中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2600118160
最近更新日期： Date of Last Refreshed on：	2026-02-02 20:35:33
注册时间： Date of Registration：	2026-02-02 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项在酒精使用障碍成人参与者中评估 brenipatide 有效性和安全性的多中心、随机、双盲、安慰剂对照的 3 期临床研究（RENEW-ALC-2）
Public title：	A Study to Investigate Brenipatide Compared with Placebo in Adult Participants with Alcohol Use Disorder (RENEW-ALC-2)
注册题目简写：
English Acronym：
研究课题的正式科学名称：	一项在酒精使用障碍成人参与者中评估 brenipatide 有效性和安全性的多中心、随机、双盲、安慰剂对照的 3 期临床研究（RENEW-ALC-2）
Scientific title：	A Phase 3, Multicenter, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Brenipatide Compared with Placebo for the Treatment of Adult Participants with Alcohol Use Disorder (RENEW-ALC-2)
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	陈东妮	研究负责人：	郭万军
Applicant：	Dongni Chen	Study leader：	Wanjun Guo
申请注册联系人电话： Applicant telephone：	+86 18616328843	研究负责人电话： Study leader's telephone：	+86 571 85127129
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	chen_dong_ni@lilly.com	研究负责人电子邮件： Study leader's E-mail：	guowjcn@163.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	上海市静安区石门一路188号兴业太古汇一座19楼	研究负责人通讯地址：	浙江省杭州市西湖区天目山路305号
Applicant address：	19th Floor, Tower 1, Xingye Taikoo Hui, No. 188 Shimen 1st Road, Jing'an District, Shanghai	Study leader's address：	No. 305, Tianmu Mountain Road, Xihu District, Hangzhou, Zhejiang Province
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	礼来苏州制药有限公司
Applicant's institution：	Eli Lilly Suzhou Pharmaceutical Co., Ltd.
研究负责人所在单位：	杭州市第七人民医院
Affiliation of the Leader：	Hangzhou Seventh People's Hospital

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	药（2025年）伦审第（018）号	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	杭州市第七人民医院药物临床试验、医疗器械试验伦理审查委员会
Name of the ethic committee：	Ethics Committee for Drug Clinical Trials and Medical Device Trials, Hangzhou Seventh People's Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-09-09 00:00:00
伦理委员会联系人：	张雨桐
Contact Name of the ethic committee：	Zhang Yutong
伦理委员会联系地址：	浙江省杭州市西湖区天目山路305号
Contact Address of the ethic committee：	No. 305, Tianmu Mountain Road, Xihu District, Hangzhou, Zhejiang Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 571 85124613	伦理委员会联系人邮箱： Contact email of the ethic committee：	767929585@qq.com

研究实施负责（组长）单位：

杭州市第七人民医院

Primary sponsor：

Hangzhou Seventh People's Hospital

研究实施负责（组长）单位地址：

浙江省杭州市西湖区天目山路305号

Primary sponsor's address：

No. 305, Tianmu Mountain Road, Xihu District, Hangzhou, Zhejiang Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	浙江省	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	杭州市第七人民医院	具体地址：	浙江省杭州市西湖区天目山路305号
Institution hospital：	Hangzhou Seventh People's Hospital	Address：	No. 305, Tianmu Mountain Road, Xihu District, Hangzhou, Zhejiang Province

经费或物资来源：

礼来苏州制药有限公司

Source(s) of funding：

Eli Lilly Suzhou Pharmaceutical Co., Ltd.

研究疾病：

酒精使用障碍

Target disease：

Alcohol use disorder

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

III期临床试验

Study phase：

3

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

证明至少1个剂量水平的brenipatide在至少1个双重主要终点方面优于安慰剂

Objectives of Study：

Demonstrate superiority of brenipatide at least at one dose level compared to placebo on at least one of the dual primary endpoints

