Obesity Associated With Defects in Leptin-melanocortin PathwayPhase 2/3NCT03651765
Long Term Extension Trial of Setmelanotide
A Phase 2/3 study testing Setmelanotide in people with Obesity Associated With Defects in Leptin-melanocortin Pathway, run by Rhythm Pharmaceuticals, Inc. at 27 sites in 8 countries.
Trial summary
This was a long-term extension trial to study the safety and tolerability of continued setmelanotide treatment in participants who had completed a previous clinical trial on treatment with setmelanotide for obesity associated with genetic defects upstream of the Melanocortin-4 (MC4) receptor in the leptin-melanocortin… Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Obesity Associated With Defects in Leptin-melanocortin Pathway
- What is being tested?
- Setmelanotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 205 participants
- Where
- 27 sitesin 8 countries
- Study dates
- 15 Jul 2018to 9 Jan 2025
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants aged 2 or older (or aged >2 years as per local regulations) who had completed participation in a previous setmelanotide trial and demonstrated adequate safety and meaningful clinical benefit (efficacy)
- Participant and/or parent or guardian was able to communicate with the investigator, understand and sign the written informed consent/assent, and comply with the trial requirements
- Agree to use a highly effective form of contraception throughout the trial
Who cannot join
- Pregnant and/or breastfeeding women
- Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
- Current, clinically significant disease
- Documented diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
- Suicidal ideation, attempt or behavior
- History of significant liver disease
Show all 9Show fewer
- Moderate to severe renal dysfunction as defined by a glomerular filtration rate (GFR)<30 milliliters per minute (mL/min).
- History or close family history of melanoma or participant history of oculocutaneous albinism
- Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
27 sites in 8 countries.
27 sites in 8 countries
United States15 sites
Synexus Clinical Research US, Inc.- Primary Care Associates, PC
Anderson, South Carolina, 29621
University at Buffalo
Buffalo, New York, 14203
Synexus Clinical Research US, Inc. - Phoenix Southeast
Chandler, Arizona, 85224
Wake Research TN
Chattanooga, Tennessee, 37421
Obesity Institute, Geisinger Clinic
Danville, Pennsylvania, 17822-2607
Duke University Medical Center
Durham, North Carolina, 27705
University of Florida College of Medicine
Gainesville, Florida, 32610
Marshfield Clinic Research Institute
Marshfield, Wisconsin, 54449
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
Childrens Hospital of Philadephia
Philadelphia, Pennsylvania, 19104
Wake Research
Raleigh, North Carolina, 27612
San Diego Wake Research
San Diego, California, 92108
Honor Health Research Institute
Scottsdale, Arizona, 85258
Seattle Children's Research Institute
Seattle, Washington, 98101
Baystate Medical Center
Springfield, Massachusetts, 01107
Germany3 sites
Charité - Universitätsmedizin Berlin
Berlin, 13354
University of Leipzig
Leipzig, 04103
University of Ulm
Ulm, 89075
United Kingdom3 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2GW
Wellcome Trust-MRC Institute of Metabolic Science
Cambridge, CB2 0QQ
Hammersmith Hospital
London, W12 0NN
France2 sites
Hôpital Trousseau
Paris, 75012
Hôpital de la Pitié Salpêtrière
Paris, 75013
About this study
Official title: Long Term Extension Trial of Setmelanotide (RM-493) for Patients Who Have Completed a Trial of Setmelanotide for the Treatment of Obesity Associated With Genetic Defects Upstream of the MC4 Receptor in the Leptin-melanocortin Pathway
This was a long-term extension trial to study the safety and tolerability of continued setmelanotide treatment in participants who had completed a previous clinical trial on treatment with setmelanotide for obesity associated with genetic defects upstream of the Melanocortin-4 (MC4) receptor in the leptin-melanocortin pathway.
Read the detailed description
The primary objectives of this extension trial were to explore the long-term safety and tolerability of setmelanotide for up to 7 years or until drug was otherwise available through authorized use. Participants entered this protocol immediately upon completion of their index protocol such that dosing of setmelanotide continued without gaps in therapy.
