Phase 3 Trial of Setmelanotide in Acquired Hypothalamic Obesity

Phase 1

Recruiting

Conditions: Acquired Hypothalamic Obesity
Therapeutic area: Phenomena and Processes [G] - Metabolism [G03]
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: CTIS2022-503116-16-00

Lead Sponsor: Rhythm Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 120

Inclusion Criteria

Inclusion 1. Patient has documented evidence of acquired HO defined as: • Diagnosis of craniopharyngioma or other brain lesion affecting the hypothalamic region and has undergone surgery, or chemotherapy, or radiation therapy involving the hypothalamus at least 6 months before Screening, OR • Documented injury to the hypothalamus at least 6 months before Screening for which surgery/radiation is not indicated, Inclusion 2. Aged 4 years and older at time of enrollment, Inclusion 3. Documented weight gain associated with the hypothalamic injury either before therapy or following therapy (surgery and/or following chemotherapy or radiotherapy), and a BMI of =30 kg/m2 for patients =18 years of age or BMI =95th percentile for age and sex for patients 4 to <18 years of age based on the US Centers for Disease Control and Prevention criteria., UPD Inclusion 4. Patients must meet contraception requirements as outlined in Section 6.8.9 unless otherwise indicated., Inclusion 5. Ability to communicate well with the Investigator, understand and comply with the requirements of the trial, and understand and sign the written informed consent and/or assent for patients aged <18 years, a parent/legal guardian that can sign., UPD Inclusion 6. If receiving hormone replacement therapy (ie, thyroid hormones, glucocorticoids, growth hormone or other medications known to affect metabolism or weight/body composition), the dose of such therapy has remained stable for at least 2 months prior to Screening. Note: Changes in dose of =25% may be permissible, with the Sponsor’s approval). If results of free thyroxine (FT4) warrant changes in therapy >50% or the addition of new medication the patient is screen failed and can be reassessed after 2 months. This doesnot apply to patients experiencing adrenal crisis.

Exclusion Criteria

Exclusion 1. Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET), Exclusion 18. The patient or a relative of the patient is the Investigator or a sub-investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the trial., Exclusion 2. Weight loss >2% in the previous 3 months for patients aged =18 years or >2% reduction in BMI for patients aged 4 to <18 years --NOTE: Dietary and/or exercise regimens, with or without the use of medications, supplements or herbal treatments associated with weight loss (eg, orlistat, lorcaserin, phentermine, topiramate, naltrexone, bupropion, glucagon-like peptide-1 [GLP-1] receptor agonists, etc) 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% (for patients =18 years) or >2% BMI (for patients aged 4 to <18 years) during the previous 3 months, and - the patient intends to keep the regimen and/or dose stable throughout the course of the trial., Exclusion 3. Bariatric surgery or procedure (eg, gastric bypass/band/sleeve, duodenal switch, gastric balloon, intestinal barrier, etc) within the last 2 years. All patients with a history of bariatric surgery or procedures must be discussed with and receive approval from the Sponsor prior to enrollment., Exclusion 4. Diagnosis of severe psychiatric disorders (eg, schizophrenia, bipolar disorder, personality disorder), or Major Depressive Disorder (MDD) within the previous 2 years, or Screening Patient Health Questionnaire (PHQ)-9/PHQ-A score =15, or any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (CSSRS), or a Children’s Depression Inventory 2 (CDI-2) T-score =70 during Screening, or lifetime history of suicide attempts, or any suicidal behavior in the last month., Exclusion 5. HbA1c >11.0% at Screening., Exclusion 6. Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results. Any patient with a potentially clinically significant disease should be reviewed with the Sponsor or contract research organization (CRO) monitor to determine eligibility., UPD Exclusion 7. End stage renal disease (GFR <15 mL min/1.73 m2) in any age or glomerular filtration rate (GFR) <30 mL/min/1.73 m2 during Screening in patients <12 years of age (GFR is calculated using the Bedside Schwartz Formula for patients <18 years of age)., Exclusion 8. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion), determined as part of a comprehensive skin evaluation performed by the Investigator during Screening. Any concerning lesions identified during Screening will be biopsied and results known to be benign prior to enrollment. If the pre-treatment biopsy results are of significant concern, the patient is not eligible for trial participation., Exclusion 9. History or close family history (parents or siblings) of skin cancer or melanoma (not including noninvasive, infiltrative basal or squamous cell lesion), or patient history of ocular-cutaneous albinism., Exclusion 19. Hypersensitivity to setmelanotide and/or any excipients contained in the investigational drug., Exclusion 10. Participation in any clinical tr