Long Term Extension Trial of Setmelanotide
Long Term Extension Trial of Setmelanotide
This is a long-term extension trial to study the safety and tolerability of continued
 setmelanotide treatment in patients who have completed a previous clinical trial on treatment
 with setmelanotide for obesity associated with genetic defects upstream of the MC4 receptor
 in the leptin-melanocortin pathway.
The purpose of this protocol is to continue the assessment of setmelanotide treatment in
 patients who have successfully completed all critical study evaluations in a prior trial
 (index protocol) of setmelanotide for the treatment of obesity associated with genetic
 defects in the leptin-melanocortin pathway upstream of the MC4 receptor. The primary
 objectives of this extension trial are to explore the long-term safety and tolerability of
 setmelanotide for up to 5 years or until drug is otherwise available through authorized use.
 Patients can enter this protocol immediately upon completion of their index protocol such
 that dosing of setmelanotide continues without gaps in therapy.
Inclusion Criteria:

 1. Patients aged 6 or older that have completed participation on active drug and
 demonstrated adequate safety and meaningful clinical benefit (efficacy) in a previous
 setmelanotide study for obesity associated with genetic defects upstream of the MC4
 receptor in the leptin-melanocortin pathway.

 Note: The index study may have a primary endpoint relied on efficacy, safety or
 tolerability. Patient will be eligible for extension study if the Primary Investigator
 believes the patient exhibited a clinically meaningful benefit (i,e, efficacy) to
 setmelanotide treatment, and would benefit from continued treatment, after discussion
 with the Sponsor.

 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. All patients must agree to follow
 requirements for contraception outlined in the protocol.

 Exclusion Criteria:

 1. Pregnant and/or breastfeeding women

 2. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions
 (excluding non-invasive basal or squamous cell lesion), 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.

 3. Patient is, in the opinion of the Study Investigator, not suitable to participate in
 the study. In addition, any patient who experiences a gap in treatment of at least one
 month between completing the Index study and Screening for this study, should have the
 following exclusion criteria evaluated:

 4. 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

 5. 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.

 6. A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15.

 7. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale
 (CSSRS). Any lifetime history of a suicide attempt, or any suicidal behavior in the
 last month. Note: Patients who are unable to complete the PHQ-9 or C-SSRS due to
 significant neurocognitive defects may be enrolled in the study, as long as in the
 opinion of the Primary Investigator there are no clinical signs or symptoms of
 suicidal behavior.

 8. History of significant liver disease or liver injury, or a current liver assessment
 due to abnormal liver tests (as indicated by abnormal liver function tests, alanine
 transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, or serum
 bilirubin >1.5× the upper limit of normal [ULN] for any of these tests) for an
 etiology other than nonalcoholic 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 is exclusionary, but the
 presence of NAFLD is not be exclusionary.

 9. Moderate to severe renal dysfunction as defined by a glomerular filtration rate (GFR)
 <30 mL/min.

 10. History or close family history (parents or siblings) of skin cancer or melanoma (not
 including non-invasive/infiltrative basal or squamous cell lesion), or patient history
 of ocular-cutaneous albinism.