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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity

NCTNCT03746522 (opens ClinicalTrials.gov in a new tab)Other idRM-493-023Other id2018-004058-11Other id2018

Overview

Status
Completed
Phase
Phase 3
Enrollment
52 participants (actual)
Sponsor
Rhythm Pharmaceuticals, Inc. · Industry
Design
Randomized · Quadruple masking
Countries
6 countries

United States, Canada, France, Puerto Rico, Spain, United Kingdom

Start
23 Nov 2018
Primary completion
16 Nov 2020
Completion
8 Mar 2021
First posted
19 Nov 2018
Last update posted
1 Dec 2023
Conditions
Bardet Biedl Syndrome (BBS) · Alström Syndrome (AS)

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20182019202020212022
  1. Ph 3

    Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity

    NCT03746522

    23 Nov 2018 to 8 Mar 2021

Registry summary

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

This pivotal, phase 3 study is designed to confirm the efficacy and safety of setmelanotide, a potent melanocortin receptor type 4 (MC4R) agonist, for the treatment of obesity and hyperphagia in participants with Bardet Biedl syndrome (BBS) or Alström syndrome (AS). The study's primary efficacy endpoint is to evaluate the proportion of participants (≥ 12 years of age at baseline) who lose ≥ 10% of their baseline body weight following approximately (\~) 52 weeks of treatment with setmelanotide compared to a historical control rate.

Interventions

  • SetmelanotideDrug
  • PlaceboDrug

Arms3

  • Experimental

    Setmelanotide (Double-Blind)

    Participants received once daily SC injection of setmelanotide for 14 weeks in a double-blind placebo-controlled treatment period (Period 1). Participants ≥16 years of age started on setmelanotide 2.0 mg with dose escalation to 3.0 mg. Participants \<16 years of age started on setmelanotide 1.0 mg with dose escalation to 3.0 mg.

  • Placebo comparator

    Placebo (Double-Blind)

    Participants received once daily SC injection of placebo (matching setmelanotide) for 14 weeks in a double-blind placebo-controlled treatment period (Period 1).

  • Experimental

    Setmelanotide (Open-label)

    After the initial 14-week double-blind treatment period, all participants immediately transitioned to open-label setmelanotide once daily SC injection for 38 weeks (Period 2) and then continued to receive setmelanotide in the 14-week open-label treatment period (Period 3).

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percentage of Participants (≥12 Years of Age at Baseline) Who Reached ≥10% Weight Loss Threshold After 1 Year (Period 2): Pivotal Cohort

    Time frame · 52 weeks

    Registry description

    The percentage of participants (≥12 years of age at baseline) who achieved a ≥10% reduction from baseline in body weight at Period 2 or after 52 weeks of treatment with setmelanotide were analyzed. There was a 14-week placebo-controlled period at the beginning of the trial. After completion of the placebo-controlled period, all participants from the placebo group switched to setmelanotide treatment. The placebo group was integrated into the 52-week analysis so that the participants who received placebo, had 52 weeks of setmelanotide treatment after the first dose of "active" treatment. Placebo participants were also included in this analysis.

Secondary outcomes(3)
  1. Mean Percent Change From Baseline in Body Weight (≥12 Years of Age) at Week 52 (Period 2): Pivotal Cohort

    Time frame · Baseline, Week 52

    Registry description

    The mean percent change from baseline in body weight at 52 weeks was analyzed. There was a 14-week placebo-controlled period at the beginning of the trial. After completion of the placebo-controlled period, all participants from the placebo group switched to setmelanotide treatment. The placebo group was integrated into the 52-week analysis so that the participants who received placebo, had 52 weeks of setmelanotide treatment after the first dose of "active" treatment. Placebo participants were also included in this analysis.

  2. Mean Percent Change From Baseline in the Weekly Average of the Daily Hunger Score (≥12 Years of Age) at Week 52 (Period 2): Pivotal Cohort

    Time frame · Baseline, Week 52

    Registry description

    Mean percent change in hunger scores for participants ≥12 years of age with leptin receptor (LEPR) deficiency obesity in treatment with setmelanotide was evaluated. Hunger score ranged from 0= "not hungry at all" to 10= "hungriest possible" on Likert-type scale. On Daily Hunger Questionnaire, each of the 3 items (average hunger, most/worst hunger, and morning hunger) was scored separately and averaged on weekly basis. Weekly average hunger score of daily worst (most) hunger score in 24 hours is the hunger score used to assess this study endpoint. There was a 14-week placebo-controlled period at the beginning of the trial. After completion of the placebo-controlled period, all participants from the placebo group switched to setmelanotide treatment. Placebo group was integrated into the 52-week analysis so that participants who received placebo, had 52 weeks of setmelanotide treatment after the first dose of "active" treatment. Placebo participants were also included in this analysis.

