Bardet-Biedl SyndromePhase 3NCT04966741
Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
A Phase 3 study testing Setmelanotide in people with Bardet-Biedl Syndrome and POMC Deficiency Obesity, run by Rhythm Pharmaceuticals, Inc. at 6 sites in 4 countries.
Trial summary
This is a phase 3 open-label, clinical study to evaluate the efficacy, safety and tolerability of setmelanotide over 1 year of treatment, in pediatric participants aged 2 to <6 years with obesity due to either biallelic variants of the pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1)… Read more about this study
- Who is it for?
- Ages 2 to 5 years
- Conditions the study is for
- Bardet-Biedl Syndrome, POMC Deficiency Obesity, PCSK1 Deficiency Obesity
- 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
- 12 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 8 Mar 2022to 8 Nov 2024
- Phase
- Phase 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 to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Participants must have obesity due to either:
- POMC, PCSK1, or LEPR deficiency, confirmed by genetic testing demonstrating biallelic variants that are interpreted as pathogenic, likely pathogenic, or of undetermined significance (VUS) by the American College of Medical Genetics and Genomics criteria (ACMG), or
- BBS confirmed clinical and genetic diagnosis
- Age between 2 to <6 years at the time of informed consent
- Obesity, defined as body mass index (BMI) ≥97th percentile for age and gender and body weight of at least 15 kilograms (kg) at the time of enrollment.
- Symptoms or behaviors of hyperphagia
- Parent or guardian of study participant is able to understand and comply with the requirements of the study (including QD injection regimen and all other study procedures) and is able to understand and sign the written consent/assent.
Who cannot join
- Glycated hemoglobin (HbA1c) >9.0% at screening
- History of significant liver disease
- Glomerular filtration rate (GFR) <60 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2)
- History or close family history of melanoma, or participant 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.
Show all 11Show fewer
- Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
- Significant hypersensitivity to any excipient in the study drug.
- Inadequate hepatic function
- Any other uncontrolled endocrine, metabolic or medical condition(s) known to impact body weight
- Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
United States3 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Marshfield Clinic Research Foundation
Marshfield, Wisconsin, 54449
Columbia University Medical Center, Division of Pediatric Endocrinology, Diabetes and Metabolism
New York, New York, 10032
United Kingdom1 site
Addenbrooke's Hospital, Wellcome Trust-MRC Institute of Metabolic Science
Cambridge, CB2 0QQ
About this study
Official title: A Phase 3 Multi-Center, 1-Year, Open-Label Study of Setmelanotide in Pediatric Patients Aged 2 to <6 Years of Age With Rare Genetic Causes of Obesity
This is a phase 3 open-label, clinical study to evaluate the efficacy, safety and tolerability of setmelanotide over 1 year of treatment, in pediatric participants aged 2 to <6 years with obesity due to either biallelic variants of the pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) genes or Bardet-Biedl Syndrome (BBS).
Read the detailed description
Pediatric participants aged 2 to <6 years with obesity due to either biallelic variants of the POMC, PCSK1 or LEPR genes or BBS will be enrolled into this phase 3 open-label clinical trial at one of approximately 8 clinical centers in North America, Europe, or Australia. All participants will be assigned to receive setmelanotide via daily subcutaneous (SC) injection for 1 year.
- Conditions
- Bardet-Biedl Syndrome, POMC Deficiency Obesity, PCSK1 Deficiency Obesity, LEPR Deficiency Obesity
- Being tested
- Setmelanotide
- Keywords
- Bardet Biedl Syndrome, POMC Deficiency, PCSK1, LEPR, Obesity, Pediatric Obesity
- Medical subject headings
- Bardet-Biedl Syndrome, Proopiomelanocortin Deficiency, Obesity, Pediatric Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SetmelanotideDrug
Also called IMCIVREE
SC injection once daily.
