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

Bardet-Biedl Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05194124
• Other study ID #: RM-493-037
• Status: Completed
• Phase: Phase 3
• Start date: December 21, 2021
• Est. completion date: October 19, 2023

Study information

• Verified date: November 2023
• Source: Rhythm Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 19, 2023
• Est. primary completion date: October 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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 study with acceptable safety and tolerability, and dose level.

• Patient 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:

• 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 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.

Related Conditions & MeSH terms

• Bardet-Biedl Syndrome

Intervention

Drug:
• Setmelanotide 20mg weekly
1:1 randomization in the double blind period, followed by open label
• Placebo daily
1:1 randomization in the double blind period
• Setmelanotide 30mg weekly
1:1 randomization in the double blind period, followed by open label
• Setmelanotide 2mg daily
1:1 randomization in the double blind period
• Setmelanotide 3mg daily
1:1 randomization in the double blind period
• Placebo weekly
1:1 randomization in the double blind period

Locations

Country	Name	City	State
Canada	Alberta Health Services	Edmonton	Alberta
Germany	Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum	Berlin
Netherlands	Erasmus MC	Rotterdam
Puerto Rico	UPR Medical Sciences Campus	Rio Piedras
United Kingdom	Addenbrooke's Hospital	Cambridge
United States	Marshfield Clinic Research Institute	Marshfield	Wisconsin
United States	Honor Health Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Rhythm Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Netherlands,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax)	Comparison of steady-state PK parameter (Cmax) between weekly and daily formulations	27 weeks
Primary	Time to maximum plasma concentration (Tmax)	Comparison of steady-state PK parameter (Tmax) between weekly and daily formulations	27 weeks
Primary	Trough plasma concentration (Ctrough)	Comparison of steady-state PK parameter (Ctrough) between weekly and daily formulations	27 weeks
Primary	Area under the plasma concentration-time curve over the dosing interval (AUC0-tau)	Comparison of steady-state PK parameter (AUC0-tau) between weekly and daily formulations	27 weeks
Secondary	Number of adverse events and serious adverse events	Number of adverse events and serious adverse events throughout the trial	27 weeks