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Completed

NCT Number: NCT05194124

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

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

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Key information

Conditions

Bardet-Biedl Syndrome Abnormalities, Multiple Brain Diseases Central Nervous System Diseases Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Eye Diseases Eye Diseases, Hereditary Genetic Diseases, Inborn Hyperphagia Hypothalamic Diseases Nervous System Diseases POMC Deficiency Pathological Conditions, Signs and Symptoms Proopiomelanocortin Deficiency Retinitis Pigmentosa Signs and Symptoms Signs and Symptoms, Digestive

Age range

6 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Alberta Health Services, Edmonton, Alberta, Canada

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Setmelanotide 2 mg

Drug

Administered as SC injection

Setmelanotide 2.5 mg

Drug

Administered as SC injection

Setmelanotide 3 mg

Drug

Administered as SC injection

Setmelanotide 20 mg

Drug

Administered as SC injection

Setmelanotide 25 mg

Drug

Administered as SC injection

Setmelanotide 30 mg

Drug

Administered as SC injection

Primary outcomes

  1. 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.

  2. 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).

  3. 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.

  4. 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).

  5. 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).

  6. 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).

  7. 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).

  8. 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).

  9. 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).

  10. 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).

  11. 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.

  12. 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).

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

Sponsors and collaborators

Lead sponsor

Rhythm Pharmaceuticals, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Jan 18, 2022
Registry last updated
Nov 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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