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

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.

Study Overview

• Status: Unknown
• Conditions: Homozygous or Compound Heterozygous POMC, LEPR or PCSK1 Gene Mutation
• Intervention / Treatment: Drug: RM-493

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité - Universitätsmedizin Berlin
    • Contact: Susanna Wiegand, PD Dr.; Phone Number: +49 30 450 566887; Email: susanna.wiegand@charite.de
    • Contact: Peter Kühnen, Dr.; Phone Number: +49 30 450 450 666839; Email: peter.kuehnen@charite.de
    • Sub-Investigator: Heiko Krude, Prof. Dr.
    • Sub-Investigator: Peter Kühnen, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RM-493 Once Daily; Dose once daily in the morning	Drug: RM-493; 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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): January 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: May 29, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimate): July 24, 2015

Study Record Updates

• Last Update Posted (Estimate): February 22, 2016
• Last Update Submitted That Met QC Criteria: February 19, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: POMC, LEPR, PCSK1
• Other Study ID Numbers: RM-493-011; 2014-002392-28 (EudraCT Number)