Treatment of obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway
Conditions
Sponsors
Rhythm Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients aged 6 or older that have completed participation on active drug and demonstrated adequate safety in a previous setmelanotide study for obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway. 2. 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 to understand and sign the written informed consent/assent. The patient must assent/consent to participate in the trial. 3. 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), postmenopausal for at least 12 months (and confirmed with a screening FSH level in the postmenopausal lab range), or have delayed pubertal development and failure to have achieved menarche, do not require contraception during the study. Any female participant in this latter category of having failed to reach menarche upon study entry and who now suspects this status may have changed should promptly inform the investigator and undergo pregnancy testing. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Current, clinically significant disease, if severe enough to interfere with the study and/or would confound the results. Any such patients should be discussed with the sponsor prior to inclusion. 2. Pregnant and/or breastfeeding women are excluded. 3. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnostic and Statistical Manual of Mental Disorders (DSM-III) disorders that the investigator believes will interfere significantly with study compliance. 4. A Patient Health Questionnaire-9 (PHQ-9) score of = 15. 5. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS). Any lifetime history of a suicide attempt, or any suicidal behavior in the last month. 6. Current, severe stable restrictive or obstructive lung disease as a consequence of extreme obesity, evidence of significant heart failure (NYHA Class 3 or greater), or oncologic disease, if these were severe enough to interfere with the study and/or would confound the results. Any such patients should be discussed with the sponsor prior to inclusion. 7. History of significant liver disease or liver injury, or current liver assessment for a cause of abnormal liver tests [as indicated by abnormal liver function tests, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, or serum bilirubin (> 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 if 17 years or older or by Schwartz if 16 years or less. 9. History or close family history (parents or siblings) of skin cancer or melanoma, or patient history of ocularcutaneous 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 pretreatment 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. Significant hypersensitivity to study drug. 13. Inability to comply with injection regimen. 14. Patients who have been placed in an institution through an official or court order, as well as those who are dependent on the sponsor, Investigator or study site.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary •To characterize safety and tolerability of setmelanotide in patients who have completed a previous trial on treatment of setmelanotide for obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway. ;Secondary Objective: Exploratory To assess the effect of setmelanotide, long term, on: •Maintenance or continued weight loss •Hunger •Percent change in body fat mass •Waist circumference •Percent change in total body mass, non-bone lean mass, and bone density •Fasting lipid (cholesterol and triglyceride) panel •Changes in quality of life and health status •Biomarkers predictive of a setmelanotide response and/or that change when the rate of weight loss may change later in the treatment regimen.;Primary end point(s): Safety and tolerability of setmelanotide;Timepoint(s) of evaluation of this end point: Throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The yearly mean percent change from baseline in body weight. Hunger will be assessed at each visit using a daily questionnaire as well as a set of two global questions. Yearly body composition including total body weight loss, fat loss, and non-bone lean mass. Waist circumference will be measured according to US National Heart Lung and Blood Institute criteria [2000 NHLBI] over time. Potential improvements in lipids (fasting cholesterol and triglycerides) will be assessed over time. Quality of life will be assessed yearly. Biomarkers predictive of a setmelanotide response and/or that change when the rate of weight loss may change later in the treatment regimen may be evaluated including biomarkers of metabolic and lipid metabolism changes. Additionally, as required by the Food and Drug Administration (FDA) for all CNS-active obesity medications, changes in depression/suicidality as assessed by the C- SSRS and PHQ-9 will be monitored. ;Timepoint(s) of evaluation of this end point: Yearly unless stated otherwise in the protocol. | — |
Countries
Belgium, Canada, France, Germany, Greece, Netherlands, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactTara Parsons
Rhythm Pharmaceuticals, Inc.
Outcome results
None listed