Open-Label Study of Setmelanotide in Hypothalamic Obesity

NCT04725240 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: RM-493-0302022-004107-32
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

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).

Conditions

Hypothalamic Obesity

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With ≥ 5% Reduction in BMI From Baseline After 16 Weeks of Setmelanotide Treatment

  BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. Baseline was defined as the most recent measurement prior to the first administration of study drug.

  Baseline to 16 weeks

Secondary Outcomes (9)

• 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

  Baseline to Week 16

• Percentage of Participants Aged ≥6 to <18 Years With ≥0.2 Reduction of BMI Z-Score From Baseline After 16 Weeks of Setmelanotide Treatment

  Baseline to 16 weeks

• Percentage of Participants Aged ≥18 Years With ≥5% Reduction of Body Weight From Baseline After 16 Weeks of Setmelanotide Treatment

  Baseline to Week 16

• Change From Baseline in Waist Circumference in Participants Aged ≥18 Years After 16 Weeks of Setmelanotide Treatment

  Baseline, Week 16

• Change From Baseline in Daily Hunger Questionnaire Score in Participants Aged <12 Years After 16 Weeks of Setmelanotide Treatment

  Baseline, Week 16

Study Arms (1)

Setmelanotide

EXPERIMENTAL

Participants received setmelanotide once daily (QD) via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and dose escalated up to a maximum dose of 3.0 milligrams (mg) QD.

Drug: Setmelanotide

Interventions

Setmelanotide DRUG

Setmelanotide for SC injection

Setmelanotide

Eligibility Criteria

• Age: 6 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead

Study Sites (5)

Rady Children's Hospital

San Diego, California, 92123, United States

Location

University of Florida

Gainesville, Florida, 32610-0296, United States

Location

Children's Minnesota

Saint Paul, Minnesota, 55102, United States

Location

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232, United States

Location

Seattle Children's Research Institute

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• 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.

  PMID: 38697184 BACKGROUND

MeSH Terms

Conditions

Sexual Infantilism

Interventions

setmelanotide

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Hypogonadism

Results Point of Contact

• Title: Rhythm Clinical Trials
• Organization: Rhythm Pharmaceuticals, Inc.

clinicaltrials@rhythmtx.com

857-264-4280

Study Officials

• David Meeker, MD

  Rhythm Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 26, 2021
• Study Start: June 7, 2021
• Primary Completion: June 28, 2022
• Study Completion: June 28, 2022
• Last Updated: February 7, 2025
• Results First Posted: September 21, 2023

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)