A Phase 3 interventional study of Setmelanotide in Bardet-Biedl Syndrome, POMC Deficiency Obesity and PCSK1 Deficiency Obesity, sponsored by Rhythm Pharmaceuticals, Inc.. Completed at 6 sites in 4 countries. Open to participants aged 2 Years to 5 Years. Per ClinicalTrials.gov, last updated 2024-11-27.
Sponsored by Rhythm Pharmaceuticals, Inc. · Phase 3, Interventional, and Treatment
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).
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.
6,296 studies on the registry are indexed under Obesity; 1,692 are open to participants now.
This study's enrollment of 12 is below the median of 78 across 4,878 interventional studies indexed under Obesity.
Browse Obesity studies →Rhythm Pharmaceuticals, Inc. is the lead sponsor of 28 studies on the registry; 3 are open to participants now.
Of its 18 completed or terminated interventional studies of FDA-regulated products, 12 (67%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Participants must have obesity due to either:
Key Exclusion Criteria
Other protocol defined Inclusion/Exclusion criteria may apply.
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.
Drug: Setmelanotide
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.
Drug: Setmelanotide
SC injection once daily.
Also known as: IMCIVREE
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.
Time frame: 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.
Time frame: Baseline, Week 52
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From Baseline to Week 52
Change From Baseline in Body Weight
Change from baseline to Week 52 in body weight was reported.
Time frame: 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.
Time frame: 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.
Time frame: From first dose of study drug up to Week 56
| Milestone | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Started | 7 | 5 |
| Completed | 6 | 5 |
| Not completed | 1 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
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.
| percentage of participants | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Percentage of Participants With Greater Than or Equal to (≥) 0.2 Reduction of BMI Z-Score From Baseline to Week 52 | 85.7 (54.1 to 100) | 80.0 (28.4 to 99.5) |
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.
| percent change | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Mean Percent Change From Baseline in BMI | -25.597 ± 11.4911 | -9.719 ± 8.8383 |
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.
| Z-score | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Mean Absolute Change From Baseline in BMI Z-score | -5.185 ± 1.8585 | -1.331 ± 1.2295 |
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.
| percentage relative to 95th percentile | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Mean Change From Baseline in Percent of the 95th Percentile of BMI | -47.595 ± 17.3280 | -14.462 ± 13.8571 |
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.
| years | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Mean Change From Baseline in Bone Age | 1.020 ± 1.0733 | 0.700 ± 0.8367 |
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.
| Participants | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Communication — Baseline (Above): Week 52 (Above) | 5 | 2 |
| Communication — Baseline (Above): Week 52 (Monitor) | 0 | 0 |
| Communication — Baseline (Above): Week 52 (Below) | 0 | 0 |
| Communication — Baseline (Monitor): Week 52 (Above) | 0 | 0 |
| Communication — Baseline (Monitor): Week 52 (Monitor) | 0 | 1 |
| Communication — Baseline (Monitor): Week 52 (Below) | 0 | 0 |
| Communication — Baseline (Below): Week 52 (Above) | 0 | 0 |
| Communication — Baseline (Below): Week 52 (Monitor) | 0 | 0 |
| Communication — Baseline (Below): Week 52 (Below) | 1 | 2 |
| Fine Motor — Baseline (Above): Week 52 (Above) | 4 | 2 |
| Fine Motor — Baseline (Above): Week 52 (Monitor) | 0 | 0 |
| Fine Motor — Baseline (Above): Week 52 (Below) | 0 | 0 |
| Fine Motor — Baseline (Monitor): Week 52 (Above) | 0 | 1 |
| Fine Motor — Baseline (Monitor): Week 52 (Monitor) | 0 | 0 |
| Fine Motor — Baseline (Monitor): Week 52 (Below) | 1 | 1 |
| Fine Motor — Baseline (Below): Week 52 (Above) | 0 | 0 |
| Fine Motor — Baseline (Below): Week 52 (Monitor) | 0 | 0 |
| Fine Motor — Baseline (Below): Week 52 (Below) | 1 | 1 |
| Gross Motor — Baseline (Above): Week 52 (Above) | 1 | 0 |
| Gross Motor — Baseline (Above): Week 52 (Monitor) | 0 | 0 |
