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NCT02311673

Phase 2 Trial to Evaluate Safety and Efficacy of Setmelanotide (RM-493) in Obese Participants With Prader-Willi Syndrome

Completed Phase 2 Results posted Last updated 27 July 2023
What this trial tests

Phase 2 trial testing Setmelanotide in Prader-Willi Syndrome in 40 participants. Completed in 26 October 2016.

Timeline
19 March 2015
Primary endpoint
26 October 2016
26 October 2016

Quick facts

Lead sponsorRhythm Pharmaceuticals, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment40
Start date19 March 2015
Primary completion26 October 2016
Estimated completion26 October 2016
Sites5 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Rhythm Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 16 to 65, any sex, with Prader-Willi Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced a Treatment-Emergent Adverse Event (TEAE) - Period 2 Primary · Days 15 to 41

An adverse event (AE) was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. A serious adverse event (SAE) was an

Participants with at least 1 TEAE
GroupValue95% CI
Setmelanotide 0.5 mg (Double-blind Randomized Treatment)4
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)11
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)6
Placebo (Double-blind Randomized Treatment)11
Participants with at least 1 SAE
GroupValue95% CI
Setmelanotide 0.5 mg (Double-blind Randomized Treatment)0
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)0
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)0
Placebo (Double-blind Randomized Treatment)0
Number of Participants Who Experienced a TEAE - Period 3 Primary · Days 42 to 55

An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. An SAE was any untoward medical occurrence that, at

Participants with at least 1 TEAE
GroupValue95% CI
Setmelanotide 0.5 mg (Randomized Withdrawal Period)3
Setmelanotide 1.5 mg (Randomized Withdrawal Period)7
Setmelanotide 2.5 mg (Randomized Withdrawal Period)4
Placebo (Randomized Withdrawal Period)11
Participants with at least 1 SAE
GroupValue95% CI
Setmelanotide 0.5 mg (Randomized Withdrawal Period)0
Setmelanotide 1.5 mg (Randomized Withdrawal Period)0
Setmelanotide 2.5 mg (Randomized Withdrawal Period)0
Placebo (Randomized Withdrawal Period)0
Number of Participants Who Experienced a TEAE - Period 4 Primary · Days 56 to 69

An AE was any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE is considered to be treatment-emergent if the onset date/time is during or after administration of double-blind study drug or, in the event that onset time precedes double-blind study drug administration, the AE increases in severity during or after administration of double-blind study drug; in either case through 1-week after the last treatment dose. An SAE was any untoward medical occurrence that, at

Participants with at least 1 TEAE
GroupValue95% CI
Setmelanotide 1.5 mg (Open-Label Extension)17
Setmelanotide 2.5 mg (Open-Label Extension)12
Placebo (Open-Label Extension)0
Participants with at least 1 SAE
GroupValue95% CI
Setmelanotide 1.5 mg (Open-Label Extension)0
Setmelanotide 2.5 mg (Open-Label Extension)0
Placebo (Open-Label Extension)0
Mean Body Weight - Period 2 Primary · Baseline (Day 15)
GroupValue95% CI
Setmelanotide 0.5 mg (Double-blind Randomized Treatment)94.3± 16.84
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)92.7± 5.50
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)101.6± 5.35
Placebo (Double-blind Randomized Treatment)102.2± 9.16
Percent Change From Baseline in Body Weight - Period 2 Primary · Baseline (Day 15) and Day 42
GroupValue95% CI
Setmelanotide 0.5 mg (Double-blind Randomized Treatment)-0.7-3.1 – 1.8
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)-0.8-2.2 – 0.6
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)0.4-1.2 – 2.0
Placebo (Double-blind Randomized Treatment)-0.4-1.8 – 0.9
Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 Primary · Baseline (Day 15)

The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (n

GroupValue95% CI
Setmelanotide 0.5 mg (Double-blind Randomized Treatment)31.0± 2.86
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)21.2± 2.28
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)20.2± 2.79
Placebo (Double-blind Randomized Treatment)18.7± 2.33
Percent Change From Baseline in Overall Score of Prader-Willi Syndrome (PWS) Hyperphagia Questionnaire - Period 2 Primary · Baseline (Day 15) and Day 42

The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (n

GroupValue95% CI
Setmelanotide 0.5 mg (Double-blind Randomized Treatment)20.2-8.7 – 49.1
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)-5.2-21.3 – 10.9
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)-5.0-23.7 – 13.6
Placebo (Double-blind Randomized Treatment)-1.3-16.9 – 14.3
Percent Change From Baseline in Hyperphagic Drive Score of PWS Hyperphagia Questionnaire - Period 2 Secondary · Baseline (Day 15) and Day 42

