ong Term Extension Trial of setmelanotide (RM-493) for patients who have completed a trial of Setmelanotide for the treatment of obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway
- Conditions
- genetic mutationObesity10003018
- Registration Number
- NL-OMON54784
- Lead Sponsor
- RHYTHM Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 14
1. Patients aged 2 or older (or aged >2 years as per local regulations; only
patients aged 12 years or older may be enrolled in the trial in Greece; only
patients 6 years or older may be enrolled in the trial in Germany) who have
completed participation in a previous setmelanotide clinical trial.
2. If patient received setmelanotide on an open-label basis in a previous
setmelanotide clinical trial, patient demonstrated adequate safety and
meaningful clinical benefit (efficacy) in the previous setmelanotide trial.
Meaningful clinical benefit is defined as follows:
• Patients 18 years of age or younger that have completed participation on
active drug and demonstrated adequate safety and at least 3% BMI reduction or
reduction in BMI Z-score of 0.2 compared to baseline.
• Patients over 18 years of age should show reduction of 3% BMI compared to
baseline. If the patient received trial drug in a double-blind basis in the
previous placebo-controlled clinical trial, patient tolerated trial drug in the
previous clinical trial.
3. Patient and/or parent or guardian is able to communicate well with the
Principal Investigator, to understand and comply with the requirements of the
trial, and to understand and sign the written informed consent/assent. The
patient must assent/consent to participate in the trial.
4. Patient must meet one of the following requirements regarding contraception:
• If a female of childbearing potential, defined as fertile, following menarche
and until becoming post-menopausal unless permanently sterile (hysterectomy,
bilateral salpingectomy, or bilateral oophorectomy), must use a highly
effective form of contraception as outlined in Section 6.2.1.
• If a female of non-childbearing potential, defined as permanently sterile
(status post hysterectomy, bilateral oophorectomy, or bilateral salpingectomy)
or post-menopausal for at least 12 months (and confirmed with a screening
follicle-stimulating hormone (FSH) level in the post-menopausal laboratory
range), contraception is not required during the trial.
* Younger female patients who have not reached menarche upon trial entry will
be assessed for Tanner staging and at first menarche will be required to comply
with contraception requirements and pregnancy testing as outlined in the
protocol.
• If a male with female partner(s) of childbearing potential, must agree to a
double barrier method if they become sexually active during the study.
Furthermore, male patients must not donate sperm during and for 90 days
following their participation in the study.
ALL Patients:
1. Pregnant and/or breastfeeding women
2. Significant dermatologic findings relating to melanoma or premelanoma skin
lesions (excluding non-invasive basal or squamous cell lesion), determined as
part of a screening comprehensive skin evaluation performed by a qualified
dermatologist. Any concerning lesions identified during the screening period
will be biopsied and results known to be benign prior to enrollment. If the
pre-treatment biopsy results are of concern, the patient may need to be
excluded from the trial.
3. Patient is, in the opinion of the Study Investigator, not suitable to
participate in the trial.
4. Current, clinically significant disease, if severe enough to interfere with
the study and/or would confound the results. Any such patients should be
discussed with the Sponsor prior to enrollment in the trial
5. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other
Diagnostic and Statistical Manual of Mental Disorders (DSM-III) disorders that
the investigator believes will interfere significantly with trial compliance.
6. A Patient Health Questionnaire-9 (PHQ-9) score of >= 15.
7. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating
Scale (C-SSRS). 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 enrolled in the study, as long as in
the opinion of the Primary Investigator there are no clinical signs or symptoms
of suicidal behavior since the last visit in the index study.
8. History of significant liver disease or liver injury, or a current liver
assessment due to abnormal liver tests (as indicated by abnormal liver function
tests, alanine transaminase [ALT], aspartate transaminase [AST], alkaline
phosphatase, or serum bilirubin >1.5× the upper limit of 4 normal [ULN] for any
of these tests) for an etiology other than nonalcoholic fatty liver disease
(NAFLD). Thus, any underlying etiology besides NAFLD, including diagnosed
non-alcoholic steatohepatitis (NASH), other causes of hepatitis, or history of
hepatic cirrhosis is exclusionary, but the presence of NAFLD is not be
exclusionary.
9. Severe renal dysfunction as defined by a glomerular filtration rate (GFR)
<30 mL/min/1.73 m2 in patiënts >12 years of age.
10. History or close family history (parents or siblings) of skin cancer or
melanoma (not including non-invasive/infiltrative basal or squamous cell
lesion) or patient history of ocularcutaneous albinism.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To characterize safety and tolerability of setmelanotide in patients who have<br /><br>completed treatment in a previous trial of setmelanotide for obesity associated<br /><br>with genetic defects upstream of the MC4 receptor in the leptin-melanocortin<br /><br>pathway.</p><br>
- Secondary Outcome Measures
Name Time Method