  3. Number of Participants (≥12 Years of Age With no Cognitive Impairment) Who Achieved a ≥ 25% Improvement in the Weekly Average of the Daily Hunger Score From Baseline at Week 52 (Period 2): Pivotal Cohort

    Time frame · Baseline, Week 52

    Registry description

    Number of participants (≥12 years of age with no cognitive impairment) achieving ≥25% improvement from baseline in hunger score at Week 52 was assessed. Hunger score ranged from 0= "not hungry at all" to 10= "hungriest possible" on Likert-type scale. On Daily Hunger Questionnaire, each of the 3 items (average hunger, most/worst hunger, and morning hunger) was scored separately and averaged on weekly basis. Weekly average hunger score of daily worst (most) hunger score in 24 hours is the hunger score used to assess this study endpoint. There was a 14-week placebo-controlled period at the beginning of the trial. After completion of placebo-controlled period, all participants from placebo group switched to setmelanotide treatment. Placebo group was integrated into the 52-week analysis so that participants who received placebo, had 52 weeks of setmelanotide treatment after the first dose of "active" treatment. Placebo participants were also included in this analysis.

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 outcomeNumber· 52 weeks

Percentage of Participants (≥12 Years of Age at Baseline) Who Reached ≥10% Weight Loss Threshold After 1 Year (Period 2): Pivotal Cohort

GroupValue (percentage of participants)
Pivotal Cohort32.3
Secondary and other outcome results(3)
Secondary outcomeMean· Baseline, Week 52

Mean Percent Change From Baseline in Body Weight (≥12 Years of Age) at Week 52 (Period 2): Pivotal Cohort

GroupValue (percent change)Spread
Pivotal Cohort-5.217.895
Secondary outcomeMean· Baseline, Week 52

Mean Percent Change From Baseline in the Weekly Average of the Daily Hunger Score (≥12 Years of Age) at Week 52 (Period 2): Pivotal Cohort

GroupValue (percent change)Spread
Pivotal Cohort-30.9124.733
Secondary outcomeCount of participants· Baseline, Week 52

Number of Participants (≥12 Years of Age With no Cognitive Impairment) Who Achieved a ≥ 25% Improvement in the Weekly Average of the Daily Hunger Score From Baseline at Week 52 (Period 2): Pivotal Cohort

GroupValue (Participants)
Pivotal Cohort10

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Setmelanotide (Double-Blind Period)Participants received once daily SC injection of setmelanotide for 14 weeks in a double-blind placebo-controlled treatment period (Period 1).0 / 271 / 2726 / 27
Placebo (Double-Blind Period)Participants received once daily SC injection of placebo (matching setmelanotide) for 14 weeks in a double-blind placebo-controlled treatment period (Period 1).0 / 252 / 2524 / 25
Setmelanotide (Open-label)After the initial 14-week double-blind treatment period, all participants immediately transitioned to open-label setmelanotide once daily SC injection for 38 weeks (Period 2) and then continued to receive setmelanotide in the 14-week open-label treatment period (Period 3).0 / 500 / 5045 / 50

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

Studies6

Studies that cite this trial.

Studies with results

2 studies on this page

PubMed tag: none · 2026

Measuring Hunger Severity in Rare MC4R Pathway Diseases: Development and Psychometric Evaluation of the Most Hunger Item.

Clément et al. 2026Advances in therapy

PMID 42821228DOI 10.1007/s12325-026-03741-xPUB-42821228

Full text at the publisher
Publisher page

Indexing hint: Clinical trial · 2023

6 results

Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results.

Forsythe et al. 2023Orphanet journal of rare diseasescited by 34

PMID 36647077PMC9841937DOI 10.1186/s13023-022-02602-4PUB-36647077

CC BY6 results

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

More studies

3 studies on this page

Indexing hint: Clinical trial · 2026

Corrected

Setmelanotide in Bardet-Biedl Syndrome: A 52-Week Comparison of Phase 3 Trial Participants With a Matched Registry Cohort.

