EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial: Multiple Independent Sub-studies of Setmelanotide in Patients With POMC/PCSK1, LEPR, NCOA1(SRC1), or SH2B1 Gene Variants in the Melanocortin-4 Receptor Pathway

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.

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