NCT06239116招募中1 期
A Study of RM-718 Weekly Formulation in Healthy Subjects With Obesity and in Patients With Obesity Due to MC4R Impairment
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 14
- 主要终点
- Parts A, B, C, D: Safety and Tolerability Assessed by Number of Study Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and PK of RM-718 in healthy subjects with obesity and in patients with MC4R Pathway Impairment
详细描述
This is a first-in-human and first-in-patient, 4-part study that includes the evaluation of safety, tolerability, and PK of: single ascending doses (SAD) of RM-718 weekly (RM-718) in healthy subjects 18 to 55 years of age with obesity (Part A), multiple ascending doses (MAD) of RM-718 in healthy subjects 18 to 55 years of age with obesity (Part B), MAD of RM-718 in patients 12 to 65 years of age with HO (Part C), and MAD of RM-718 in patients with PWS (Part D). Cohorts in Parts A and B are double-blind, placebo-controlled, and randomized 2:1 (4 subjects receive RM-718, 2 subjects receive placebo). Part C evaluates open-label dose escalation in patients 12 to 65 years of age with HO. Part D evaluates open-label dose escalation in patients 12 to 65 years of age. Study participants will receive: 1 weekly dose of either RM-718 or placebo in Part A, 4 weekly doses of either RM-718 or placebo in Part B,16 weekly doses of open-label RM-718 in Part C, and 26 weekly doses of RM-718 in Part D. Study drug (RM-718 or placebo) doses are administered weekly via subcutaneous injection.
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
Study Parts A and B are blinded. Study Parts C and D are open-label.
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Parts A and B:
- •Male and female subjects in good health aged 18-55 years of age at Screening.
- •Body mass index (BMI) ≥30 kg/m
- •Subjects who are medically healthy with normal or clinically insignificant screening results.
- •Subjects must use a highly effective form of contraception and follow the study contraception requirements.
- •Ability to communicate well with the Investigator, understand and comply with the requirements of the trial, and understand English and sign the written informed consent.
- •Male and female patients with HO, aged 12-65 years of age at Screening.
- •Patient has documented evidence of acquired HO defined as:
- •Diagnosis of craniopharyngioma or other brain lesion affecting the hypothalamic region and has undergone surgery, or chemotherapy, or radiation therapy involving the hypothalamus at least 6 months before Screening, OR
- •Documented injury to the hypothalamus at least 6 months before Screening for which surgery/radiation is not indicated.
- •Weight gain associated with the hypothalamic injury either before or following therapy (surgery and/or following chemotherapy or radiotherapy), and a BMI of ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and sex for patients 12 to <18 years of age.
- •Patients must use a highly effective form of contraception and follow the study contraception requirements.
- •Ability to communicate with the Investigator, understand and comply with the requirements of the trial, and understand and sign the written informed consent and assent (for patients aged <18 years), and informed consent for a parent or guardian of any patient <
- •Confirmed diagnosis of PWS as determined by the Investigator at the time of Screening.
- •Age ≥12 to 65, inclusive, at the time of signing Informed Consent and/or Assent.
- •BMI ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th Percentile for age and sex for patients <18 years of age based on the US CDC criteria.
- •Able to meet contraception requirements.
排除标准
- •Parts A and B
- •Any clinically significant abnormalities on screening laboratories or physical examination as determined by the Investigator.
- •Active or history of any significant medical condition such as and including renal, hepatic, pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic, metabolic, neurologic or hematological disease.
- •Obesity due to genetic, syndromic, or endocrine etiologies.
- •History of renal transplant, end stage renal disease.
- •Diagnosis of severe psychiatric disorders.
- •Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results.
- •Cigarette smoking or dependence on caffeine, alcohol or drugs; unable or unwilling to abstain completely from caffeine, alcohol and related substances for 24 hours prior to and after study visits.
- •History of recent surgery (within 60 days of Screening).
- •Participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first trial dose.
- •Pregnant and/or breastfeeding or desiring to become pregnant during this trial.
- •Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET).
- •Weight loss >2% in the previous 3 months for patients aged ≥18 years or >2% reduction in BMI for patients aged 12 to <18 years and/or anti-obesity medications for the treatment of obesity.
- •Bariatric surgery or procedure within the last 2 years.
- •Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior.
- •Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results.
- •History of renal transplant, end stage renal disease.
- •Participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first trial dose, or previous participation in a trial with setmelanotide.
- •Pregnant and/or breastfeeding or desiring to become pregnant during this trial.
- •Obesity attributable to other genetic or syndromic conditions (eg, PPL [pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), leptin receptor (LEPR), collectively], Bardet-Biedl syndrome [BBS]) prior to the hypothalamic injury.
- •Weight loss >2% in the previous 3 months for patients aged ≥18 years or >2% reduction in BMI for patients aged 12 to <18 years or therapies for the treatment of obesity or hyperphagia.
- •Metabolic and bariatric surgery (MBS) or procedure within last 6 months.
- •Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior.
- •Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results.
- •Pregnant and/or breastfeeding or desiring to become pregnant during this trial.
- •Other protocol defined Inclusion/Exclusion criteria may apply.
结局指标
主要结局
Parts A, B, C, D: Safety and Tolerability Assessed by Number of Study Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: From Day 1 through the Safety-Follow-up call (up to Day 43 for all Part A cohorts, up to Day 70 for all Part B cohorts, up to Day 140 for Part C cohort, up to Day 210 for Part D cohort)
次要结局
- CL/F measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Vz/F measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Accumulation ratio of RM-718(Week 1 to Week 4 (AUC on Week 4/AUC on Week 1) (Parts B, C))
- Change from baseline in BMI (Part C only)(Baseline to Week 16)
- Mean change in weight (Part C only)(Baseline to Week 16)
- Mean change in waist circumference (Part C only)(Baseline to Week 16)
- Mean change in weekly average of the daily most hunger score in patients ≥12 years of age (Part C only)(Baseline to Week 16)
- Mean change in weekly average of the Symptoms of Hyperphagia composite score (Part C only)(Baseline to Week 16)
- Ctrough measurement of RM-718 (Part D)(up to 168 hours post-dose on Day 8 and up to 168 hours post-dose on Day 29)
- Change from baseline in BMI (Part D)(Baseline to Week 26)
- Mean change in weight (Part D)(Baseline to Week 26)
- Mean change in waist circumference (Part D)(Baseline to Week 26)
- Mean change in the weekly average of the Prader-Willi Syndrome Food Problem Diary (PWS-FPD) total score (Part D)(Baseline to Week 26)
- Mean change in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score (Part D)(Baseline to Week 26)
- Change in total body mass (Part D)(Baseline to Week 26)
- AUCtau measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Cmax measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Cmin measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Tmax measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Ctrough measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Cavg measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- t1/2 measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- λz measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Tmin measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- CL/F measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Vz/F measurement of RM-718(up to 168 hours post-dose on Day 1 (Parts A, B and C) and 168 hours post-dose on Day 22 (Parts B and C).)
- Accumulation ratio of RM-718(Week 1 to Week 4 (AUC on Week 4/AUC on Week 1) (Parts B, C))
- Change from baseline in BMI (Part C only)(Baseline to Week 16)
- Mean change in weight (Part C only)(Baseline to Week 16)
- Mean change in waist circumference (Part C only)(Baseline to Week 16)
- Mean change in weekly average of the daily most hunger score in patients ≥12 years of age (Part C only)(Baseline to Week 16)
- Mean change in weekly average of the Symptoms of Hyperphagia composite score (Part C only)(Baseline to Week 16)
研究者
研究点 (14)
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