Open-Label Study of Setmelanotide in Hypothalamic Obesity

• Status: Recruiting
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the percent change in body weight in response to setmelanotide administered subcutaneously (SC) daily in obese subjects with hypothalamic obesity (HO).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Criteria

Inclusion Criteria:

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

• Subject has documented evidence of HO, including:

• Recent (within the previous 8 months before Screening) 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 ≥6 months and ≤8 years before Screening.

• Subject has either unilateral hypothalamic lesions (at least 6 subjects) or bilateral hypothalamic lesions (at least 7 subjects), as assessed by MRI.

• Note: Although the intention of the study is to enroll at least six patients with unilateral hypothalamic lesions, the Sponsor may decrease the required number during the course of the study.

• Aged 6 to 28 years, inclusive, at time of enrollment. (A maximum of 5 subjects between the ages of 6 and 12 will be enrolled in the study.)

• Obese, defined as a BMI ≥35 kg/m2 for subjects ≥16 years of age or BMI ≥99th percentile for age and gender for subjects 6 to <16 years of age based on the US Centers for Disease Control and Prevention criteria.

• Documented increase in BMI (change from pre-surgery baseline in BMI z-score ≥0.25) 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.

• If male or a female of child-bearing potential, agrees to use a highly reliable form of contraception throughout the study and for 90 days following the study.

• Highly reliable acceptable forms of contraception include hormonal (ie, oral, implantable, or injectable) AND single-barrier method (ie, condom), or an Intrauterine Device (IUD) AND single-barrier method (ie, condom) or vasectomy/vasectomized partner. True abstinence is acceptable only if it is the preferred and usual lifestyle of the subject.

• Females of non-childbearing potential, defined as surgically sterile (status post-hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), post-menopausal for at least 12 months, or delayed pubertal development and failure to achieve menarche, do not require contraception during the study. Younger female subjects who are not sexually mature will be assessed for Tanner Staging and advised accordingly. Females who begin the study having failed to reach Tanner Stage 5 or achieve menarche, but do so during the study, will be counseled on pregnancy and contraception, and will immediately be treated as a female of child bearing potential for the remainder of the study, with the required pregnancy test at all visits.

• 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 subjects aged <18 years, a parent/legal guardian that can sign.

• 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. (Changes in dose of ≤15% may be permissible, with the Sponsor's approval.)

Subjects meeting any of the following criteria are not eligible for study participation:

• Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents (including herbal medications) that has resulted in >3% weight loss. These subjects may be reconsidered approximately 1 month after cessation of such intensive regimens.

• Use of any medication that is approved to treat obesity (eg, orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion) within 3 months before the first setmelanotide dose.

• Note: Glucagon-like peptide-1 (GLP-1) receptor agonists may be used up to the dose approved for the treatment of diabetes mellitus (eg, liraglutide up to a daily dose of 1.8 mg) as long as (1) it is not being prescribed for the treatment of obesity, (2) the dose has been stable for at least 3 months prior to enrollment, (3) the subject has not experienced >3% weight loss during the previous 3 months, AND (4) the subject intends to keep the dose stable throughout the course of the study.

• 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 C-SSRS during Screening, or lifetime history of suicide attempts, or any suicidal behavior in the last month.

• Glycated hemoglobin (HbA1c) >9.0% at Screening.

• Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results. Any subject with a potentially clinically significant disease should be reviewed with the Sponsor to determine eligibility.

• Glomerular filtration rate (GFR) <30mL/min during Screening.

• 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 subject is not eligible for study participation.

• History or close family history (parents or siblings) of skin cancer or melanoma (not including noninvasive, infiltrative basal or squamous cell lesion), or subject history of ocular-cutaneous albinism.

• 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 once daily (QD) injection regimen.

• If female, breastfeeding or nursing.

• Previous history of weight loss surgery, eg, gastric bypass or gastric banding.

• Cognitive impairment that, in the Investigator's opinion, precludes participation to the study and completions of study procedures or questionnaires.

• Subject is, in Investigator's opinion, otherwise not suitable to participate in the study.