Genetic Obesity
Conditions
Keywords
Melanocortin-4 Receptor, Genetic Obesity, Leptin
Brief summary
The purpose of this study was to evaluate the safety and efficacy of once daily subcutaneous (SC) administration of setmelanotide in participants with obesity and specific gene variants in the MC4R pathway.
Interventions
DRUGSetmelanotide
SC injection
DRUGPlacebo
SC injection
Sponsors
Rhythm Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Stage 1 of the trial is open-label. Participants who were eligible to enter Stage 2 of the trial were randomized in a blinded manner at the Stage 2 Entry Visit in a 2:1 ratio to receive either setmelanotide or placebo.
Eligibility
Sex/Gender
ALL
Age
6 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants must have had a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity * Age 6 to 65 years, inclusive * Obesity, defined as Body Mass Index (BMI) ≥40 kilograms per square meter (kg/m\^2) for participants ≥18 years of age or BMI ≥97th percentile for age and gender for participants 6 to \<18 years of age * Study participant and/or parent or guardian were able to understand all study procedures and provide consent/assent * Use of highly effective contraception * Symptoms or behaviors of hyperphagia Key
Exclusion criteria
* Participants with the following genetic variants: biallelic Bardet-Biedl Syndrome (BBS); biallelic Alström Syndrome 1 (ALMS1); homozygous, heterozygous, or compound heterozygous variants in MC4R, Pro-opiomelanocortin (POMC), Proprotein convertase subtilisin/kexin type 1 (PCSK1), Leptin receptor (LEPR), nuclear receptor coactivator 1 (NCOA1; steroid receptor coactivator-1 \[SRC1\]) or SRC homology 2 B adapter protein 1 (SH2B1) genes as well as 16p11.2 chromosomal deletions that included the SH2B1 gene * Recent intensive diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that had resulted in weight loss \>2% within previous 3 months * Bariatric surgery within the previous 6 months * Documented diagnosis of current unstable major psychiatric disorder or a documented worsening of psychiatric condition that required changes in treatment within 2 years * Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) or Patient Health Questionnaire 9 (PHQ 9) score of ≥15 during Screening, any suicide attempt in participant's lifetime years, or any suicidal behavior in the last month. * Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study * Has significant features of (or meets the diagnostic criteria for) a genetic syndrome that is associated with obesity * Glycated hemoglobin (HbA1C) \>10.0% at Screening * History of significant liver disease * Glomerular filtration rate (GFR) \<30 milliliter per minute (mL/min) at Screening * History or close family history of melanoma or participant history of oculocutaneous albinism * Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions * Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing * Participants previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide * Significant hypersensitivity to any excipient in the study drug * Females who were breastfeeding or nursing Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Baseline to Week 16 | BMI was calculated using participant's weight and height assessments, using the following formula: BMI = Kilogram (kg)/ square meter (m\^2). A significant clinically meaningful response was defined as achieving a ≥5% reduction in BMI from Baseline. Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Baseline, Week 16 | BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2 Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration. |
| Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Baseline, Week 16 | BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2 Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration. |
| Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Baseline, Week 16 | BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2 Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration. |
| Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Baseline, Week 16 | Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration. |
| Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Baseline, Week 16 | BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration. |
| Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Baseline, Week 16 | BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. The BMI Z-score indicated the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score indicates a reduction in BMI from Baseline whereas an increase of BMI-Z score indicates an increase in BMI from Baseline. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration. |
| Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Baseline, Week 16 | Daily Hunger Questionnaire for participants ≥12 years of age is self-administered questionnaire and comprises three items. For the assessment of this endpoint, maximal hunger was corresponding to the following question: In the last 24 hours, how hungry did you feel when you were the most hungry? The response was scored separately and averaged on weekly basis. Participants rated their hunger on an 11-point numeric rating scale ranging from 0 to 10 (0 = not hungry at all, and 10 = hungriest possible). Weekly average at Week 16 was defined as average of the available score values within 7 days in Week 16. Baseline was defined as the average of the available score values within 7 days before or on the stage 1 open-label treatment. Results are reported by overall participant results and by specific gene cohort. |
| Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Baseline, Week 16 | Daily Hunger Questionnaire for participants ≥12 years of age is self-administered questionnaire and comprises three items. For the assessment of this endpoint, maximal hunger was corresponding to the following question: In the last 24 hours, how hungry did you feel when you were the most hungry? The response was scored separately and averaged on weekly basis. Participants rated their hunger on an 11-point numeric rating scale ranging from 0 to 10 (0 = not hungry at all, and 10 = hungriest possible). Weekly average at Week 16 was defined as average of the available score values within 7 days in Week 16. Baseline was defined as the average of the available score values within 7 days before or on the stage 1 open-label treatment. Results are reported by overall participant results and by specific gene cohort. |
| Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Baseline, Week 16 | Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration. |
Countries
Canada, Germany, Greece, Israel, Netherlands, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 218 participants were screened and 164 participants received at least one dose of trial medication in Stage 1.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Stage 1: All participants received once daily SC injection of setmelanotide for 16 weeks in an open-label treatment Stage. Participants ≥12 years of age started on setmelanotide 2.0 mg once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants \<12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.
