Clinical trial NCT06548100: A Study of the Safety of Mibavademab in Pediatric and Adult Participants Switching From Metreleptin to Mibavademab for the Treatment of Generalized Lipodystrophy (GLD)
Official title: A Single-Arm, Open-Label, Safety Study in Patients With Generalized Lipodystrophy Switching From Metreleptin to Mibavademab, A Leptin Receptor Agonist Antibody
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Generalized Lipodystrophy
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
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-08-12
Enrollment: 8
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility 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 / exclusion criteria apply

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to week 68
measure: Severity of TEAEs
timeFrame: Up to week 68
Secondary outcomes:
measure: Change in Hemoglobin A1c (HbA1c)
timeFrame: Baseline, week 20 and week 52
measure: Occurrence of HbA1c <7%
timeFrame: Week 20 and week 52
measure: Occurrence of HbA1c <6.5%
timeFrame: Week 20 and week 52
measure: Occurrence of requiring therapy with insulin in participants treated with mibavademab
timeFrame: Week 20 and week 52
measure: Change in total insulin dose
timeFrame: Baseline, week 20 and week 52
measure: Change in fasting plasma glucose
timeFrame: Baseline, week 20 and week 52
measure: Percent change in fasting triglycerides
timeFrame: Baseline, week 20 and week 52
measure: Occurrence of fasting triglycerides <500 mg/dL in participants treated with mibavademab
timeFrame: Baseline, week 20 and week 52
measure: Occurrence of fasting triglycerides <200 mg/dL in participants treated with mibavademab
timeFrame: Baseline, week 20 and week 52
measure: Occurrence of fasting triglycerides <150 mg/dL in participants treated with mibavademab
timeFrame: Baseline, week 20 and week 52
measure: Concentrations of total mibavademab in serum
timeFrame: Up to week 68
measure: Incidence of anti-drug antibodies (ADAs) to mibavademab
timeFrame: Up to week 68
measure: Titer of ADAs to mibavademab
timeFrame: Up to week 68
measure: Incidence of neutralizing antibodies (Nabs) to mibavademab
timeFrame: Up to week 68
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: