ObesityPhase 3NCT05093634
EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway
A Phase 3 study testing Setmelanotide in people with Obesity and Genetic Obesity, run by Rhythm Pharmaceuticals, Inc. at 56 sites in 10 countries.
Trial summary
The protocol describes a randomized, double-blind, placebo-controlled trial with independent sub-studies of setmelanotide in patients with obesity and at least one of the specific gene variants in the Melanocortin-4 Receptor pathway: POMC or PCSK1 (Sub-study 035a) LEPR (Sub-study 035b) SRC1 (Sub-study 035c) SH2B1… Read more about this study
- Who is it for?
- Ages 6 to 65 years
- Conditions the study is for
- Obesity, Genetic Obesity
- What is being tested?
- Setmelanotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 296 participants
- Where
- 56 sitesin 10 countries
- Study dates
- 10 Dec 2021to 30 Jun 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a pre-identified:
- Heterozygous genetic variant in the POMC gene or PCSK1 gene
- Heterozygous genetic variant in the LEPR gene
- Homozygous, heterozygous, or compound heterozygous variant in the NCOA1 (SRC1)
- Homozygous, heterozygous, or compound heterozygous variant in SH2B1 gene, or chromosomal 16p11.2 deletion encompassing the SH2B1 gene
- Between 6 and 65 years of age at the time of provision of informed consent/assent
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- Obesity, defined as BMI ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and gender for patients 6 up to 17 years of age
- Patient 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
- Patient and/or parent or guardian reports that patient experienced childhood obesity, defined as the patient and/or parent or guardian reporting that the patient was significantly overweight during childhood
- Agree to use a highly effective form of contraception throughout the study and for 90 days following the study
- Reported history of lifestyle intervention of diet and exercise
- Reported history of hyperphagia
Who cannot join
- Weight loss of 2% or greater in the previous 3 months
- Recent history of bariatric surgery
- Significant psychiatric disorder(s)
- Suicidal ideation, attempt or behavior
- Clinically significant pulmonary, cardiac, endocrine/metabolic, hepatic or oncologic disease
- Glycated hemoglobin (HbA1C) >10% at Screening
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- History of significant liver disease or severe kidney disease
- History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism
- Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
- Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing
- Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide
- Significant hypersensitivity to any excipient in the study drug
- If female, pregnant or breastfeeding
Trial locations and contacts
56 sites in 10 countries.
56 sites in 10 countries
United States32 sites
Advent Health
Altamonte Springs, Florida, 32701
Texas Tech
Amarillo, Texas, 79106
University of Michigan
Ann Arbor, Michigan, 48105
Children's Hospital Colorado
Aurora, Colorado, 80045
University of Buffalo
Buffalo, New York, 14260
St. Luke's Hospital
Chesterfield, Missouri, 63017
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Geisinger Clinic
Danville, Pennsylvania, 17822
Metro Detroit Endocrinology Center
Dearborn, Michigan, 48126-2619
Texas Children's Hospital
Houston, Texas, 77030
Biopharma Informatic
Houston, Texas, 77084
Children's Hospital Los Angeles
Los Angeles, California, 90027
Marshfield Clinic Research Foundation, a Division of Marshfield Clinic, Inc
Marshfield, Wisconsin, 54449
Rio Grande Valley Endocrine Center
McAllen, Texas, 78503
West Virginia University
Morgantown, West Virginia, 26506
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232
Yale Center for Clinical Investigation
New Haven, Connecticut, 06519
Metropolitan Hospital Center
New York, New York, 10029
Mount Sinai Hospital
New York, New York, 10029
Columbia University
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85016
UPMC Montefiore
Pittsburgh, Pennsylvania, 15213
Endocrine Associates of Dallas and Plano
Plano, Texas, 75093
Oregon Health & Science University
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55902
HonorHealth Bariatric Center
Scottsdale, Arizona, 85258
Washington University in St. Louis
St Louis, Missouri, 63130
Ten's Medical Center - Pediatric Endocrinology Clinic
Staten Island, New York, 10306
InQuest Medical Research
Suwanee, Georgia, 30024
MultiCare Health System Institute for Research and Innovation
Tacoma, Washington, 98405
UMASS Memorial Medical Center
Worcester, Massachusetts, 01655
France5 sites
GH Est Hopital Femme Mere Enfant
Lyon, 69677
Hu Pitie Salpetriere Aphp
Paris, 75651
Hopital Armand Trousseau
Paris, 75771
Centre Hospitalier Universitaire (CHU) de Bordeaux
Pessac, 33604
Hôpital Félix Guyon Bellepierre
Saint-Denis, 97400
United Kingdom5 sites
Bristol Royal Hospital for Children
Bristol, BS2 8AE
University of Cambridge
Cambridge, CB2 0QQ
Aintree University Hospital
Liverpool, L9 7AL
London Medical - The London Diabetes Centre
London, NW1 2PG
University College London Hospitals NHS Foundation Trust
London, WC1E6JF
Germany4 sites
Charite - Universitatsmedizin Berlin
Berlin, 10117
Endokrinologikum Frankfurt
Frankfurt, 60596
Universitaetsklinikum Leipzig
Leipzig, 04103
Universitaetsklinikum Ulm
Ulm, 89075
Spain4 sites
Hospital Sant Joan de Deu, Barcelona
Barcelona, 08950
Hospital Fundación Jimenez Díaz
Madrid, 28040
Hospital Universitario Virgen de la Victoria de Málaga
Málaga, 29010
Hospital General de Valencia
Valencia, 46014
Israel2 sites
Hasharon Hospital
Petah Tikva, 49372
Chaim Sheba MC, Safra Children's Hospital
Ramat Gan, 52621
Canada1 site
University of Alberta - Alberta Diabetes Institute (ADI)
Edmonton, Alberta, T6G 2E1
About this study
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial: Multiple Independent Sub-studies of Setmelanotide in Patients With POMC/PCSK1, LEPR, NCOA1(SRC1), or SH2B1 Gene Variants in the Melanocortin-4 Receptor Pathway
The protocol describes a randomized, double-blind, placebo-controlled trial with independent sub-studies of setmelanotide in patients with obesity and at least one of the specific gene variants in the Melanocortin-4 Receptor pathway:
- POMC or PCSK1 (Sub-study 035a)
- LEPR (Sub-study 035b)
- SRC1 (Sub-study 035c)
- SH2B1 (Sub-study 035d)
The objectives and endpoints are identical for these sub-studies.
- Conditions
- Obesity, Genetic Obesity
- Being tested
- Setmelanotide, Placebo
- Keywords
- Melanocortin-4 Receptor Pathway, Genetic Obesity, Hunger, Hyperphagia, POMC, PCSK1, LEPR, SH2B1, NCOA1 (SRC1)
- Medical subject headings
- Obesity, Hyperphagia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SetmelanotideDrug
Subcutaneous Injection
PlaceboDrug
Subcutaneous Injection
| Study group | Role | What they receive |
|---|---|---|
| POMC or PCSK1 variant | Experimental | 1:1 Randomization Receives: Drug: Setmelanotide; Drug: Placebo |
| LEPR variant | Experimental | 1:1 Randomization Receives: Drug: Setmelanotide; Drug: Placebo |
| NCOA1 (SRC1) variant | Experimental | 1:1 Randomization Receives: Drug: Setmelanotide; Drug: Placebo |
| SH2B1 variant | Experimental | 1:1 Randomization Receives: Drug: Setmelanotide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI
Measured: Baseline to 52 weeks
Secondary outcomes (4)
The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo
Measured: Baseline to 52 weeks
The difference in mean change in body weight in adult patients treated with setmelanotide compared to placebo, assessed as percent change in baseline body weight
Measured: Baseline to 52 weeks
The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo
Measured: Baseline to 52 weeks
The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo
Measured: Baseline to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2021
- Study start10 Dec 2021
- Primary completion22 Dec 2025
- Study completion30 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies 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
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 296 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Meeker, MD, Study chair, Rhythm Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05093634
- Sponsor's protocol ID
- RM-493-035
- Status last verified
- Aug 2026
- First submitted
- 30 Sep 2021
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Delplanque J, Le Collen L, Loiselle H, Leloire A, Toussaint B, Vaillant E, Charpentier G, Franc S, Balkau B, Marre M, Henriques E, Buse Falay E, Derhourhi M, Froguel P, Bonnefond A. Monoallelic pathogenic variants in LEPR do not cause obesity. Am J Hum Genet. 2024 Dec 5;111(12):2668-2674. doi: 10.1016/j.ajhg.2024.10.014. Epub 2024 Nov 18.
PubMed 39561769
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial: Multiple Independent Sub-studies of Setmelanotide in Patients With POMC/PCSK1, LEPR, NCOA1(SRC1), or SH2B1 Gene Variants in the Melanocortin-4 Receptor Pathway
- ClinicalTrials.gov ID
- NCT05093634
- Acronym / sponsor ID
- RM-493-035
- Conditions
- Obesity, Genetic Obesity
- Keywords
- Melanocortin-4 Receptor Pathway, Genetic Obesity, Hunger, Hyperphagia, POMC, PCSK1, LEPR, SH2B1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 296 participants (actual)
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Dec 2021 (actual)
- Primary completion
- 22 Dec 2025 (actual)
- Study completion
- 30 Jun 2026 (actual)
- First posted
- 26 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The protocol describes a randomized, double-blind, placebo-controlled trial with independent sub-studies of setmelanotide in patients with obesity and at least one of the specific gene variants in the Melanocortin-4 Receptor pathway:
- POMC or PCSK1 (Sub-study 035a)
- LEPR (Sub-study 035b)
- SRC1 (Sub-study 035c)
- SH2B1 (Sub-study 035d)
The objectives and endpoints are identical for these sub-studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| POMC or PCSK1 variant | Experimental | Drug: Setmelanotide, Drug: Placebo1:1 Randomization |
| LEPR variant | Experimental | Drug: Setmelanotide, Drug: Placebo1:1 Randomization |
| NCOA1 (SRC1) variant | Experimental | Drug: Setmelanotide, Drug: Placebo1:1 Randomization |
| SH2B1 variant | Experimental | Drug: Setmelanotide, Drug: Placebo1:1 Randomization |
Who may qualify
- Ages
- 6 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must have a pre-identified:
- Between 6 and 65 years of age at the time of provision of informed consent/assent
- Obesity, defined as BMI ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and gender for patients 6 up to 17 years of age
- Patient 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
- Patient and/or parent or guardian reports that patient experienced childhood obesity, defined as the patient and/or parent or guardian reporting that the patient was significantly overweight during childhood
Key exclusion criteria (13 listed)
- Weight loss of 2% or greater in the previous 3 months
- Recent history of bariatric surgery
- Significant psychiatric disorder(s)
- Suicidal ideation, attempt or behavior
- Clinically significant pulmonary, cardiac, endocrine/metabolic, hepatic or oncologic disease
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 |
|---|---|---|
| SetmelanotideSubcutaneous Injection | Drug | LEPR variant, NCOA1 (SRC1) variant, POMC or PCSK1 variant, SH2B1 variant |
| PlaceboSubcutaneous Injection | Drug | LEPR variant, NCOA1 (SRC1) variant, POMC or PCSK1 variant, SH2B1 variant |
Primary outcome
Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI
Time frame: Baseline to 52 weeks
4 secondary outcomes
The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo
Time frame: Baseline to 52 weeks
The difference in mean change in body weight in adult patients treated with setmelanotide compared to placebo, assessed as percent change in baseline body weight
Time frame: Baseline to 52 weeks
The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo
Time frame: Baseline to 52 weeks
The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo
Time frame: Baseline to 52 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Derived from this study: PubMed 39561769Delplanque J, Le Collen L, Loiselle H, Leloire A, Toussaint B, Vaillant E, Charpentier G, Franc S, Balkau B, Marre M, Henriques E, Buse Falay E, Derhourhi M, Froguel P, Bonnefond A. Monoallelic pathogenic variants in LEPR do not cause obesity. Am J Hum Genet. 2024 Dec 5;111(12):2668-2674. doi: 10.1016/j.ajhg.2024.10.014. Epub 2024 Nov 18.
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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.
56 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Setmelanotide in people with Obesity and Genetic Obesity, run by Rhythm Pharmaceuticals, Inc. at 56 sites in 10 countries.
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 12 inclusion and 13 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 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, France, United Kingdom, Germany, Spain and 5 more countries. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI (time frame: Baseline to 52 weeks). 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 NCT05093634, which also lists 1 linked publication.
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 6 Aug 2026.