Stage 2: Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of setmelanotide 3.0 mg or matching placebo from Week 16 to Week 40 in a double-blind treatment Stage. | 164 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Stage 1 (Open-Label, Duration: 16 Weeks) | Adverse Event | 43 | 0 | 0 |
| Stage 1 (Open-Label, Duration: 16 Weeks) | Lost to Follow-up | 2 | 0 | 0 |
| Stage 1 (Open-Label, Duration: 16 Weeks) | Protocol Violation | 3 | 0 | 0 |
| Stage 1 (Open-Label, Duration: 16 Weeks) | Withdrawal by Subject | 16 | 0 | 0 |
| Stage 2 (Double-Blind, Duration:24 Week) | Adverse Event | 0 | 0 | 1 |
| Stage 2 (Double-Blind, Duration:24 Week) | Other than specified | 0 | 1 | 4 |
| Stage 2 (Double-Blind, Duration:24 Week) | Withdrawal by Subject | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 30.2 years STANDARD_DEVIATION 16.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 124 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants |
| Race (NIH/OMB) White | 128 Participants |
| Sex: Female, Male Female | 110 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 164 | 0 / 35 | 0 / 14 |
| other Total, other adverse events | 160 / 164 | 25 / 35 | 10 / 14 |
| serious Total, serious adverse events | 6 / 164 | 0 / 35 | 0 / 14 |
Outcome results
Primary
Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = Kilogram (kg)/ square meter (m\^2). A significant clinically meaningful response was defined as achieving a ≥5% reduction in BMI from Baseline. Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
Time frame: Baseline to Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Overall | 49 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: NRP1 | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: NRP2 | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: PLXNA1 | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: PLXNA2 | 3 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: PLXNA3 | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: PLXNA4 | 5 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: SEMA3A | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: SEMA3B | 1 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: SEMA3C | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: SEMA3D | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: SEMA3E | 3 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: SEMA3F | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: SEMA3G | 8 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: PHIP | 9 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: SIM1 | 5 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: MAGEL2 | 3 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: CREBBP | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: DNMT3A | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: HTR2C | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: KSR2 | 1 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: MRAP2 | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: RPGRIP1L | 1 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: TBX3 | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 | Gene: TRPC5 | 0 Participants |
Secondary
Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
Time frame: Baseline, Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Overall: At Baseline | 45.338 Kg/m^2 | Standard Deviation 9.5526 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Overall: Change at Week 16 | -1.916 Kg/m^2 | Standard Deviation 1.7971 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: NRP1, At Baseline | 48.601 Kg/m^2 | Standard Deviation 2.7893 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: NRP1, Change at Week 16 | 0.229 Kg/m^2 | Standard Deviation 1.6024 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: NRP2, At Baseline | 46.568 Kg/m^2 | Standard Deviation 10.6754 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: NRP2, Change at Week 16 | -1.040 Kg/m^2 | Standard Deviation 0.865 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA1, At Baseline | 45.576 Kg/m^2 | Standard Deviation 5.5644 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA1, Change at Week 16 | -1.884 Kg/m^2 | Standard Deviation 1.8912 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA2, At Baseline | 48.577 Kg/m^2 | Standard Deviation 12.1795 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA2, Change at Week 16 | -2.492 Kg/m^2 | Standard Deviation 2.0273 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA3, At Baseline | 34.083 Kg/m^2 | Standard Deviation 6.4705 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA3, Change at Week 16 | -3.333 Kg/m^2 | Standard Deviation 0.5166 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA4, At Baseline | 46.634 Kg/m^2 | Standard