Clinical trial NCT05194124: Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bardet-Biedl Syndrome
POMC Deficiency
Keywords: Melanocortin-4 Receptor Pathway
Genetic Obesity
Hunger
Hyperphagia
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-18
Enrollment: 19
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period
timeFrame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
measure: Cmax of Setmelanotide After QW Administration
timeFrame: 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
measure: Time to Maximum Plasma Concentration (Tmax) of Setmelanotide After QD Administration in the Run-in Period
timeFrame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
measure: Tmax of Setmelanotide After QW Administration
timeFrame: 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
measure: Mean Trough Plasma Concentration (Ctrough) of Setmelanotide After QD or QW Administration at Week 1
timeFrame: 30 minutes predose at Week 1
measure: Mean Setmelanotide Ctrough After QD or QW Administration at Week 5
timeFrame: 30 minutes predose at Week 5
measure: Mean Setmelanotide Ctrough After QD or QW Administration at Week 9
timeFrame: 30 minutes predose at Week 9
measure: Mean Setmelanotide Ctrough After QD or QW Administration at Week 18
timeFrame: 30 minutes predose at Week 18
measure: Mean Setmelanotide Ctrough After QD or QW Administration at Week 22
timeFrame: 30 minutes predose at Week 22
measure: Mean Setmelanotide Ctrough After QD or QW Administration at Week 27
timeFrame: 30 minutes predose at Week 27
measure: Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of Setmelanotide After QD Administration in the Run-in Period
timeFrame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, and 8 hours postdose at Week -1
measure: AUC0-tau of Setmelanotide After QD Administration in the Run-in Period
timeFrame: 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:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug administration up to Week 30
measure: Number of Participants With Injection Site Reactions (ISRs) From Baseline Through Week 13
timeFrame: Baseline through Week 13
measure: Number of Participants With ISRs From Week 14 Through Week 27
timeFrame: Week 14 through Week 27
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Marshfield
country: United States
facility: Marshfield Clinic Research Institute
state: Wisconsin
city: Edmonton
country: Canada
facility: Alberta Health Services
state: Alberta
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Rio Piedras
country: Puerto Rico
facility: UPR Medical Sciences Campus
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
Study officials:
affiliation: Rhythm Pharmaceuticals, Inc.
name: David Meeker, MD
role: STUDY_CHAIR
References: