Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

NCTNCT05194124Other idRM-493-037

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Overview

Status: Completed
Phase: Phase 3
Enrollment: 19 participants (actual)
Sponsor: Rhythm Pharmaceuticals, Inc. · Industry
Design: Randomized · Triple masking
Countries: 6 countries
United States, Canada, Germany, Netherlands, Puerto Rico, United Kingdom
Start: 21 Dec 2021
Primary completion: 19 Oct 2023
Completion: 19 Oct 2023
First posted: 18 Jan 2022
Last update posted: 26 Nov 2024
Conditions: Bardet-Biedl Syndrome · POMC Deficiency

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2021202220232024

Ph 3
Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
NCT05194124
21 Dec 2021 to 19 Oct 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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

Interventions

Setmelanotide 2 mgDrug
Setmelanotide 2.5 mgDrug
Setmelanotide 3 mgDrug
Setmelanotide 20 mgDrug
Setmelanotide 25 mgDrug
Setmelanotide 30 mgDrug

Arms10

Experimental
Run-in Period: Setmelanotide 2 mg QD
Participants received subcutaneous (SC) injection of 2 mg setmelanotide once daily (QD) for 1 week in the run-in period.
Experimental
Run-in Period: Setmelanotide 2.5 mg QD
Participants received SC injection of 2.5 mg setmelanotide QD for 1 week in the run-in period.
Experimental
Run-in Period: Setmelanotide 3 mg QD
Participants received SC injection of 3 mg setmelanotide QD for 1 week in the run-in period.
Experimental
DB Period: Setmelanotide 20 mg QW
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.
Experimental
DB Period: Setmelanotide 25 mg QW
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.
Experimental
DB Period: Setmelanotide 3 mg QD
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.
Experimental
DB Period: Setmelanotide 30 mg QW
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.
Experimental
OL Period: Setmelanotide 20 mg QW
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.
Experimental
OL Period: Setmelanotide 25 mg QW
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.
Experimental
OL Period: Setmelanotide 30 mg QW
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.

Primary outcomes12

Outcomes the sponsor listed as primary.

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
Registry description
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
Registry description
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
Registry description
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
Registry description
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
Registry description
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
Registry description
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
Registry description
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
Registry description
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
Registry description
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
Registry description
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
Registry description
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
Registry description
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(3)

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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 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 (Cmax) of Setmelanotide After QD Administration in the Run-in Period

Group	Value (nanograms per milliliter (ng/mL))	Spread
Setmelanotide 2 mg QD	29.4	3.49
Setmelanotide 2.5 mg QD	44.8	–
Setmelanotide 3 mg QD	59.9	29.6

Primary outcomeMean· 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

Cmax of Setmelanotide After QW Administration

Group	Value (ng/mL)	Spread
Setmelanotide 20 mg QW (QD-QW-QW)	22.4	–
Setmelanotide 25 mg QW (QD-QW-QW)	32.7	–
Setmelanotide 30 mg QW (QD-QD-QW)	31.8	28.6
Setmelanotide 30 mg QW (QD-QW-QW)	57.3	33.0

Primary outcomeMedian· Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1

Time to Maximum Plasma Concentration (Tmax) of Setmelanotide After QD Administration in the Run-in Period

Group	Value (hours)
Setmelanotide 2 mg QD	6.91
Setmelanotide 2.5 mg QD	5.88
Setmelanotide 3 mg QD	6.02

Primary outcomeMedian· 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

Tmax of Setmelanotide After QW Administration

Group	Value (hours)
Setmelanotide 20 mg QW (QD-QW-QW)	3.93
Setmelanotide 25 mg QW (QD-QW-QW)	5.93
Setmelanotide 30 mg QW (QD-QD-QW)	1.98
Setmelanotide 30 mg QW (QD-QW-QW)	5.95

Primary outcomeMean· 30 minutes predose at Week 1

Mean Trough Plasma Concentration (Ctrough) of Setmelanotide After QD or QW Administration at Week 1

Group	Value (ng/mL)	Spread
Setmelanotide 20 mg QW (QD-QW-QW)	5.17	0.856
Setmelanotide 25 mg QW (QD-QW-QW)	4.36	–
Setmelanotide 3 mg QD (QD-QD-QW)	11.7	13.5
Setmelanotide 30 mg QW (QD-QW-QW)	16.6	16.3

Primary outcomeMean· 30 minutes predose at Week 5

Mean Setmelanotide Ctrough After QD or QW Administration at Week 5

Group	Value (ng/mL)	Spread
Setmelanotide 20 mg QW (QD-QW-QW)	not posted	–
Setmelanotide 25 mg QW (QD-QW-QW)	9.54	–
Setmelanotide 3 mg QD (QD-QD-QW)	12.2	7.62
Setmelanotide 30 mg QW (QD-QW-QW)	15.6	13.3

Primary outcomeMean· 30 minutes predose at Week 9

Mean Setmelanotide Ctrough After QD or QW Administration at Week 9

Group	Value (ng/mL)	Spread
Setmelanotide 20 mg QW (QD-QW-QW)	11.1	–
Setmelanotide 25 mg QW (QD-QW-QW)	6.43	–
Setmelanotide 3 mg QD (QD-QD-QW)	12.3	11.4
Setmelanotide 30 mg QW (QD-QW-QW)	20.1	13.7

Primary outcomeMean· 30 minutes predose at Week 18

Mean Setmelanotide Ctrough After QD or QW Administration at Week 18

Group	Value (ng/mL)	Spread
Setmelanotide 20 mg QW (QD-QW-QW)	14.4	–
Setmelanotide 25 mg QW (QD-QW-QW)	12.6	–
Setmelanotide 3 mg QD (QD-QD-QW)	13.6	13.9
Setmelanotide 30 mg QW (QD-QW-QW)	26.2	23.8

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Run-in Period: Setmelanotide 2 mg QDParticipants received SC injection of 2 mg setmelanotide QD for 1 week in the run-in period.	0 / 2	0 / 2	0 / 2
Run-in Period: Setmelanotide 2.5 mg QDParticipants received SC injection of 2.5 mg setmelanotide QD for 1 week in the run-in period.	0 / 1	0 / 1	0 / 1
Run-in Period: Setmelanotide 3 mg QDParticipants received SC injection of 3 mg setmelanotide QD for 1 week in the run-in period.	0 / 16	0 / 16	1 / 16
DB Period: Setmelanotide 20 mg QWParticipants who received 2 mg setmelanotide QD in the run-in period, received SC injection of 20 mg setmelanotide QW and placebo matched to setmelanotide QD for 13 weeks in the DB period.	0 / 2	0 / 2	2 / 2
DB Period: Setmelanotide 25 mg QWParticipants 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.	0 / 1	0 / 1	1 / 1
DB Period: Setmelanotide 3 mg QDParticipants 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.	0 / 9	0 / 9	9 / 9
DB Period: Setmelanotide 30 mg QWParticipants 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.	0 / 7	0 / 7	6 / 7
OL Period: Setmelanotide 20 mg QWParticipants 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.	0 / 1	0 / 1	0 / 1
OL Period: Setmelanotide 25 mg QWParticipants 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.	0 / 1	0 / 1	1 / 1
OL Period: Setmelanotide 30 mg QWParticipants who received 3 setmelanotide QD in the run-in period and 30 mg setmelanotide QD or QW in the DB period, received SC injection of 30 mg setmelanotide QW for 13 weeks in the OL period.	0 / 14	0 / 14	10 / 14

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: All
Age: from 6 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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.

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