Deviation 8.5714 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA4, Change at Week 16 | -2.218 Kg/m^2 | Standard Deviation 2.9947 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3A, At Baseline | 39.405 Kg/m^2 | Standard Deviation 7.8242 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3A, Change at Week 16 | -2.328 Kg/m^2 | Standard Deviation 0.2612 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3B, At Baseline | 42.890 Kg/m^2 | Standard Deviation 5.01 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3B, Change at Week 16 | -2.557 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3C, At Baseline | 47.543 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3C, Change at Week 16 | -2.334 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3D, At Baseline | 45.814 Kg/m^2 | Standard Deviation 5.769 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3D, Change at Week 16 | -1.638 Kg/m^2 | Standard Deviation 0.6445 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3E, At Baseline | 43.005 Kg/m^2 | Standard Deviation 1.6275 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3E, Change at Week 16 | -3.132 Kg/m^2 | Standard Deviation 2.418 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3F, At Baseline | 54.979 Kg/m^2 | Standard Deviation 15.1825 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3F, Change at Week 16 | -3.556 Kg/m^2 | Standard Deviation 1.1758 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3G, At Baseline | 44.464 Kg/m^2 | Standard Deviation 8.4848 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3G, Change at Week 16 | -2.124 Kg/m^2 | Standard Deviation 1.5203 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PHIP, At Baseline | 40.808 Kg/m^2 | Standard Deviation 10.0222 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PHIP, Change at Week 16 | -2.120 Kg/m^2 | Standard Deviation 1.0108 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SIM1, At Baseline | 47.729 Kg/m^2 | Standard Deviation 9.7294 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SIM1, Change at Week 16 | -1.698 Kg/m^2 | Standard Deviation 1.8931 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: MAGEL2, At Baseline | 42.047 Kg/m^2 | Standard Deviation 8.2605 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: MAGEL2, Change at Week 16 | -1.637 Kg/m^2 | Standard Deviation 1.3549 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: CREBBP, At Baseline | 47.490 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: CREBBP, Change at Week 16 | 0.165 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: DNMT3A, At Baseline | 44.138 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: DNMT3A, Change at Week 16 | -1.080 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: HTR2C, At Baseline | 52.105 Kg/m^2 | Standard Deviation 3.0212 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: HTR2C, Change at Week 16 | -1.381 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: KSR2, At Baseline | 47.624 Kg/m^2 | Standard Deviation 11.4457 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: KSR2, Change at Week 16 | -1.073 Kg/m^2 | Standard Deviation 1.441 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: MRAP2, At Baseline | 58.100 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: MRAP2, Change at Week 16 | -1.470 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: RPGRIP1L, At Baseline | 43.442 Kg/m^2 | Standard Deviation 2.6778 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: RPGRIP1L, Change at Week 16 | -3.603 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: TBX3, At Baseline | 40.170 Kg/m^2 | Standard Deviation 10.5867 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: TBX3, Change at Week 16 | -1.951 Kg/m^2 | Standard Deviation 1.3582 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: TRPC5, At Baseline | 49.974 Kg/m^2 | Standard Deviation 24.5155 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: TRPC5, Change at Week 16 | 0.161 Kg/m^2 | Standard Deviation 1.2979 |
Secondary
Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2 Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
