Setmelanotide (RM-493) Treatment Trial in Patients with rare genetic disorders of obesity
- Conditions
- Body weight is regulated within the hypothalamus. In rare cases mutations in genes, which are embedded in the signaling cascades of the hypothalamus lead to early onset severe obesity. POMC is one important gene and encodes the hormone Melanocortin (MSH), which regulates via the MC-4 receptor energy expenditure and satiety. Moreover within the pituitary POMC encodes the hormone ACTH. In total the failure of these hormone leads to obesity and secondary adrenal insufficiency in this POMC patients.Therapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2014-002392-28-DE
- Lead Sponsor
- Charité Univeritaetsmedizin Berlin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
• Written informed consent by the patients or the responsible relatives
• Rare genetic disease populations in adults (=18 years):
o Homozygous or compound heterozygous (different gene mutation on both alleles) POMC, LEPR, MC4R or PCSK1 gene mutation
o Heterozygous POMC, MC4R mutations
o POMC hypermethylation (epigenetic) variant (>51.92 % POMC methylation intensity at the specific analysed POMC region)
o Bardet-Biedl Syndrome
o Alstrom’s Syndrome
• Non-adult adolescent patients (= 12 years of age)
o Homozygous or compound heterozygous POMC, LEPR or MC4R gene mutations
o POMC hypermethylation (epigenetic) variant (> 35.79% POMC methylation intensity for individuals younger than 30 years at the specific analysed POMC region)
o As substantial efficacy is shown in adult patients within each rare genetic disorder, then adolescent patients (greater than or equal to 12 years of age) can enter the study.
• 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 (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)
o normal values Alanin-Aminotransferase (ALT) (female): < 31 U/l
o normal values Alanin-Aminotransferase (ALT) (male): < 41 U/l
o normal values Aspartat-Aminotransferase (AST) (female > 17 years): < 35 U/l; (female < 17 years): 16-46 U/l
o normal values Aspartat-Aminotransferase (AST) (male > 17 years): < 50 U/l; (male < 17 years): 16-46 U/l
o normal values Bilirubine (male and female) up to 1,2 mg/dl
o normal values Creatinine (female > 15 years): 0,51-0,95 mg/dl) ; (female < 15 years): 0,46-0,77 mg/dl
o normal values Creatinine (male > 15 years): 0,67 – 1,17 mg/dl) ; (male < 15 years): 0,46-0,77 mg/dl
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
•Pregnancy or Breastfeeding
•All contraindications against study medication (including auxiliary substances)
•Interactions with study medication
•Participation of the patient in a clincial 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 or MC4R gene disorders
•Renal insufficiency (Creatinine > 0.95 mg/dl (female), > 1.17 mg/dl (male))
•Impaired liver function (Bilirubine > 1.2 mg/dl)
•history of Neurological / psychiatric diseases
•history of HIV Infection
•history of Active Hepatitis B or C
•Melanoma or Melanoma occurrence in the family history
•Non-compliance
•Subjects who are legally detained in an official institution
•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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Primary objectives: <br>•Body weight <br>;Secondary Objective: Secondary objectives:<br>•Pubertal development <br>•Metabolic serum parameters (insulin, liver function)<br>•Blood pressure<br>• Body-weight after a treatment duration of 2 years;Primary end point(s): •Body weight course before and with RM-493 Treatment<br>;Timepoint(s) of evaluation of this end point: Body weight will be measured weekly throughout the study. The primary endpoint will be the body weight before and after the treatment period with RM-493.
- Secondary Outcome Measures
Name Time Method