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

Phase 2

• Conditions: Homozygous or Compound Heterozygous POMC, LEPR or PCSK1 Gene Mutation
• Interventions: Drug: RM-493

• Registration Number: NCT02507492
• Lead Sponsor: Charite University, Berlin, Germany

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-05-29
• Study First Submitted QC: 2015-07-22
• Study First Posted: 2015-07-24
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-19
• Last Update Posted: 2016-02-22
• Primary Completion: 2018-01
• Study Completion: 2018-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RM-493 Once Daily	RM-493	Dose once daily in the morning

Primary Outcome Measures

Name	Time	Method
Effect of RM-493 on Body weight	Day 1 through Day 84	Change of body weight after Treatment with RM-493.

Secondary Outcome Measures

Name	Time	Method
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 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
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.

Trial Locations

Locations (1)

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany