A 2-Stage (Open-Label Followed by Randomized Double-Blind, Placebo-Controlled Stage), Phase 2 Trial of Setmelanotide in Patients With Specific Gene Variants in the Melanocortin-4 Receptor Pathway
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 164
- 试验地点
- 36
- 主要终点
- Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1
研究概览
简要总结
The purpose of this study was to evaluate the safety and efficacy of once daily subcutaneous (SC) administration of setmelanotide in participants with obesity and specific gene variants in the MC4R pathway.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Stage 1 of the trial is open-label. Participants who were eligible to enter Stage 2 of the trial were randomized in a blinded manner at the Stage 2 Entry Visit in a 2:1 ratio to receive either setmelanotide or placebo.
入排标准
- 年龄范围
- 6 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have had a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity
- •Age 6 to 65 years, inclusive
- •Obesity, defined as Body Mass Index (BMI) ≥40 kilograms per square meter (kg/m^2) for participants ≥18 years of age or BMI ≥97th percentile for age and gender for participants 6 to <18 years of age
- •Study participant and/or parent or guardian were able to understand all study procedures and provide consent/assent
- •Use of highly effective contraception
- •Symptoms or behaviors of hyperphagia
排除标准
- •Participants with the following genetic variants: biallelic Bardet-Biedl Syndrome (BBS); biallelic Alström Syndrome 1 (ALMS1); homozygous, heterozygous, or compound heterozygous variants in MC4R, Pro-opiomelanocortin (POMC), Proprotein convertase subtilisin/kexin type 1 (PCSK1), Leptin receptor (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 included the SH2B1 gene
- •Recent intensive diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that had resulted in weight loss >2% within previous 3 months
- •Bariatric surgery within the previous 6 months
- •Documented diagnosis of current unstable major psychiatric disorder or a documented worsening of psychiatric condition that required changes in treatment within 2 years
- •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 participant'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
- •Glycated hemoglobin (HbA1C) >10.0% at Screening
- •History of significant liver disease
- •Glomerular filtration rate (GFR) <30 milliliter per minute (mL/min) at Screening
- •History or close family history of melanoma or participant 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
- •Participants 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 were breastfeeding or nursing
- •Other protocol defined Inclusion/Exclusion criteria applied.
研究组 & 干预措施
Stage 1: Setmelanotide (Open-Label)
Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 milligrams (mg) once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants <12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.
干预措施: Setmelanotide (Drug)
Stage 2: Setmelanotide (Double-Blind)
Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of setmelanotide 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).
干预措施: Setmelanotide (Drug)
Stage 2: Placebo (Double-Blind)
Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of matching placebo 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).
干预措施: Placebo (Drug)
结局指标
主要结局
Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1
时间窗: Baseline to Week 16
BMI was calculated using participant's weight and height assessments, using the following formula: BMI = Kilogram (kg)/ square meter (m\^2). A significant clinically meaningful response was defined as achieving a ≥5% reduction in BMI from Baseline. Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
次要结局
- Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype(Baseline, Week 16)
- Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype(Baseline, Week 16)
- Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype(Baseline, Week 16)
- Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype(Baseline, Week 16)
- Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype(Baseline, Week 16)
- Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype(Baseline, Week 16)
- Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype(Baseline, Week 16)
- Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype(Baseline, Week 16)
- Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype(Baseline, Week 16)