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CompletedNCT05194124Updated Nov 26, 2024Results posted

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

A Phase 3 interventional study of Setmelanotide 2 mg and Setmelanotide 2.5 mg in Bardet-Biedl Syndrome and POMC Deficiency, sponsored by Rhythm Pharmaceuticals, Inc.. Completed at 7 sites in 6 countries. Open to participants aged 6 Years and older. Per ClinicalTrials.gov, last updated 2024-11-26.

Sponsored by Rhythm Pharmaceuticals, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
19
Allocation
Randomized
Ages
6 Years and older
Sex
All
01

Study summary

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).

02

Conditions studied

  • Bardet-Biedl Syndrome
  • POMC Deficiency

Keywords

  • Melanocortin-4 Receptor Pathway
  • Genetic Obesity
  • Hunger
  • Hyperphagia
03

In context

Lead sponsor

Rhythm Pharmaceuticals, Inc. is the lead sponsor of 28 studies on the registry; 3 are open to participants now.

Of its 18 completed or terminated interventional studies of FDA-regulated products, 12 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Years and older
Sexes eligible
All
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 (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.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
19 participants (actual)

Study arms

  • 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.

    Drug: Setmelanotide 2 mg

  • 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.

    Drug: Setmelanotide 2.5 mg

  • 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.

    Drug: Setmelanotide 3 mg

  • 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.

    Drug: Setmelanotide 20 mg

  • 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.

    Drug: Setmelanotide 25 mg

  • 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.

    Drug: Setmelanotide 3 mg

  • 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.

    Drug: Setmelanotide 30 mg

  • 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.

    Drug: Setmelanotide 20 mg

  • 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.

    Drug: Setmelanotide 25 mg

  • 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.

    Drug: Setmelanotide 30 mg

Interventions

  • DrugSetmelanotide 2 mg

    Administered as SC injection

  • DrugSetmelanotide 2.5 mg

    Administered as SC injection

  • DrugSetmelanotide 3 mg

    Administered as SC injection

  • DrugSetmelanotide 20 mg

    Administered as SC injection

  • DrugSetmelanotide 25 mg

    Administered as SC injection

  • DrugSetmelanotide 30 mg

    Administered as SC injection

06

What researchers measure

Primary outcomes

  1. Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period

    Maximum drug concentration determined directly from individual concentration-time data.

    Time frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1

  2. 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).

    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

  3. 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.

    Time frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1

  4. 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).

    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

  5. 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).

    Time frame: 30 minutes predose at Week 1

  6. 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).

    Time frame: 30 minutes predose at Week 5

  7. 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).

    Time frame: 30 minutes predose at Week 9

  8. 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).

    Time frame: 30 minutes predose at Week 18

  9. 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).

    Time frame: 30 minutes predose at Week 22

  10. 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).

    Time frame: 30 minutes predose at Week 27

  11. 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.

    Time frame: Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, and 8 hours postdose at Week -1

  12. 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).

    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

Secondary outcomes

  1. 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.

    Time frame: From first dose of study drug administration up to Week 30

  2. 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.

    Time frame: Baseline through Week 13

  3. 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.

