RM-493 Treatment Trial in Proopiomelanocortin (POMC) Deficient Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effects of a once daily subcutaneous (SC) injection of RM-493, in subjects with POMC (propiomelanocortin) or other related rare genetic mutations, on body weight, metabolic function and blood pressure. Patients who respond during the initial 84 days of treatment can enter into long-term (2-year) extensions. The study drug (RM-493) will be administered in an unblinded fashion.

Official Title
-----------------
RM-493 Treatment Trial in Proopiomelanocortin (POMC) Deficient Patients

Conditions
-----------------
Homozygous or Compound Heterozygous POMC, LEPR or PCSK1 Gene Mutation

Intervention / Treatment
-----------------
* Drug: RM-493


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Homozygous or compound heterozygous (different gene mutation on both alleles) POMC, LEPR or PCSK1 gene mutation Obesity (BMI > 30 kg/m2; + 2 BMI SDS) No other therapeutic option, which might cure the patient (e.g. bariatric surgery (see chapter 8)) Negative Pregnancy test Highly effective contraception in women (defined as pearl index < 1), if necessary also for partners of test persons) No participation in other clinical trials according to AMG (Arzneimittelgesetz) (2 months before and after) at the time of this trial Normal or minimally elevated blood pressure (measured in 24RR monitoring or similar methods) according the guidelines of the ESH (European Society of Hypertension) and Deutsche Hochdruckliga: systolic > 159 mmHg/diastolic 99 mmHg sufficient kidney and liver function (Creatinine, ALT, AST) normal values Alanine-Aminotransferase (ALT) (female): < 31 U/l normal values Alanine-Aminotransferase (ALT) (male): < 41 U/l normal values Aspartate-Aminotransferase (AST) (female > 17 years): < 35 U/l; (female < 17 years): 16- 46 U/l normal values Aspartate-Aminotransferase (AST) (male > 17 years): < 50 U/l; (male < 17 years): 16-46 U/l normal values bilirubins (male and female) up to 1,2 mg/dl normal values Creatinine (female > 15 years): 0,51-0,95 mg/dl) ; (female < 15 years): 0,46-0,77 mg/dl normal values Creatinine (male > 15 years): 0,67 - 1,17 mg/dl) ; (male < 15 years): 0,46-0,77 mg/dl Exclusion Criteria: Pregnancy or Breastfeeding All contraindications against study medication (including auxiliary substances) Interactions with study medication Participation of the patient in a clinical study within the last 2 months Intolerance against albumin Concomitant diseases, impaired organ functions, except for known, concurrent GI disorders or other clinical findings expected in PCSK1 or LEPR gene disorders Renal insufficiency (Creatinine > 0,95 mg/dl (female), > 1,17 mg/dl (male)) Impaired liver function (Bilirubins > 1.2 mg/dl) Neurological / psychiatric diseases HIV Infection Active Hepatitis B or C Melanoma or Melanoma occurrence in the family history Non-compliance Subjects who are legally detained in an official institution

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RM-493 Once Daily<br>Dose once daily in the morning | Drug: RM-493<br> <br> * Other names: setmelanotide;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of RM-493 on Body weight | Change of body weight after Treatment with RM-493. | Day 1 through Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of RM-493 on metabolic serum parameters | Measurement of the effect of RM-493 on metabolic serum parameters as measured by blood test. | Day 1 through Day 84 | 
| Effect of RM-493 on blood pressure | Measurement of the effect of RM-493 on blood pressure by daily blood pressure measurements. | Day 1 through Day 84 | 
| Effect of RM-493 on hunger | Measurement of the effect of RM-493 on hunger as measured by the Global Hunger Scale | Day 1 through Day 84 | 
| Effect of RM-493 on body composition/Energy expenditure | Measurement of the effect of RM-493 on body composition/Energy expenditure | Day 1 through Day 84 | 
| Effect of RM-493 on weight loss after treatment continuation of 2 years | Measurement of the effect of RM-493 on weight loss after treatment continuation of 2 years | Day 1 through Day 730 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
POMC, LEPR, PCSK1