A Study Evaluating Mibavademab Treatment of Obesity Due to Leptin (LEP) Gene Mutations in Children, Adolescents and Adults

• Mibavademab (Drug), also known as REGN4461: Administered as per the protocol

Primary outcomes

• Percent change in Body Mass Index (BMI) [Baseline to Week 24]

Secondary outcomes

• Percent change in BMI [Baseline to Week 52]
• Absolute change in BMI [Baseline, Through Week 52]
• Percent change in body weight [Baseline, Through Week 52]
• Absolute change in body weight [Baseline, Through Week 52]
• Change in waist circumference [Baseline, Through Week 52]: Participants aged ≥18 years
• Change in absolute total fat mass by whole body DXA [Baseline, Through Week 52]
• Change in percent total fat mass by whole body DXA [Baseline, Through Week 52]
• Change in absolute regional fat mass by whole body DXA [Baseline, Through Week 52]
• Change in percent regional fat mass by whole body DXA [Baseline, Through Week 52]
• Change in scores in the symptoms of hyperphagia questionnaire [Baseline, Through Week 52]: Symptoms of Hyperphagia - Caregiver Version© is completed by a caregiver. Symptoms of Hyperphagia - Patient Version© is completed by the participants who are aged <12 years or for participants who are unable to self-complete. The questionnaires both assesses the frequency of hunger symptoms on a categorical scale (Never, 1 or 2 times, 3 or more times) over the past 24 hours and are scored combining the total scores across the items. Higher scores indicate greater severity.
• Change in scores in the impacts of hyperphagia questionnaire [Baseline, Through Week 52]: For participants who are aged <12 years or for participants who are unable to self-complete, the Impacts of Hyperphagia - Caregiver Version© is completed by a caregiver. For participants aged ≥12 years who are able to self-report, the Impacts of Hyperphagia - Patient Version© is completed by the participant. Both questionnaires assess the impact of hyperphagia on a categorical scale (range: not at all, a little, moderately, a great deal). The participant version is scored using a total score across the 5 items. The caregiver version is scored separately for each section. Higher scores indicate a greater impact of hyperphagia.
• Change in scores in the hunger questionnaire [Baseline, Through Week 52]: The Daily Hunger Assessment is a daily, single item measuring hunger for participants aged ≥12 years who are able to self-complete, participants are asked to rate their highest level of hunger over for the day, where "0" is "not hungry at all" to "10" the hungriest possible."
• Number of treatment-emergent adverse events (TEAEs) [Through Week 65]
• Severity of TEAEs [Through Week 65]
• Concentrations of total mibavademab in serum [Through Week 65]
• Incidence of anti-drug antibody (ADA) to mibavademab [Through Week 65]
• Titer of ADA to mibavademab [Through Week 65]

Sex: All, ages: 2 Years to any

Key Inclusion Criteria:

1. Has documented medical history of biallelic loss of function variants of the LEP gene prior to the screening visit
2. Has class ≥2 obesity at screening and at baseline, as defined in the protocol

Key Exclusion Criteria:

1. Unwilling or unable to provide, or have the treating physician provide, documented historical weight for at least 6 months prior to screening
2. History of bariatric surgery within approximately the past 12 months of study screening
3. History of weight loss of ≥5% of body weight in approximately the past 3 months of study screening
4. History of genetic causes of obesity other than/in addition to biallelic loss of function variants of the LEP gene
5. History of schizophrenia, bipolar disorder, or other mental illness that, in the opinion of the investigator, might pose a safety risk to participation in a clinical study of an investigational drug
6. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) during screening or baseline, or any lifetime history of a suicide attempt, or any lifetime history of suicidal behavior, including ideation
7. Treatment with medications for weight loss or medications with known side effects of weight loss within the past approximately 3 months of study screening
8. Participants currently being treated with metreleptin, or a history of prior treatment with metreleptin as defined in the protocol

NOTE: Other Protocol-defined Inclusion/Exclusion Criteria Apply

• Clinical Trial Management, Study director, Regeneron Pharmaceuticals