Argente et al. 2026Obesity (Silver Spring, Md.)cited by 3

PMID 41703984PMC12933228DOI 10.1002/oby.70125PUB-41703984

CC BY

Indexing hint: Randomized controlled trial · 2022

Corrected

Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period.

Haqq et al. 2022The lancet. Diabetes & endocrinologycited by 149

PMID 36356613PMC9847480DOI 10.1016/s2213-8587(22)00277-7PUB-36356613

Rights unknown

PubMed tag: none · 2021

The efficacy and safety of setmelanotide in individuals with Bardet-Biedl syndrome or Alström syndrome: Phase 3 trial design.

Haws et al. 2021Contemporary clinical trials communicationscited by 32

PMID 34013094PMC8114053DOI 10.1016/j.conctc.2021.100780PUB-34013094

CC BY
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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. BBS clinical diagnosis or AS diagnosis 2. Greater than or equal to (≥) 6 years of age. 3. Obese, defined as BMI ≥30 kilograms/meters\^2 for participants ≥16 years of age or weight \>97th percentile for age and sex on growth chart assessment for participants 6 to 15 years of age. 4. Study 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. 5. Female participants of child-bearing potential must be confirmed non-pregnant and agree to use contraception as outlined in the protocol. Female participants of non-childbearing potential, defined as: surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), post-menopausal for at least 12 months (and confirmed with a screening follicle stimulating hormone (FSH) level in the post-menopausal lab range), or failure to have progressed to Tanner Stage V and/or failure to have achieved menarche, do not require contraception during the study. 6. Male participants with female partners of childbearing potential must agree to use a double barrier method contraception if they become sexually active during the study or within 90 days following their participation in the study. Male participants must also not donate sperm during and for 90 days following their participation in the study. Exclusion Criteria: 1. Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents (including herbal medications) that has resulted in \>2% weight loss. These participants may be reconsidered approximately 1 month after cessation of such intensive regimens. 2. Current or prior (within prior 2 months) use of any medication, including those approved to treat obesity, that could impact the efficacy results of this study (e.g., orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, liraglutide). Participants on a stable dose and regimen (for at least 2 months) of medication to treat attention deficit hyperactivity disorder (ADHD) may be enrolled in the study as long as they agree to remain on the same dose and regimen during the study. 3. Prior gastric bypass surgery resulting in \>10% weight loss durably maintained from the baseline pre-operative weight with no evidence of weight regain. Specifically, participants may be considered if surgery was not successful, resulted in \<10% weight loss compared to pre-operative baseline weight, or there is clear evidence of weight regain after an initial response to bariatric surgery. All participants with a history of bariatric surgery must be discussed with, and receive approval from, the Sponsor prior to enrollment. 4. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-V) disorders that the Investigator believes will interfere significantly with study compliance. Neurocognitive disorders affecting ability to consent will not be disqualifying as long as an appropriate guardian able to give consent has been appointed. 5. In participants with no significant neurocognitive deficits: * A Patient Health Questionnaire-9 (PHQ-9) score of ≥15 and/or * Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS), any lifetime history of a suicide attempt, or any suicidal behavior in the last month. 6. Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results. Any participant with a potentially clinically significant disease should be reviewed with the Sponsor to determine eligibility. 7. History of significant liver disease or liver injury, or a current liver assessment due to abnormal liver tests (as indicated by abnormal liver function tests, alanine transaminase \[ALT\], aspartate transaminase \[AST\], alkaline phosphatase, or serum bilirubin \>1.5x the upper limit of normal \[ULN\] for any of these tests) for an etiology other than non-alcoholic fatty liver disease (NAFLD). Thus, any underlying etiology besides NAFLD, including diagnosed non-alcoholic steatohepatitis (NASH), other causes of hepatitis, or history of hepatic cirrhosis is exclusionary, but the presence of NAFLD is not exclusionary. 8. Moderate to severe renal dysfunction defined as \<30 mL/min. 9. History or close family history (parents or siblings) of skin cancer or melanoma (excluding non-invasive basal or squamous cell lesion), or participant history of ocular-cutaneous albinism. 10. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion). 11. Participant is, in the opinion of the Study Investigator, not suitable to participate in the study. 12. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing. 13. Significant hypersensitivity to study drug. 14. Inability to comply with once daily (QD) injection regimen.

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