- Being tested
- Setmelanotide
- Keywords
- setmelanotide, RM-493, obesity, leptin-melanocortin, melanocortin 4 receptor
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SetmelanotideDrug
Also called RM-493
Once daily subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Setmelanotide | Experimental | Participants received setmelanotide at the same starting dose as received in the index trials as a Subcutaneous (SC) injection once daily for up to 5.6 years in this extension trial. Receives: Drug: Setmelanotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A TEAE was defined as any AE that began or worsened in intensity on or after the date of the first administration of study drug.
Measured: From first dose up to 5.6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start15 Jul 2018
- Primary completion9 Jan 2025
- Study completion9 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Obesity Associated With Defects in Leptin-melanocortin PathwayStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label treatment
- Masking
- None (open label)
- Enrolment
- 205 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
- NCT03651765
- Sponsor's protocol ID
- RM-493-022
- Other IDs
- 2017-005006-35, 2017
- Status last verified
- May 2025
- First submitted
- 18 Jan 2018
- Last updated
- 31 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Roth CL, Scimia C, Shoemaker AH, Gottschalk M, Miller J, Yuan G, Malhotra S, Abuzzahab MJ. Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. Lancet Diabetes Endocrinol. 2024 Jun;12(6):380-389. doi: 10.1016/S2213-8587(24)00087-1. Epub 2024 Apr 30.
PubMed 38697184Meyer 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.
PubMed 35112343
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long Term Extension Trial of Setmelanotide (RM-493) for Patients Who Have Completed a Trial of Setmelanotide for the Treatment of Obesity Associated With Genetic Defects Upstream of the MC4 Receptor in the Leptin-melanocortin Pathway
- ClinicalTrials.gov ID
- NCT03651765
- Acronym / sponsor ID
- RM-493-022
- Keywords
- setmelanotide, RM-493, obesity, leptin-melanocortin, melanocortin 4 receptor
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 205 participants (actual)
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Jul 2018 (actual)
- Primary completion
- 9 Jan 2025 (actual)
- Study completion
- 9 Jan 2025 (actual)
- First posted
- 29 Aug 2018 (actual)
- Results
- Posted 31 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a long-term extension trial to study the safety and tolerability of continued setmelanotide treatment in participants who had completed a previous clinical trial on treatment with setmelanotide for obesity associated with genetic defects upstream of the Melanocortin-4 (MC4) receptor in the leptin-melanocortin pathway.
Detailed description
The primary objectives of this extension trial were to explore the long-term safety and tolerability of setmelanotide for up to 7 years or until drug was otherwise available through authorized use. Participants entered this protocol immediately upon completion of their index protocol such that dosing of setmelanotide continued without gaps in therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label treatment
| Arm | Type | Receives |
|---|---|---|
| Setmelanotide | Experimental | Drug: SetmelanotideParticipants received setmelanotide at the same starting dose as received in the index trials as a Subcutaneous (SC) injection once daily for up to 5.6 years in this extension trial. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Participants aged 2 or older (or aged >2 years as per local regulations) who had completed participation in a previous setmelanotide trial and demonstrated adequate safety and meaningful clinical benefit (efficacy)
- Participant and/or parent or guardian was able to communicate with the investigator, understand and sign the written informed consent/assent, and comply with the trial requirements
- Agree to use a highly effective form of contraception throughout the trial
Key exclusion criteria (9 listed)
- Pregnant and/or breastfeeding women
- Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
- Current, clinically significant disease
- Documented diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
- Suicidal ideation, attempt or behavior
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 |
|---|---|---|
| SetmelanotideAlso: RM-493Once daily subcutaneous injection | Drug | Setmelanotide |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose up to 5.6 years
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A TEAE was defined as any AE that began or worsened in intensity on or after the date of the first administration of study drug.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38697184Roth CL, Scimia C, Shoemaker AH, Gottschalk M, Miller J, Yuan G, Malhotra S, Abuzzahab MJ. Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. Lancet Diabetes Endocrinol. 2024 Jun;12(6):380-389. doi: 10.1016/S2213-8587(24)00087-1. Epub 2024 Apr 30.
- Derived from this study: PubMed 35112343Meyer 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.
- Individual participant dataSharing planned: No
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.
27 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Setmelanotide in people with Obesity Associated With Defects in Leptin-melanocortin Pathway, run by Rhythm Pharmaceuticals, Inc. at 27 sites in 8 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 3 inclusion and 9 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 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Germany, United Kingdom, France, Canada and 3 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: From first dose up to 5.6 years). 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 NCT03651765, which also lists 2 linked publications.
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 31 May 2025.