| Gross Motor — Baseline (Above): Week 52 (Below) | 0 | 0 |
| Gross Motor — Baseline (Monitor): Week 52 (Above) | 0 | 0 |
| Gross Motor — Baseline (Monitor): Week 52 (Monitor) | 0 | 0 |
| Gross Motor — Baseline (Monitor): Week 52 (Below) | 0 | 0 |
| Gross Motor — Baseline (Below): Week 52 (Above) | 3 | 1 |
| Gross Motor — Baseline (Below): Week 52 (Monitor) | 0 | 2 |
| Gross Motor — Baseline (Below): Week 52 (Below) | 2 | 2 |
| Personal - Social — Baseline (Above): Week 52 (Above) | 3 | 2 |
| Personal - Social — Baseline (Above): Week 52 (Monitor) | 0 | 0 |
| Personal - Social — Baseline (Above): Week 52 (Below) | 0 | 0 |
| Personal - Social — Baseline (Monitor): Week 52 (Above) | 2 | 0 |
| Personal - Social — Baseline (Monitor): Week 52 (Monitor) | 0 | 0 |
| Personal - Social — Baseline (Monitor): Week 52 (Below) | 0 | 0 |
| Personal - Social — Baseline (Below): Week 52 (Above) | 1 | 1 |
| Personal - Social — Baseline (Below): Week 52 (Monitor) | 0 | 0 |
| Personal - Social — Baseline (Below): Week 52 (Below) | 0 | 2 |
| Problem Solving — Baseline (Above): Week 52 (Above) | 4 | 3 |
| Problem Solving — Baseline (Above): Week 52 (Monitor) | 0 | 0 |
| Problem Solving — Baseline (Above): Week 52 (Below) | 0 | 0 |
| Problem Solving — Baseline (Monitor): Week 52 (Above) | 0 | 0 |
| Problem Solving — Baseline (Monitor): Week 52 (Monitor) | 0 | 0 |
| Problem Solving — Baseline (Monitor): Week 52 (Below) | 0 | 0 |
| Problem Solving — Baseline (Below): Week 52 (Above) | 1 | 0 |
| Problem Solving — Baseline (Below): Week 52 (Monitor) | 1 | 0 |
| Problem Solving — Baseline (Below): Week 52 (Below) | 0 | 2 |
Change from baseline to Week 52 in body weight was reported.
| kilograms | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Change From Baseline in Body Weight | -7.139 ± 5.0834 | -0.327 ± 2.9572 |
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.
| Participants | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 7 | 5 |
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.
| Participants | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Mild | 2 | 5 |
| Moderate | 5 | 0 |
| Severe | 0 | 0 |
| Life Threatening | 0 | 0 |
| Death | 0 | 0 |
Collected over From first dose of study drug up to Week 56. Non-serious events are listed at a 2% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Setmelanotide: PPL Group | 0/7 (0%) | 0/7 (0%) | 7/7 (100%) |
| Setmelanotide: BBS Group | 0/5 (0%) | 0/5 (0%) | 5/5 (100%) |
| Event | Setmelanotide: PPL Group | Setmelanotide: BBS Group |
|---|---|---|
| Skin hyperpigmentationSkin and subcutaneous tissue disorders | 5/7 | 4/5 |
| NasopharyngitisInfections and infestations | 2/7 | 3/5 |
| Injection site bruisingGeneral disorders | 1/7 | 3/5 |
| Injection site pruritusGeneral disorders | 1/7 | 3/5 |
| VomitingGastrointestinal disorders | 4/7 | 3/5 |
| Upper respiratory tract infectionInfections and infestations | 4/7 | 0/5 |
| FallInjury, poisoning and procedural complications | 4/7 | 0/5 |
| Melanocytic naevusNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 3/7 | 1/5 |
| InfluenzaInfections and infestations | 0/7 | 2/5 |
| PyrexiaGeneral disorders | 2/7 | 2/5 |
The safety analysis set included all participants who received at least 1 dose of study drug.
| Age, Continuous(years) | Setmelanotide: PPL Group | Setmelanotide: BBS Group | Total |
|---|---|---|---|
| Mean | 3.4 ± 0.53 | 3.8 ± 1.30 | 3.6 ± 0.90 |
| Sex: Female, Male(Participants) | Setmelanotide: PPL Group | Setmelanotide: BBS Group | Total |
|---|---|---|---|
| Female | 2 | 3 | 5 |
| Male | 5 | 2 | 7 |
| Ethnicity (NIH/OMB)(Participants) | Setmelanotide: PPL Group | Setmelanotide: BBS Group | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 |
| Not Hispanic or Latino | 4 | 5 | 9 |
| Unknown or Not Reported | 2 | 0 | 2 |
| Race/Ethnicity, Customized(Participants) | Setmelanotide: PPL Group | Setmelanotide: BBS Group | Total |
|---|---|---|---|
| Race — American Indian or Alaska Native | 0 | 0 | 0 |
| Race — Asian | 0 | 1 | 1 |
| Race — White | 3 | 4 | 7 |
| Race — Other | 2 | 0 | 2 |
| Race — Unknown or Not Reported | 2 | 0 | 2 |
| Body Mass Index (BMI) Z-score(z-score) | Setmelanotide: PPL Group | Setmelanotide: BBS Group | Total |
|---|---|---|---|
| Mean | 10.749 ± 3.8400 | 4.233 ± 1.0742 | 8.034 ± 4.4408 |
| BMI(kg/m^2) | Setmelanotide: PPL Group | Setmelanotide: BBS Group | Total |
|---|---|---|---|
| Mean | 34.347 ± 7.0673 | 23.716 ± 3.5184 | 29.918 ± 7.8559 |
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Bardet-Biedl Syndrome
Rhythm Pharmaceuticals, Inc.