Setmelanotide trial in patients with rare genetic disorders of obesity
Research type
Research Study
Full title
Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients with rare genetic disorders of obesity
IRAS ID
223480
Contact name
Tarekegn Hiwot
Contact email
Sponsor organisation
Rhythm Pharmaceuticals, Inc.
Eudract number
2017-000387-14
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Research Summary
This study is designed for patients with ultra-rare genetic conditions characterized by severe early onset obesity and profound hyperphagia (increased appetite and hunger with impaired satiety) with numerous comorbidities, and likely early mortality.
Setmelanotide is a novel investigational drug, which works by activating neurons responsible for decreased appetite and weight. So far research results have demonstrated that the use of setmelanotide has been associated with significant weight and appetite reduction and that it has been well-tolerated.
Up to ~ 30 patients may be included in this study, with up to a maximum of ~ 5 patients of each rare genetic cause of obesity:
• Leptin Receptor Deficiency Obesity
• POMC Heterozygous Deficiency Obesity
• POMC Epigenetic Deficiency Obesity
• Bardet-Biedl syndrome
• Alström syndrome
The study will begin with an initial period of dose titration where the individual patient’s therapeutic dose will be established by upwards dose titration in 2 week intervals. Thereafter, patients will continue on active treatment at their individually titrated optimal therapeutic dose for an additional 10 weeks, for a total combined dosing duration of 12 weeks. For patients who demonstrate at least 5 kg weight loss at the end of the 12-week open label treatment period (or 4 kg weight loss over this 12-week period in adolescent patients younger than age 18), they will continue one-year extensions for evaluation of setmelanotide’s effects at 1 year (and onwards) of total therapeutic dosing.
The patients will daily receive sub-cutaneous injections of setmelanotide.
Study procedures primarily include frequent obesity measurements including hunger assessment, body composition assessments (including total body weight, fat mass, and non-bone lean mass) and waist circumference. Other study procedures include vital signs, collection of blood and urine samples, physical examination and ECG.
There are also optional sub-studies to evaluate PK, energy expenditure, skin coloration changes, and blood pressure/heart rate.Summary of Results
In the overall population, 30.5% of patients met the study's primary efficacy endpoint achieving a > 5% reduction from baseline in body weight after 3 months of treatment with Setmelanotide. Achievement of the primary endpoint occurred in age groups with a larger effect in patients > 12 years of age versus < 12 years of age, presumably because wight loss in children and adolescents is often masked by concomitant linear growth. The overall population of patients lost a mean of -3.5kg of body weight after 3 months resulted in a mean change from baseline in BMI of -1718 kg/m2 and reductions in BMI Z-score of -0.391 AND -0.235 in pediatric patients < 12 years of age and > 12 and <18 years respectively. Of note, changes in BMI Z-scores of > 0.2 are considered clinically meaningful. In conclusion Setmelanotide was well tolerated by this diverse population of patients with range of MC4R pathway diseases characterised by early onset obesity and hyperphagia. Promising efficacy results were observed in a subset of the populations treated.
REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
17/WM/0117
Date of REC Opinion
24 May 2017
REC opinion
Further Information Favourable Opinion