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. Are 18 to 75 years of age, inclusive, at the time of signing the informed consent;
2. Must report an average alcohol consumption using TLFB during the 28 days prior to screening (V1) and during the screening period leading up to randomization (V3) as follows: 
(1). for individuals AMAB: >=20 standard drinks per week (equivalent to at least 280 grams of alcohol per week), and  for individuals AFAB: >=10 standard drinks per week (equivalent to at least 140 grams of alcohol per week). Note: For purposes of conversion to grams of alcohol, use the conversion that 1 standard drink is equivalent to 14 grams of alcohol. 
3. Alcohol consumption pattern should reflect the participant’s average monthly alcohol intake, sustained for a minimum period of 12 months, as determined through participant self-report and investigator’s clinical judgment;
4. Must report having at least a pre-specified number of HDDs per month at screening (V1) and during the screening period leading up to randomization (V3), as assessed by TLFB.
 Note: A participant will be excluded from the study if a pre-defined reduction in alcohol consumption is identified between screening (V1) and randomization (V3). To mitigate bias and placebo response, the minimum number of HDDs and the pre-defined reduction in alcohol consumption will be specified in a separate ERB supplement. 
HDD is defined as  for individuals AMAB: >=5 standard drinks per day, and  for individuals AFAB: >=4 standard drinks per day. Note: To avoid biased reporting, study participants must not be told the definition of HDDs;
5. Have a current AUD diagnosis as defined by meeting 2 to 3 DSM-5 criteria, at screening (V1);
6. Are seeking treatment and are motivated to stop or cut down on drinking;
7. Have a BMI >=22.0 kg/m^2 at screening (V1) and randomization (V3);
8. Have had a stable body weight for the 90 days prior to randomization (V3) defined as less than 5% body weight reduction. Sex assigned at birth and contraceptive/barrier requirements ;
9. Are individuals AMAB or AFAB, including both IOCBP and INOCBP. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For the reproduction definitions and the contraception requirements of this protocol, refer to Section 10.4. Study procedures ;
10. Are reliable and willing to make themselves available for the duration of the study and attend required study visits, and are willing and able to follow study procedures as required, such as  self-inject study intervention Note: Participants who are not able to perform the injections must receive assistance from a support person trained to administer the study intervention.  store and use the provided blinded study intervention, as directed  maintain electronic and paper study diaries, as applicable, and  complete the required questionnaires. Informed consent 
11. Are capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

