A Randomized, Double-Blind, Placebo-Controlled Multi-Center Study of Oral NA-931, Alone or in Addition to Open Label Subcutaneous Tirzepatide , to Investigate the Efficacy and Safety in Overweight or Obese Men and Women
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 224
- 试验地点
- 17
- 主要终点
- Change from baseline in body weight at 48 weeks
研究概览
简要总结
A phase 2 study to assess the efficacy of NA-931 alone or in addition to Tirzepatide to assess efficacy and safety in overweight or obese men and women
详细描述
This Phase 2 study investigates if NA-931 in addition to Tirzepatide can demonstrate synergic effects by enhancing efficacy and reducing adverse events including preserve/increase muscle mass in the presence of weight and/or fat mass loss.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
With regards to NA-931 and placebo-NA-931, the participants, Investigator and Sponsor will be blinded.
Due to Tirzepatide being pre-filled, packaged and labeled by manufacturer, it is not possible to blind Tirzepatide
入排标准
- 年龄范围
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A written informed consent must be obtained before any study-related assessments are performed.
- •Men and women between 18 and 80 years, inclusive; women of child-bearing potential (defined as those who are not post-menopausal or post-surgical sterilization) must meet both of the following criteria:
- •Two negative pregnancy tests (at screening and at randomization, prior to dosing)
- •Use of intrauterine device, from at least 3 months before the baseline visit through at least 4 months after the last dose of NA-931/placebo oral, and an additional contraceptive (barrier) method from screening through at least 4 months after the last dose of NA-931/placebo oral.
- •Body mass index (BMI) ≥ 30 or BMI ≥ 27 with one or more obesity-associated comorbidities (e.g., hypertension, insulin resistance, sleep apnea, or dyslipidemia)
- •Stable body weight (± 5 kg) within 90 days of screening, and body weight <150 kg
- •Have a history of at least one self-reported unsuccessful behavioral effort to lose body weight
- •Able to communicate well with the Investigator, comply with the study requirements and adhere to the diet and activity programs for the study duration
排除标准
- •• History of, or known hypersensitivity to, monoclonal antibody drugs or a contraindication to Tirzepatide (Zepbound® or Mounjaro®)
- •Use of other investigational drugs at the time of enrollment or within 30 days or 5 half-lives of enrollment, whichever is longer, or longer if required by local regulations
- •Treatment with any medication for the indication of obesity within the past 30 days before screening
- •Diagnosis of diabetes requiring current use of any antidiabetic drug or HbA1c ≥ 6.5% Note: Metabolic syndrome is not an exclusion, even if managed with an anti-diabetic drug such as metformin or an SGLT2 inhibitor. A diagnosis of prediabetes or impaired glucose tolerance managed exclusively with non-pharmacologic approaches (e.g., diet and exercise) is not an exclusion.
- •Any chronic infections likely to interfere with study conduct or interpretation such as hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV). History of hepatitis A or hepatitis C successfully treated is not exclusionary. Active COVID-19 infection.
- •Donation or loss of 400 mL or more of blood within 8 weeks prior to initial dosing, or longer if required by local regulation, or plasma donation (> 250 mL) within 14 days prior to the first dose
- •Any disorder, unwillingness, or inability not covered by any of the other exclusion criteria, which in the Investigator's opinion, might jeopardize the participant's safety or compliance with the protocol
研究组 & 干预措施
Placebo Comparator: Placebo
Placebo Comparator: Placebo to oral NA-931 120 mg daily + no Tirzepatide Participants will receive oral placebo at baseline and at Weeks 4, 12, and 24, 36, and 48 during the core treatment period and will switch during the extension period to receive NA-931 60 mg daily at Weeks 60 and 72.
干预措施: NA-931 (Drug)
Placebo + Tirzepatide 5 mg
Other: Placebo + Tirzepatide 5 mg Participants will receive oral placebo at baseline and at Weeks 4, 12, and 24, 36, and 48, and s.c. Tirzepatide 5 mg weekly per the dose escalation schedule.
干预措施: NA-931 (Drug)
Placebo + Tirzepatide 10 mg
Placebo + Tirzepatide 10 mg Participants will receive oral placebo at baseline and at Weeks 4, 12, and 24, 36, and 48 and s.c. Tirzepatide 10 mg weekly per the dose escalation schedule.
