A clinical study designed to evaluate the body weight response to setmelanotide in patients with hypothalamic obesity.

Phase 1

• Conditions: Hypothalamic Obesity; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2022-004107-32-Outside-EU/EEA
• Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-01-23
• Last Update Posted: 30 January 2023

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Patients must meet all of the following criteria to be eligible for study participation:
-Patient has documented evidence of HO, including:
-Recent evidence of hypothalamic injury on magnetic resonance imaging (MRI); AND
-Diagnosis of craniopharyngioma or other non-malignant brain tumor affecting the hypothalamic region; AND
-Has undergone surgery, or chemotherapy, or radiation =6 months and =15 years before Screening.
-Patient has either unilateral hypothalamic lesions or bilateral hypothalamic lesions, as assessed by MRI.
-Aged 6 to 40 years.
-Obesity, documented by a BMI =35 kg/m2 for patients =18 years of age or BMI =95th percentile for age and gender for patients 6 to <18 years of age.
-Documented increase in BMI (change from pre-surgery baseline in BMI z-score =0.2 for patients <18 years of age or BMI >5% for patients >18 years of age) either during the first 6 months following surgery or within 1 year before surgery AND still present at Screening.
-More than 6 months after the end of post-tumor treatment, including chemotherapy, surgery, or radiation.
-Highly effective contraception throughout the study and for 90 days following the study.
-Ability to communicate well with the Investigator, understand and comply with the requirements of the study, and understand and sign the written informed consent, or, for patients aged <18 years, a parent/legal guardian that can sign.
-If receiving hormone replacement therapy, the dose of such therapy has remained stable for at least 2 months prior to Screening.
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Patients meeting any of the following criteria are not eligible for study participation:
-Weight gain >5% in the previous 3 months.
-Weight loss =2% in the previous 3 months.
-Note: Dietary and/or exercise regimens, with or without the use of medications, supplements, or herbal treatments associated with weight loss are allowed if:
-the regimen and/or dose has been stable for at least 3 months prior to randomization
-the patient has not experienced weight loss =2% during the previous 3 months, AND
-the patient intends to keep the regimen and/or dose stable throughout the course of the study.
-Bariatric surgery or procedure within the last 6 months.
-Diagnosis of severe psychiatric disorders
-HbA1c >10.0% at Screening.
-Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results.
-Glomerular filtration rate (GFR) <30mL/min/1.73m^2 during Screening.
-Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.
-History or close family history (parents or siblings) of skin cancer or melanoma
-Participation in any clinical study with an investigational drug/device within 3 months, prior to the first setmelanotide dose.
-Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
-Inability to comply with once daily (QD) injection regimen.
-Pregnant and/or breastfeeding, or desiring to become pregnant during this trial.
-Cognitive impairment that, in the Investigator's opinion, precludes participation to the study and completions of study procedures or questionnaires.
-Patient is, in Investigator's opinion, otherwise not suitable to participate in the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective was to evaluate the change in body weight in response to setmelanotide administered subcutaneously (SC) daily in patients with HO.;Secondary Objective: The secondary objectives were to evaluate changes in parameters of body weight, BMI, waist circumference, and hunger in response to setmelanotide in patients with HO and to evaluate the safety and tolerability of setmelanotide in patients with HO.;Primary end point(s): The primary endpoint was defined as the proportion of patients who achieve at least 5% BMI reduction from baseline at ~16 weeks of treatment with setmelanotide.;Timepoint(s) of evaluation of this end point: ~16 weeks of treatment with setmelanotide.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -The proportion of patients, aged = 6 to < 18 years, with = 0.2 reduction of BMI Z-score along with the proportion of patients aged = 18 years with 5% reduction of body weight from baseline after 16 weeks of setmelanotide treatment.<br>-The proportion of patients aged = 18 years with = 5% reduction of body weight from baseline after 16 weeks of setmelanotide treatment.<br>-The change from baseline in waist circumference (cm) in patients aged = 18 years after 16 weeks of setmelanotide treatment<br>-The change in hunger in response to 16 weeks of setmelanotide treatment as measured by change from baseline in daily and global hunger scores <br><br><br>;Timepoint(s) of evaluation of this end point: ~16 weeks of treatment with setmelanotide.