Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients with rare genetic disorders of obesity
- Conditions
- POMC/PCSK1/LEPR heterozygousPOMC/PCSK1/LEPR compound heterozygous (two different mutations ingene) or homozygous deficiency obesityPOMC/PCSK1/LEPR composite heterozygous deficiency obesitySmith-Magenis Syndrome (SMS)SH2B1 deficiency obesityChromosomal rearrangement of the 16p11.2 locus causing obesityCPE compound heterozygous or homozygous deficiency obesityLeptin deficiency obesity with loss of response to metreleptin.SRC1 deficiency obesityMC4R deficiency obesityTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2017-000387-14-DE
- Lead Sponsor
- Rhythm Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 213
1. Patients with the following Genotypes and/or clinical assessment:
a. POMC/PCSK1/LEPR heterozygous
b. POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity
c. POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity)
d. Smith-Magenis Syndrome (SMS)
e. SH2B1 deficiency obesity
f. Chromosomal rearrangement of the 16p11.2 locus causing obesity
g. CPE compound heterozygous or homozygous deficiency obesity
h. Leptin deficiency obesity with loss of response to metreleptin
i. SRC1 deficiency obesity
j. MC4R deficiency obesity
Note: The specific genotype for all patients must be reviewed by the Sponsor prior to study enrollment to confirm that the patient meets Inclusion Criterion #1. In addition, enrollment of patients in some subgroups may be prioritized by the Sponsor in order to ensure enrollment of patients with (1) well described, loss-of-function genetic mutations, (2) a variety of genetic variants, or (3) genetic variants likely to respond to setmelanotide.
2. Age 6 years and above.
3. Obese, defined as Body Mass Index (BMI) =30 kg/m2 for patients =16 years of age or BMI =95th percentile for age and gender for patients 6 up to 16 years of age.
4. Study participant and/or parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and be able to understand and sign the written informed consent/assent.
5. Female participants of child-bearing potential must confirmed non-pregnant, and agree to use contraception as outlined in the protocol. Female participants of nonchildbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), post-menopausal for at least 12 months (and confirmed with a screening FSH level in the postmenopausal
lab range), and failure to have achieved menarche,
do not require contraception during the study.
6. Male participants with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study. Male patients must not donate sperm during and for 90 days following their participation in the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 67
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 156
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9
1. Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents including herbal medications, that has resulted in > 2% weight loss. Patients may be reconsidered approximately 1 month after cessation of such intensive regimens.
2. Use of any medication that is approved to treat obesity within three months of first dose of study drug (e.g., orlistat, lorcaserin,phentermine-topiramate, naltrexone-bupropion). Note: Glucagon-like peptide-1 (GLP-1) receptor agonists may be used up to the dose approved for the treatment of diabetes mellitus (e.g., liraglutide up to a daily dose of 1.8 mg) as long as (1) is it not being prescribed for the treatment of obesity, (2) the dose has been stable for at least three months prior to enrollment, (3) the patient has not experienced weight loss during the previous three months, AND (4) the patient intends to keep the dose stable throughout the course of the study.
3. Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained from the baseline pre-operative weight with no evidence of weight regain. Specifically, patients may be considered if surgery was not successful, or resulted in <10% weight loss compared to preoperative baseline weight or clear evidence of weight regain after an initial response to bariatric surgery. All patients with a history of bariatric surgery must be discussed with, and receive approval from Rhythm prior to enrollment.
4. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other psychiatric disorder(s) that the Investigator believes will interfere significantly with study compliance. Neurocognitive disorders affecting ability to consent will not be disqualifying as long as an appropriate guardian able to give consent has been appointed.
5. A PHQ-9 score of = 15 or any suicidal ideation of type 4 or 5 on the CSSRS during Screening, any lifetime history of a suicide attempt, or any
suicidal behavior in the last month. Note: Patients who are unable to complete the PHQ-9 or C-SSRS due to significant neurocognitive defects may be allowed to enroll in the study, as long as in the opinion of the Primary Investigator there are no clinical signs or symptoms of suicidal behavior.
6. Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound
the results. Any patient with a potentially clinically significant disease should be reviewed with the Sponsor to determine eligibility.
7. HbA1c >9.0% at Screening
8. History of significant liver disease or abnormal liver tests on Screening (i.e. > 1.5 x upper limit of normal [ULN] for alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, or serum bilirubin). Note: Patients entering the study with SRC1 haploinsufficiency obesity must be evaluated during the Screening Period for hepatic fibrosis by appropriate imaging techniques (e.g., transient elastography or magnetic resonance elastography). Any patient with moderate or greater fibrosis (e.g., the equivalent of a METAVIR score =2) will be excluded from the study. Note: A patient with a diagnosis of non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) may be allowed to enroll in the study,
after consultation with the Sponsor. Other significant liver disease, such as cirrhosis, are exclusionary
9. Glomerular fi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method