Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial.

Argente J, Verge CF, Okorie U, Fennoy I, Kelsey MM, Cokkinias C, Scimia C, Lee HM, Farooqi IS

The lancet. Diabetes & endocrinology13 Nov 2024Cited by 33 (Europe PMC)

PMID39549719DOI10.1016/s2213-8587(24)00273-0PepBankPUB-39549719

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study16

16 results from studies that gave the peptide. 16 results from people.

01HumanNon-randomized trialEfficacy outcome
In children aged 2-5 years, 10 of 12 (83%) reached a BMI Z score reduction of at least 0.2 at week 52 with setmelanotide (95% CI 58.7-99.8).
In plain wordsIn children aged 2-5 years, 83% reached a BMI Z score reduction of at least 0.2 with setmelanotide.
Peptide
Setmelanotide
Outcome
Not applicableBMI Z score responder proportion
Study
n = 12
Comparator
Baseline
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Measurements
Responders with BMI Z score reduction of 0.2 or more
10 patients
Overall, week 52
Responders
83%
Overall, week 52
Responders CI lower
58.7%
Overall, week 52
Responders CI upper
99.8%
Overall, week 52
Source sentences
Summary
Ten (83%) of the 12 overall participants reached a 0·2-point reduction or more in BMI Z score per WHO methodology at week 52 (95% CI 58·7-99·8).
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971901
02HumanNon-randomized trialEfficacy outcome
In children aged 2-5 years, mean BMI changed by -18% (SD 13) from baseline at week 52 with setmelanotide.
In plain wordsIn children aged 2-5 years, BMI decreased by an average of 18% from baseline with setmelanotide at week 52.
Peptide
Setmelanotide
Outcome
DecreaseOverall BMI change
Study
n = 12
Comparator
Baseline
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Measurements
BMI percent change
−18%
Overall safety population, week 52
BMI percent change SD
13%
Overall safety population, week 52
Source sentences
Summary
The mean percent change in BMI from baseline at week 52 was -18% (SD 13) in the overall safety population.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971902
03HumanNon-randomized trialEfficacy outcome
In children aged 2-5 years, BMI Z score was reduced by a mean 3.4 (2.5 in brackets) at week 52 with setmelanotide in this open-label trial.
In plain wordsIn children aged 2-5 years, BMI Z score decreased from baseline with setmelanotide at week 52.
Peptide
Setmelanotide
Outcome
DecreaseBMI Z score reduction
Study
n: not reported in source
Comparator
Baseline
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Measurements
BMI Z score reduction
3.4 BMI Z score points
Week 52
BMI Z score reduction bracketed value
2.5 BMI Z score points
Week 52
Source sentences
Summary
Mean reductions in secondary endpoints of BMI Z score (3·4 [2·5]) and percent of the BMI 95th percentile (32·5 [22·9]) were seen at Week 52.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971905
04HumanNon-randomized trialEfficacy outcome
In children aged 2-5 years with rare MC4R pathway-associated obesity, setmelanotide reduced percent of the BMI 95th percentile by a mean of 32.5 [22.9] at week 52 versus baseline.
In plain wordsIn children aged 2-5 years, percent of the BMI 95th percentile decreased from baseline with setmelanotide at week 52.
Peptide
Setmelanotide
Outcome
DecreasePercent of BMI 95th percentile reduction
Study
n: not reported in source
Comparator
Baseline
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Measurements
Mean reduction in percent of the BMI 95th percentile
32.5 percent of the BMI 95th percentile
Week 52, change from baseline
Bracketed value for percent of the BMI 95th percentile
22.9 percent of the BMI 95th percentile
Week 52; spread not labeled in abstract
Source sentences
Summary
Mean reductions in secondary endpoints of BMI Z score (3·4 [2·5]) and percent of the BMI 95th percentile (32·5 [22·9]) were seen at Week 52.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971906
05HumanNon-randomized trialSafety outcome
In children aged 2-5 years receiving setmelanotide, all adverse events were mild or moderate.
In plain wordsIn children aged 2-5 years receiving setmelanotide, all adverse events were mild or moderate.
Peptide
Setmelanotide
Outcome
Not applicableAdverse event severity
Study
n = 12
Outcome group
Adverse events · Whole body
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