Time frame: Baseline, Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA3, At Baseline | 40.801 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Overall: At Baseline | 48.464 Kg/m^2 | Standard Deviation 8.0877 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Overall: Change at Week 16 | -1.872 Kg/m^2 | Standard Deviation 1.8963 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: NRP2, At Baseline | 51.640 Kg/m^2 | Standard Deviation 8.5762 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: NRP2, Change at Week 16 | -0.783 Kg/m^2 | Standard Deviation 1.0489 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA1, At Baseline | 46.959 Kg/m^2 | Standard Deviation 6.2279 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA1, Change at Week 16 | -0.678 Kg/m^2 | Standard Deviation 0.8796 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA2, At Baseline | 50.335 Kg/m^2 | Standard Deviation 12.3004 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA2, Change at Week 16 | -2.324 Kg/m^2 | Standard Deviation 0.6565 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA3, Change at Week 16 | -3.698 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA4, At Baseline | 48.420 Kg/m^2 | Standard Deviation 7.434 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA4, Change at Week 16 | -2.532 Kg/m^2 | Standard Deviation 3.1514 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3A, At Baseline | 47.366 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3A, Change at Week 16 | -2.513 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3B, At Baseline | 43.320 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3D, At Baseline | 47.296 Kg/m^2 | Standard Deviation 6.0613 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3D, Change at Week 16 | -1.638 Kg/m^2 | Standard Deviation 0.6445 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3E, At Baseline | 42.004 Kg/m^2 | Standard Deviation 1.1954 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3E, Change at Week 16 | -4.716 Kg/m^2 | Standard Deviation 0.0565 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3F, At Baseline | 64.964 Kg/m^2 | Standard Deviation 9.9946 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3F, Change at Week 16 | -4.388 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3G, At Baseline | 46.762 Kg/m^2 | Standard Deviation 6.5047 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3G, Change at Week 16 | -2.302 Kg/m^2 | Standard Deviation 1.6478 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PHIP, At Baseline | 45.343 Kg/m^2 | Standard Deviation 7.0089 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PHIP, Change at Week 16 | -2.110 Kg/m^2 | Standard Deviation 1.1464 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SIM1, At Baseline | 50.790 Kg/m^2 | Standard Deviation 8.9593 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SIM1, Change at Week 16 | -1.465 Kg/m^2 | Standard Deviation 1.7916 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: MAGEL2, At Baseline | 46.198 Kg/m^2 | Standard Deviation 5.0997 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: MAGEL2, Change at Week 16 | -1.191 Kg/m^2 | Standard Deviation 1.0137 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: CREBBP, At Baseline | 47.490 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: CREBBP, Change at Week 16 | 0.165 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: DNMT3A, At Baseline | 44.138 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: DNMT3A, Change at Week 16 | -1.080 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: HTR2C, At Baseline | 52.105 Kg/m^2 | Standard Deviation 3.0212 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: HTR2C, Change at Week 16 | -1.381 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: KSR2, At Baseline | 51.397 Kg/m^2 | Standard Deviation 9.2011 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: KSR2, Change at Week 16 | -0.792 Kg/m^2 | Standard Deviation 1.5759 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: RPGRIP1L, At Baseline | 43.442 Kg/m^2 | Standard Deviation 2.6778 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: RPGRIP1L, Change at Week 16 | -3.603 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TBX3, At Baseline | 44.494 Kg/m^2 | Standard Deviation 4.3444 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TBX3, Change at Week 16 | -0.705 Kg/m^2 | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TRPC5, At Baseline | 62.246 Kg/m^2 | Standard Deviation 17.2758 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TRPC5, Change at Week 16 | 0.161 Kg/m^2 | Standard Deviation 1.2979 |
Secondary
Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. The BMI Z-score indicated the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score indicates a reduction in BMI from Baseline whereas an increase of BMI-Z score indicates an increase in BMI from Baseline. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
Time frame: Baseline, Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Overall, At Baseline | 2.649 z-score | Standard Deviation 0.3708 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Overall: Change at Week 16 | -0.126 z-score | Standard Deviation 0.1425 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: NRP1, At Baseline | 2.919 z-score | Standard Deviation 0.0848 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: NRP1, Change at Week 16 | -0.000 z-score | Standard Deviation 0.0124 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: NRP2, At Baseline | 2.386 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: NRP2, Change at Week 16 | -0.086 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PLXNA1, At Baseline | 2.729 z-score | Standard Deviation 0.125 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PLXNA1, Change at Week 16 | -0.112 z-score | Standard Deviation 0.0671 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PLXNA2, At Baseline | 2.955 z-score | Standard Deviation 0.0601 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PLXNA2, Change at Week 16 | -0.043 z-score | Standard Deviation 0.0707 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PLXNA3, At Baseline | 2.485 z-score | Standard Deviation 0.497 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PLXNA3, Change at Week 16 | -0.234 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PLXNA4, At Baseline | 2.693 z-score | Standard Deviation 0.3653 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PLXNA4, Change at Week 16 | -0.063 z-score | Standard Deviation 0.111 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3A, At Baseline | 2.498 z-score | Standard Deviation 0.2057 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3A, Change at Week 16 | -0.078 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3B, At Baseline | 2.595 z-score | Standard Deviation 0.5201 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3B, Change at Week 16 | -0.140 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3C, At Baseline | 2.828 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3C, Change at Week 16 | -0.037 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3D, At Baseline | 2.454 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3E, At Baseline | 2.913 z-score | Standard Deviation 0.4705 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3E, Change at Week 16 | -0.053 z-score | Standard Deviation 0.0808 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3F, At Baseline | 2.847 z-score | Standard Deviation 0.5676 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3F, Change at Week 16 | -0.192 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3G, At Baseline | 2.826 z-score | Standard Deviation 0.489 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SEMA3G, Change at Week 16 | -0.115 z-score | Standard Deviation 0.102 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PHIP, At Baseline | 2.457 z-score | Standard Deviation 0.4515 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: PHIP, Change at Week 16 | -0.201 z-score | Standard Deviation 0.1923 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SIM1, At Baseline | 2.510 z-score | Standard Deviation 0.3107 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: SIM1, Change at Week 16 | -0.182 z-score | Standard Deviation 0.2355 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: MAGEL2, At Baseline | 2.503 z-score | Standard Deviation 0.3034 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: MAGEL2, Change at Week 16 | -0.184 z-score | Standard Deviation 0.1615 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: MRAP2, At Baseline | 2.738 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: MRAP2, Change at Week 16 | -0.019 z-score | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: KSR2, At Baseline | 2.831 z-score | Standard Deviation 0.226 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: KSR2, Change at Week 16 | -0.037 z-score | Standard Deviation 0.0131 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: TBX3, At Baseline | 2.471 z-score | Standard Deviation 0.4419 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: TBX3, Change at Week 16 | -0.254 z-score | Standard Deviation 0.1661 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype | Gene: TRPC5, At Baseline | 2.078 z-score | — |
Secondary
Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype
Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
