Early onset pro-opiomelanocortin deficiency obesity
Conditions
Sponsors
Rhythm Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on each allele) genetic status for either the POMC or PCSK1 genes, with the loss-of-function (LOF) variant for each allele conferring a severe obesity phenotype. 2. Age 6 years and above. 3. If adult age =18 years, obesity with BMI = 30 kg/m2; if child or adolescent, obesity with weight > 95th percentile for age 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, , after being informed about the study. 5. Female participants of child-bearing potential must 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 FSH level in the post-menopausal lab range), delayed pubertal development 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: 9 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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 weight loss or weight stabilization. Patients may be reconsidered approximately 1 month after cessation of such intensive regimens. 2. 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 2.0 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. 8. 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 the Cockroft Gault equation < 30 mL/min (Appendix 11.10). 9. History or close family history (parents or siblings) of skin cancer or melanoma, or patient history of ocular-cutaneous albinism. 10. 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 pre-treatment biopsy results are of concern, the patient may need to be excluded from the study. 11. Volunteer is, in the opinion of the Study Investigator, not suitable to participate in the study. 12. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing. 13. Significant hypersensitivity to study drug. 14. Inability to comply with QD injection regimen. 15. Patients who have be
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate statistically significant and clinically meaningful effects of setmelanotide on percent body weight change in patients with pro-opiomelanocortin (POMC) deficiency obesity due to rare bi-allelic or loss-of function mutations at the end of 1 year of treatment.;Secondary Objective: To assess the effect of setmelanotide, over one year, on: • Safety and tolerability of setmelanotide (including blood pressure [BP] and heart rate [HR]). • Hunger in patients >= 12 years of age. • Percent change in body fat mass. • Glucose parameters: fasting glucose, glycated hemoglobin (HbA1c), oral glucose tolerate test (OGTT) with focus on parameters of insulin sensitivity. • Waist circumference. • During withdrawal from drug: reversal of weight and hunger reduction during the double-blind placebo-controlled withdrawal period. ;Primary end point(s): The primary endpoint is proportion of patients in the FAS who demonstrate at least 10% weight at ~1 year (10-14 months post baseline) compared to baseline.;Timepoint(s) of evaluation of this end point: End of 1 year of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Supporting secondary, tertiary and exploratory endpoints will include: safety and tolerability of setmelanotide, hunger in patients >= 12 years of age; 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.;Timepoint(s) of evaluation of this end point: Various | — |
Countries
Belgium, Canada, France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactHillori Connors
Rhythm Pharmaceuticals, Inc.
Outcome results
None listed