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

Primary Purpose

Bardet-Biedl Syndrome, POMC Deficiency

Status
Enrolling by invitation
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Setmelanotide 20mg weekly
Placebo daily
Setmelanotide 30mg weekly
Setmelanotide 2mg daily
Setmelanotide 3mg daily
Placebo weekly
Sponsored by
Rhythm Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bardet-Biedl Syndrome focused on measuring Melanocortin-4 Receptor Pathway, Genetic Obesity, Hunger, Hyperphagia

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 study with acceptable safety and tolerability, and dose level.
  • Patient 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:

  • 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 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.

Sites / Locations

  • Honor Health Research Institute
  • Marshfield Clinic Research Institute
  • Alberta Health Services
  • Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
  • Erasmus MC
  • UPR Medical Sciences Campus
  • Addenbrooke's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Setmelanotide subcutaneous injection Weekly 20 mg

Setmelanotide subcutaneous injection Weekly 30 mg

Setmelanotide subcutaneous injection Daily 2 mg

Setmelanotide subcutaneous injection Daily 3 mg

Placebo subcutaneous injection Daily

Placebo subcutaneous injection Weekly

Arm Description

Patients on 2mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period, and all will be assigned to this arm in the open label period.

Patients on 3mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period, and all will be assigned to this arm in the open label period.

Patients on 2mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period.

Patients on 3mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period.

Patients will be randomized 1:1 to receive either QD or QW placebo during the double blind period (and setmelanotide in the other formulation).

Patients will be randomized 1:1 to receive either QD or QW placebo during the double blind period (and setmelanotide in the other formulation).

Outcomes

Primary Outcome Measures

Maximum plasma concentration (Cmax)
Comparison of steady-state PK parameter (Cmax) between weekly and daily formulations
Time to maximum plasma concentration (Tmax)
Comparison of steady-state PK parameter (Tmax) between weekly and daily formulations
Trough plasma concentration (Ctrough)
Comparison of steady-state PK parameter (Ctrough) between weekly and daily formulations
Area under the plasma concentration-time curve over the dosing interval (AUC0-tau)
Comparison of steady-state PK parameter (AUC0-tau) between weekly and daily formulations

Secondary Outcome Measures

Number of adverse events and serious adverse events
Number of adverse events and serious adverse events throughout the trial

Full Information

First Posted
July 27, 2021
Last Updated
September 6, 2023
Sponsor
Rhythm Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05194124
Brief Title
Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Patients 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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
December 21, 2021 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rhythm Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A trial to compare the weekly and daily formulations of setmelanotide in patients 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 patients with obesity associated with biallelic or heterozygous POMC (pro-opiomelanocortin), PCSK1 (proprotein convertase subtilisin/kexin Type 1), LEPR (leptin receptor) genetic variants, and patients with Bardet-Biedl Syndrome (BBS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bardet-Biedl Syndrome, POMC Deficiency
Keywords
Melanocortin-4 Receptor Pathway, Genetic Obesity, Hunger, Hyperphagia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Setmelanotide subcutaneous injection Weekly 20 mg
Arm Type
Experimental
Arm Description
Patients on 2mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period, and all will be assigned to this arm in the open label period.
Arm Title
Setmelanotide subcutaneous injection Weekly 30 mg
Arm Type
Experimental
Arm Description
Patients on 3mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period, and all will be assigned to this arm in the open label period.
Arm Title
Setmelanotide subcutaneous injection Daily 2 mg
Arm Type
Experimental
Arm Description
Patients on 2mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period.
Arm Title
Setmelanotide subcutaneous injection Daily 3 mg
Arm Type
Experimental
Arm Description
Patients on 3mg setmelanotide daily will be randomized 1:1 to receive setmelanotide either QD or QW during the double blind period.
Arm Title
Placebo subcutaneous injection Daily
Arm Type
Placebo Comparator
Arm Description
Patients will be randomized 1:1 to receive either QD or QW placebo during the double blind period (and setmelanotide in the other formulation).
Arm Title
Placebo subcutaneous injection Weekly
Arm Type
Placebo Comparator
Arm Description
Patients will be randomized 1:1 to receive either QD or QW placebo during the double blind period (and setmelanotide in the other formulation).
Intervention Type
Drug
Intervention Name(s)
Setmelanotide 20mg weekly
Intervention Description
1:1 randomization in the double blind period, followed by open label
Intervention Type
Drug
Intervention Name(s)
Placebo daily
Intervention Description
1:1 randomization in the double blind period
Intervention Type
Drug
Intervention Name(s)
Setmelanotide 30mg weekly
Intervention Description
1:1 randomization in the double blind period, followed by open label
Intervention Type
Drug
Intervention Name(s)
Setmelanotide 2mg daily
Intervention Description
1:1 randomization in the double blind period
Intervention Type
Drug
Intervention Name(s)
Setmelanotide 3mg daily
Intervention Description
1:1 randomization in the double blind period
Intervention Type
Drug
Intervention Name(s)
Placebo weekly
Intervention Description
1:1 randomization in the double blind period
Primary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax)
Description
Comparison of steady-state PK parameter (Cmax) between weekly and daily formulations
Time Frame
27 weeks
Title
Time to maximum plasma concentration (Tmax)
Description
Comparison of steady-state PK parameter (Tmax) between weekly and daily formulations
Time Frame
27 weeks
Title
Trough plasma concentration (Ctrough)
Description
Comparison of steady-state PK parameter (Ctrough) between weekly and daily formulations
Time Frame
27 weeks
Title
Area under the plasma concentration-time curve over the dosing interval (AUC0-tau)
Description
Comparison of steady-state PK parameter (AUC0-tau) between weekly and daily formulations
Time Frame
27 weeks
Secondary Outcome Measure Information:
Title
Number of adverse events and serious adverse events
Description
Number of adverse events and serious adverse events throughout the trial
Time Frame
27 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
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 study with acceptable safety and tolerability, and dose level. Patient 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: 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Meeker, MD
Organizational Affiliation
Rhythm Pharmaceuticals, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Honor Health Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Marshfield Clinic Research Institute
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
Facility Name
Alberta Health Services
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2E1
Country
Canada
Facility Name
Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
UPR Medical Sciences Campus
City
Rio Piedras
ZIP/Postal Code
00935
Country
Puerto Rico
Facility Name
Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CA2 0QQ
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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