Time frame: Baseline, Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TBX3, At Baseline | 119.00 Kg | Standard Deviation 11.644 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TBX3, Change at Week 16 | -2.17 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TRPC5, At Baseline | 203.00 Kg | Standard Deviation 25.173 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TRPC5, Change at Week 16 | 0.20 Kg | Standard Deviation 4.243 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Overall, At Baseline | 136.01 Kg | Standard Deviation 29.815 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Overall: Change at Week 16 | -5.33 Kg | Standard Deviation 5.315 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: NRP2, At Baseline | 147.35 Kg | Standard Deviation 2.098 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: NRP2, Change at Week 16 | -2.03 Kg | Standard Deviation 2.687 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA1, At Baseline | 145.30 Kg | Standard Deviation 33.751 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA1, Change at Week 16 | -2.33 Kg | Standard Deviation 3.144 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA2, At Baseline | 137.94 Kg | Standard Deviation 37.878 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA2, Change at Week 16 | -6.50 Kg | Standard Deviation 2.234 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA3, At Baseline | 89.73 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA3, Change at Week 16 | -8.13 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA4, At Baseline | 135.87 Kg | Standard Deviation 24.052 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA4, Change at Week 16 | -7.55 Kg | Standard Deviation 8.772 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3A, At Baseline | 157.07 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3A, Change at Week 16 | -8.33 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3B, At Baseline | 97.60 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3D, At Baseline | 128.09 Kg | Standard Deviation 49.981 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3D, Change at Week 16 | -4.48 Kg | Standard Deviation 0.589 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3E, At Baseline | 115.77 Kg | Standard Deviation 19.328 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3E, Change at Week 16 | -12.98 Kg | Standard Deviation 1.956 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3F, At Baseline | 176.65 Kg | Standard Deviation 10.96 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3F, Change at Week 16 | -12.80 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3G, At Baseline | 129.41 Kg | Standard Deviation 21.874 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3G, Change at Week 16 | -6.59 Kg | Standard Deviation 4.622 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PHIP, At Baseline | 134.11 Kg | Standard Deviation 36.996 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PHIP, Change at Week 16 | -5.77 Kg | Standard Deviation 3.504 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SIM1, At Baseline | 141.25 Kg | Standard Deviation 35.591 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SIM1, Change at Week 16 | -4.13 Kg | Standard Deviation 4.72 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: MAGEL2, At Baseline | 134.41 Kg | Standard Deviation 20.544 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: MAGEL2, Change at Week 16 | -3.88 Kg | Standard Deviation 3.681 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: CREBBP, At Baseline | 103.60 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: CREBBP, Change at Week 16 | 0.36 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: DNMT3A, At Baseline | 129.37 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: DNMT3A, Change at Week 16 | -3.17 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: HTR2C, At Baseline | 126.23 Kg | Standard Deviation 9.78 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: HTR2C, Change at Week 16 | -3.40 Kg | — |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: KSR2, At Baseline | 150.16 Kg | Standard Deviation 19.63 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: KSR2, Change at Week 16 | -2.13 Kg | Standard Deviation 4.721 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: RPGRIP1L, At Baseline | 103.47 Kg | Standard Deviation 11.193 |
| Stage 1: Setmelanotide (Open-Label) | Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: RPGRIP1L, Change at Week 16 | -8.63 Kg | — |
Secondary
Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype
Daily Hunger Questionnaire for participants ≥12 years of age is self-administered questionnaire and comprises three items. For the assessment of this endpoint, maximal hunger was corresponding to the following question: In the last 24 hours, how hungry did you feel when you were the most hungry? The response was scored separately and averaged on weekly basis. Participants rated their hunger on an 11-point numeric rating scale ranging from 0 to 10 (0 = not hungry at all, and 10 = hungriest possible). Weekly average at Week 16 was defined as average of the available score values within 7 days in Week 16. Baseline was defined as the average of the available score values within 7 days before or on the stage 1 open-label treatment. Results are reported by overall participant results and by specific gene cohort.
