Setmelanotide in Pediatric Patients With Rare Genetic Diseases of Obesity

• ClinicalTrials.gov Identifier: NCT04966741
• Recruitment Status: Active, not recruiting
• First Posted: July 19, 2021
• Last Update Posted: December 15, 2022
• Sponsor: Rhythm Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Rhythm Pharmaceuticals, Inc.

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 (Clinical Trial)
• Actual 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: February 16, 2022
• Estimated Primary Completion Date: September 20, 2023
• Estimated Study Completion Date: September 20, 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 Name: IMCIVREE

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients demonstrating >0.2 decrease from baseline in body weight [ Time Frame: Baseline to Week 52 ]
   To evaluate the effect of setmelanotide on weight-related parameters by using measurement of decrease in body weight
2. Mean percent change in BMI [ Time Frame: Baseline to Week 52 ]
   To evaluate the effect of setmelanotide on weight-related parameters by using the Body Mass Index measurement

Secondary Outcome Measures :

1. Mean absolute change from baseline in BMI Z-score [ Time Frame: Baseline to Week 52 ]
   Mean absolute change from baseline in BMI Z-score by age and gender
2. Mean change in percent of the 95th percentile of BMI [ Time Frame: Baseline to Week 52 ]
   Mean change in percent of the 95th percentile of BMI by age and gender
3. Mean change in bone age [ Time Frame: Baseline to Week 52 ]
   Mean change in bone age
4. Mean change in Ages & Stages Questionnaires (ASQ®-3) [ Time Frame: Baseline to Week 52 ]
   Mean change in Ages & Stages Questionnaires score (ASQ®-3)

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 5 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

United States, New York

Columbia University Medical Center, Division of Pediatric Endocrinology, Diabetes and Metabolism

New York, New York, United States, 10032

United States, Wisconsin

Marshfield Clinic Research Foundation

Marshfield, Wisconsin, United States, 54449

Australia

Sydney Children's Hospital

Randwick, Australia, NSW 2031

Spain

Hospital Infantil Niño Jesus

Madrid, Spain, 28009

United Kingdom

Addenbrooke's Hospital, Wellcome Trust-MRC Institute of Metabolic Science

Cambridge, United Kingdom, CB2 0QQ

Sponsors and Collaborators

Rhythm Pharmaceuticals, Inc.

Investigators

• Study Chair: David Meeker, MD; Rhythm Pharmaceuticals, Inc.

More Information

• Responsible Party: Rhythm Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04966741
• Other Study ID Numbers: RM-493-033
• First Posted: July 19, 2021
• Last Update Posted: December 15, 2022
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rhythm Pharmaceuticals, Inc.:

Bardet Biedl Syndrome; POMC Deficiency; PCSK1; LEPR; Obesity; Pediatric Obesity

Additional relevant MeSH terms:

Bardet-Biedl Syndrome; Laurence-Moon Syndrome; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Retinitis Pigmentosa; Eye Diseases, Hereditary; Eye Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Genetic Diseases, Inborn