All adverse events were mild or moderate; skin hyperpigmentation, vomiting, nasopharyngitis, upper respiratory tract infection, and injection site reactions were most common.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971908
06HumanNon-randomized trialSafety outcome
In children aged 2-5 years receiving setmelanotide, skin hyperpigmentation was among the most common adverse events.
In plain wordsIn children aged 2-5 years receiving setmelanotide, skin darkening was among the most common adverse events.
Peptide
Setmelanotide
Outcome
Not applicableSkin hyperpigmentation
Study
n = 12
Outcome group
Pigmentation · Skin and wound
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
All adverse events were mild or moderate; skin hyperpigmentation, vomiting, nasopharyngitis, upper respiratory tract infection, and injection site reactions were most common.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971909
07HumanNon-randomized trialSafety outcome
In children aged 2-5 years receiving setmelanotide, vomiting was among the most common adverse events.
In plain wordsIn children aged 2-5 years receiving setmelanotide, vomiting was among the most common adverse events.
Peptide
Setmelanotide
Outcome
Not applicableVomiting
Study
n = 12
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
All adverse events were mild or moderate; skin hyperpigmentation, vomiting, nasopharyngitis, upper respiratory tract infection, and injection site reactions were most common.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971910
08HumanNon-randomized trialSafety outcome
In children aged 2-5 years receiving setmelanotide, nasopharyngitis was among the most common adverse events.
In plain wordsIn children aged 2-5 years receiving setmelanotide, nose and throat inflammation was among the most common adverse events.
Peptide
Setmelanotide
Outcome
Not applicableNasopharyngitis
Study
n = 12
Outcome group
Adverse events · Respiratory
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
All adverse events were mild or moderate; skin hyperpigmentation, vomiting, nasopharyngitis, upper respiratory tract infection, and injection site reactions were most common.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971911
09HumanNon-randomized trialSafety outcome
In children aged 2-5 years receiving setmelanotide, upper respiratory tract infection was among the most common adverse events.
In plain wordsIn children aged 2-5 years receiving setmelanotide, upper respiratory tract infection was among the most common adverse events.
Peptide
Setmelanotide
Outcome
Not applicableUpper respiratory tract infection
Study
n = 12
Outcome group
Adverse events · Respiratory
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
All adverse events were mild or moderate; skin hyperpigmentation, vomiting, nasopharyngitis, upper respiratory tract infection, and injection site reactions were most common.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971912
10HumanNon-randomized trialSafety outcome
In children aged 2-5 years receiving setmelanotide, injection site reactions were among the most common adverse events.
In plain wordsIn children aged 2-5 years receiving setmelanotide, injection site reactions were among the most common adverse events.
Peptide
Setmelanotide
Outcome
Not applicableInjection site reactions
Study
n = 12
Outcome group
Adverse events · Skin and wound
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
All adverse events were mild or moderate; skin hyperpigmentation, vomiting, nasopharyngitis, upper respiratory tract infection, and injection site reactions were most common.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971913
11HumanNon-randomized trialSafety outcome
In children aged 2-5 years receiving setmelanotide, no serious adverse events were reported.
In plain wordsIn children aged 2-5 years receiving setmelanotide, no serious adverse events were reported.
Peptide
Setmelanotide
Outcome
Not applicableSerious adverse events
Study
n = 12
Outcome group
Adverse events · Whole body
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
No serious adverse events or adverse events leading to study discontinuation or death were reported.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971914
12HumanNon-randomized trialSafety outcome
In children aged 2-5 years receiving setmelanotide, no adverse events led to study discontinuation.
In plain wordsIn children aged 2-5 years receiving setmelanotide, no adverse events led to study discontinuation.
Peptide
Setmelanotide
Outcome
