A Randomized, Double-blind, Placebo-controlled Phase 2 Trial to Assess Efficacy, Safety, and Tolerability of RO7204239 in Combination With Tirzepatide in Participants With Obesity or Overweight With At Least One Weight-related Comorbidity
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 285
- 试验地点
- 36
- 主要终点
- Percent Change From Baseline in Body Weight
研究概览
简要总结
The main aim of the study is to assess the effect of RO7204239 in combination with tirzepatide, compared to placebo in combination with tirzepatide, on body weight loss after 48 weeks of treatment in adults with obesity or overweight with at least one weight-related comorbidity, but without diabetes mellitus (DM). The study comprises of a 4-week screening period; a 48-week core treatment period, where all participants will receive tirzepatide as background treatment and will be randomized to one of the 4 treatment arms; a 24-week treatment extension period, where participants will stop treatment with tirzepatide and a 24-week post-treatment follow-up (FU) period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI ≥ 30.0 kilograms per square meter (kg/m²) (additional weight-related comorbidities are not required for inclusion)
- •BMI ≥ 27.0 kg/m² and < 30.0 kg/m² with at least one weight-related comorbidity such as: hypertension, dyslipidemia, obstructive sleep apnea and any cardiovascular disease
- •History of at least one self-reported unsuccessful dietary or exercise effort to lose body weight
- •Weight stability: self-reported change in body weight less than 5 kilograms (kg) (11 pounds [lbs]) within 3 months prior to screening
排除标准
- •Prior history or diagnosis of DM
- •Presence of non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy or diabetic macular edema
- •Have obesity induced by other endocrinologic disorders
- •Participation in unbalanced/extreme diets
- •Prior or planned surgical treatment for obesity
- •Endoscopic and/or device-based therapy for obesity or device removal within 6 months prior to screening
- •Have a known clinically significant gastric emptying abnormality
- •Have any of the following cardiovascular conditions within 6 months prior to screening: acute myocardial infarction, cerebrovascular accident (stroke), unstable angina, or hospitalization due to congestive heart failure (CHF)
- •Have evidence of significant active, uncontrolled cardiovascular, autoimmune, endocrine, renal, hepatic, dermatological, chronic respiratory or gastrointestinal disease, a neurological or psychiatric condition, or a history of any neuromuscular disorder or autoimmune/inflammatory disorders that may cause muscle wasting or medical condition capable of constituting a risk when taking the study medication or interfering with the interpretation of data, as judged by the investigator at screening
- •Have evidence of a significant, uncontrolled endocrine abnormality
- •Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy
- •Have evidence of a significant, active autoimmune abnormality
- •Have anemia
- •Have signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease
- •Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females)
研究组 & 干预措施
Placebo + Tirzepatide
Participants will receive RO7204239 matching placebo via subcutaneous (SC) injection every 4 weeks (Q4W) for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, every week (QW) during the core treatment period of 48 weeks.
干预措施: RO7204239 (Drug)
RO7204239 low dose + Tirzepatide
Participants will receive RO7204239, low dose, SC, Q4W for the core treatment period of 48 weeks. During the treatment extension period participants will receive placebo for the period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks.
干预措施: RO7204239 (Drug)
RO7204239 medium dose + Tirzepatide
Participants will receive RO7204239, medium dose, SC, Q4W for the core treatment period of 48 weeks. During the treatment extension period participants will receive placebo for the period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks.
干预措施: Tirzepatide (Drug)
RO7204239 low dose + Tirzepatide
Participants will receive RO7204239, low dose, SC, Q4W for the core treatment period of 48 weeks. During the treatment extension period participants will receive placebo for the period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks.
干预措施: Tirzepatide (Drug)
Placebo + Tirzepatide
Participants will receive RO7204239 matching placebo via subcutaneous (SC) injection every 4 weeks (Q4W) for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, every week (QW) during the core treatment period of 48 weeks.
