Setmelanotide in Pediatric Patients With Rare Genetic Diseases of Obesity

Bardet-Biedl Syndrome Clinical Trial

Official title:

A Phase 3 Multi-Center, One-Year, Open-Label Study of Setmelanotide in Pediatric Patients Aged 2 to <6 Years of Age With Rare Genetic Causes of Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04966741
• Other study ID #: RM-493-033
• Status: Completed
• Phase: Phase 3
• Start date: February 16, 2022
• Est. completion date: September 19, 2023

Study information

• Verified date: October 2023
• Source: Rhythm Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 3 open-label, one-arm, clinical study to evaluate the efficacy, safety and tolerability of setmelanotide over 1 year of treatment, in pediatric patients aged 2 to <6 years with obesity due to either biallelic variants of the POMC, PCSK1 or LEPR genes or Bardet-Biedl Syndrome (BBS).

Description:

Pediatric patients aged 2 to <6 years with obesity due to either biallelic variants of the POMC, PCSK1 or LEPR genes or Bardet-Biedl Syndrome (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 patients will be assigned to receive setmelanotide via daily subcutaneous injection for 1 year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 19, 2023
• Est. primary completion date: September 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 5 Years

Eligibility

Key Inclusion Criteria:

1. Patients 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 BMI =97th percentile for age and gender AND body weight of at least 15 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 once daily [QD] injection regimen and all other study procedures) and is able to understand and sign the written consent/assent.

Key Exclusion Criteria

1. HbA1c >9.0% at screening

2. History of significant liver disease

3. Glomerular filtration rate (GFR) <60 mL/min/1.73 m2

4. History or close family history of melanoma, or patient 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.

Related Conditions & MeSH terms

• Bardet-Biedl Syndrome
• LEPR Deficiency Obesity
• Obesity
• PCSK1 Deficiency Obesity
• POMC Deficiency Obesity

Intervention

Drug:
• Setmelanotide
All patients will begin treatment at a dose of 0.5 mg of setmelanotide per day. Patients will then increase their dose by 0.5 mg increments, every 2 weeks, until reaching their target maximum dose (not to exceed 2mg daily). The target maximum dose of setmelanotide used in this study will be based on the weight bands.

Locations

Country	Name	City	State
Australia	Sydney Children's Hospital	Randwick
Spain	Hospital Infantil Niño Jesus	Madrid
United Kingdom	Addenbrooke's Hospital, Wellcome Trust-MRC Institute of Metabolic Science	Cambridge
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Columbia University Medical Center, Division of Pediatric Endocrinology, Diabetes and Metabolism	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Rhythm Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients demonstrating >0.2 decrease from baseline in body weight	To evaluate the effect of setmelanotide on weight-related parameters by using measurement of decrease in body weight	Baseline to Week 52
Primary	Mean percent change in BMI	To evaluate the effect of setmelanotide on weight-related parameters by using the Body Mass Index measurement	Baseline to Week 52
Secondary	Mean absolute change from baseline in BMI Z-score	Mean absolute change from baseline in BMI Z-score by age and gender	Baseline to Week 52
Secondary	Mean change in percent of the 95th percentile of BMI	Mean change in percent of the 95th percentile of BMI by age and gender	Baseline to Week 52
Secondary	Mean change in bone age	Mean change in bone age	Baseline to Week 52
Secondary	Mean change in Ages & Stages Questionnaires (ASQ®-3)	Mean change in Ages & Stages Questionnaires score (ASQ®-3)	Baseline to Week 52