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

Phase 3CompletedNCT05194124

Rhythm Pharmaceuticals, Inc.19 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Bardet-Biedl Syndrome POMC Deficiency

Interventions

Setmelanotide 2 mgDRUG

Administered as SC injection

Setmelanotide 2.5 mgDRUG

Administered as SC injection

Setmelanotide 3 mgDRUG

Administered as SC injection

Setmelanotide 20 mg

Eligibility

Sex: ALLMin age: 6 Years

Medical Language ↔ Plain English

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.

Locations (7)

Honor Health Research Institute

Scottsdale, Arizona, United States

Marshfield Clinic Research Institute

Marshfield, Wisconsin, United States

Alberta Health Services

Edmonton, Alberta, Canada

Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum

Berlin, Germany

Outcomes

Primary Outcomes

Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period

Maximum drug concentration determined directly from individual concentration-time data.

Time frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1

Cmax of Setmelanotide After QW Administration

Maximum drug concentration determined directly from individual concentration-time data. Data are reported by dose level (treatment regimen) in the OL Period and dosing sequence (QD-QD-QW or QD-QW-QW).

Time frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours postdose at Week 14

Time to Maximum Plasma Concentration (Tmax) of Setmelanotide After QD Administration in the Run-in Period

Maximum drug concentration determined directly from individual concentration-time data.

Time frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1

Tmax of Setmelanotide After QW Administration

Time frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours postdose at Week 14

Mean Trough Plasma Concentration (Ctrough) of Setmelanotide After QD or QW Administration at Week 1

Ctrough is concentration at the end of the dosing interval, prior to subsequent dose administration. Data are reported by dose level (treatment regimen) in the DB Period and dosing sequence (QD-QD-QW or QD-QW-QW).

Time frame: 30 minutes predose at Week 1

Mean Setmelanotide Ctrough After QD or QW Administration at Week 5

Data from ClinicalTrials.gov

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Administered as SC injection

Setmelanotide 25 mgDRUG

Administered as SC injection

Setmelanotide 30 mgDRUG

Administered as SC injection

Erasmus MC

Rotterdam, Netherlands

UPR Medical Sciences Campus

Rio Piedras, Puerto Rico

Addenbrooke's Hospital

Cambridge, United Kingdom

Time frame: 30 minutes predose at Week 5

Mean Setmelanotide Ctrough After QD or QW Administration at Week 9

Time frame: 30 minutes predose at Week 9

Mean Setmelanotide Ctrough After QD or QW Administration at Week 18

Time frame: 30 minutes predose at Week 18

Mean Setmelanotide Ctrough After QD or QW Administration at Week 22

Time frame: 30 minutes predose at Week 22

Mean Setmelanotide Ctrough After QD or QW Administration at Week 27

Time frame: 30 minutes predose at Week 27

Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of Setmelanotide After QD Administration in the Run-in Period

AUC0-tau was recorded from collected blood samples.

Time frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, and 8 hours postdose at Week -1

AUC0-tau of Setmelanotide After QD Administration in the Run-in Period

AUC0-tau was recorded from collected blood samples. Data are reported by dose level (treatment regimen) in the OL Period and dosing sequence (QD-QD-QW or QD-QW-QW).

Time frame: Pre-dose (0 hour) and 0.5, 1, 2, 6, 8, 12, 24, 48, 72, 96, 120, and 168-hours postdose at Week 14

Secondary Outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) is any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The AEs reported after the start of the run-in period were considered TEAEs.

Time frame: From first dose of study drug administration up to Week 30

Number of Participants With Injection Site Reactions (ISRs) From Baseline Through Week 13

The injection site evaluation included the identification of areas of erythema, edema, and induration, as well as the presence of localized pain, tenderness, and itching. Baseline was defined as the last available measurement prior to the first dose of setmelanotide or placebo. Injection site reactions frequency of once daily (QD) and once weekly (QW) were reported. Data are reported by dose level (treatment regimen) in the DB Period. Number of participants with injection site reactions according to severity were reported.

Time frame: Baseline through Week 13

Number of Participants With ISRs From Week 14 Through Week 27

The injection site evaluation included the identification of areas of erythema, edema, and induration, as well as the presence of localized pain, tenderness, and itching. Injection site reactions frequency of QD and QW were reported. Data are reported by dose level (treatment regimen) in the OL Period. Number of participants with injection site reactions according to severity were reported.

Time frame: Week 14 through Week 27