결과변수 | 측정값 설명 | 시간 범위 |
|---|---|---|
Change in Hemoglobin A1c (HbA1c) | Part A | Through 36 weeks of exposure to mibavademab |
Percent change in fasting Triglycerides (TG) | Part A | Through 36 weeks of exposure to mibavademab |
Occurrence of Treatment Emergent Adverse Events (TEAEs) | Part B | Up to 15 months |
Severity of TEAEs | Part B | Up to 15 months |
Concentrations of total mibavademab in serum | Part B | Up to 15 months |
| 결과변수 | 측정값 설명 | 시간 범위 |
|---|---|---|
Change in HbA1c compared to placebo | Part A | From baseline to week 20 |
Change in HbA1c compared to placebo | Part A | From week 56 to week 64 |
Change in HbA1c | Part B | From baseline to week 52 |
Percent change in fasting TG compared to placebo | Part A | From baseline to week 20 |
Percent change in fasting TG compared to placebo | Part A | From week 56 to week 64 |
Percent change in fasting TG | Part B | From baseline to week 52 |
Occurrence of HbA1c <7% | Part A | At week 20 |
Occurrence of HbA1c <7% | Part A | Through 36 weeks of exposure to mibavademab |
Occurrence of HbA1c <6.5% | Part A | At week 20 |
Occurrence of HbA1c <6.5% | Part A | Through 36 weeks of exposure to mibavademab |
Occurrence of fasting TG <500 mg/dL | Part A | At week 20 |
Occurrence of fasting TG <500 mg/dL | Part A | Through 36 weeks of exposure to mibavademab |
Occurrence of fasting TG <200 mg/dL | Part A | At week 20 |
Occurrence of fasting TG <200 mg/dL | Part A | Through 36 weeks of exposure to mibavademab |
Occurrence of fasting TG <150 mg/dL | Part A | At week 20 |
Occurrence of fasting TG <150 mg/dL | Part A | Through 36 weeks of exposure to mibavademab |
Percent change in Liver Fat Content (LFC) | Part A | From baseline to week 20 |
Percent change in Liver Fat Content (LFC) | Part A | From pre-mibavademab exposure to week 56 |
Change in liver volume | Part A | From baseline to week 20 |
Change in liver volume | Part A | From pre-mibavademab exposure to week 56 |
Change in fasting glucose | Part A | From baseline to week 20 |
Change in fasting glucose | Part A | Through 36 weeks of exposure to mibavademab |
Change in fasting glucose | Part A | From week 56 to week 64 |
Change in total daily insulin dose | Part A | From baseline to week 20 |
Change in total daily insulin dose | Part A | Through 36 weeks of exposure to mibavademab |
Change in total daily insulin dose | Part A | From week 56 to week 64 |
Change in total daily insulin dose | Part B | From baseline to week 52 |
Concentrations of total mibavademab in serum | Part A | Through Week 72 |
Occurrence of anti-drug antibodies (ADA) to mibavademab | Part A | Through Week 72 |
Occurrence of ADA to mibavademab | Part B | Through Week 60 |
Titer of ADA to mibavademab | Part A | Through Week 72 |
Titer of ADA to mibavademab | Part B | Through Week 60 |
Occurrence of TEAEs | Part A | Through Week 72 |
Severity of TEAEs | Part A | Through Week 72 |
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 ≥2 and <12 years of age at screening
- No metabolic criteria or minimum weight for study entry is required
- 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.