Bardet-Biedl SyndromePhase 3NCT05194124

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

A Phase 3 study testing Setmelanotide 2 mg, Setmelanotide 2.5 mg and Setmelanotide 3 mg in people with Bardet-Biedl Syndrome and POMC Deficiency, run by Rhythm Pharmaceuticals, Inc. at 7 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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

Who is it for?: Ages 6 years and older
Conditions the study is for: Bardet-Biedl Syndrome, POMC Deficiency
What is being tested?: Setmelanotide 2 mg, Setmelanotide 2.5 mg and Setmelanotide 3 mg
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 7 sitesin 6 countries
Study dates: 21 Dec 2021to 19 Oct 2023
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 11Show fewer

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.

Trial locations and contacts

7 sites in 6 countries.

Country

City, postcode or hospital

7 sites in 6 countries

United States2 sites

Marshfield Clinic Research Institute
Marshfield, Wisconsin, 54449
Honor Health Research Institute
Scottsdale, Arizona, 85258

Other trials in United States

Canada1 site

Alberta Health Services
Edmonton, Alberta, T6G 2E1

Other trials in Canada

Germany1 site

Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
Berlin, 13353

Other trials in Germany

Netherlands1 site

Erasmus MC
Rotterdam, 3015 CE

Other trials in Netherlands

Puerto Rico1 site

UPR Medical Sciences Campus
Rio Piedras, 00935

Other trials in Puerto Rico

United Kingdom1 site

Addenbrooke's Hospital
Cambridge, CA2 0QQ

Other trials in United Kingdom

About this study

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

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

Read the 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).

Conditions: Bardet-Biedl Syndrome, POMC Deficiency
Being tested: Setmelanotide 2 mg, Setmelanotide 2.5 mg, Setmelanotide 3 mg, Setmelanotide 20 mg, Setmelanotide 25 mg
Keywords: Melanocortin-4 Receptor Pathway, Genetic Obesity, Hunger, Hyperphagia
Medical subject headings: Bardet-Biedl Syndrome, Proopiomelanocortin Deficiency, Hyperphagia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Setmelanotide 2 mgDrug
Administered as SC injection
Setmelanotide 2.5 mgDrug
Administered as SC injection
Setmelanotide 3 mgDrug
Administered as SC injection
Setmelanotide 20 mgDrug
Administered as SC injection
Setmelanotide 25 mgDrug
Administered as SC injection
Setmelanotide 30 mgDrug
Administered as SC injection

Study groups in NCT05194124
Study group	Role	What they receive
Run-in Period: Setmelanotide 2 mg QD	Experimental	Participants received subcutaneous (SC) injection of 2 mg setmelanotide once daily (QD) for 1 week in the run-in period. Receives: Drug: Setmelanotide 2 mg
Run-in Period: Setmelanotide 2.5 mg QD	Experimental	Participants received SC injection of 2.5 mg setmelanotide QD for 1 week in the run-in period. Receives: Drug: Setmelanotide 2.5 mg
Run-in Period: Setmelanotide 3 mg QD	Experimental	Participants received SC injection of 3 mg setmelanotide QD for 1 week in the run-in period. Receives: Drug: Setmelanotide 3 mg
DB Period: Setmelanotide 20 mg QW	Experimental	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. Receives: Drug: Setmelanotide 20 mg
DB Period: Setmelanotide 25 mg QW	Experimental	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. Receives: Drug: Setmelanotide 25 mg
DB Period: Setmelanotide 3 mg QD	Experimental	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. Receives: Drug: Setmelanotide 3 mg
DB Period: Setmelanotide 30 mg QW	Experimental	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. Receives: Drug: Setmelanotide 30 mg
OL Period: Setmelanotide 20 mg QW	Experimental	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. Receives: Drug: Setmelanotide 20 mg
OL Period: Setmelanotide 25 mg QW	Experimental	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. Receives: Drug: Setmelanotide 25 mg
OL Period: Setmelanotide 30 mg QW	Experimental	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. Receives: Drug: Setmelanotide 30 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period
Maximum drug concentration determined directly from individual concentration-time data.
Measured: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
Cmax of Setmelanotide After QW Administration
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).
Measured: 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
Time to Maximum Plasma Concentration (Tmax) of Setmelanotide After QD Administration in the Run-in Period
Maximum drug concentration determined directly from individual concentration-time data.
Measured: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
Tmax of Setmelanotide After QW Administration
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).
Measured: 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
Mean Trough Plasma Concentration (Ctrough) of Setmelanotide After QD or QW Administration 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).
Measured: 30 minutes predose at Week 1
Mean Setmelanotide Ctrough After QD or QW Administration 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).
Measured: 30 minutes predose at Week 5
Mean Setmelanotide Ctrough After QD or QW Administration 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).
Measured: 30 minutes predose at Week 9
Mean Setmelanotide Ctrough After QD or QW Administration 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).
Measured: 30 minutes predose at Week 18
Mean Setmelanotide Ctrough After QD or QW Administration 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).
Measured: 30 minutes predose at Week 22
Mean Setmelanotide Ctrough After QD or QW Administration 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).
Measured: 30 minutes predose at Week 27
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of Setmelanotide After QD Administration in the Run-in Period
AUC0-tau was recorded from collected blood samples.
Measured: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, and 8 hours postdose at Week -1
AUC0-tau of Setmelanotide After QD Administration in the Run-in Period
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).
Measured: 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 (3)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Measured: From first dose of study drug administration up to Week 30
Number of Participants With Injection Site Reactions (ISRs) From 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.
Measured: Baseline through Week 13
Number of Participants With ISRs From 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.
Measured: Week 14 through Week 27

