Purpose

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).

Condition

Eligibility

Eligible Ages
Between 6 Years and 28 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Setmelanotide
Investigational product: Setmelanotide, 10 mg/mL in a sterile solution for Subcutaneous (SC) injection . Dosage: 1.0, 2.0, 3.0 mg QD for subjects 6 to <16 years of age, and 2.0 to 3.0 mg QD for subjects ≥16 years of age. All subjects will receive study treatment for 16 weeks.
  • Drug: Setmelanotide
    Subjects aged 6 to <16 years, inclusive Starting at Baseline (Day 1; Visit 2) through approximately Day 14, subjects will receive setmelanotide 1.0 mg/day. Starting at approximately Day 15 through 28, subjects will receive setmelanotide 2.0 mg/day. Subjects/caregivers will be contacted by study center personnel on Day 15 to ensure dose titration has occurred and to document any adverse events (AEs). • Starting on approximately Day 29 (Visit 3), subjects will receive setmelanotide 3.0 mg/day; subjects will continue to receive setmelanotide 3.0 mg/day for 12 weeks. The dose of setmelanotide should be titrated as explained in the SoA. Subjects aged ≥16 years, inclusive Starting at Baseline (Day 1; Visit 2) through approximately Day 14, subjects will receive setmelanotide 2.0 mg/day. Starting at approximately Day 15, subjects will receive setmelanotide 3.0 mg/day; subjects will continue to receive setmelanotide 3.0 mg/day for 14 weeks.

Recruiting Locations

Vanderbilt University School of Medicine
Nashville, Tennessee 37232
Contact:
Laura Maynard
615-875-4274
laura.e.maynard@vumc.org

More Details

Status
Recruiting
Sponsor
Rhythm Pharmaceuticals, Inc.

Study Contact

Sarah Pilley, BS/MS
857-264-4281
spilley@rhythmtx.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.