genetic mutation Obesity
Conditions
Interventions
Daily and/or weekly subcutaneous administration of setmelanotide from 2, 2,5 or
3 mg (QD) and 20, 25 or 30 mg (QW)
Venipunctures for blood determinations
Skin examination for suspicious lesions at sc
Sponsors
Rhythm Pharmaceuticals, Inc.
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: 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.
Exclusion criteria
Exclusion criteria: 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 =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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of steady-state PK parameters (maximum plasma concentration [Cmax,], time to maximum plasma concentration [Tmax], trough plasma concentration [Ctrough], area under the plasma concentration-time curve over the dosing interval [AUC0-tau]) for QW compared with QD setmelanotide | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints : Safety outcomes, including AEs/SAEs, ISRs and changes in laboratory parameters, vital signs, ECG recordings, and physical examination findings, etc. Exploratory endpoints: Proportion of patients who achieve the following change in body mass index (BMI) from baseline to Week 14 for QW vs QD setmelanotide groups: 1. > -2.5% and 18 years of age, and change in BMI Z-score and change in percentage of 95th percentile of age- and sex-predicted BMI for patients | — |
Countries
Netherlands
Outcome results
None listed