Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients with rare genetic disorders of obesity
- Conditions
- genetic mutationObesity10003018
- Registration Number
- NL-OMON49642
- Lead Sponsor
- RHYTHM Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
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 is able to understand and sign the written informed consent/assent.
5. Female participants of child-bearing potential must be confirmed
non-pregnant, and agree to use contraception as outlined in the protocol.
Female participants of non-childbearing 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 Follicle-Stimulating Hormone [FSH] level in the post-menopausal 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.
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.
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 pre-operative 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 the Sponsor 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 C-SSRS
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
non-alcoholic steatohepatitis (NASH) may be allowed to enroll in the study,
after consultation with the S
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The proportion of patients in each subgroup of RGDO who achieve at least 5%<br /><br>body weight reduction from baseline, at ~3 months treatment with setmelanotide.<br /><br><br /><br>Measured At the end of ~3 months of treatment.</p><br>
- Secondary Outcome Measures
Name Time Method