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

November 15, 2024 updated by: Rhythm Pharmaceuticals, Inc.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
19

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2E1
        • Alberta Health services
  • Germany
      • Berlin, Germany, 13353
        • Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
  • Netherlands
      • Rotterdam, Netherlands, 3015 CE
        • Erasmus MC
  • Puerto Rico
      • Rio Piedras, Puerto Rico, 00935
        • UPR Medical Sciences Campus
  • United Kingdom
      • Cambridge, United Kingdom, CA2 0QQ
        • Addenbrooke's Hospital
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Honor Health Research Institute
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Run-in Period: Setmelanotide 2 mg QD
Participants received subcutaneous (SC) injection of 2 mg setmelanotide once daily (QD) for 1 week in the run-in period.
Drug: Setmelanotide 2 mg
Administered as SC injection
Experimental: Run-in Period: Setmelanotide 2.5 mg QD
Participants received SC injection of 2.5 mg setmelanotide QD for 1 week in the run-in period.
Drug: Setmelanotide 2.5 mg
Administered as SC injection
Experimental: Run-in Period: Setmelanotide 3 mg QD
Participants received SC injection of 3 mg setmelanotide QD for 1 week in the run-in period.
Drug: Setmelanotide 3 mg
Administered as SC injection
Experimental: DB Period: Setmelanotide 20 mg QW
Participants who received 2 mg setmelanotide QD in the run-in period, received SC injection of 20 mg setmelanotide once weekly (QW) and placebo matched to setmelanotide QD for 13 weeks in the DB period.
Drug: Setmelanotide 20 mg
Administered as SC injection
Experimental: DB Period: Setmelanotide 25 mg QW
Participants who received 2.5 mg setmelanotide QD in the run-in period, received SC injection of 25 mg setmelanotide QW and placebo matched to setmelanotide QD for 13 weeks in the DB period.
Drug: Setmelanotide 25 mg
Administered as SC injection
Experimental: DB Period: Setmelanotide 3 mg QD
Participants who received 3 mg setmelanotide QD in the run-in period, received SC injection of 3 mg setmelanotide QD and placebo matched to setmelanotide QW for 13 weeks in the DB period.
Drug: Setmelanotide 3 mg
Administered as SC injection
Experimental: DB Period: Setmelanotide 30 mg QW
Participants who received 3 mg setmelanotide QD in the run-in period, received SC injection of 30 mg setmelanotide QW and placebo matched to setmelanotide QD for 13 weeks in the DB period.
Drug: Setmelanotide 30 mg
Administered as SC injection
Experimental: OL Period: Setmelanotide 20 mg QW
Participants who received 2 mg setmelanotide QD in the run-in period and 20 mg setmelanotide QW in the DB period, received SC injection of 20 mg setmelanotide QW for 13 weeks in the OL period.
Drug: Setmelanotide 20 mg
Administered as SC injection
Experimental: OL Period: Setmelanotide 25 mg QW
Participants who received 2.5 mg setmelanotide QD in the run-in period and 25 mg setmelanotide QW in the DB period, received SC injection of 25 mg setmelanotide QW for 13 weeks in the OL period.
Drug: Setmelanotide 25 mg
Administered as SC injection
Experimental: OL Period: Setmelanotide 30 mg QW
Participants who received 3 setmelanotide QD in the run-in period and 3 mg setmelanotide QD or 30 mg setmelanotide QW in the DB period, received SC injection of 30 mg setmelanotide QW for 13 weeks in the OL period.
Drug: Setmelanotide 30 mg
Administered as SC injection

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period
Time Frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
Maximum drug concentration determined directly from individual concentration-time data.
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
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
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).
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
Time Frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
Maximum drug concentration determined directly from individual concentration-time data.
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
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).
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
Time Frame: 30 minutes predose 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).
30 minutes predose at Week 1
Mean Setmelanotide Ctrough After QD or QW Administration at Week 5
Time Frame: 30 minutes predose at Week 5
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).
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
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).
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
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).
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
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).
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
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).
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
Time Frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, and 8 hours postdose at Week -1
AUC0-tau was recorded from collected blood samples.
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
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
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).
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From first dose of study drug administration up to Week 30
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.
From first dose of study drug administration up to Week 30
Number of Participants With Injection Site Reactions (ISRs) From Baseline Through Week 13
Time Frame: 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.
Baseline through Week 13
Number of Participants With ISRs From Week 14 Through Week 27
Time Frame: 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.
Week 14 through Week 27

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Rhythm Pharmaceuticals, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: David Meeker, MD, Rhythm Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 21, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 19, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 19, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 27, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 18, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RM-493-037

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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