Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway

A Phase 3, Randomized, Double-Blind Trial of Two Formulations of Setmelanotide (Daily and Weekly) With a Crossover to Open-Label Once Weekly Setmelanotide in Patients With Specific Gene Defects in the Melanocortin-4 Receptor Pathway Who Are Currently on a Stable Dose of the Once Daily Formulation

A trial to compare the weekly and daily formulations of setmelanotide in participants with genetic defects in the melanocortin-4 receptor pathway.

This study is designed to compare the safety, pharmacokinetics, and efficacy of weekly and daily formulations of setmelanotide in participants with obesity associated with biallelic or heterozygous POMC (pro-opiomelanocortin), PCSK1 (proprotein convertase subtilisin/kexin Type 1), LEPR (leptin receptor) genetic variants, and participants with Bardet-Biedl Syndrome (BBS).

Key Inclusion Criteria:

• Biallelic or heterozygous POMC/PCSK1 or LEPR (PPL) genetic variants or Bardet-Biedl syndrome (BBS), for which they are being treated with QD setmelanotide.
• 6 years or older at screening.
• Taking the setmelanotide QD formulation for at least 6 months in the RM-493-022 (NCT03013543) study with acceptable safety and tolerability, and dose level.
• 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 is able to understand and sign the written informed consent/assent.
• Use of a highly effective form of contraception throughout the study and for 90 days following the study.

Key Exclusion Criteria:

• Glycosylated hemoglobin (HbA1C) >9.0% at screening.
• Anti-obesity medications within 3 months prior to starting the Run-in Period.
• History of significant liver disease or liver injury.
• Glomerular filtration rate <30 milliliter per minute (mL/min).
• Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.
• Major psychiatric disorders.
• Any suicidal ideation or behavior, or any lifetime history of a suicide attempt.
• Significant hypersensitivity to any excipient in the study drug.
• Inability to comply with the QW and QD injection regimens.
• Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing, with the exception of a setmelanotide clinical trial.

Other protocol defined Inclusion/Exclusion criteria may apply.