Mibavademab for obesity caused by leptin (LEP) gene mutations in children, adolescents, and adults

An Open-Label Study of Mibavademab (REGN4461), a Leptin Receptor Agonist, for the Treatment of Monogenic Obesity Due to Biallelic Loss of Function Variants of the LEP Gene

This trial will try mibavademab in children, adolescents, and adults with leptin gene–related obesity to help control body weight and check safety.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 4 (estimated)
• Ages: 2 Years and up
• Sex: All
• Sponsor: Regeneron Pharmaceuticals (Industry-sponsored)
• Drugs / interventions: mibavademab
• Locations: 1 site (Ulm)
• Trial ID: NCT07220772 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial gives mibavademab to people with biallelic loss-of-function variants in the LEP gene and class ≥2 obesity. Participants will receive mibavademab and be followed for changes in body weight, safety and side effects, blood drug levels, and whether the body develops antibodies to the drug. The protocol requires documented historical weight records and excludes recent bariatric surgery, recent significant weight loss, other genetic causes of obesity, and certain psychiatric conditions. The study is sponsored by Regeneron and conducted at Ulm University Medical Centre.

Who should consider this trial

Good fit: Ideal candidates are children, adolescents, or adults with confirmed biallelic loss-of-function LEP mutations, class ≥2 obesity, and available historical weight documentation.

Not a fit: People with other genetic causes of obesity, recent bariatric surgery, recent weight loss of ≥5%, or certain disqualifying psychiatric conditions are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, mibavademab could substantially reduce hunger and produce meaningful weight loss for people whose obesity is caused by leptin deficiency.

How similar studies have performed: Leptin-replacement approaches have previously improved hunger and weight in people with congenital leptin deficiency, though mibavademab itself is a newer therapy now in late-stage testing.

Eligibility criteria

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

Where this trial is running

Ulm

• ULM University Medical Centre — Ulm, Germany (Recruiting)

Study contacts

• Study coordinator: Clinical Trials Administrator

Conditions Monogenic Obesity; Biallelic loss of function variants of the LEP gene mutations; Leptin deficiency