| Study group | Role | What they receive |
|---|---|---|
| Setmelanotide: PPL Group | Experimental | Participants with POMC)/PCSK1/LEPR biallelic mutations collectively referred to as PPL received setmelanotide at a dose of 0.5 milligrams (mg) per day (QD) via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide. Receives: Drug: Setmelanotide |
| Setmelanotide: BBS Group | Experimental | Participants with BBS received setmelanotide at a dose of 0.5 mg QD via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide. Receives: Drug: Setmelanotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Greater Than or Equal to (≥) 0.2 Reduction of BMI Z-Score From Baseline to Week 52
A "responder" was defined as a decrease from baseline to 52 weeks in the participant's BMI z-score of ≥0.2. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. The BMI Z-scores were based on the World Health Organization's Child Growth Standards 2007 and indicated the number of standard deviations away from the mean. A Z-score of 0 was equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score (< 0) indicated a reduction in BMI from Baseline whereas an increase of BMI-Z score (> 0) indicated an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline up to Week 52
Mean Percent Change From Baseline in BMI
Mean percent change from baseline to Week 52 in BMI was reported. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline, Week 52
Secondary outcomes (7)
Mean Absolute Change From Baseline in BMI Z-score
Mean absolute change from baseline to Week 52 in BMI Z-score was reported. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. The BMI Z-scores were based on the World Health Organization's Child Growth Standards 2007 and indicated the number of standard deviations away from the mean. A Z-score of 0 was equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score (< 0) indicated a reduction in BMI from Baseline whereas an increase of BMI-Z score (> 0) indicated an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline, Week 52
Mean Change From Baseline in Percent of the 95th Percentile of BMI
Mean change from baseline to Week 52 in percent of the 95th percentile of BMI was reported. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. BMI Percentile-scores are measures of relative weight adjusted for child age and gender. The percent of the BMI 95th percentile score expresses the participant's BMI as a percentage of the Centers for Disease Control (CDC) 95th percentile reference population. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline, Week 52
Mean Change From Baseline in Bone Age
Mean change from baseline to Week 52 in bone age was reported. A standard bone age measurement (of the hand/wrist area) was obtained at the beginning and the end of the trial to monitor for growth related safety concerns. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Measured: Baseline, Week 52
Number of Participants With Shift From Baseline in Ages & Stages Questionnaires, Third Edition (ASQ-3)
ASQ-3: developmental screening questionnaire that consists of 5 areas: communication, gross motor, fine motor, problem solving, and personal-social. Each area has 6 questions scored as Yes=10 points, Sometimes=5 points, and Not yet=0 points. A child can score between 0-60 points for each area with total score range: 0 to 300; higher scores are indicative of improvement. Total area score is then compared to age-adjusted standardized score cutoff (determined by developers of tool) which indicate whether child's development appears to be on schedule according to these categories: Below=Total analysis score (TAS) is below cutoff. Further assessment with professional may be needed; Monitor=TAS is close to cutoff. Provide learning activities and monitor; Above= TAS is above cutoff, and child's development appears to be on schedule. Shift from baseline for each developmental area of assessment according to these 3 outcome categories was reported. Total score was not applicable.
Measured: From Baseline to Week 52
Change From Baseline in Body Weight
Change from baseline to Week 52 in body weight was reported.
Measured: Baseline, Week 52
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 started or worsened in intensity on or after the date of the first administration of study drug.
Measured: From first dose of study drug up to Week 56
Number of Participants With TEAEs Graded by Severity
A TEAE 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 started or worsened in intensity on or after the date of the first administration of study drug. TEAEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life Threatening; Grade 5- Death related to AE.
Measured: From first dose of study drug up to Week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2021
- Study start8 Mar 2022
- Primary completion18 Sep 2023
- Study completion8 Nov 2024
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 (1)Papers the sponsor has linked to this study.
- Other trials for Bardet-Biedl SyndromeStudies 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
- None (open label)
- Enrolment
- 12 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
- NCT04966741
- Sponsor's protocol ID
- RM-493-033
- Status last verified
- Nov 2024
- First submitted
- 29 Mar 2021
- Last updated
- 27 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Argente J, Verge CF, Okorie U, Fennoy I, Kelsey MM, Cokkinias C, Scimia C, Lee HM, Farooqi IS. Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial. Lancet Diabetes Endocrinol. 2025 Jan;13(1):29-37. doi: 10.1016/S2213-8587(24)00273-0. Epub 2024 Nov 13.
PubMed 39549719
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Multi-Center, 1-Year, Open-Label Study of Setmelanotide in Pediatric Patients Aged 2 to <6 Years of Age With Rare Genetic Causes of Obesity
- ClinicalTrials.gov ID
- NCT04966741
- Acronym / sponsor ID
- RM-493-033
- Conditions
- Bardet-Biedl Syndrome, POMC Deficiency Obesity, PCSK1 Deficiency Obesity, LEPR Deficiency Obesity
- Keywords
- Bardet Biedl Syndrome, POMC Deficiency, PCSK1, LEPR, Obesity, Pediatric Obesity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Rhythm Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Mar 2022 (actual)
- Primary completion
- 18 Sep 2023 (actual)
- Study completion
- 8 Nov 2024 (actual)
- First posted
- 19 Jul 2021 (actual)
- Results
- Posted 10 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 3 open-label, clinical study to evaluate the efficacy, safety and tolerability of setmelanotide over 1 year of treatment, in pediatric participants aged 2 to <6 years with obesity due to either biallelic variants of the pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) genes or Bardet-Biedl Syndrome (BBS).
