Clinical trial NCT04725240: Open-Label Study of Setmelanotide in Hypothalamic Obesity
Official title: A Phase 2, Open-Label 20-Week Study to Evaluate the Safety and Efficacy of Setmelanotide in Subjects With Hypothalamic Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypothalamic Obesity
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-01-26
Enrollment: 18
Sex: ALL
Minimum age (years): 6
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Open-label, single-arm study designed to evaluate the body weight response to setmelanotide administered subcutaneously (SC) daily in participants with hypothalamic obesity (HO).


Eligibility criteria: Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for study participation:

* Participant 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.
* Participant has either unilateral hypothalamic lesions or bilateral hypothalamic lesions, as assessed by MRI.
* Obesity, documented by a body mass index (BMI) ≥35 kilograms/square meter (kg/m\^2) for participants ≥18 years of age or BMI ≥95th percentile for age and gender for participants 6 to \<18 years of age.
* Documented increase in BMI (change from pre-surgery baseline in BMI z-score ≥0.2 for participants \<18 years of age or BMI \>5% for participants \>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 participants 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.

Exclusion Criteria:

Participants 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.
* Bariatric surgery or procedure within the last 6 months.
* Diagnosis of severe psychiatric disorders
* Glycated hemoglobin (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 or 5 half-lives, whichever is longer, prior to the first setmelanotide dose.
* Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
* Inability to comply with 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.
* Participant is, in Investigator's opinion, otherwise not suitable to participate in the study.

Primary outcomes:
measure: Percentage of Participants With ≥ 5% Reduction in BMI From Baseline After 16 Weeks of Setmelanotide Treatment
timeFrame: Baseline to 16 weeks
Secondary outcomes:
measure: Composite Percentage of Participants Aged ≥6 to <18 Years With ≥0.2 Reduction of BMI Z-Score or Participants Aged ≥18 Years With 5% Reduction of Body Weight From Baseline After 16 Weeks of Setmelanotide Treatment
timeFrame: Baseline to Week 16
measure: Percentage of Participants Aged ≥6 to <18 Years With ≥0.2 Reduction of BMI Z-Score From Baseline After 16 Weeks of Setmelanotide Treatment
timeFrame: Baseline to 16 weeks
measure: Percentage of Participants Aged ≥18 Years With ≥5% Reduction of Body Weight From Baseline After 16 Weeks of Setmelanotide Treatment
timeFrame: Baseline to Week 16
measure: Change From Baseline in Waist Circumference in Participants Aged ≥18 Years After 16 Weeks of Setmelanotide Treatment
timeFrame: Baseline, Week 16
measure: Change From Baseline in Daily Hunger Questionnaire Score in Participants Aged <12 Years After 16 Weeks of Setmelanotide Treatment
timeFrame: Baseline, Week 16
measure: Change From Baseline in Daily Hunger Questionnaire Scores in Participants Aged ≥12 Years After 16 Weeks of Setmelanotide Treatment
timeFrame: Baseline, Week 16
measure: Number of Participants With Shift From Baseline in Global Hunger Questionnaire Score to Week 16 in Participants Aged < 12 Years
timeFrame: Baseline, Week 16
measure: Number of Participants With Shift From Baseline in Global Hunger Questionnaire Score to Week 16 in Participants Aged ≥12 Years
timeFrame: Baseline, Week 16
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose of study drug up to Day 141
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Saint Paul
country: United States
facility: Children's Minnesota
state: Minnesota
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
city: Seattle
country: United States
facility: Seattle Children's Research Institute
state: Washington
Study officials:
affiliation: Rhythm Pharmaceuticals, Inc.
name: David Meeker, MD
role: STUDY_CHAIR
References:
citation: Roth CL, Scimia C, Shoemaker AH, Gottschalk M, Miller J, Yuan G, Malhotra S, Abuzzahab MJ. Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial. Lancet Diabetes Endocrinol. 2024 Jun;12(6):380-389. doi: 10.1016/S2213-8587(24)00087-1. Epub 2024 Apr 30.