Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 213
- 试验地点
- 57
- 主要终点
- Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment
研究概览
简要总结
The purpose of the study was to determine the effect of setmelanotide (RM-493) on weight, hunger assessments, and other factors in participants with rare genetic disorders of obesity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with the following genotypes and/or clinical assessment:
- •POMC/PCSK1/LEPR heterozygous - not currently enrolling new participants
- •POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity
- •POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity
- •SH2B1 deficiency obesity
- •Chromosomal rearrangement of the 16p11.2 locus causing obesity
- •Carboxypeptidase E (CPE) compound heterozygous or homozygous deficiency obesity
- •Leptin deficiency obesity with loss of response to metreleptin
- •SRC1 deficiency obesity
- •MC4R deficiency obesity
- •Age 6 years and above
- •Obese, defined as Body Mass Index (BMI) ≥ 30 kilogram per meter square (kg/m^2) for participants ≥16 years of age or BMI≥ 95th percentile for age and gender for participants 6 up to 16 years of age.
- •Participant and/or parent or guardian is able to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent
- •Female participants of childbearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol.
- •Male participants with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study. Male participants must not donate sperm during and for 90 days following their participation in the study.
排除标准
- •Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents that has resulted in > 2% weight loss.
- •Use of any medication that is approved to treat obesity within three months of first dose of study drug (e.g., orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion).
- •Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained
- •Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
- •Suicidal ideation, attempt or behavior
- •Clinically significant pulmonary, cardiac, or oncologic disease
- •hemoglobin A1c (HbA1c) > 9.0% at Screening
- •History of significant liver disease
- •Glomerular filtration rate (GFR) < 30 milliliter/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.
- •Inability to comply with QD injection regimen.
- •Females who are breastfeeding or nursing.
- •Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
16p11.2 Cohort
Participants with chromosomal rearrangement of the p11.2 region of chromosome 16 (16p11.2) locus causing obesity received setmelanotide once daily (QD) via subcutaneous (SC) injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
AS Cohort
Participants with Alström syndrome (AS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
BBS Cohort
Participants with Bardet-Biedl syndrome (BBS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
MC4R Cohort
Participants with melanocortin-4 receptor (MC4R) deficiency obesity received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
POMC/PCSK1/LEPR Heterozygous Cohort
Participants with pro-opiomelanocortin (POMC)/proprotein convertase subtilisin/kexin type 1 (PCSK1)/leptin receptor (LEPR) heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
POMC/PCSK1/LEPR Composite Heterozygous Cohort
Participants with POMC/PCSK1/LEPR composite heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
POMC/PCSK1/LEPR Compound Heterozygous Cohort
Participants with POMC/PCSK1/LEPR compound heterozygous mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
SH2B1 Cohort
Participants with steroid receptor coactivator (SRC) homology 2B adapter protein 1 (SH2B1) haploinsufficiency received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
SMS Cohort
Participants with Smith-Magenis Syndrome (SMS) received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
SRC1 Cohort
Participants with steroid receptor coactivator 1 (SRC1) mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
干预措施: Setmelanotide (Drug)
结局指标
主要结局
Number of Participants With ≥ 5% Reduction in Body Weight From Baseline After 3 Months of Setmelanotide Treatment
时间窗: Baseline to Month 3
次要结局
- Percent Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment(Baseline, Month 3)
- Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years(Baseline, Month 3)
- Change From Baseline in Daily Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years(Baseline, Month 3)
- Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged ≥ 12 Years(Baseline, Month 3)
- Percent Change From Baseline in Waist Circumference After 3 Months of Setmelanotide Treatment(Baseline, Month 3)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From first dose up to Month 16)
- Change From Baseline in Body Weight After 3 Months of Setmelanotide Treatment(Baseline, Month 3)
- Number of Participants With Shifts From Baseline in Global Hunger Questionnaire Scores After 3 Months of Setmelanotide Treatment in Participants Aged < 12 Years(Baseline, Month 3)