Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
- Conditions
- Bardet-Biedl SyndromePOMC Deficiency
- Interventions
- Registration Number
- NCT05194124
- Lead Sponsor
- Rhythm Pharmaceuticals, Inc.
- Brief Summary
A trial to compare the weekly and daily formulations of setmelanotide in participants with genetic defects in the melanocortin-4 receptor pathway.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description OL Period: Setmelanotide 20 mg QW Setmelanotide 20 mg 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. OL Period: Setmelanotide 25 mg QW Setmelanotide 25 mg 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. OL Period: Setmelanotide 30 mg QW Setmelanotide 30 mg 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. DB Period: Setmelanotide 20 mg QW Setmelanotide 20 mg 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. DB Period: Setmelanotide 25 mg QW Setmelanotide 25 mg 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. DB Period: Setmelanotide 3 mg QD Setmelanotide 3 mg 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. DB Period: Setmelanotide 30 mg QW Setmelanotide 30 mg 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. Run-in Period: Setmelanotide 2 mg QD Setmelanotide 2 mg Participants received subcutaneous (SC) injection of 2 mg setmelanotide once daily (QD) for 1 week in the run-in period. Run-in Period: Setmelanotide 2.5 mg QD Setmelanotide 2.5 mg Participants received SC injection of 2.5 mg setmelanotide QD for 1 week in the run-in period. Run-in Period: Setmelanotide 3 mg QD Setmelanotide 3 mg Participants received SC injection of 3 mg setmelanotide QD for 1 week in the run-in period.
- Primary Outcome Measures
Name Time Method Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period 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.
Cmax of Setmelanotide After QW Administration 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).
Time to Maximum Plasma Concentration (Tmax) of Setmelanotide After QD Administration in the Run-in Period 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.
Tmax of Setmelanotide After QW Administration 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).
Mean Trough Plasma Concentration (Ctrough) of Setmelanotide After QD or QW Administration at Week 1 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).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 5 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).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 18 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).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 22 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).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 9 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).
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of Setmelanotide After QD Administration in the Run-in Period 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.
AUC0-tau of Setmelanotide After QD Administration in the Run-in Period 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).
Mean Setmelanotide Ctrough After QD or QW Administration at Week 27 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).
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) 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.
Number of Participants With Injection Site Reactions (ISRs) From Baseline Through Week 13 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.
Number of Participants With ISRs From Week 14 Through Week 27 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.
Trial Locations
- Locations (7)
UPR Medical Sciences Campus
🇵🇷Rio Piedras, Puerto Rico
Erasmus MC
🇳🇱Rotterdam, Netherlands
Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Alberta Health Services
🇨🇦Edmonton, Alberta, Canada
Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Marshfield Clinic Research Institute
🇺🇸Marshfield, Wisconsin, United States