Homozygous or Compound Heterozygous POMC, LEPR or PCSK1 Gene Mutation
Conditions
Keywords
POMC, LEPR, PCSK1
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.
Interventions
DRUGRM-493
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of RM-493 on Body weight | Day 1 through Day 84 | Change of body weight after Treatment with RM-493. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of RM-493 on metabolic serum parameters | Day 1 through Day 84 | Measurement of the effect of RM-493 on metabolic serum parameters as measured by blood test. |
| Effect of RM-493 on blood pressure | Day 1 through Day 84 | Measurement of the effect of RM-493 on blood pressure by daily blood pressure measurements. |
| Effect of RM-493 on hunger | Day 1 through Day 84 | Measurement of the effect of RM-493 on hunger as measured by the Global Hunger Scale |
| Effect of RM-493 on body composition/Energy expenditure | Day 1 through Day 84 | Measurement of the effect of RM-493 on body composition/Energy expenditure |
| Effect of RM-493 on weight loss after treatment continuation of 2 years | Day 1 through Day 730 | Measurement of the effect of RM-493 on weight loss after treatment continuation of 2 years |
Countries
Germany
Contacts
Primary ContactSusanna Wiegand, PD Dr.
Backup ContactPeter Kühnen, Dr.
Outcome results
None listed