Setmelanotide in Pediatric Rare Genetic Diseases of Obesity

Sponsor

Rhythm Pharmaceuticals, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04966741

Collaborator

(none)

Enrollment

Locations

Arm

15.4

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Bardet-Biedl Syndrome POMC Deficiency Obesity PCSK1 Deficiency Obesity LEPR Deficiency Obesity	Drug: Setmelanotide	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 16, 2022

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Setmelanotide Investigational product: Setmelanotide,10 mg/mL in a sterile solution for Subcutaneous (SC) injection	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. Other Names: IMCIVREE

Arm

Intervention/Treatment

Experimental: Setmelanotide

Investigational product: Setmelanotide,10 mg/mL in a sterile solution for Subcutaneous (SC) injection

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.

Other Names:

IMCIVREE

Outcome Measures

Primary Outcome Measures

Proportion of patients demonstrating >0.2 decrease from baseline in body weight [1 year]
related measure (BMI Z-score)

Secondary Outcome Measures

Mean change from baseline in BMI Z-score [1 year]
Mean change from baseline in percent of the 95th percentile of BMI [1 year]
Mean percent change from baseline in BMI [1 year]
Frequency and severity of adverse events [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 5 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have obesity due to either:
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
BBS as defined by both (1) the Beales Criteria, 1999 (Beales 1999 [Appendix 1]) AND (2) genetic confirmation of homozygous or compound heterozygous loss-off-function mutation in BBS genes.
Age between 2 to <6 years at the time of informed consent
Obesity, defined as BMI ≥97th percentile for age and gender AND body weight of at least 15 kg at the time of enrollment.
Symptoms or behaviors of hyperphagia at any time during the patient's life, as determined by the Investigator at screening
Parent or guardian of study participant is able to communicate well with the Investigator, 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.

Exclusion Criteria

HbA1c >9.0% at screening
History of significant liver disease other than non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
Glomerular filtration rate (GFR) <60 mL/min/1.73 m2
History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism.
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.
Patient is, in the opinion of the Study investigator, not suitable to participate in the study.
Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
Significant hypersensitivity to any excipient in the study drug.
Inadequate hepatic function as evidenced by elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) values >5x Upper limit of normal (ULN).
Any other uncontrolled endocrine, metabolic or medical condition(s) known to impact body weight that could potentially interfere with interpretation of trial results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Colorado	Aurora	Colorado	United States	80045
2	Columbia University Medical Center, Division of Pediatric Endocrinology, Diabetes and Metabolism	New York	New York	United States	10032
3	Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449
4	Sydney Children's Hospital	Randwick		Australia	NSW 2031
5	Hospital Infantil Niño Jesus	Madrid		Spain	28009
6	Addenbrooke's Hospital, Wellcome Trust-MRC Institute of Metabolic Science	Cambridge		United Kingdom	CB2 0QQ