干预措施: Tirzepatide (Drug)
Placebo + Tirzepatide
Participants will receive RO7204239 matching placebo via subcutaneous (SC) injection every 4 weeks (Q4W) for the core treatment period of 48 weeks and the treatment extension period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, every week (QW) during the core treatment period of 48 weeks.
干预措施: RO7204239 Matching Placebo (Drug)
RO7204239 high dose + Tirzepatide
Participants will receive RO7204239, high dose, SC, Q4W along with tirzepatide, given as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks. During the treatment extension period participants will be randomized to receive RO7204239 or matching placebo, SC, Q4W for 24 weeks.
干预措施: RO7204239 (Drug)
RO7204239 high dose + Tirzepatide
Participants will receive RO7204239, high dose, SC, Q4W along with tirzepatide, given as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks. During the treatment extension period participants will be randomized to receive RO7204239 or matching placebo, SC, Q4W for 24 weeks.
干预措施: Tirzepatide (Drug)
RO7204239 medium dose + Tirzepatide
Participants will receive RO7204239, medium dose, SC, Q4W for the core treatment period of 48 weeks. During the treatment extension period participants will receive placebo for the period of 24 weeks. Participants will also receive tirzepatide, as a background therapy, up-titrated according to the approved tirzepatide prescribing information, SC, QW during the core treatment period of 48 weeks.
干预措施: RO7204239 (Drug)
结局指标
主要结局
Percent Change From Baseline in Body Weight
时间窗: Baseline, Week 48
次要结局
- Absolute Change From Baseline in Body Weight(Baseline, Week 48)
- Change From Baseline in Body Mass Index (BMI)(Baseline, Week 48)
- Change From Baseline in Waist-to-height Ratio(Baseline, Week 48)
- Change From Baseline in Waist Circumference(Baseline, Week 48)
- Change From Baseline in Total Body Fat Mass Measured by Dual-energy X-ray Absorptiometry (DXA)(Baseline, Week 48)
- Change From Baseline in Total Lean Body Mass Measured by DXA(Baseline, Week 48)
- Change From Baseline in Appendicular Lean Mass Measured by DXA at Week 48(Baseline, Week 48)
- Change From Baseline in Muscle Volume Measured by Magnetic Resonance Imaging (MRI)(Baseline, Week 48)
- Change From Baseline in Muscle Fat Infiltration Measured by MRI(Baseline, Week 48)
- Change From Baseline in Glycated Hemoglobin (HbA1C) Levels(Baseline, Week 48)
- Change From Baseline in Fasting Plasma Glucose Levels(Baseline, Week 48)
- Change From Baseline in Fasting C-peptide and Fasting Insulin Levels(Baseline, Week 48)
- Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)(Baseline, Week 48)
- Change From Baseline in Quantitative Insulin Sensitivity Check Index (QUICKI)(Baseline, Week 48)
- Apparent Volume of Distribution (Vd/F) of RO7204239(Up to approximately 96 weeks)
- Number of Participants With Anti-drug Antibodies (ADAs) to RO7204239(Up to approximately 96 weeks)
- Change From Baseline in Fasting Lipid Profile(Baseline, Week 48)
- Number of Participants With Adverse Events (AEs)(Up to approximately 100 weeks)
- Number of Participants With Local and Systemic Injection Reactions(Up to approximately 100 weeks)
- Serum Concentrations of RO7204239(Up to approximately 96 weeks)
- Steady-state Trough Concentration (Ctrough,ss) of RO7204239(Up to approximately 96 weeks)
- Half-life (t1/2) of RO7204239(Up to approximately 96 weeks)
- Steady-state Area Under the Concentration-time Curve Over One Dosing Interval (AUCtau,ss) of RO7204239(Up to approximately 96 weeks)
- Steady-state Maximum Concentration (Cmax,ss) of RO7204239(Up to approximately 96 weeks)
- Apparent Clearance (CL/F) of RO7204239(Up to approximately 96 weeks)