None listed
Conditions
Sponsors
Rhythm Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with the following genotypes and/or clinical assessment: a. POMC/PCSK1/LEPR heterozygous b. POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity c. POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity d. Smith-Magenis Syndrome (SMS) e. SH2B1 deficiency obesity f. Chromosomal rearrangement of the 16p11.2 locus causing obesity g. CPE compound heterozygous or homozygous deficiency obesity h. Leptin deficiency obesity with loss of response to metreleptin i. SRC1 deficiency obesity j. MC4R deficiency obesity Note: The specific genotype for all patients must be reviewed by the Sponsor prior to study enrollment to confirm that the patient meets Inclusion Criterion #1. In addition, enrollment of patients in some subgroups may be prioritized by the Sponsor in order to ensure enrollment of patients with (1) well described, loss-of-function genetic mutations, (2) a variety of genetic variants, or (3) genetic variants likely to respond to setmelanotide. 2. Age 6 years and above. 3. Obese, defined as Body Mass Index (BMI) = 30 kg/m2 for patients =16 years of age or BMI = 95th percentile for age and gender for patients 6 up to 16 years of age. 4. Study participant and/or parent or guardian is able to communicate well with the Investigator, to understand and comply with the requirements of the study, and is able to understand and sign the written informed consent/assent. 5. Female participants of child-bearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol. Female participants of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), post-menopausal for at least 12 months (and confirmed with a screening Follicle-Stimulating Hormone [FSH] level in the post-menopausal lab range), and failure to have achieved menarche, do not require contraception during the study. 6. Male participants with female partners of childbearing potential must agree to a double-barrier method if they become sexually active during the study. Male patients must not donate sperm during and for 90 days following their participation in the study. Are the trial subjects under 18? yes Number of subjects for this age range: 48 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 86 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: 1. Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that has resulted in > 2% weight loss. 2. Use of any medication that is approved to treat obesity within three months of first dose of study drug (e.g., orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion). Note: Glucagon-like peptide-1 (GLP-1) receptor agonists may be used up to the dose approved for the treatment of diabetes mellitus (e.g., liraglutide up to a daily dose of 1.8 mg) as long as (1) is it not being prescribed for the treatment of obesity, (2) the dose has been stable for at least three months prior to enrollment, (3) the patient has not experienced weight loss during the previous three months, AND (4) the patient intends to keep the dose stable throughout the course of the study. 3. Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained from the baseline pre-operative weight with no evidence of weight regain. Specifically, patients may be considered if surgery was not successful, or resulted in 9.0% at Screening 8. History of significant liver disease or abnormal liver tests on Screening (i.e. > 1.5 x upper limit of normal [ULN] for alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, or serum bilirubin ). Note: Patients entering the study with SRC1 haploinsufficiency obesity must be evaluated during the Screening Period for hepatic fibrosis by appropriate imaging techniques (e.g., transient elastography or magnetic resonance elastography). Any patient with moderate or greater fibrosis (e.g., the equivalent of a METAVIR score = 2) will be excluded from the study. Note: A patient with a diagnosis of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) may be allowed to enroll in the study, after consultation with the Sponsor. Other significant liver disease, such as cirrhosis, are exclusionary. 9. Glomerular filtration rate (GFR) <30 mL/min at Screening. 10. History or close family history (pare
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore the impact of setmelanotide on obesity in patients with various specific rare genetic mutations.;Secondary Objective: To assess the effects of setmelanotide on: - Safety and tolerability - Hunger - Waist circumference;Primary end point(s): The proportion of patients in each subgroup of RGDO who achieve at least 5% body weight reduction from baseline, at ~3 months treatment with setmelanotide.;Timepoint(s) of evaluation of this end point: At the end of ~3 months of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: End points are assessed from baseline to end of treatment.;Secondary end point(s): Secondary endpoints: • Safety and tolerability of setmelanotide injection, assessed by the frequency and severity of AEs, vital signs, and laboratory evaluations • Change and percentage change from baseline in body weight • Change from baseline in Daily and Global Hunger scores • Change from baseline in waist circumference Exploratory Endpoints • Change from baseline in total body mass, including body fat and non-bone lean mass, as measure by either dual-energy x-ray absorptiometry (DXA) or bioelectrical impedance (BIA) • Change from baseline in fasting lipids (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and triglycerides) • Change from baseline in metabolic assays and other exploratory biomarkers • Change from baseline in glycated hemoglobin (HbA1c) • Evaluation of plasma pharmacokinetic (PK) parameters • Change from baseline in quality of life as measured by the following assessments: - Impact of Weight on Quality of Life-Lite (IWQOL-Lite) - EuroQoL-Five Dimension-5L (EQ-5D-5L) or EuroQoL-Five Dimension-Y (EQ-5D-Y) - The 12-Item Short Form Health Survey (SF-12) or 10-Item Short Form Health Survey for Children (SF-10) - Patient-Reported Behavioral Disturbance Questionnaire • Change from baseline in mental health status as measured by the Patient Health Questionnaire-9 (PHQ-9) and Columbia-Suicide Severity Rating Scale (C-SSRS) • Tanner Staging for patients who have yet to reach Tanner Stage V | — |
Countries
Canada, France, Germany, Greece, Israel, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactSarah Pilley
Rhythm Pharmaceuticals, Inc
Outcome results
None listed