The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Hyperphagic drive score assesses the persistence in asking for food based on 4 items. All 4 items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic drive range from a minimum score of 4 (no hyperphagic drive) to a maximum score of 20 (greater hyperphagic drive). Percent change from baseline in hyperphagic drive score of PWS hyperphagia questionna

GroupValue95% CI
Setmelanotide 0.5 mg (Double-blind Randomized Treatment)27.2-8.9 – 63.3
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)-3.6-24.1 – 16.9
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)-6.8-30.5 – 16.8
Placebo (Double-blind Randomized Treatment)6.6-13.2 – 26.4
Percent Change From Baseline in Hyperphagic Behaviors Score of PWS Hyperphagia Questionnaire - Period 2 Secondary · Baseline (Day 15) and Day 42

The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Hyperphagic behavior factor score assesses food seeking behaviors based on 4 items. All 4 items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic behaviors range from a minimum score of 4 (no hyperphagic behavior) to a maximum score of 20 (greater hyperphagic behavior). Percent change from baseline in hyperphagic behaviors score of PWS hyperphagi

GroupValue95% CI
Setmelanotide 0.5 mg (Double-blind Randomized Treatment)19.1-19.3 – 57.5
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)-1.7-22.3 – 18.9
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)-3.0-26.8 – 20.8
Placebo (Double-blind Randomized Treatment)-0.4-20.4 – 19.6
Percent Change From Baseline in Hyperphagic Severity Score of PWS Hyperphagia Questionnaire - Period 2 Secondary · Baseline (Day 15) and Day 42

The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Hyperphagic severity factor score assesses the severity of hyperphagia based on 2 items. Both items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Possible scores for hyperphagic severity range from a minimum score of 2 (no hyperphagic severity) to a maximum score of 10 (greater hyperphagic severity). Percent change from baseline in hyperphagic severity score of PWS hyperpha

GroupValue95% CI
Setmelanotide 0.5 mg (Double-blind Randomized Treatment)33.2-4.4 – 70.9
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)-0.7-22.1 – 20.6
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)5.5-19.1 – 30.2
Placebo (Double-blind Randomized Treatment)-16.7-37.3 – 3.9
Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 3 Secondary · Baseline (Day 42) and Day 56

The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (n

GroupValue95% CI
Setmelanotide 0.5 mg (Randomized Withdrawal Period)35.0-2.9 – 72.9
Setmelanotide 1.5 mg (Randomized Withdrawal Period)-1.8-18.4 – 14.7
Setmelanotide 2.5 mg (Randomized Withdrawal Period)3.4-20.1 – 26.9
Placebo (Randomized Withdrawal Period)2.3-9.6 – 14.2
Percent Change From Baseline in Overall Score of PWS Hyperphagia Questionnaire - Period 4 Secondary · Baseline (Day 56) and Day 70

The hyperphagia questionnaire is a 10-item instrument designed to measure food-related preoccupations and problems in PWS, as well as the severity of these concerns. Three factors identified from this questionnaire are: Hyperphagic Drive, Hyperphagic Behaviors, and Hyperphagic Severity. Items are rated by care providers on a 5-point scale (1=not a problem to 5=a severe and/or frequent problem). Raw scores for each factor were used in data analyses, and the 3 domains were summed for an overall summary index of hyperphagia. Possible scores on the questionnaire range from a minimum score of 10 (n

GroupValue95% CI
Setmelanotide 1.5 mg (Open-Label Extension)-0.9± 23.21
Setmelanotide 2.5 mg (Open-Label Extension)-0.4± 29.94

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 15 to Day 69. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Setmelanotide 0.5 mg (Double-blind Randomized Treatment)
Serious: 0/4 (0%)
Deaths: 0/4
Setmelanotide 1.5 mg (Double-blind Randomized Treatment)
Serious: 0/13 (0%)
Deaths: 0/13
Setmelanotide 2.5 mg (Double-blind Randomized Treatment)
Serious: 0/8 (0%)
Deaths: 0/8
Placebo (Double-blind Randomized Treatment)
Serious: 0/15 (0%)
Deaths: 0/15
Setmelanotide 0.5 mg (Randomized Withdrawal Period)
Serious: 0/3 (0%)
Deaths: 0/3
Setmelanotide 1.5 mg (Randomized Withdrawal Period)
Serious: 0/10 (0%)
Deaths: 0/10
Setmelanotide 2.5 mg (Randomized Withdrawal Period)
Serious: 0/5 (0%)
Deaths: 0/5
Placebo (Randomized Withdrawal Period)
Serious: 0/20 (0%)
Deaths: 0/20
Setmelanotide 1.5 mg (Open-Label Extension)
Serious: 0/22 (0%)
Deaths: 0/22
Setmelanotide 2.5 mg (Open-Label Extension)
Serious: 0/16 (0%)
Deaths: 0/16
Placebo (Open-Label Extension)
Serious: 0/1 (0%)
Deaths: 0/1
Other adverse events (63 terms — click to expand)