Detailed description
Pediatric participants aged 2 to <6 years with obesity due to either biallelic variants of the POMC, PCSK1 or LEPR genes or BBS will be enrolled into this phase 3 open-label clinical trial at one of approximately 8 clinical centers in North America, Europe, or Australia. All participants will be assigned to receive setmelanotide via daily subcutaneous (SC) injection for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Setmelanotide: PPL Group | Experimental | Drug: SetmelanotideParticipants with POMC)/PCSK1/LEPR biallelic mutations collectively referred to as PPL received setmelanotide at a dose of 0.5 milligrams (mg) per day (QD) via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide. |
| Setmelanotide: BBS Group | Experimental | Drug: SetmelanotideParticipants with BBS received setmelanotide at a dose of 0.5 mg QD via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide. |
Who may qualify
- Ages
- 2 to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Participants must have obesity due to either:
- Age between 2 to <6 years at the time of informed consent
- Obesity, defined as body mass index (BMI) ≥97th percentile for age and gender and body weight of at least 15 kilograms (kg) at the time of enrollment.
- Symptoms or behaviors of hyperphagia
- Parent or guardian of study participant is able to understand and comply with the requirements of the study (including QD injection regimen and all other study procedures) and is able to understand and sign the written consent/assent.
Key exclusion criteria (11 listed)
- Glycated hemoglobin (HbA1c) >9.0% at screening
- History of significant liver disease
- Glomerular filtration rate (GFR) <60 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2)
- History or close family history of melanoma, or participant history of oculocutaneous albinism.
- Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
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: IMCIVREESC injection once daily. | Drug | Setmelanotide: BBS Group, Setmelanotide: PPL Group |
Primary outcome
Percentage of Participants With Greater Than or Equal to (≥) 0.2 Reduction of BMI Z-Score From Baseline to Week 52
Time frame: Baseline up to Week 52
A "responder" was defined as a decrease from baseline to 52 weeks in the participant's BMI z-score of ≥0.2. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. The BMI Z-scores were based on the World Health Organization's Child Growth Standards 2007 and indicated the number of standard deviations away from the mean. A Z-score of 0 was equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score (< 0) indicated a reduction in BMI from Baseline whereas an increase of BMI-Z score (> 0) indicated an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug.
Mean Percent Change From Baseline in BMI
Time frame: Baseline, Week 52
Mean percent change from baseline to Week 52 in BMI was reported. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. Baseline was defined as the most recent measurement prior to the first administration of study drug.
7 secondary outcomes
Mean Absolute Change From Baseline in BMI Z-score
Time frame: Baseline, Week 52
Mean Change From Baseline in Percent of the 95th Percentile of BMI
Time frame: Baseline, Week 52
Mean Change From Baseline in Bone Age
Time frame: Baseline, Week 52
Number of Participants With Shift From Baseline in Ages & Stages Questionnaires, Third Edition (ASQ-3)
Time frame: From Baseline to Week 52
Change From Baseline in Body Weight
Time frame: Baseline, Week 52
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug up to Week 56
Number of Participants With TEAEs Graded by Severity
Time frame: From first dose of study drug up to Week 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39549719Argente J, Verge CF, Okorie U, Fennoy I, Kelsey MM, Cokkinias C, Scimia C, Lee HM, Farooqi IS. Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial. Lancet Diabetes Endocrinol. 2025 Jan;13(1):29-37. doi: 10.1016/S2213-8587(24)00273-0. Epub 2024 Nov 13.
- Individual participant dataSharing planned: No
Related trials for Bardet-Biedl Syndrome
RecruitingEarly Phase 1
First-in-Human, Dose Escalation Trial of AXV-101 in BBS1-Related Retinal Degeneration
Bardet-Biedl Syndrome 1, Retinal Degeneration
RecruitingPhase 4
Real-World Effects of MC4R Agonist Therapy in BBS and Severe Genetic Obesity
Bardet Biedl Syndrome (BBS), Bardet Biedl Syndrome
RecruitingObservational study
ARPKD Database Study
Hepato/Renal Fibrocystic Disease, Autosomal Recessive Polycystic Kidney Disease
RecruitingObservational study
Inherited Retinal Degenerative Disease Registry
Eye Diseases Hereditary, Retinal Disease
Active, not recruitingObservational study
Early Genetic Identification of Obesity
Obesity, Childhood, Hyperphagia
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.
6 sites in 4 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 Bardet-Biedl Syndrome and POMC Deficiency Obesity, run by Rhythm Pharmaceuticals, Inc. at 6 sites in 4 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 7 inclusion and 11 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 27 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Australia, Spain, United Kingdom. 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?
Yes. Results are posted in the registry (first posted 10 Jul 2024). 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?
Percentage of Participants With Greater Than or Equal to (≥) 0.2 Reduction of BMI Z-Score From Baseline to Week 52 (time frame: Baseline up to Week 52). The study lists 2 primary outcomes in all. 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 NCT04966741, 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 27 Nov 2024.