干预措施: NA-931 150 mg + no Tirzepatide (Drug)
NA-931 60mg to NA-931 150 mg + no Tirzepatide
Experimental: NA-931 60mg to NA-931 150 mg + no Tirzepatide Participants will receive oral NA-931 60 mg at baseline and at Weeks 4, 12, and 24, 36, and 48 during the core treatment period and will switch during the extension period to receive NA-931 60 mg at Weeks 60 and 72.
干预措施: NA-931 (Drug)
NA-931 60 mg + Tirzepatide 5 mg
NA-931 60 mg + Tirzepatide 5 mg Participants will receive oral NA-931 60 mg at baseline and at Weeks 4, 12, and 24, 36, and 48 and s.c. Tirzepatide 5 mg weekly per the dose escalation schedule.
干预措施: NA-931 (Drug)
NA-931 120 mg + Tirzepatide 5 mg
NA-931 120 mg + Tirzepatide 5 mg Participants will receive oral NA-931 60 mg at baseline and at Weeks 4, 12, and 24, 36, and 48 and s.c. Tirzepatide 5 mg weekly per the dose escalation schedule.
干预措施: NA-931 (Drug)
NA-931 150 mg + no Tirzepatide
Experimental: NA-931 150 mg + no Tirzepatide Participants will receive oral NA-931 150 mg at baseline and at Weeks 4, 12, 24, 36 and 48
干预措施: Tirzepatide (Drug)
NA-931 150 mg + Tirzepatide 2.5 mg
NA-931 150 mg + Tirzepatide 2.5 mg Participants will receive oral NA-931 150 mg at baseline, and at Weeks 4, 12, and 24, 36, and 48 and s.c. Tirzepatide 2.5 mg weekly per the dose escalation schedule.
干预措施: Tirzepatide (Drug)
NA-931 150 mg + Tirzepatide 5 mg
NA-931 150 mg + Tirzepatide 5 mg Participants will receive oral NA-931 150mg at baseline and at Weeks 4, 12, and 24, 36, and 48 and s.c. Tirzepatide 5 mg per the dose escalation schedule.
干预措施: NA-931 (Drug)
结局指标
主要结局
Change from baseline in body weight at 48 weeks
时间窗: 48 weeks
Change in total body weight will be measured from baseline to 48 weeks
次要结局
- Change from baseline in waist circumference (cm) at 48 weeks(48 weeks)
- Change from baseline at 48 weeks in total body fat mass in kilograms (kg)(48 weeks)
- Change from baseline at 48 weeks in percent body fat(48 weeks)
- Change from baseline at 48 weeks in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and trunk fat mass by dual-energy x-ray absorptiometry (DXA)(48 weeks)
- Proportion of participants at 48 weeks with change in waist circumference ≥ 5 cm(48 weeks)
- Proportion of participants at 48 weeks with change in Body weight ≥ 5%, ≥ 10% and ≥15%(48 weeks)
- Proportion of participants at 48 weeks with change in Fat mass ≥ 5% ≥ 10% ≥ 15% by Dual energy X-ray absorptiometry (DXA)(48 weeks)
- Proportion of participants at 48 weeks with change in Fat mass ≥ 10% with <5% decrease (or and increase) in lean mass by Dual energy X-ray absorptiometry (DXA)(48 weeks)
- Percentage of weight loss due to fat mass or lean mass at 48 weeks by dual-energy x-ray absorptiometry (DXA)(48 weeks)
- Change from baseline at 48 weeks in lean mass (kg) by bioelectrical impedance analysis (BIA)(48 weeks)
- Change from baseline at 48 weeks in fat mass (kg and %) by bioelectrical impedance analysis (BIA)(48 weeks)
- Safety and tolerability measurements throughout 48 weeks by TEAEs [safety labs, vital signs](48 weeks)
- Change from baseline at 48 weeks in lean mass (kg and %) and appendicular lean mass by dual-energy x-ray absorptiometry (DXA)(48 weeks)
- Proportion of Participants with change from baseline in Body Mass Index (BMI) categories at 48 weeks(48 weeks)
- Proportion of Participants with change from baseline in waist-to-height ratio (WHtR ratio) categories at 48 weeks(48 weeks)
- Change from baseline in HbA1c (mmol/mol) at 48 weeks(48 weeks)
- Change from baseline at 48 weeks in Quality of Life Short Form 36 (SF-36) survey(48 weeks)
- Change from Baseline at 48 weeks in Impact of Weight on Quality of Life-Lite for Clinical Trials (IWQOL-Lite)(48 weeks)