Time frame: Baseline, Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Overall | 49 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: NRP2 | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: PLXNA1 | 1 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: PLXNA2 | 3 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: PLXNA3 | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: PLXNA4 | 6 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: SEMA3A | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: SEMA3B | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: SEMA3C | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: SEMA3D | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: SEMA3E | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: SEMA3F | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: SEMA3G | 4 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: PHIP | 7 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: SIM1 | 7 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: MAGEL2 | 5 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: CREBBP | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: DNMT3A | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: HTR2C | 1 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: KSR2 | 3 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: MRAP2 | 0 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: RPGRIP1L | 1 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: TBX3 | 2 Participants |
| Stage 1: Setmelanotide (Open-Label) | Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype | Gene: TRPC5 | 1 Participants |
Secondary
Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2 Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
Time frame: Baseline, Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Overall: Change at Week 16 | -4.62 percent change | Standard Deviation 4.394 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: NRP1, Change at Week 16 | 0.57 percent change | Standard Deviation 3.329 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA1, Change at Week 16 | -4.00 percent change | Standard Deviation 4.296 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: NRP2, Change at Week 16 | -2.33 percent change | Standard Deviation 2.105 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA2, Change at Week 16 | -4.90 percent change | Standard Deviation 3.909 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA3, Change at Week 16 | -8.95 percent change | Standard Deviation 0.156 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PLXNA4, Change at Week 16 | -5.00 percent change | Standard Deviation 6.577 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3A, Change at Week 16 | -5.39 percent change | Standard Deviation 0.123 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3B, Change at Week 16 | -6.79 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3C, Change at Week 16 | -4.91 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3D, Change at Week 16 | -3.57 percent change | Standard Deviation 1.96 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3E, Change at Week 16 | -7.39 percent change | Standard Deviation 5.752 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3F, Change at Week 16 | -7.66 percent change | Standard Deviation 0.119 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SEMA3G, Change at Week 16 | -5.09 percent change | Standard Deviation 3.284 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: PHIP, Change at Week 16 | -6.12 percent change | Standard Deviation 3.623 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: SIM1, Change at Week 16 | -4.02 percent change | Standard Deviation 5.31 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: MAGEL2, Change at Week 16 | -4.60 percent change | Standard Deviation 4.288 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: CREBBP, Change at Week 16 | 0.35 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: DNMT3A, Change at Week 16 | -2.45 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: HTR2C, Change at Week 16 | -2.49 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: KSR2, Change at Week 16 | -2.15 percent change | Standard Deviation 2.928 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: MRAP2, Change at Week 16 | -2.53 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: RPGRIP1L, Change at Week 16 | -8.64 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: TBX3, Change at Week 16 | -6.41 percent change | Standard Deviation 5.011 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype | Gene: TRPC5, Change at Week 16 | -0.03 percent change | Standard Deviation 2.094 |
Secondary
Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2 Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
Time frame: Baseline, Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Overall: Change at Week 16 | -3.95 percent change | Standard Deviation 4.057 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: NRP2, Change at Week 16 | -1.37 percent change | Standard Deviation 1.804 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA1, Change at Week 16 | -1.22 percent change | Standard Deviation 1.576 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA2, Change at Week 16 | -4.69 percent change | Standard Deviation 0.913 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA3, Change at Week 16 | -9.06 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA4, Change at Week 16 | -5.34 percent change | Standard Deviation 6.682 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3A, Change at Week 16 | -5.31 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3D, Change at Week 16 | -3.57 percent change | Standard Deviation 1.96 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3E, Change at Week 16 | -11.23 percent change | Standard Deviation 0.185 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3F, Change at Week 16 | -7.58 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3G, Change at Week 16 | -4.80 percent change | Standard Deviation 2.81 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PHIP, Change at Week 16 | -5.11 percent change | Standard Deviation 2.77 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SIM1, Change at Week 16 | -2.63 percent change | Standard Deviation 3.72 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: MAGEL2, Change at Week 16 | -2.67 percent change | Standard Deviation 2.227 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: CREBBP, Change at Week 16 | 0.35 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: DNMT3A, Change at Week 16 | -2.45 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: HTR2C, Change at Week 16 | -2.49 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: KSR2, Change at Week 16 | -1.23 percent change | Standard Deviation 3.189 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: RPGRIP1L, Change at Week 16 | -8.64 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TBX3, Change at Week 16 | -1.70 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TRPC5, Change at Week 16 | -0.03 percent change | Standard Deviation 2.094 |
