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.
Conditions
Interventions
Product Name: RM-493
Pharmaceutical Form: Solution for injection
INN or Proposed INN: none
CAS Number: 920014-72-8
Other descriptive name: RM-493
Concentration unit: mg/ml milligram(s)/millilitre
Conc
Sponsors
Charité Univeritaetsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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 159 mmHg/diastolic 99 mmHg • sufficient kidney and liver function (Creatinine, ALT, AST) o normal values Alanin-Aminotransferase (ALT) (female): 17 years): 17 years): 15 years): 0,51-0,95 mg/dl) ; (female 15 years): 0,67 – 1,17 mg/dl) ; (male =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objectives: • Body weight ;Secondary Objective: Secondary objectives: • Pubertal development • Metabolic serum parameters (insulin, liver function) • Blood pressure • Body-weight after a treatment duration of 2 years;Primary end point(s): • Body weight course before and with RM-493 Treatment ;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
| Measure | Time frame |
|---|---|
| Secondary end point(s): •• Pubertal development with RM-493 treatment • Changes of metabolic parameters (insulin, liver / kidney function) • Blood pressure • Body composition/Energy expenditure • Global Hunger Score (10 point scale) • Amendment: weight loss after treatment continuation of 2 years. • Changes of skin and nevi color • Psychological development of each patient during treatment period ;Timepoint(s) of evaluation of this end point: - the pubertal development will be examined just before and after the treatment period with RM-493 by a clinical examination and by performing a LHRH test. - before and after the treatment period there will be a blood collection in which metabolic parameters will be analyzed. - Blood pressure will be analyzed over 24h before and after the treatment period. Moreover, after each dosage escalation the blood pressure will be monitored carefully in the clinic for 12 hours following the new dose. Finally, patients will have blood pressure checked 3 times per day at home. the secondary endpoints were determined during the study visit every 6 months alternating with the 3-month visit; | — |
Countries
Germany
Contacts
Public ContactInstitut Experimentelle Pädiatrie
Charité - Universitätsmedizin Berlin , Campus Virchow-Klinikum
Outcome results
None listed