A Phase 3, Randomized, Double-Blind Trial of Two Formulations of Setmelanotide (Daily and Weekly) with a Crossover to Open-Label Once Weekly Setmelanotide in Patients with Specific Gene Defects in the Melanocortin-4 Receptor Pathway Who Are Currently on a Stable Dose of the Once Daily Formulatio
- Conditions
- genetic mutationObesity10021605
- Registration Number
- NL-OMON53772
- Lead Sponsor
- Rhythm Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
1. All patients must have met the criteria for diagnosis of a gene defect in
the MC4R pathway (BBS, biallelic PPL, heterozygous PPL), for which they are
being treated with QD setmelanotide.
2. Patients must be >=6 years old at screening.
3. Patients must have been taking the setmelanotide QD formulation for at least
6 months in the LTE trial with acceptable safety and tolerability, and the dose
level must have been stable at 2, 2.5 or 3 mg of setmelanotide for at least the
last 3 months prior to starting the Run-in Period.
4. Patient and/or parent or guardian is able to communicate well with the
Investigator, to understand and comply with the requirements of the trial and
is able to understand and sign the written informed consent/assent.
5. Patient must meet one of the following requirements:
Female participants of childbearing potential, defined as fertile, following
menarche and until becoming post-menopausal unless permanently sterile
(hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), must be
confirmed non-pregnant and agree to use a highly effective form of
contraception throughout the trial and for 90 days following the trial. Highly
effective forms of contraception are detailed below and in Section 8.8.7:
- Combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation (oral, intravaginal, or transdermal)
- Progestin-only hormonal contraception associated with inhibition of ovulation
(oral, implantable, or injectable)
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Vasectomy/vasectomized partner (provided that the vasectomized partner is the
sole sexual partner of the female participant, and the vasectomized partner has
received medical assessment of surgical success)
- Sexual abstinence, only if it is the preferred and usual lifestyle of the
patient
Female participants 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 lab
range) do not require contraception during the trial.
Younger female patients who have not achieved sexual maturity at study entry
will be assessed for Tanner staging and required to comply with contraception
requirements at first menarche.
Male participants with female partners of childbearing potential must agree to
use a highly effective method of contraception if they become sexually active
during the trial or within 90 days following their participation in the study.
Male patients must also not donate sperm during and for 90 days following their
participation in the trial.
1. HbA1C >9.0% at screening.
2. Has taken a medication that is approved to treat obesity (e.g., orlistat,
lorcaserin, phentermine-topiramate, naltrexone-bupropion) within 3 months prior
to starting the Run-in Period. Glucagon-like peptide-1 (GLP) -1) receptor
agonists being prescribed for the treatment of obesity are not allowed.
3. History of significant liver disease or liver injury, or a current liver
assessment due to abnormal liver tests for an etiology other than nonalcoholic
fatty liver disease (NAFLD). Thus, any underlying etiology besides NAFLD,
including diagnosed nonalcoholic steatohepatitis (NASH), other causes of
hepatitis, or history of hepatic cirrhosis is exclusionary, but the presence of
NAFLD is not exclusionary.
4. Moderate to severe renal dysfunction as defined by a glomerular filtration
rate <30 mL/min. (based upon the Chronic Kidney Disease Epidemiology
Collaboration [CKD-EPI] creatinine equation 2021 from the National Kidney
Foundation). In patients <18 years of age the Bedside Schwartz Equation should
be used to calculate estimated glomerular filtration rate (eGFR).
5. Significant dermatologic findings relating to melanoma or pre-melanoma skin
lesions (excluding non-invasive basal or squamous cell lesion), determined as
part of comprehensive skin evaluation performed by the Investigator during
screening. Any concerning lesions identified during the Screening Period will
be biopsied and results must be known to be benign prior to enrollment. If the
pretreatment biopsy results are of concern, the patient should be excluded from
the trial.
6. Diagnosis of schizophrenia, bipolar disorder, personality disorder, or other
psychiatric disorders that the Investigator believes will interfere
significantly with trial compliance. Neurocognitive disorders affecting ability
to consent will not be disqualifying as long as an appropriate guardian able to
give consent has been appointed.
7. Clinically significant depression or suicidality as defined by: any suicidal
ideation of type 4 or 5 on the C SSRS, any lifetime history of a suicide
attempt, or any suicidal behavior in the last month or a Patient Health
Questionnaire-9 (PHQ-9) score of >=15 during Screening in patients with no
significant neurocognitive deficits.
8. Patient is not suitable, in the opinion of the Investigator, to participate
in the trial.
9. Hypersensitivity to the active substance or to any of the excipients of the
investigational products (active or placebo).
10. Inability to comply with the QW and QD injection regimens.
11. Participation in any clinical trial with an investigational drug/device
within 3 months prior to the first day of dosing, with the exception of a
setmelanotide clinical trial.
12. Legally protected persons per local regulations (e.g., those that fall
under the L1121-6 article of the Public Health code in France) or other
applicable local laws.
13. The patient or a relative of the patient is the investigator or a sub
investigator, research assistant, pharmacist, trial coordinator, or other
staff directly involved with the conduct of the trial.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Comparison of steady-state PK parameters (maximum plasma concentration [Cmax,],<br /><br>time to maximum plasma concentration [Tmax], trough plasma concentration<br /><br>[Ctrough], area under the plasma concentration-time curve over the dosing<br /><br>interval [AUC0-tau]) for QW compared with QD setmelanotide</p><br>
- Secondary Outcome Measures
Name Time Method