Secondary
Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype
Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
Time frame: Baseline, Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Overall: Change at Week 16 | -3.94 percent change | Standard Deviation 4.052 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: NRP2, Change at Week 16 | -1.37 percent change | Standard Deviation 1.804 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA1, Change at Week 16 | -1.22 percent change | Standard Deviation 1.576 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA2, Change at Week 16 | -4.69 percent change | Standard Deviation 0.913 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA3, Change at Week 16 | -9.06 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PLXNA4, Change at Week 16 | -5.34 percent change | Standard Deviation 6.682 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3A, Change at Week 16 | -5.31 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3D, Change at Week 16 | -3.57 percent change | Standard Deviation 1.96 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3E, Change at Week 16 | -11.23 percent change | Standard Deviation 0.185 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3F, Change at Week 16 | -7.58 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SEMA3G, Change at Week 16 | -4.80 percent change | Standard Deviation 2.81 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: PHIP, Change at Week 16 | -5.00 percent change | Standard Deviation 2.749 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: SIM1, Change at Week 16 | -2.63 percent change | Standard Deviation 3.72 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: MAGEL2, Change at Week 16 | -2.67 percent change | Standard Deviation 2.227 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: CREBBP, Change at Week 16 | 0.35 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: DNMT3A, Change at Week 16 | -2.45 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: HTR2C, Change at Week 16 | -2.49 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: KSR2, Change at Week 16 | -1.23 percent change | Standard Deviation 3.189 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: RPGRIP1L, Change at Week 16 | -8.64 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TBX3, Change at Week 16 | -1.70 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype | Gene: TRPC5, Change at Week 16 | -0.03 percent change | Standard Deviation 2.094 |
Secondary
Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype
Daily Hunger Questionnaire for participants ≥12 years of age is self-administered questionnaire and comprises three items. For the assessment of this endpoint, maximal hunger was corresponding to the following question: In the last 24 hours, how hungry did you feel when you were the most hungry? The response was scored separately and averaged on weekly basis. Participants rated their hunger on an 11-point numeric rating scale ranging from 0 to 10 (0 = not hungry at all, and 10 = hungriest possible). Weekly average at Week 16 was defined as average of the available score values within 7 days in Week 16. Baseline was defined as the average of the available score values within 7 days before or on the stage 1 open-label treatment. Results are reported by overall participant results and by specific gene cohort.
Time frame: Baseline, Week 16
Population: Participants in the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Overall: Change at Week 16 | -31.13 percent change | Standard Deviation 63.273 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: NRP2, Change at Week 16 | -39.63 percent change | Standard Deviation 1.203 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: PLXNA1, Change at Week 16 | -21.04 percent change | Standard Deviation 10.064 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: PLXNA2, Change at Week 16 | -44.12 percent change | Standard Deviation 37.973 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: PLXNA3, Change at Week 16 | -49.25 percent change | Standard Deviation 4.785 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: PLXNA4, Change at Week 16 | -54.61 percent change | Standard Deviation 31.759 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: SEMA3A, Change at Week 16 | -15.35 percent change | Standard Deviation 5.88 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: SEMA3B, Change at Week 16 | -15.79 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: SEMA3C, Change at Week 16 | 0.00 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: SEMA3D, Change at Week 16 | 36.36 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: SEMA3E, Change at Week 16 | -37.37 percent change | Standard Deviation 23.609 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: SEMA3F, Change at Week 16 | -48.16 percent change | Standard Deviation 24.821 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: SEMA3G, Change at Week 16 | 38.70 percent change | Standard Deviation 176.373 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: PHIP, Change at Week 16 | -56.87 percent change | Standard Deviation 19.46 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: SIM1, Change at Week 16 | -25.60 percent change | Standard Deviation 51.69 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: MAGEL2, Change at Week 16 | -39.44 percent change | Standard Deviation 30.215 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: DNMT3A, Change at Week 16 | -23.00 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: HTR2C, Change at Week 16 | -37.29 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: KSR2, Change at Week 16 | -42.17 percent change | Standard Deviation 30.842 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: MRAP2, Change at Week 16 | -47.83 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: RPGRIP1L, Change at Week 16 | -100.00 percent change | — |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: TBX3, Change at Week 16 | -33.67 percent change | Standard Deviation 2.72 |
| Stage 1: Setmelanotide (Open-Label) | Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype | Gene: TRPC5, Change at Week 16 | -16.82 percent change | Standard Deviation 28.427 |