Not applicableAdverse events leading to discontinuation
Study
n = 12
Outcome group
Adverse events · Whole body
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
No serious adverse events or adverse events leading to study discontinuation or death were reported.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971915
13HumanNon-randomized trialSafety outcome
In children aged 2-5 years receiving setmelanotide, no adverse events leading to death were reported.
In plain wordsIn children aged 2-5 years receiving setmelanotide, no adverse events leading to death were reported.
Peptide
Setmelanotide
Outcome
Not applicableAdverse events leading to death
Study
n = 12
Outcome group
Mortality · Whole body
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Source sentences
Summary
No serious adverse events or adverse events leading to study discontinuation or death were reported.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971916
14HumanNon-randomized trialEfficacy outcome
In children with POMC or LEPR deficiency, mean BMI changed by -26% (SD 11) at week 52 with setmelanotide.
In plain wordsIn children with POMC or LEPR deficiency, BMI decreased by an average of 26% from baseline with setmelanotide at week 52.
Peptide
Setmelanotide
Outcome
DecreaseBMI change in POMC or LEPR deficiency
Study
n = 7
Comparator
Baseline
Outcome group
Body weight · Metabolic and weight
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Measurements
BMI percent change
−26%
POMC or LEPR deficiency, week 52
BMI percent change SD
11%
POMC or LEPR deficiency, week 52
Source sentences
Summary
Mean percent change in BMI at week 52 was -26% (SD 11) in patients with POMC or LEPR deficiency and -10% (9) in patients with BBS.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971903
15HumanNon-randomized trialEfficacy outcome
In children with BBS, mean BMI changed by -10% (9 in brackets) at week 52 with setmelanotide.
In plain wordsIn children with BBS, BMI decreased by an average of 10% from baseline with setmelanotide at week 52.
Peptide
Setmelanotide
Outcome
DecreaseBMI change in BBS
Study
n = 5
Comparator
Baseline
Outcome group
Body weight · Metabolic and weight
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Measurements
BMI percent change
−10%
BBS, week 52
Bracketed variability value
9%
BBS subgroup; variability type not stated
Source sentences
Summary
Mean percent change in BMI at week 52 was -26% (SD 11) in patients with POMC or LEPR deficiency and -10% (9) in patients with BBS.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971904
16HumanNon-randomized trialEfficacy outcome
In children aged 2-5 years receiving setmelanotide, 91% of caregivers reported less hunger than at baseline.
In plain wordsIn children aged 2-5 years receiving setmelanotide, 91% of caregivers reported less hunger than at baseline.
Peptide
Setmelanotide
Outcome
DecreaseCaregiver-reported hunger
Study
n: not reported in source
Comparator
Baseline
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Once daily, starting at 0.5 mg, increasing every 2 weeks by 0.5 mg to a weight-based maximum · subcutaneous · 52 weeksAs given in this study (human).
Measurements
Caregivers reporting less hunger than baseline
91%
Caregivers, 2-5 year olds
Source sentences
Summary
91% of caregivers reported that patients were less hungry than at baseline.
2 context sentences(design, population, supporting numbers)
Summary · context
This phase 3, open-label, multicentre trial, conducted across six sites in the USA, the UK, Spain, and Australia, enrolled eligible patients aged 2-5 years who had hyperphagia and obesity due to biallelic POMC (including PCSK1) or LEPR variants or genetically confirmed BBS.
Summary · context
Open-label subcutaneous setmelanotide was administered once daily for 52 weeks, starting at 0·5 mg with doses increasing every 2 weeks in 0·5 mg increments until reaching the maximum dose based on weight.
Report a problemFND-3954971907

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT04966741

Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity

Rhythm Pharmaceuticals, Inc.n = 128 Mar 2022 to 8 Nov 2024

Bardet-Biedl Syndrome · POMC Deficiency Obesity · PCSK1 Deficiency Obesity · LEPR Deficiency Obesity

Trial page ClinicalTrials.govUpdated 27 Nov 2024

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:36 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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