An Observational,Prospective Natural History Study of Early-Onset Extreme Obesity Due to Bi-Allelic Loss-of-Function Mutations in the POMC, PCSK1 or LEPR Genes (NHS)

Rhythm Pharmaceuticals

Status: Completed

Conditions: PCSK1 Deficiency Obesity; POMC Deficiency Obesity; LEPR Deficiency Obesity

Study type: Observational

Funder types: Industry

Identifiers

NCT03621007

RM-493-016

Details and patient eligibility

About

This is an observational study. There are no protocol-defined visits, although patients are expected to have routine office visits approximately every 6 months. Upon signing of informed consent/assent and study enrollment, historical data will be abstracted from the patient's medical chart. The patient will then be observed prospectively for up to 5 years, with additional data collected from routine healthcare encounters and direct-to-patient questionnaires (where local laws allow), including laboratory tests, physical exam and patient reported outcomes/quality of life measures. Patients will be consented/assented to provide blood samples for biomarker assessments, DNA sequencing and archiving.

Enrollment: 8 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 2 years or older
2. Study participant and/or parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and be able to understand and sign the written informed consent/assent.
3. Have documented results of DNA sequencing for the three genes of interest: POMC, PCSK1 and LEPR.
4. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on each allele) genetic status for either the POMC or PCSK1 genes, resulting in a severe POMC deficiency obesity clinical phenotype, or a similar bi-allelic gene status for the LEPR gene leading to identified LEPR deficiency obesity.
5. Patients who are willing to come in for routine office visits approximately every 6 months.

Exclusion criteria

1. Participation within the past 3 months in a clinical trial of any investigational medicine for obesity.
2. Confirmed diagnosis of Prader-Willi syndrome, Bardet-Biedl syndrome, Alström syndrome, or other syndromic form of genetic obesity.

Trial design

8 participants in 3 patient groups

POMC deficiency obesity

LEPR deficiency obesity

PCSK1 deficiency obesity