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

• ClinicalTrials.gov Identifier: NCT05194124
• Recruitment Status: Enrolling by invitation
• First Posted: January 18, 2022
• Last Update Posted: December 28, 2022
• Sponsor: Rhythm Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Rhythm Pharmaceuticals, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Bardet-Biedl Syndrome; POMC Deficiency	Drug: Setmelanotide 20mg weekly; Drug: Placebo daily; Drug: Setmelanotide 30mg weekly; Drug: Setmelanotide 2mg daily; Drug: Setmelanotide 3mg daily; Drug: Placebo weekly	Phase 3

Detailed 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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 21, 2021
• Estimated Primary Completion Date: August 20, 2023
• Estimated Study Completion Date: August 20, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Setmelanotide subcutaneous injection Weekly 20 mg; Patients on 2mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period, and all will be assigned to this arm in the open label period.	Drug: Setmelanotide 20mg weekly; 1:1 randomization in the double blind period, followed by open label
Experimental: Setmelanotide subcutaneous injection Weekly 30 mg; Patients on 3mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period, and all will be assigned to this arm in the open label period.	Drug: Setmelanotide 30mg weekly; 1:1 randomization in the double blind period, followed by open label
Experimental: Setmelanotide subcutaneous injection Daily 2 mg; Patients on 2mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period.	Drug: Setmelanotide 2mg daily; 1:1 randomization in the double blind period
Experimental: Setmelanotide subcutaneous injection Daily 3 mg; Patients on 3mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period.	Drug: Setmelanotide 3mg daily; 1:1 randomization in the double blind period
Placebo Comparator: Placebo subcutaneous injection Daily; Patients will be randomized 1:1 to receive either QD or QW placebo during the double blind period (and setmelanotide in the other formulation).	Drug: Placebo daily; 1:1 randomization in the double blind period
Placebo Comparator: Placebo subcutaneous injection Weekly; Patients will be randomized 1:1 to receive either QD or QW placebo during the double blind period (and setmelanotide in the other formulation).	Drug: Placebo weekly; 1:1 randomization in the double blind period

Outcome Measures

Primary Outcome Measures :

1. Maximum plasma concentration (Cmax) [ Time Frame: 27 weeks ]
   Comparison of steady-state PK parameter (Cmax) between weekly and daily formulations
2. Time to maximum plasma concentration (Tmax) [ Time Frame: 27 weeks ]
   Comparison of steady-state PK parameter (Tmax) between weekly and daily formulations
3. Trough plasma concentration (Ctrough) [ Time Frame: 27 weeks ]
   Comparison of steady-state PK parameter (Ctrough) between weekly and daily formulations
4. Area under the plasma concentration-time curve over the dosing interval (AUC0-tau) [ Time Frame: 27 weeks ]
   Comparison of steady-state PK parameter (AUC0-tau) between weekly and daily formulations

Secondary Outcome Measures :

1. Number of adverse events and serious adverse events [ Time Frame: 27 weeks ]
   Number of adverse events and serious adverse events throughout the trial

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Honor Health Research Institute

Scottsdale, Arizona, United States, 85258

United States, Wisconsin

Marshfield Clinic Research Institute

Marshfield, Wisconsin, United States, 54449

Canada, Alberta

Alberta Health Services

Edmonton, Alberta, Canada, T6G 2E1

Germany

Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum

Berlin, Germany, 13353

Netherlands

Erasmus MC

Rotterdam, Netherlands, 3015 CE

Puerto Rico

UPR Medical Sciences Campus

Rio Piedras, Puerto Rico, 00935

United Kingdom

Addenbrooke's Hospital

Cambridge, United Kingdom, CA2 0QQ

Sponsors and Collaborators

Rhythm Pharmaceuticals, Inc.

Investigators

• Study Chair: David Meeker, MD; Rhythm Pharmaceuticals, Inc.

More Information

• Responsible Party: Rhythm Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT05194124
• Other Study ID Numbers: RM-493-037
• First Posted: January 18, 2022
• Last Update Posted: December 28, 2022
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rhythm Pharmaceuticals, Inc.:

Melanocortin-4 Receptor Pathway; Genetic Obesity; Hunger; Hyperphagia

Additional relevant MeSH terms:

Bardet-Biedl Syndrome; Laurence-Moon Syndrome; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Retinitis Pigmentosa; Eye Diseases, Hereditary; Eye Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Genetic Diseases, Inborn; alpha-MSH; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs