Trial · Interventional

CompletedPhase 2Results postedRegistry data

Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity

NCTNCT03013543Other idRM-493-014Other id2017-000387-14Other id2017

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 2
Enrollment: 213 participants (actual)
Sponsor: Rhythm Pharmaceuticals, Inc. · Industry
Design: Not randomized · Open label (no masking)
Countries: 9 countries
United States, Canada, France, Germany, Greece, Israel, Netherlands, Spain, United Kingdom
Start: 10 Feb 2017
Primary completion: 1 Mar 2022
Completion: 1 Mar 2022
First posted: 6 Jan 2017 (estimated)
Last update posted: 18 Aug 2023
Conditions: Genetic Obesity · Obesity · Obesity Due to Melanocortin 4 Receptor Deficiency

Timeline

1 trial · 1 completed · 1 with posted results

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

2017201820192020202120222023

Ph 2
Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity
NCT03013543
10 Feb 2017 to 1 Mar 2022

Registry summary

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

The purpose of the study was to determine the effect of setmelanotide (RM-493) on weight, hunger assessments, and other factors in participants with rare genetic disorders of obesity.

Interventions

SetmelanotideDrug

Arms10

Experimental
16p11.2 Cohort
Participants with chromosomal rearrangement of the p11.2 region of chromosome 16 (16p11.2) locus causing obesity received setmelanotide once daily (QD) via subcutaneous (SC) injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Experimental
AS Cohort
Participants with Alström syndrome (AS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Experimental
BBS Cohort
Participants with Bardet-Biedl syndrome (BBS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Experimental
MC4R Cohort
Participants with melanocortin-4 receptor (MC4R) deficiency obesity received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Experimental
POMC/PCSK1/LEPR Heterozygous Cohort
Participants with pro-opiomelanocortin (POMC)/proprotein convertase subtilisin/kexin type 1 (PCSK1)/leptin receptor (LEPR) heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Experimental
POMC/PCSK1/LEPR Composite Heterozygous Cohort
Participants with POMC/PCSK1/LEPR composite heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Experimental
POMC/PCSK1/LEPR Compound Heterozygous Cohort
Participants with POMC/PCSK1/LEPR compound heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Experimental
SH2B1 Cohort
Participants with steroid receptor coactivator (SRC) homology 2B adapter protein 1 (SH2B1) haploinsufficiency received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Experimental
SMS Cohort
Participants with Smith-Magenis Syndrome (SMS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Experimental
SRC1 Cohort
Participants with steroid receptor coactivator 1 (SRC1) mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.

Primary outcomes1

Outcomes the sponsor listed as primary.

Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment
Time frame · Baseline to Month 3

Secondary outcomes(8)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame · From first dose up to Month 16
Registry description
An adverse event (AE) was any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE (also referred to as an adverse experience) could be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. TEAEs were defined as AEs reported after dosing on Day 1.
Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment
Time frame · Baseline, Month 3
Percent Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment
Time frame · Baseline, Month 3
Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years
Time frame · Baseline, Month 3
Registry description
The mean change in daily hunger questionnaire scores for participants ≥ 12 years of age with obesity in treatment with setmelanotide was evaluated. On the Daily Hunger Questionnaire, each of the 3 items (average hunger in the last 24 hours, most/worst hunger in the last 24 hours, and morning hunger) was assessed daily and scored separately using a numeric rating score for each from 0 to 10, with 0 = not hungry at all and 10 = hungriest possible.
Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years
Time frame · Baseline, Month 3
Registry description
The mean change in daily hunger questionnaire scores for participants \< 12 years of age with obesity in treatment with setmelanotide was evaluated. Hunger was assessed daily using a Daily Hunger Questionnaire with a pictorial (smiley face) version of the Likert rating scale with scores ranged from 0 to 4, with 0 = not hungry at all and 4 = hungriest possible.
Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years
Time frame · Baseline, Month 3
Registry description
For participants ≥ 12 years of age, the following question was asked using the Global Hunger Questionnaire: Overall, how would you rate the hunger you experience now? Possible responses were: No hunger; Mild hunger; Moderate hunger; Severe hunger; and Not answered.
Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years
Time frame · Baseline, Month 3
Registry description
For participants \< 12 years of age, the following question was asked to parents or caregivers of participants using the Global Hunger Questionnaire: How hungry is your child acting now? Possible responses were: Not hungry at all; A little hungry; Moderately hungry; Extremely hungry; and Not answered.
Percent Change From Baseline in Waist Circumference After 3 Months of Setmelanotide Treatment
Time frame · Baseline, Month 3
Registry description
Waist circumference (cm) was measured according to the National Heart, Lung, and Blood Institute (NHLBI) criteria. All measurements were single measures. Waist circumference was measured when participants were in fasting condition and at approximately the same time at each visit.

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 outcomeCount of participants· Baseline to Month 3

Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment

Group	Value (Participants)
16p11.2 Cohort	6
AS Cohort	3
BBS Cohort	7
MC4R Cohort	7
POMC/PCSK1/LEPR Heterozygous Cohort	10
POMC/PCSK1/LEPR Composite Heterozygous Cohort	0
POMC/PCSK1/LEPR Compound Heterozygous Cohort	14
SH2B1 Cohort	8
SMS Cohort	1
SRC1 Cohort	9

Secondary and other outcome results(7)

Secondary outcomeCount of participants· From first dose up to Month 16

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Group	Value (Participants)
16p11.2 Cohort	19
AS Cohort	4
BBS Cohort	10
MC4R Cohort	49
POMC/PCSK1/LEPR Heterozygous Cohort	33
POMC/PCSK1/LEPR Composite Heterozygous Cohort	5
POMC/PCSK1/LEPR Compound Heterozygous Cohort	27
SH2B1 Cohort	21
SMS Cohort	12
SRC1 Cohort	29

Secondary outcomeMean· Baseline, Month 3

Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment

Group	Value (kg)	Spread
16p11.2 Cohort	-2.58	4.886
AS Cohort	-5.16	3.860
BBS Cohort	-4.61	7.771
MC4R Cohort	-1.26	4.851
POMC/PCSK1/LEPR Heterozygous Cohort	-4.74	7.689
POMC/PCSK1/LEPR Composite Heterozygous Cohort	-0.11	2.432
POMC/PCSK1/LEPR Compound Heterozygous Cohort	-7.24	6.657
SH2B1 Cohort	-3.98	5.164
SMS Cohort	-0.14	2.805
SRC1 Cohort	-3.96	4.370

Secondary outcomeMean· Baseline, Month 3

Percent Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment

Group	Value (percent change)	Spread
16p11.2 Cohort	-2.19	3.685
AS Cohort	-6.38	5.043
BBS Cohort	-4.19	5.579
MC4R Cohort	-0.75	4.291
POMC/PCSK1/LEPR Heterozygous Cohort	-3.50	5.817
POMC/PCSK1/LEPR Composite Heterozygous Cohort	-0.31	1.772
POMC/PCSK1/LEPR Compound Heterozygous Cohort	-5.57	5.170
SH2B1 Cohort	-2.92	3.834
SMS Cohort	-0.00	3.651
SRC1 Cohort	-3.34	3.607

Secondary outcomeMean· Baseline, Month 3

Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years

Group	Value (units on a scale)	Spread
16p11.2 Cohort	6.11	2.102
AS Cohort	5.07	1.860
BBS Cohort	6.37	1.719
MC4R Cohort	5.74	1.915
POMC/PCSK1/LEPR Heterozygous Cohort	5.73	2.178
POMC/PCSK1/LEPR Composite Heterozygous Cohort	8.07	1.348
POMC/PCSK1/LEPR Compound Heterozygous Cohort	6.32	2.062
SH2B1 Cohort	6.66	1.966
SMS Cohort	not posted	–
SRC1 Cohort	6.04	2.049

Secondary outcomeMean· Baseline, Month 3

Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years

Group	Value (units on a scale)	Spread
16p11.2 Cohort	2.32	0.741
AS Cohort	not posted	–
BBS Cohort	not posted	–
MC4R Cohort	2.02	1.300
POMC/PCSK1/LEPR Heterozygous Cohort	not posted	–
POMC/PCSK1/LEPR Composite Heterozygous Cohort	not posted	–
POMC/PCSK1/LEPR Compound Heterozygous Cohort	2.17	1.443
SH2B1 Cohort	1.87	0.125
SMS Cohort	not posted	–
SRC1 Cohort	not posted	–

Secondary outcomeNumber· Baseline, Month 3

Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years

Group	Value (participants)
16p11.2 Cohort	2
AS Cohort	0
BBS Cohort	0
MC4R Cohort	1
POMC/PCSK1/LEPR Heterozygous Cohort	2
POMC/PCSK1/LEPR Composite Heterozygous Cohort	0
POMC/PCSK1/LEPR Compound Heterozygous Cohort	0
SH2B1 Cohort	0
SMS Cohort	0
SRC1 Cohort	1

Secondary outcomeNumber· Baseline, Month 3

Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years

Group	Value (participants)
16p11.2 Cohort	0
AS Cohort	not posted
BBS Cohort	not posted
MC4R Cohort	1
POMC/PCSK1/LEPR Heterozygous Cohort	not posted
POMC/PCSK1/LEPR Composite Heterozygous Cohort	0
POMC/PCSK1/LEPR Compound Heterozygous Cohort	0
SH2B1 Cohort	0
SMS Cohort	not posted
SRC1 Cohort	0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
16p11.2 CohortParticipants with chromosomal rearrangement of the 16p11.2 locus causing obesity received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	0 / 19	1 / 19	19 / 19
AS CohortParticipants with AS received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	0 / 4	0 / 4	4 / 4
BBS CohortParticipants with BBS received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	0 / 10	1 / 10	10 / 10
MC4R CohortParticipants with MC4R deficiency obesity received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	1 / 49	1 / 49	48 / 49
POMC/PCSK1/LEPR Heterozygous CohortParticipants with PCSK1/LEPR heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	0 / 33	1 / 33	33 / 33
POMC/PCSK1/LEPR Composite Heterozygous CohortParticipants with POMC/PCSK1/LEPR composite heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	0 / 5	1 / 5	5 / 5
POMC/PCSK1/LEPR Compound Heterozygous CohortParticipants with POMC/PCSK1/LEPR compound heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	0 / 27	2 / 27	27 / 27
SH2B1 CohortParticipants with SH2B1 haploinsufficiency received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	0 / 22	0 / 22	21 / 22
SMS CohortParticipants with SMS received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	0 / 12	0 / 12	12 / 12
SRC1 CohortParticipants with SRC1 mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.	0 / 32	0 / 32	29 / 32

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

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

PubMed tag: none · 2023

3 results

Interview-Based Patient- and Caregiver-Reported Experiences of Hunger and Improved Quality of Life with Setmelanotide Treatment in Bardet-Biedl Syndrome.

Ervin et al. 2023Advances in therapycited by 19

PMID 36961653PMC10036981DOI 10.1007/s12325-023-02443-yPUB-36961653

Free to read · publisher termsCC BY-NC3 results

Read at source See results (3)

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

DerivedMeyer JR, Krentz AD, Berg RL, Richardson JG, Pomeroy J, Hebbring SJ, Haws RM. Kidney failure in Bardet-Biedl syndrome. Clin Genet. 2022 Apr;101(4):429-441. doi: 10.1111/cge.14119. PMID 35112343

Eligibility

Who could join, as posted.

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

Inclusion and exclusion criteria, as posted

Inclusion Criteria: 1. Participants with the following genotypes and/or clinical assessment: 1. POMC/PCSK1/LEPR heterozygous - not currently enrolling new participants 2. POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity 3. POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity 4. SMS 5. SH2B1 deficiency obesity 6. Chromosomal rearrangement of the 16p11.2 locus causing obesity 7. Carboxypeptidase E (CPE) compound heterozygous or homozygous deficiency obesity 8. Leptin deficiency obesity with loss of response to metreleptin 9. SRC1 deficiency obesity 10. MC4R deficiency obesity 2. Age 6 years and above 3. Obese, defined as Body Mass Index (BMI) ≥ 30 kilogram per meter square (kg/m\^2) for participants ≥16 years of age or BMI≥ 95th percentile for age and gender for participants 6 up to 16 years of age. 4. Participant and/or parent or guardian is able to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent 5. Female participants of childbearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol. 6. Male participants with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study. Male participants must not donate sperm during and for 90 days following their participation in the study. Key Exclusion Criteria: 1. Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents that has resulted in \> 2% weight loss. 2. Use of any medication that is approved to treat obesity within three months of first dose of study drug (e.g., orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion). 3. Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in \>10% weight loss durably maintained 4. Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s) 5. Suicidal ideation, attempt or behavior 6. Clinically significant pulmonary, cardiac, or oncologic disease 7. hemoglobin A1c (HbA1c) \> 9.0% at Screening 8. History of significant liver disease 9. Glomerular filtration rate (GFR) \< 30 milliliter/minute (mL/min) at Screening. 10. History or close family history of melanoma or participant history of oculocutaneous albinism 11. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions. 12. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing. 13. Participants previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide. 14. Inability to comply with QD injection regimen. 15. Females who are breastfeeding or nursing. Other protocol defined Inclusion/Exclusion criteria may apply.

PepBank is a research reference. Talk to a doctor before you use any peptide.