None listed
Conditions
Interventions
Product Name: setmelanotide
Product Code: RM-493
Pharmaceutical Form: Solution for injection
INN or Proposed INN: setmelanotide
Other de
Sponsors
Rhythm Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Rare genetic disease patients genetically confirmed diagnoses (may be confirmed by test at Screening) of: a. Homozygous or compound heterozygous (different gene mutation on both alleles) LepR mutations b. Heterozygous POMC mutations c. POMC hypermethylation (epigenetic) variants (>51.92 % POMC methylation intensity at the specific analyzed POMC region) d. Bardet-Biedl Syndrome e. Alström Syndrome f. LEPR Heterozygous Deficiency Obesity g. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on each allele) genetic status for either the POMC, PCSK1, or LEPR genes, with the loss-of-function (LOF) variant for each allele conferring a severe obesity phenotype. h) Smith-Magenis Syndrome (SMS) i) SH2B1 Haploinsufficiency j) Carboxypeptidase E deficiency k) Leptin deficient obesity 2. Age 12 years and above. 3. If adult age =18 years, obesity with body mass index (BMI) = 30 kg/m2; if age 12 and above, obesity with weight > 97th percentile for age and sex on growth chart assessment. 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 be able to understand and sign the written informed consent/assent. 5. Female participants of child-bearing potential must confirmed non-pregnant, and agree to use contraception as outlined in the protocol. Female participants of nonchildbearing 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 FSH level in the postmenopausal 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: 32 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 62 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
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. Patients may be reconsidered approximately 1 month after cessation of such intensive regimens. 2. Recent (within 1 month) participation in another clinical trial that would confound the results of this study. 3. 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 1.5 x upper limit of normal (ULN) for any of these tests)] for an etiology other than non-alcoholic fatty liver disease (NAFLD). Thus, any underlying etiology besides NAFLD, including diagnosed non-alcoholic steatohepatitis (NASH), other causes of hepatitis, or history of hepatic cirrhosis will be exclusionary, but the presence of NAFLD would not be exclusionary. 9. History or presence of impaired renal function as indicated by clinically significant abnormal creatinine, blood urea nitrogen (BUN), or urinary constituents (e.g., albuminuria) or moderate to severe renal dysfunction as defined by ta glomerular filtration rate (GFR) <30 mL/min 10. History or close family history (parents or siblings) of skin cancer or melanoma, or patient history of ocularcutaneous albinism. 11. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions, determined as part of a screening comprehensive skin evaluation performed by a qualified dermatologist. Any concerning lesions identified during the screening period will be biopsied and results known to be benign prior to enrollment. If the pretreatment biopsy results
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate clinically meaningful effects of setmelanotide, after 3 months of treatment, on percent body weight change in each type of these rare genetic disorders of obesity included in this protocol. ; Secondary Objective: To assess setmelanotide effect after 3 months of treatment on: Safety and tolerability of setmelanotide (including blood pressure [BP] and heart rate [HR]), Hunger, Percent change in body fat mass, Glucose parameters: fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), oral glucose tolerate test (OGTT) with focus on parameters of insulin sensitivity, Waist circumference. For patients who continue into the long term extension: To assess the effect of setmelanotide after 6 and 12 months of treatment on: Safety and tolerability of setmelanotide (including blood pressure [BP] and heart rate [HR]), Hunger, Percent change in body fat mass, Glucose parameters: fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), oral glucose tolerate test (OGTT) with focus on parameters of insulin sensitivity, Waist circumference. For consenting patients who agree to participate in a withdrawal phase: during withdrawal from drug, evaluate reversal of weight and hunger reduction. ;Primary end point(s): The primary efficacy endpoint is the mean percent change from baseline for body weight.;Timepoint(s) of evaluation of this end point: At the end of ~3 months of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Supporting secondary, tertiary and exploratory endpoints will include: safety and tolerability of setmelanotide, hunger assessed daily by a questionnaire using a Likert-type scale for each patient over time, including during the Screening Period; body composition assessments including total body weight loss, fat loss, and non-bone lean mass, measured in kg as well as percent change from baseline; glucose parameters as measured by fasting glucose, HbA1c and OGTT with focus on parameters of insulin sensitivity over time, and waist circumference; potential improvement in lipids, PK of setmelanotide, quality of life as assessed by IWQOL-Lite, PedsQL and SF-36; change in pubertal development; biomarkers predictive of setmelanotide response; changes in depression/suicidality as assessed by the C-SSRS and PHQ-9. ;Timepoint(s) of evaluation of this end point: Over time. | — |
Countries
Australia, Canada, France, Germany, Greece, Ireland, Israel, Netherlands, Portugal, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactSarah Pilley
Rhythm Pharmaceuticals, Inc
Outcome results
None listed