A Phase 2, Two-Stage (Open-Label Run-in Followed by Randomized Withdrawal), Double-Blind, Placebo-Controlled Study of Setmelanotide in Patients With Specific Gene Variants in the Melanocortin-4 Receptor Pathway

RM-493-034

A 2-stage (open-label run-in, followed by randomized, double-blind, placebo-controlled withdrawal) trial of setmelanotide in patients with obesity and specific gene defects variants in the melanocortin-4 receptor (MC4R) pathway.

2021-11-30

2024-02-14

2024-07-17

Active (not recruiting)

Early phase I

150

Inclusion Criteria: * Patients must have a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity * Age 6 to 65 years, inclusive * Obesity, defined as BMI ≥40 kg/m2 for patients≥18 years of age or BMI ≥97th percentile for age and gender for patients 6 up to 17 years of age * Study participant and/or parent or guardian is able to understand all study procedures and provide consent/assent * Use of highly effective contraception * Symptoms or behaviors of hyperphagia Exclusion Criteria: * Patients with the following genetic variants: biallelic Bardet-Biedl Syndrome (BBS); biallelic Alström Syndrome 1 (ALMS1); homozygous, heterozygous, or compound heterozygous variants in MC4R, POMC, PCSK1, LEPR, nuclear receptor coactivator 1 (NCOA1; steroid receptor coactivator-1 \[SRC1\]) or SRC homology 2 B adapter protein 1 (SH2B1) genes as well as 16p11.2 chromosomal deletions that include the SH2B1 gene * Recent intensive diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that has resulted in weight loss \>2% within previous 3 months * Bariatric surgery within the previous 6 months. * Documented diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s) * Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) or Patient Health Questionnaire 9 (PHQ 9) score of ≥15 during Screening, any suicide attempt in patient's lifetime years, or any suicidal behavior in the last month. * Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study * Has significant features of (or meets the diagnostic criteria for) a genetic syndrome that is associated with obesity * HbA1C \>10.0% at Screening * History of significant liver disease * Glomerular filtration rate (GFR) \<30 mL/min at Screening * History or close family history of melanoma or patient history of oculocutaneous albinism * Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions * Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing * Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide * Significant hypersensitivity to any excipient in the study drug * Females who are breastfeeding or nursing

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'Stage 1 of the trial is open-label. Patients who are eligible to enter Stage 2 of the trial will be randomized in a blinded manner at the Stage 2 Entry Visit in a 2:1 ratio to receive either setmelanotide (2) or placebo (1).', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 150, 'type': 'ESTIMATED'}}

2024-04-22