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

NCT05194124 | Completed Phase 3 Results FDA Drug

• 1 other identifier: RM-493-037
• Study Type: interventional
• Target: 19
• Locations: 6 countries
• Sites: 7

Brief Summary

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

Conditions

Bardet-Biedl Syndrome; POMC Deficiency

Keywords

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

Outcome Measures

Primary Outcomes (12)

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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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 Outcomes (3)

• Number of Participants With Treatment-Emergent Adverse Events (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

  Baseline through Week 13

• Number of Participants With ISRs From Week 14 Through Week 27

  Week 14 through Week 27

Study Arms (10)

Run-in Period: Setmelanotide 2 mg QD

EXPERIMENTAL

Participants received subcutaneous (SC) injection of 2 mg setmelanotide once daily (QD) for 1 week in the run-in period.

Drug: Setmelanotide 2 mg

Run-in Period: Setmelanotide 2.5 mg QD

EXPERIMENTAL

Participants received SC injection of 2.5 mg setmelanotide QD for 1 week in the run-in period.

Drug: Setmelanotide 2.5 mg

Run-in Period: Setmelanotide 3 mg QD

EXPERIMENTAL

Participants received SC injection of 3 mg setmelanotide QD for 1 week in the run-in period.

Drug: Setmelanotide 3 mg

DB Period: Setmelanotide 20 mg QW

EXPERIMENTAL

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

DB Period: Setmelanotide 25 mg QW

EXPERIMENTAL

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

DB Period: Setmelanotide 3 mg QD

EXPERIMENTAL

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

DB Period: Setmelanotide 30 mg QW

EXPERIMENTAL

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

OL Period: Setmelanotide 20 mg QW

EXPERIMENTAL

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

OL Period: Setmelanotide 25 mg QW

EXPERIMENTAL

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

OL Period: Setmelanotide 30 mg QW

EXPERIMENTAL

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

Interventions

Setmelanotide 2 mg DRUG

Administered as SC injection

Run-in Period: Setmelanotide 2 mg QD

Setmelanotide 25 mg DRUG

Administered as SC injection

DB Period: Setmelanotide 25 mg QW; OL Period: Setmelanotide 25 mg QW

Setmelanotide 3 mg DRUG

Administered as SC injection

DB Period: Setmelanotide 3 mg QD; Run-in Period: Setmelanotide 3 mg QD

Setmelanotide 20 mg DRUG

Administered as SC injection

DB Period: Setmelanotide 20 mg QW; OL Period: Setmelanotide 20 mg QW

Setmelanotide 30 mg DRUG

Administered as SC injection

DB Period: Setmelanotide 30 mg QW; OL Period: Setmelanotide 30 mg QW

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Biallelic or heterozygous POMC/PCSK1 or LEPR (PPL) genetic variants or Bardet-Biedl syndrome (BBS), for which they are being treated with QD setmelanotide.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead

Study Sites (7)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

Marshfield Clinic Research Institute

Marshfield, Wisconsin, 54449, United States

Location

Alberta Health Services

Edmonton, Alberta, T6G 2E1, Canada

Location

Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Erasmus MC

Rotterdam, 3015 CE, Netherlands

Location

UPR Medical Sciences Campus

Rio Piedras, 00935, Puerto Rico

Location

Addenbrooke's Hospital

Cambridge, CA2 0QQ, United Kingdom

Location

MeSH Terms

Conditions

Bardet-Biedl Syndrome; Proopiomelanocortin Deficiency; Hyperphagia

Interventions

setmelanotide

Condition Hierarchy (Ancestors)

Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Retinitis Pigmentosa; Eye Diseases, Hereditary; Eye Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Rhythm Clinical Trials
• Organization: Rhythm Pharmaceuticals, Inc.

clinicaltrials@rhythmtx.com

857-264-4280

Study Officials

• David Meeker, MD

  Rhythm Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: January 18, 2022
• Study Start: December 21, 2021
• Primary Completion: October 19, 2023
• Study Completion: October 19, 2023
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-11

Locations

US (2); DE (1); PR (1); NL (1); GB (1); CA (1)