    Time frame: Week 14 through Week 27

07

Results

Posted Nov 26, 2024

Participant flow

Run-in Period (1 Week)
Participant flow — Run-in Period (1 Week)
MilestoneRun-in Period: Setmelanotide 2 mg QDRun-in Period: Setmelanotide 2.5 mg QDRun-in Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 20 mg QWDB Period: Setmelanotide 25 mg QWDB Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 30 mg QWOL Period: Setmelanotide 20 mg QWOL Period: Setmelanotide 25 mg QWOL Period: Setmelanotide 30 mg QW
Started21160000000
Completed21160000000
Not completed0000000000
Double Blind (DB) Period (13 Weeks)
Participant flow — Double Blind (DB) Period (13 Weeks)
MilestoneRun-in Period: Setmelanotide 2 mg QDRun-in Period: Setmelanotide 2.5 mg QDRun-in Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 20 mg QWDB Period: Setmelanotide 25 mg QWDB Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 30 mg QWOL Period: Setmelanotide 20 mg QWOL Period: Setmelanotide 25 mg QWOL Period: Setmelanotide 30 mg QW
Started0002197000
Completed0001177000
Not completed0001020000
Withdrew: Withdrawal by parent/guardian0001020000
Open Label (OL) Period (13 Weeks)
Participant flow — Open Label (OL) Period (13 Weeks)
MilestoneRun-in Period: Setmelanotide 2 mg QDRun-in Period: Setmelanotide 2.5 mg QDRun-in Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 20 mg QWDB Period: Setmelanotide 25 mg QWDB Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 30 mg QWOL Period: Setmelanotide 20 mg QWOL Period: Setmelanotide 25 mg QWOL Period: Setmelanotide 30 mg QW
Started00000001114
Completed00000001113
Not completed0000000001
Withdrew: Lack of efficacy0000000001

Outcome measures

PrimaryMaximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period

Maximum drug concentration determined directly from individual concentration-time data.

Time frame:
Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
Reported as:
Mean · nanograms per milliliter (ng/mL)
Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period
nanograms per milliliter (ng/mL)Setmelanotide 2 mg QDSetmelanotide 2.5 mg QDSetmelanotide 3 mg QD
Maximum Drug Concentration (Cmax) of Setmelanotide After QD Administration in the Run-in Period29.4 ± 3.4944.859.9 ± 29.6
PrimaryCmax 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).

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
Reported as:
Mean · ng/mL
Cmax of Setmelanotide After QW Administration
ng/mLSetmelanotide 20 mg QW (QD-QW-QW)Setmelanotide 25 mg QW (QD-QW-QW)Setmelanotide 30 mg QW (QD-QD-QW)Setmelanotide 30 mg QW (QD-QW-QW)
Cmax of Setmelanotide After QW Administration22.432.731.8 ± 28.657.3 ± 33.0
PrimaryTime 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.

Time frame:
Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose at Week -1
Reported as:
Median · hours
Time to Maximum Plasma Concentration (Tmax) of Setmelanotide After QD Administration in the Run-in Period
hoursSetmelanotide 2 mg QDSetmelanotide 2.5 mg QDSetmelanotide 3 mg QD
Time to Maximum Plasma Concentration (Tmax) of Setmelanotide After QD Administration in the Run-in Period6.91 (5.92 to 7.90)5.886.02 (2.00 to 8.00)
PrimaryTmax 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).

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
Reported as:
Median · hours
Tmax of Setmelanotide After QW Administration
hoursSetmelanotide 20 mg QW (QD-QW-QW)Setmelanotide 25 mg QW (QD-QW-QW)Setmelanotide 30 mg QW (QD-QD-QW)Setmelanotide 30 mg QW (QD-QW-QW)
Tmax of Setmelanotide After QW Administration3.935.931.98 (0.500 to 6.00)5.95 (2.03 to 6.03)
PrimaryMean 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).

Time frame:
30 minutes predose at Week 1
Reported as:
Mean · ng/mL
Mean Trough Plasma Concentration (Ctrough) of Setmelanotide After QD or QW Administration at Week 1
ng/mLSetmelanotide 20 mg QW (QD-QW-QW)Setmelanotide 25 mg QW (QD-QW-QW)Setmelanotide 3 mg QD (QD-QD-QW)Setmelanotide 30 mg QW (QD-QW-QW)
Mean Trough Plasma Concentration (Ctrough) of Setmelanotide After QD or QW Administration at Week 15.17 ± 0.8564.3611.7 ± 13.516.6 ± 16.3
PrimaryMean 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).

Time frame:
30 minutes predose at Week 5
Reported as:
Mean · ng/mL
Mean Setmelanotide Ctrough After QD or QW Administration at Week 5
ng/mLSetmelanotide 20 mg QW (QD-QW-QW)Setmelanotide 25 mg QW (QD-QW-QW)Setmelanotide 3 mg QD (QD-QD-QW)Setmelanotide 30 mg QW (QD-QW-QW)
Mean Setmelanotide Ctrough After QD or QW Administration at Week 5—9.5412.2 ± 7.6215.6 ± 13.3
PrimaryMean 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).

Time frame:
30 minutes predose at Week 9
Reported as:
Mean · ng/mL
Mean Setmelanotide Ctrough After QD or QW Administration at Week 9
ng/mLSetmelanotide 20 mg QW (QD-QW-QW)Setmelanotide 25 mg QW (QD-QW-QW)Setmelanotide 3 mg QD (QD-QD-QW)Setmelanotide 30 mg QW (QD-QW-QW)
Mean Setmelanotide Ctrough After QD or QW Administration at Week 911.16.4312.3 ± 11.420.1 ± 13.7
PrimaryMean 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).

Time frame:
30 minutes predose at Week 18
Reported as:
Mean · ng/mL
Mean Setmelanotide Ctrough After QD or QW Administration at Week 18
ng/mLSetmelanotide 20 mg QW (QD-QW-QW)Setmelanotide 25 mg QW (QD-QW-QW)Setmelanotide 3 mg QD (QD-QD-QW)Setmelanotide 30 mg QW (QD-QW-QW)
Mean Setmelanotide Ctrough After QD or QW Administration at Week 1814.412.613.6 ± 13.926.2 ± 23.8
PrimaryMean 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).

Time frame:
30 minutes predose at Week 22
Reported as:
Mean · ng/mL
Mean Setmelanotide Ctrough After QD or QW Administration at Week 22
ng/mLSetmelanotide 20 mg QW (QD-QW-QW)Setmelanotide 25 mg QW (QD-QW-QW)Setmelanotide 3 mg QD (QD-QD-QW)Setmelanotide 30 mg QW (QD-QW-QW)
Mean Setmelanotide Ctrough After QD or QW Administration at Week 2211.914.317.0 ± 15.427.9 ± 25.4
PrimaryMean 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).

Time frame:
30 minutes predose at Week 27
Reported as:
Mean · ng/mL
Mean Setmelanotide Ctrough After QD or QW Administration at Week 27
ng/mLSetmelanotide 20 mg QW (QD-QW-QW)Setmelanotide 25 mg QW (QD-QW-QW)Setmelanotide 3 mg QD (QD-QD-QW)Setmelanotide 30 mg QW (QD-QW-QW)
Mean Setmelanotide Ctrough After QD or QW Administration at Week 2714.29.9120.3 ± 19.432.1 ± 23.9
PrimaryArea 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.

Time frame:
Pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 6, and 8 hours postdose at Week -1
Reported as:
Mean · hours*ng/mL
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of Setmelanotide After QD Administration in the Run-in Period
hours*ng/mLSetmelanotide 2 mg QDSetmelanotide 2.5 mg QDSetmelanotide 3 mg QD
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of Setmelanotide After QD Administration in the Run-in Period——975 ± 659
PrimaryAUC0-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).

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
Reported as:
Mean · hours*mg/mL
AUC0-tau of Setmelanotide After QD Administration in the Run-in Period
hours*mg/mLSetmelanotide 20 mg QW (QD-QW-QW)Setmelanotide 25 mg QW (QD-QW-QW)Setmelanotide 30 mg QW (QD-QD-QW)Setmelanotide 30 mg QW (QD-QW-QW)
AUC0-tau of Setmelanotide After QD Administration in the Run-in Period159022602470 ± 28905010 ± 4000
SecondaryNumber 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.

Time frame:
From first dose of study drug administration up to Week 30
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
ParticipantsRun-in Period: Setmelanotide 2 mg QDRun-in Period: Setmelanotide 2.5 mg QDRun-in Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 20 mg QWDB Period: Setmelanotide 25 mg QWDB Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 30 mg QWOL Period: Setmelanotide 20 mg QWOL Period: Setmelanotide 25 mg QWOL Period: Setmelanotide 30 mg QW
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)00121960110
SecondaryNumber 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.

Time frame:
Baseline through Week 13
Reported as:
Count of participants · Participants
Number of Participants With Injection Site Reactions (ISRs) From Baseline Through Week 13
ParticipantsSetmelanotide 20 mg QWSetmelanotide 25 mg QWSetmelanotide 3 mg QDSetmelanotide 30 mg QW
Erythema QD — None2075
Erythema QD — Mild0122
Erythema QD — Moderate0000
Erythema QD — Severe0000
Erythema QW — None1043
Erythema QW — Mild1143
Erythema QW — Moderate0011
Erythema QW — Severe0000
Edema QD — None2197
Edema QD — Mild0000
Edema QD — Moderate0000
Edema QD — Severe0000
Edema QW — None2196
Edema QW — Mild0001
Edema QW — Moderate0000
Edema QW — Severe0000
Induration QD — None1196
Induration QD — Mild1000
Induration QD — Moderate0001
Induration QD — Severe0000
Induration QW — None1084
Induration QW — Mild1112
Induration QW — Moderate0001
Induration QW — Severe0000
Itching QD — None2183
Itching QD — Mild0014
Itching QD — Moderate0000
Itching QD — Severe0000
Itching QW — None2192
Itching QW — Mild0004
Itching QW — Moderate0001
Itching QW — Severe0000
Pain or Tenderness QD — None2065
Pain or Tenderness QD — Mild0132
Pain or Tenderness QD — Moderate0000
Pain or Tenderness QD — Severe0000
Pain or Tenderness QW — None2061
Pain or Tenderness QW — Mild0132
Pain or Tenderness QW — Moderate0004
Pain or Tenderness QW — Severe0000
Other QD — None1197
Other QD — Mild1000
Other QD — Moderate0000
Other QD — Severe0000
Other QW — None0165
Other QW — Mild2031
Other QW — Moderate0001
Other QW — Severe0000
SecondaryNumber 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.

Time frame:
Week 14 through Week 27
Reported as:
Count of participants · Participants
Number of Participants With ISRs From Week 14 Through Week 27
ParticipantsSetmelanotide 20 mg QWSetmelanotide 25 mg QWSetmelanotide 30 mg QW
Erythema QD — None1113
Erythema QD — Mild001
Erythema QD — Moderate000
Erythema QD — Severe000
Erythema QW — None1012
Erythema QW — Mild012
Erythema QW — Moderate000
Erythema QW — Severe000
Edema QD — None1113
Edema QD — Mild001
Edema QD — Moderate000
Edema QD — Severe000
Edema QW — None1114
Edema QW — Mild000
Edema QW — Moderate000
Edema QW — Severe000
Induration QD — None1113
Induration QD — Mild001
Induration QD — Moderate000
Induration QD — Severe000
Induration QW — None008
Induration QW — Mild114
Induration QW — Moderate002
Induration QW — Severe000
Itching QD — None1114
Itching QD — Mild000
Itching QD — Moderate000
Itching QD — Severe000
Itching QW — None1110
Itching QW — Mild004
Itching QW — Moderate000
Itching QW — Severe000
Pain or Tenderness QD — None1113
Pain or Tenderness QD — Mild001
Pain or Tenderness QD — Moderate000
Pain or Tenderness QD — Severe000
Pain or Tenderness QW — None118
Pain or Tenderness QW — Mild006
Pain or Tenderness QW — Moderate000
Pain or Tenderness QW — Severe000

