To characterize safety and tolerability of setmelanotide in patients who have completed treatment in a previous trial of setmelanotide for obesityassociated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway and…
ID
Source
Brief title
Condition
- Appetite and general nutritional disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To characterize safety and tolerability of setmelanotide in patients who have
completed treatment in a previous trial of setmelanotide for obesity associated
with genetic defects upstream of the MC4 receptor in the leptin-melanocortin
pathway.
Secondary outcome
Exploratory
• Mean percent change from baseline in body weight in patients >=18 years of age.
• Mean change from baseline in BMI Z-score and percent of 95th BMI percentile
in patients <18 years of age.
• Mean change in BMI and mean percent change in BMI from baseline in all
patients.
• Change in hunger from baseline, as assessed at each visit using a set of 2
global questions.
• Change from baseline in waist circumference, as measured by US National Heart
Lung and Blood Institute criteria [2000 NHLBI] over time.
• Yearly change in body composition including total body weight loss, fat loss,
and non-bone lean mass, as measured by DXA scan or BIA.
• Change from baseline in lipid values (e.g., fasting cholesterol and
triglycerides)
Changes from baseline in Quality of life as assessed by following instruments:
o Impact of Weight on Quality of Life-Lite (IWQOL-Lite)
o 10-Item Short Form Health Survey for Children (SF-10)
Change from baseline in mental health status as measured by the Patient Health
Questionnaire-9 (PHQ-9) and Columbia-Suicide Severity RatingScale (C-SSRS)
Change from baseline in metabolic and hormonal assays and other exploratory
biomarkers.
Background summary
A genetic modification has been identified on the genes that play a key role in
the regulation of our body weight. Sometimes there is a genetic change
(variation) in one of the genes which are important for body weight regulation.
These genes are responsible for helping to control weight and hunger regulators
located in the hypothalamic centre in the brain that controls appetite and
weight. When there are variations in these genes, they do not function as they
should and the messenger substances (Melanocyte stimulating hormone - MSH)
which signal the feeling of being full are no longer produced. This can result
in you not feeling full and cause you to eat too much and become overweight
Rhythm Pharmaceuticals, Inc. is developing the trial drug setmelanotide, a MSH
messenger substance, to replace the messenger substances that are missing in
someone with certain gene variations.
The drug is administered once a day by subcutaneous injection (under the
skin). Patients will be taught how to give the injection to themselves, so the
daily injections can be performed at home. There will also be home nurse who is
able to assist with the injections at home if required.
Setmelanotide has been given to more than 476 people with obesity ranging from
1 dose to more than a year of dosing. It is only possible to tell what side
effects these people have experienced. The studies were conducted to test the
safety of setmelanotide and in some cases to measure weight loss.
An extension study is a research study designed to enable participants to
continue receiving the study drug after the previous clinical study has end.
This will be an open label extension study with setmelanotide.
Study objective
To characterize safety and tolerability of setmelanotide in patients who have
completed treatment in a previous trial of setmelanotide for obesity
associated with genetic defects upstream of the MC4 receptor in the
leptin-melanocortin pathway and with obesity related to other abnormalities in
the MC4R pathway.
Study design
This is a long-term extension trial to study the safety and tolerability of
continued setmelanotide treatment in patients who have completed a previous
clinical trial on treatment with setmelanotide for obesity associated with
genetic defects upstream of the MC4 receptor in the leptin-melanocortin.
Patients who complete treatment in a previous trial (index trial) of
setmelanotide and wish to continue with setmelanotide treatment will be
considered for eligibility to enter this extension study. Patients will be
consented and eligibility confirmed prior to completion of their index trial.
Visit one of this trial will coincide with the final visit of the index trial.
There should be no gaps of setmelanotide treatment during transition from their
index trial to this extension trial. Patients will begin this extension trial
on the same dose of setmelanotide that they were taking when they complete
their index trail. Patients will be evaluated every 3months at the study site
for adverse events, concomitant meds, weight, waist circumference and hunger
score.
Additional tests will be completed at longer study visit intervals.
Intervention
Patient questionnaires
Blood sampling (safety, Metabolic and Hormonal assays, PK and Anti-RM -493
antibody)
Body composition (BIA, DXA)
Study burden and risks
Overall, setmelanotide has been generally well-tolerated in previous studies.
Drug -Related Treatment Emerengy AE*s (for which the adverse event was assessed
as possible or probably related to the study drug by the investigator) wer
reported.
Because very few studies have been done using setmalanotide, there may be other
unknown side effects.
Pharmacodynamic data from a variety of animal models have shown improvements in
weight regulation, appetite suppression and energy expenditure. Setmelanotide
has also demonstrated meaningful weight reductions in early healthy obese
volunteer clinical studies. In a Phase 2 proof-of concept study, three LEPR
deficient patients were treated with setmelanotide and each demonstrated
compelling improvements on weight loss and hunger, with no signs of increased
blood pressure or heart rate.
The PI and staff (and other covering clinicians) will be available at all times
to study participants in the event of a clinical emergency: both this
availability and how to reach the investigator in an emergency will be clearly
communicated orally and in writing to the study participants. All study
interventions will be provided free of cost. The current Investigator Brochure
describes a comprehensive summary of AEs reported to date
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Listed location countries
Age
Inclusion criteria
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.
Exclusion criteria
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-005006-35-NL |
| ClinicalTrials.gov | NCT03651765 |
| CCMO | NL69205.078.19 |