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Dec 202119 Oct 2023

First posted18 Jan 2022
Study start21 Dec 2021
Primary completion19 Oct 2023
Study completion19 Oct 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Bardet-Biedl SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05194124
Sponsor's protocol ID: RM-493-037
Status last verified: Nov 2024
First submitted: 27 Jul 2021
Last updated: 26 Nov 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingEarly Phase 1
First-in-Human, Dose Escalation Trial of AXV-101 in BBS1-Related Retinal Degeneration
Bardet-Biedl Syndrome 1, Retinal Degeneration
RecruitingPhase 4
Real-World Effects of MC4R Agonist Therapy in BBS and Severe Genetic Obesity
Bardet Biedl Syndrome (BBS), Bardet Biedl Syndrome
RecruitingObservational study
ARPKD Database Study
Hepato/Renal Fibrocystic Disease, Autosomal Recessive Polycystic Kidney Disease
RecruitingObservational study
Inherited Retinal Degenerative Disease Registry
Eye Diseases Hereditary, Retinal Disease
Active, not recruitingObservational study
Early Genetic Identification of Obesity
Obesity, Childhood, Hyperphagia

All Bardet-Biedl Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05194124
Acronym / sponsor ID: RM-493-037
Conditions: Bardet-Biedl Syndrome, POMC Deficiency
Keywords: Melanocortin-4 Receptor Pathway, Genetic Obesity, Hunger, Hyperphagia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 21 Dec 2021 (actual)
Primary completion: 19 Oct 2023 (actual)
Study completion: 19 Oct 2023 (actual)
First posted: 18 Jan 2022 (actual)
Results: Posted 26 Nov 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 10

Arm	Type	Receives
Run-in Period: Setmelanotide 2 mg QD	Experimental	Drug: Setmelanotide 2 mgParticipants 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	Experimental	Drug: Setmelanotide 2.5 mgParticipants received SC injection of 2.5 mg setmelanotide QD for 1 week in the run-in period.
Run-in Period: Setmelanotide 3 mg QD	Experimental	Drug: Setmelanotide 3 mgParticipants received SC injection of 3 mg setmelanotide QD for 1 week in the run-in period.
DB Period: Setmelanotide 20 mg QW	Experimental	Drug: Setmelanotide 20 mgParticipants 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	Experimental	Drug: Setmelanotide 25 mgParticipants 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	Experimental	Drug: Setmelanotide 3 mgParticipants 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	Experimental	Drug: Setmelanotide 30 mgParticipants 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.
OL Period: Setmelanotide 20 mg QW	Experimental	Drug: Setmelanotide 20 mgParticipants 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	Experimental	Drug: Setmelanotide 25 mgParticipants 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	Experimental	Drug: Setmelanotide 30 mgParticipants 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.

Who may qualify

Ages: 6 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

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 (11 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Setmelanotide 2 mgAdministered as SC injection	Drug	Run-in Period: Setmelanotide 2 mg QD
Setmelanotide 2.5 mgAdministered as SC injection	Drug	Run-in Period: Setmelanotide 2.5 mg QD
Setmelanotide 3 mgAdministered as SC injection	Drug	DB Period: Setmelanotide 3 mg QD, Run-in Period: Setmelanotide 3 mg QD
Setmelanotide 20 mgAdministered as SC injection	Drug	DB Period: Setmelanotide 20 mg QW, OL Period: Setmelanotide 20 mg QW
Setmelanotide 25 mgAdministered as SC injection	Drug	DB Period: Setmelanotide 25 mg QW, OL Period: Setmelanotide 25 mg QW
Setmelanotide 30 mgAdministered as SC injection	Drug	DB Period: Setmelanotide 30 mg QW, OL Period: Setmelanotide 30 mg QW

Primary outcome

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.
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).
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.
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).
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).
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).
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).
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).
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).
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).
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.
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).

3 secondary outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug administration up to Week 30
Number of Participants With Injection Site Reactions (ISRs) From Baseline Through Week 13
Time frame: Baseline through Week 13
Number of Participants With ISRs From Week 14 Through Week 27
Time frame: Week 14 through Week 27

Results and safety

Results posted to the registry on 26 Nov 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Run-in Period: Setmelanotide 2 mg QD	2	2
Run-in Period: Setmelanotide 2.5 mg QD	1	1
Run-in Period: Setmelanotide 3 mg QD	16	16
DB Period: Setmelanotide 20 mg QW	0	0
DB Period: Setmelanotide 25 mg QW	0	0
DB Period: Setmelanotide 3 mg QD	0	0
DB Period: Setmelanotide 30 mg QW	0	0
OL Period: Setmelanotide 20 mg QW	0	0
OL Period: Setmelanotide 25 mg QW	0	0
OL Period: Setmelanotide 30 mg QW	0	0

Primary outcome: 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. Mean (Standard Deviation). Unit: nanograms per milliliter (ng/mL)

Measure	Setmelanotide 2 mg QD n = 2	Setmelanotide 2.5 mg QD n = 1	Setmelanotide 3 mg QD n = 16
Value	29.4 (3.49)	44.8	59.9 (29.6)

Population analysed: Participants in the Pharmacokinetic Analysis Set (PKAS) (all participants who received at least 1 dose of setmelanotide and who had a sufficient number of measurable plasma concentrations to permit assessment of noncompartmental parameters) with available data were analyzed.

Primary outcome: 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. Mean (Standard Deviation). Unit: ng/mL

Measure	Setmelanotide 20 mg QW (QD-QW-QW) n = 1	Setmelanotide 25 mg QW (QD-QW-QW) n = 1	Setmelanotide 30 mg QW (QD-QD-QW) n = 7	Setmelanotide 30 mg QW (QD-QW-QW) n = 7
Value	22.4	32.7	31.8 (28.6)	57.3 (33.0)

Population analysed: Participants in the PKAS with available data were analyzed.

Primary outcome: 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. Median (Full Range). Unit: hours

Measure	Setmelanotide 2 mg QD n = 2	Setmelanotide 2.5 mg QD n = 1	Setmelanotide 3 mg QD n = 16
Value	6.91 (5.92 to 7.90)	5.88	6.02 (2.00 to 8.00)

Population analysed: Participants in the PKAS with available data were analyzed.

Primary outcome: 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. Median (Full Range). Unit: hours

Measure	Setmelanotide 20 mg QW (QD-QW-QW) n = 1	Setmelanotide 25 mg QW (QD-QW-QW) n = 1	Setmelanotide 30 mg QW (QD-QD-QW) n = 7	Setmelanotide 30 mg QW (QD-QW-QW) n = 7
Value	3.93	5.93	1.98 (0.500 to 6.00)	5.95 (2.03 to 6.03)

Population analysed: Participants in the PKAS with available data were analyzed.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of study drug administration up to week 30. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Run-in Period: Setmelanotide 2 mg QD	0 of 2 (0%)	0 of 2 (0%)	0 of 2
Run-in Period: Setmelanotide 2.5 mg QD	0 of 1 (0%)	0 of 1 (0%)	0 of 1
Run-in Period: Setmelanotide 3 mg QD	0 of 16 (0%)	1 of 16 (6.3%)	0 of 16
DB Period: Setmelanotide 20 mg QW	0 of 2 (0%)	2 of 2 (100%)	0 of 2
DB Period: Setmelanotide 25 mg QW	0 of 1 (0%)	1 of 1 (100%)	0 of 1
DB Period: Setmelanotide 3 mg QD	0 of 9 (0%)	9 of 9 (100%)	0 of 9
DB Period: Setmelanotide 30 mg QW	0 of 7 (0%)	6 of 7 (85.7%)	0 of 7
OL Period: Setmelanotide 20 mg QW	0 of 1 (0%)	0 of 1 (0%)	0 of 1
OL Period: Setmelanotide 25 mg QW	0 of 1 (0%)	1 of 1 (100%)	0 of 1
OL Period: Setmelanotide 30 mg QW	0 of 14 (0%)	10 of 14 (71.4%)	0 of 14

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Bardet-Biedl Syndrome

RecruitingEarly Phase 1
First-in-Human, Dose Escalation Trial of AXV-101 in BBS1-Related Retinal Degeneration
Bardet-Biedl Syndrome 1, Retinal Degeneration
RecruitingPhase 4
Real-World Effects of MC4R Agonist Therapy in BBS and Severe Genetic Obesity
Bardet Biedl Syndrome (BBS), Bardet Biedl Syndrome
RecruitingObservational study
ARPKD Database Study
Hepato/Renal Fibrocystic Disease, Autosomal Recessive Polycystic Kidney Disease
RecruitingObservational study
Inherited Retinal Degenerative Disease Registry
Eye Diseases Hereditary, Retinal Disease
Active, not recruitingObservational study
Early Genetic Identification of Obesity
Obesity, Childhood, Hyperphagia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Meeker, MD study chair

Rhythm Pharmaceuticals, Inc.

7 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Canada, Germany, Netherlands, Puerto Rico and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05194124.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2024.