ReactionSystemSetmelanotide 0.5 mg (Doub…Setmelanotide 1.5 mg (Doub…Setmelanotide 2.5 mg (Doub…Placebo (Double-blind Rand…Setmelanotide 0.5 mg (Rand…Setmelanotide 1.5 mg (Rand…Setmelanotide 2.5 mg (Rand…Placebo (Randomized Withdr…Setmelanotide 1.5 mg (Open…Setmelanotide 2.5 mg (Open…Placebo (Open-Label Extens…
Injection site erythemaGeneral disorders
Injection site indurationGeneral disorders
Injection site oedemaGeneral disorders
Injection site bruisingGeneral disorders
Injection site pruritusGeneral disorders
Injection site painGeneral disorders
Injection site discolourationGeneral disorders
Injection site erosionGeneral disorders
Skin hyperpigmentationSkin and subcutaneous tissue disorders
Skin discolourationSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
Melanocytic naevusNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Influenza like illnessGeneral disorders
Injection site noduleGeneral disorders
Injection site reactionGeneral disorders
Injection site swellingGeneral disorders
Non-cardiac chest painGeneral disorders
Chest discomfortGeneral disorders
EphelidesSkin and subcutaneous tissue disorders
Ingrowing nailSkin and subcutaneous tissue disorders
HyperkeratosisSkin and subcutaneous tissue disorders
Skin erosionSkin and subcutaneous tissue disorders
MiliariaSkin and subcutaneous tissue disorders
Seborrhoeic dermatitisSkin and subcutaneous tissue disorders
Skin lesionSkin and subcutaneous tissue disorders
Solar lentigoSkin and subcutaneous tissue disorders
Erection increasedReproductive system and breast disorders
Spontaneous penile erectionReproductive system and breast disorders
DysmenorrhoeaReproductive system and breast disorders
MenorrhagiaReproductive system and breast disorders
Genital disorder femaleReproductive system and breast disorders
Blood creatine phosphokinase increasedInvestigations
Soft tissue massMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
AggressionPsychiatric disorders
Sleep disorderPsychiatric disorders
TearfulnessPsychiatric disorders
Abnormal behaviourPsychiatric disorders
IrritabilityPsychiatric disorders
Mood alteredPsychiatric disorders

Data from ClinicalTrials.gov NCT02311673 adverse events section.

Sponsor's own description

The purpose of this study was to evaluate the effects of a once daily subcutaneous injectable formulation of setmelanotide in obese participants with Prader-Willi syndrome on tolerability, weight loss, and hyperphagia-related behavior. The study drug (setmelanotide and placebo) was administered in a blinded fashion.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?
    Tak YJ, Lee SY. · · 2021 · cited 196× · PMID 33410104 · DOI 10.1007/s13679-020-00422-w
  2. Obesity management in Prader-Willi syndrome: current perspectives.
    Crinò A, Fintini D, Bocchini S, Grugni G. · · 2018 · cited 88× · PMID 30323638 · DOI 10.2147/dmso.s141352
  3. The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits.
    Hinney A, Körner A, Fischer-Posovszky P. · · 2022 · cited 63× · PMID 35902734 · DOI 10.1038/s41574-022-00716-0
  4. Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.
    Ericson MD, Lensing CJ, Fleming KA, Schlasner KN, et al · · 2017 · cited 60× · PMID 28363699 · DOI 10.1016/j.bbadis.2017.03.020
  5. Magel2-null mice are hyper-responsive to setmelanotide, a melanocortin 4 receptor agonist.
    Bischof JM, Van Der Ploeg LH, Colmers WF, Wevrick R. · · 2016 · cited 26× · PMID 27339818 · DOI 10.1111/bph.13540
  6. Preclinical Testing in Translational Animal Models of Prader-Willi Syndrome: Overview and Gap Analysis.
    Carias KV, Wevrick R. · · 2019 · cited 19× · PMID 30989085 · DOI 10.1016/j.omtm.2019.03.001
  7. Advances in Anti-obesity Pharmacotherapy: Current Treatments, Emerging Therapies, and Challenges.
    Brandfon S, Eylon A, Khanna D, Parmar MS. · · 2023 · cited 15× · PMID 37937009 · DOI 10.7759/cureus.46623
  8. Prader-Willi syndrome: an update on obesity and endocrine problems.
    Kim SJ, Cho SY, Jin DK. · · 2021 · cited 14× · PMID 34991300 · DOI 10.6065/apem.2142164.082

Verify or expand the search:

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Trials by the same sponsor.

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Data sources for this page

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