Open-Label Study of Setmelanotide in Hypothalamic Obesity

Rhythm Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Hypothalamic Obesity

Treatments: Drug: Setmelanotide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04725240

2022-004107-32 (EudraCT Number)

RM-493-030

Details and patient eligibility

About

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

Enrollment: 18 patients

Sex: All

Ages: 6 to 40 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Setmelanotide

Experimental group

Description:

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.

Treatment:

Drug: Setmelanotide