Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity

Rhythm Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Bardet-Biedl Syndrome; PCSK1 Deficiency Obesity; POMC Deficiency Obesity; LEPR Deficiency Obesity

Treatments: Drug: Setmelanotide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04966741

RM-493-033

Details and patient eligibility

About

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).

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 2 to 5 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Setmelanotide: PPL Group

Experimental group

Description:

Participants with POMC)/PCSK1/LEPR biallelic mutations collectively referred to as PPL received setmelanotide at a dose of 0.5 milligrams (mg) per day (QD) via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide.

Treatment:

Drug: Setmelanotide

Setmelanotide: BBS Group

Experimental group

Description:

Participants with BBS received setmelanotide at a dose of 0.5 mg QD via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide.

Treatment:

Drug: Setmelanotide