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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

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

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).

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

NCT ID

NCT05194124

First Posted

July 27, 2021

Last Updated

September 6, 2023

Sponsor

Rhythm Pharmaceuticals, Inc.

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

Data Monitoring Committee

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

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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