Clinical trial NCT04966741: Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
Official title: A Phase 3 Multi-Center, 1-Year, Open-Label Study of Setmelanotide in Pediatric Patients Aged 2 to <6 Years of Age With Rare Genetic Causes of Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bardet-Biedl Syndrome
POMC Deficiency Obesity
PCSK1 Deficiency Obesity
LEPR Deficiency Obesity
Keywords: Bardet Biedl Syndrome
POMC Deficiency
PCSK1
LEPR
Obesity
Pediatric Obesity
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-19
Enrollment: 12
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 3 open-label, clinical study to evaluate the efficacy, safety and tolerability of setmelanotide over 1 year of treatment, in pediatric participants aged 2 to \<6 years with obesity due to either biallelic variants of the pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) genes or Bardet-Biedl Syndrome (BBS).

Detailed description: Pediatric participants aged 2 to \<6 years with obesity due to either biallelic variants of the POMC, PCSK1 or LEPR genes or BBS will be enrolled into this phase 3 open-label clinical trial at one of approximately 8 clinical centers in North America, Europe, or Australia. All participants will be assigned to receive setmelanotide via daily subcutaneous (SC) injection for 1 year.

Eligibility criteria: Key Inclusion Criteria:

1. Participants must have obesity due to either:

   1. POMC, PCSK1, or LEPR deficiency, confirmed by genetic testing demonstrating biallelic variants that are interpreted as pathogenic, likely pathogenic, or of undetermined significance (VUS) by the American College of Medical Genetics and Genomics criteria (ACMG), or
   2. BBS confirmed clinical and genetic diagnosis
2. Age between 2 to \<6 years at the time of informed consent
3. Obesity, defined as body mass index (BMI) ≥97th percentile for age and gender and body weight of at least 15 kilograms (kg) at the time of enrollment.
4. Symptoms or behaviors of hyperphagia
5. Parent or guardian of study participant is able to understand and comply with the requirements of the study (including QD injection regimen and all other study procedures) and is able to understand and sign the written consent/assent.

Key Exclusion Criteria

1. Glycated hemoglobin (HbA1c) \>9.0% at screening
2. History of significant liver disease
3. Glomerular filtration rate (GFR) \<60 milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2)
4. History or close family history of melanoma, or participant history of oculocutaneous albinism.
5. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
6. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
7. Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
8. Significant hypersensitivity to any excipient in the study drug.
9. Inadequate hepatic function
10. Any other uncontrolled endocrine, metabolic or medical condition(s) known to impact body weight

Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Greater Than or Equal to (≥) 0.2 Reduction of BMI Z-Score From Baseline to Week 52
timeFrame: Baseline up to Week 52
measure: Mean Percent Change From Baseline in BMI
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Mean Absolute Change From Baseline in BMI Z-score
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline in Percent of the 95th Percentile of BMI
timeFrame: Baseline, Week 52
measure: Mean Change From Baseline in Bone Age
timeFrame: Baseline, Week 52
measure: Number of Participants With Shift From Baseline in Ages & Stages Questionnaires, Third Edition (ASQ-3)
timeFrame: From Baseline to Week 52
measure: Change From Baseline in Body Weight
timeFrame: Baseline, Week 52
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to Week 56
measure: Number of Participants With TEAEs Graded by Severity
timeFrame: From first dose of study drug up to Week 56
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New York
country: United States
facility: Columbia University Medical Center, Division of Pediatric Endocrinology, Diabetes and Metabolism
state: New York
city: Marshfield
country: United States
facility: Marshfield Clinic Research Foundation
state: Wisconsin
city: Randwick
country: Australia
facility: Sydney Children's Hospital
city: Madrid
country: Spain
facility: Hospital Infantil Niño Jesus
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, Wellcome Trust-MRC Institute of Metabolic Science
Study officials:
affiliation: Rhythm Pharmaceuticals, Inc.
name: David Meeker, MD
role: STUDY_CHAIR
References: