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Phase 3 N=19 Randomized Triple-blind Treatment

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

Bardet-Biedl Syndrome · POMC Deficiency

Enrolled (actual)
19
Serious AEs
0.0%
Results posted
Nov 2024
Primary outcome: Primary: Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period — 29.4; 44.8; 59.9 nanograms per milliliter (ng/mL)

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Setmelanotide 2 mg (Drug); Setmelanotide 2.5 mg (Drug); Setmelanotide 3 mg (Drug); Setmelanotide 20 mg (Drug); Setmelanotide 25 mg (Drug); Setmelanotide 30 mg (Drug)
Age
Pediatric, Adult, Older Adult · 6+ yrs
Sex
All
Sponsor
Rhythm Pharmaceuticals, Inc.
Primary completion
Oct 2023

Outcome Measures

OutcomeResultp-value
PRIMARY
Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period
29.4; 44.8; 59.9
PRIMARY
Cmax of Setmelanotide After QW Administration
22.4; 32.7; 31.8; 57.3
PRIMARY
Time to Maximum Plasma Concentration (Tmax) of Setmelanotide After QD Administration in the Run-in Period
6.91; 5.88; 6.02
PRIMARY
Tmax of Setmelanotide After QW Administration
3.93; 5.93; 1.98; 5.95
PRIMARY
Mean Trough Plasma Concentration (Ctrough) of Setmelanotide After QD or QW Administration at Week 1
5.17; 4.36; 11.7; 16.6
PRIMARY
Mean Setmelanotide Ctrough After QD or QW Administration at Week 5
9.54; 12.2; 15.6
PRIMARY
Mean Setmelanotide Ctrough After QD or QW Administration at Week 9
11.1; 6.43; 12.3; 20.1
PRIMARY
Mean Setmelanotide Ctrough After QD or QW Administration at Week 18
14.4; 12.6; 13.6; 26.2
PRIMARY
Mean Setmelanotide Ctrough After QD or QW Administration at Week 22
11.9; 14.3; 17.0; 27.9
PRIMARY
Mean Setmelanotide Ctrough After QD or QW Administration at Week 27
14.2; 9.91; 20.3; 32.1
PRIMARY
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of Setmelanotide After QD Administration in the Run-in Period
975
PRIMARY
AUC0-tau of Setmelanotide After QD Administration in the Run-in Period
1590; 2260; 2470; 5010
SECONDARY
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
0; 0; 1; 2; 1; 9
SECONDARY
Number of Participants With Injection Site Reactions (ISRs) From Baseline Through Week 13
2; 0; 7; 5; 0; 1
SECONDARY
Number of Participants With ISRs From Week 14 Through Week 27
1; 1; 13; 0; 0; 1

Summary

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

Eligibility 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 (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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05194124). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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