Adverse events

Collected over From first dose of study drug administration up to week 30. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Run-in Period: Setmelanotide 2 mg QD0/2 (0%)0/2 (0%)0/2 (0%)
Run-in Period: Setmelanotide 2.5 mg QD0/1 (0%)0/1 (0%)0/1 (0%)
Run-in Period: Setmelanotide 3 mg QD0/16 (0%)0/16 (0%)1/16 (6.3%)
DB Period: Setmelanotide 20 mg QW0/2 (0%)0/2 (0%)2/2 (100%)
DB Period: Setmelanotide 25 mg QW0/1 (0%)0/1 (0%)1/1 (100%)
DB Period: Setmelanotide 3 mg QD0/9 (0%)0/9 (0%)9/9 (100%)
DB Period: Setmelanotide 30 mg QW0/7 (0%)0/7 (0%)6/7 (85.7%)
OL Period: Setmelanotide 20 mg QW0/1 (0%)0/1 (0%)0/1 (0%)
OL Period: Setmelanotide 25 mg QW0/1 (0%)0/1 (0%)1/1 (100%)
OL Period: Setmelanotide 30 mg QW0/14 (0%)0/14 (0%)10/14 (71.4%)
Most frequent other events
Showing 10 of 47
Most frequent other events
EventRun-in Period: Setmelanotide 2 mg QDRun-in Period: Setmelanotide 2.5 mg QDRun-in Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 20 mg QWDB Period: Setmelanotide 25 mg QWDB Period: Setmelanotide 3 mg QDDB Period: Setmelanotide 30 mg QWOL Period: Setmelanotide 20 mg QWOL Period: Setmelanotide 25 mg QWOL Period: Setmelanotide 30 mg QW
Injection site erythemaGeneral disorders0/20/11/161/21/14/92/70/11/10/14
Injection site painGeneral disorders0/20/10/160/21/14/95/70/11/11/14
Injection site indurationGeneral disorders0/20/10/161/21/12/92/70/11/11/14
NasopharyngitisInfections and infestations0/20/10/160/21/11/91/70/11/12/14
NauseaGastrointestinal disorders0/20/10/160/21/13/90/70/11/10/14
Skin hyperpigmentationSkin and subcutaneous tissue disorders0/20/10/160/21/12/90/70/11/11/14
AlopeciaSkin and subcutaneous tissue disorders0/20/10/160/20/10/90/70/11/10/14
Meniscus injuryInjury, poisoning and procedural complications0/20/10/160/20/10/90/70/11/10/14
CoughRespiratory, thoracic and mediastinal disorders0/20/10/160/21/10/90/70/10/11/14
Oropharyngeal painRespiratory, thoracic and mediastinal disorders0/20/10/160/21/10/91/70/10/11/14

Baseline characteristics

Full Analysis Set (FAS) included all participants who received at least 1 dose of setmelanotide after the randomization.

Age, Continuous
Age, Continuous(years)Setmelanotide 2 mg QDSetmelanotide 2.5 mg QDSetmelanotide 3 mg QDTotal
Mean20.0 ± 12.7319.020.8 ± 8.3020.6 ± 8.16
Sex: Female, Male
Sex: Female, Male(Participants)Setmelanotide 2 mg QDSetmelanotide 2.5 mg QDSetmelanotide 3 mg QDTotal
Female011011
Male2068
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Setmelanotide 2 mg QDSetmelanotide 2.5 mg QDSetmelanotide 3 mg QDTotal
Hispanic or Latino0022
Not Hispanic or Latino211417
Unknown or Not Reported0000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Setmelanotide 2 mg QDSetmelanotide 2.5 mg QDSetmelanotide 3 mg QDTotal
Race — Asian1001
Race — White111416
Race — Other0022
08

Study locations

7 sites
  • Honor Health Research Institute
    Scottsdale, Arizona 85258, United States
  • Marshfield Clinic Research Institute
    Marshfield, Wisconsin 54449, United States
  • Alberta Health Services
    Edmonton, Alberta T6G 2E1, Canada
  • Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
    Berlin, 13353, Germany
  • Erasmus MC
    Rotterdam, 3015 CE, Netherlands
  • UPR Medical Sciences Campus
    Rio Piedras, 00935, Puerto Rico
  • Addenbrooke's Hospital
    Cambridge, CA2 0QQ, United Kingdom
09

References and documents

Study documents

  • Study protocol · Jul 7, 2022
  • Statistical analysis plan · Jul 24, 2023

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 26, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05194124
Lead sponsor
Rhythm Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Jan 18, 2022
Start date
Dec 21, 2021
Primary completion
Oct 19, 2023
Completion
Oct 19, 2023
Results posted
Nov 26, 2024
Last update
Nov 26, 2024

Study contacts

David Meeker, MD
study chair · Rhythm Pharmaceuticals, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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