Genetic Obesity, Obesity
Conditions
Keywords
Melanocortin-4 Receptor Pathway, Genetic Obesity, Hunger, Hyperphagia, POMC, PCSK1, LEPR, SH2B1, NCOA1 (SRC1)
Brief summary
The protocol describes a randomized, double-blind, placebo-controlled trial with independent sub-studies of setmelanotide in patients with obesity and at least one of the specific gene variants in the Melanocortin-4 Receptor pathway: * POMC or PCSK1 (Sub-study 035a) * LEPR (Sub-study 035b) * SRC1 (Sub-study 035c) * SH2B1 (Sub-study 035d) The objectives and endpoints are identical for these sub-studies.
Interventions
DRUGSetmelanotide
Subcutaneous Injection
DRUGPlacebo
Subcutaneous Injection
Sponsors
Rhythm Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have a pre-identified: * Heterozygous genetic variant in the POMC gene or PCSK1 gene * Heterozygous genetic variant in the LEPR gene * Homozygous, heterozygous, or compound heterozygous variant in the NCOA1 (SRC1) * Homozygous, heterozygous, or compound heterozygous variant in SH2B1 gene, or chromosomal 16p11.2 deletion encompassing the SH2B1 gene * Between 6 and 65 years of age at the time of provision of informed consent/assent * Obesity, defined as BMI ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and gender for patients 6 up to 17 years of age * Patient and/or parent or guardian is able to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent * Patient and/or parent or guardian reports that patient experienced childhood obesity, defined as the patient and/or parent or guardian reporting that the patient was significantly overweight during childhood * Agree to use a highly effective form of contraception throughout the study and for 90 days following the study * Reported history of lifestyle intervention of diet and exercise * Reported history of hyperphagia Key
Exclusion criteria
* Weight loss of 2% or greater in the previous 3 months * Recent history of bariatric surgery * Significant psychiatric disorder(s) * Suicidal ideation, attempt or behavior * Clinically significant pulmonary, cardiac, endocrine/metabolic, hepatic or oncologic disease * Glycated hemoglobin (HbA1C) \>10% at Screening * History of significant liver disease or severe kidney disease * History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism * Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion) * Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing * Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide * Significant hypersensitivity to any excipient in the study drug * If female, pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI | Baseline to 52 weeks |
Secondary
| Measure | Time frame |
|---|---|
| The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo | Baseline to 52 weeks |
| The difference in mean change in body weight in adult patients treated with setmelanotide compared to placebo, assessed as percent change in baseline body weight | Baseline to 52 weeks |
| The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo | Baseline to 52 weeks |
| The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo | Baseline to 52 weeks |
Countries
Canada, France, Germany, Greece, Israel, Netherlands, Puerto Rico, Spain, United Kingdom, United States
Contacts
STUDY_CHAIRDavid Meeker, MD
Rhythm Pharmaceuticals, Inc.
Outcome results
None listed