排除标准：

1 在筛选（V1）和随机化（V3）之间，启动了针对AUD的认知行为治疗或其他心理治疗，或计划在试验期间开始此类治疗。例外情况：允许匿名戒酒会（AA）、自助团体、支持性心理治疗或其他已经启动并在筛选（V1）前持续至少30天的常规咨询。
2 筛选（V1）前180天内或筛选（V1）和随机化（V3）之间： • 根据研究者判断，需要住院治疗的严重的或复杂性的酒精戒断综合征（第10.9节详细说明了戒断症状的严重程度） • 需在门诊接受药物以预防或治疗酒精戒断综合征，或根据研究者判断，目前存在急性酒精戒断综合征（定义为停止酒精使用后立即发生）的重大风险，如癫痫发作和震颤性谵妄，或筛选（V1）和随机化（V3）时临床机构酒精戒断评估量表-修订版（CIWA-Ar）评分≥10分。
3 有已知酒精性酮症酸中毒或马-魏二氏综合征（继发于呕吐的食管撕裂）病史。
4 在当前或筛选（V1）前180天内，曾有任何严重程度的物质使用障碍史，通过临床访谈确认的持续性非法或非处方的物质使用模式，不包括酒精、尼古丁或咖啡因。
5 筛选（V1）时，根据SCID-5评估，符合DSM-5中度至重度大麻使用障碍的诊断标准。注：轻度大麻使用障碍的参与者允许参加研究。
6 不同意在研究期间避免使用所有滥用药物，酒精、尼古丁和大麻除外。
7 筛选（V1）和/或随机化（V3）时尿液药物滥用（尼古丁或大麻除外）筛查呈阳性。注：任何滥用药物尿筛结果呈阳性，如果是针对已知既往疾病的处方合并用药，则不视为非法使用。
8 筛选（V1）前30天内或筛选（V1）和随机化（V3）之间，因具有临床意义的酒精相关损伤或相关疾病需要急诊或住院治疗。
9 根据DSM-5标准，有任何进食障碍的病史或当前诊断。
10 筛选（V1）前90天内因当前精神疾病或障碍，调整过精神活性药物给药方案，包括但不限于抗抑郁药、抗精神病药或情绪稳定剂。例外情况：允许按需（根据需要）使用苯二氮卓类药物处方以缓解焦虑或失眠症状。注：不允许用于酒精戒断症状。
11 筛选（V1）前180天内有显著的活动性或不稳定性经DSM-5诊断的抑郁症、自杀意念或其他严重的精神疾病（如精神分裂症、分裂性情感障碍或其他严重情感障碍）病史。或根据研究者判断，存在任何可能增加使参与者参加研究的风险的严重的精神疾病。注：根据研究者判断，可允许筛选（V1）前180天内疾病状态稳定且预计在整个研究期间保持稳定的参与者入选研究。
12 筛选（V1）或随机化（V3）时： • 患者健康问卷-9（PHQ-9）评分≥15分，且 • 未接受稳定的抗抑郁治疗，定义为在过去90天内调整过精神活性药物（包括但不限于抗抑郁药、抗精神病药或情绪稳定剂）的给药方案。例外情况：允许按需使用苯二氮卓类处方药物以缓解任何症状。
13 过去1年内有过自杀行为史。
14 根据研究者判断，参与者有主动自杀倾向，被视为存在重大自杀风险。
15 对哥伦比亚-自杀严重程度评定量表（C-SSRS）“自杀意念”部分问题4或问题5的回答为“是”，且自杀意念发生在过去6个月内，或在C-SSRS“自杀行为”部分，自杀行为相关的回答为“是”，且自杀行为发生在过去6个月内注：非自杀性自我伤害行为不被视为自杀相关行为。
16 患有1型糖尿病，或有以下病史 • 酮症酸中毒，或 • 高渗状态或昏迷。
17 既往无糖尿病病史，但在筛选（V1）时糖化血红蛋白（HbA1c）≥6.5%（48 mmol/mol）或随机血糖≥200 mg/dL（≥11.1 mmol/L）。
18 对于T2DM参与者：筛选（V1）时HbA1c >8.5%（69 mmol/mol）或筛选（V1）前30天内调整过T2DM药物治疗。
19 筛选（V1）前90天内或筛选（V1）和随机化（V3）之间，使用过以下任何药物： • 二肽基肽酶-4（DPP-4）抑制剂 • 胰淀素类似物 • 肠促胰素，包括但不限于含GLP1-RA活性成分的药物 • 胰岛素，或 • 磺脲类药物。例外情况：对于特定临床状况，如择期手术、在住院期间、高渗状态或急性疾病，允许短期使用胰岛素治疗，疗程不超过14天。
20 基线时存在T2DM的参与者，随机化（V3）前有糖尿病性视网膜病变和/或黄斑性水肿病史（通过自行报告或病历记录）或目前患有上述疾病的参与者。注：对于在筛选（V1）时确诊为2型糖尿病且无糖尿病视网膜病变病史或疾病状态未知的参与者，必须进行糖尿病视网膜病变筛查评估以确认其资格。该视网膜病变评估应符合当地标准诊疗规范，且须由眼科医生或同等资质的当地眼科保健专业人员执行。若糖尿病视网膜病变评估符合上述相同标准，并在筛选前30天内完成，亦可作为筛选依据。
21 筛选（V1）时，降钙素水平≥35 ng/L（≥35 pg/mL）。
22 有甲状腺髓样癌或多发性内分泌腺瘤综合征2型家族史或个人史。
23 研究者认为有显著、控制不佳的内分泌异常证据，例如控制不佳的甲状腺功能减退症、甲状腺毒症或肾上腺危象。
24 筛选（V1）期间由中心实验室确定存在肾功能损害，即根据慢性肾病流行病学协作组胱抑素C公式（2012）计算的eGFR<30 mL/min/1.73 m2。
25 有已知食管静脉曲张病史。
26 根据既往肝组织学或影像学检查（例如瞬时弹性成像、超声、计算机断层扫描[CT]和磁共振成像[MRI]）或强化肝纤维化评分，有晚期肝病（包括晚期肝纤维化或肝硬化）或酒精性肝炎病史。
27 存在急性或慢性肝炎（包括自身免疫性肝炎病史），任何其他肝病的体征或症状（代谢功能障碍相关脂肪性肝病或代谢功能障碍和酒精相关性脂肪性肝病（MetALD）除外），或筛选（V1）期间出现以下任何实验室检测值。
28 筛选（V1）前5年内诊断为恶性疾病或有恶性疾病史，以下情况除外： 1. 已切除且3年无转移性疾病证据的基底细胞或鳞状上皮细胞皮肤癌 2. 宫颈原位癌，在基线之前的5年内无复发证据，或 3. 1级（例如，Gleason评分≤6分）前列腺癌。
29 患有已知的具有临床意义的胃排空异常（例如重度糖尿病性胃轻瘫或胃出口梗阻），曾接受或者计划在研究期间接受胃旁路（减肥）手术或限制性代谢手术（例如LAP-BAND®，Apollo Endosurgery US, Inc Austin, Texas），或存在研究者认为与当前药物治疗方案相关的具有临床意义的胃肠动力的变化。
30 诊断为微量营养素或宏量营养素吸收不良（例如，克罗恩病、乳糜泻和小肠切除术），且经研究者判断具有临床意义。
31 患有任何可能干扰HbA1c测量的血液系统疾病（例如，溶血性贫血）或血红蛋白水平≤8.0 g/dL。
32 筛选（V1）前180天内，发生以下任何一种情况： • 急性心肌梗死 • 脑血管意外（卒中） • 因不稳定型心绞痛而住院治疗，或 • 因充血性心力衰竭住院治疗。
33 患有纽约心脏协会心功能分级IV级的充血性心力衰竭。
34 筛选（V1）时存在12导联心电图（ECG）异常，经研究者判断，该异常可能增加参加研究的相关风险，或可能干扰心电图数据分析。
35 有慢性或急性胰腺炎病史。
36 在筛选（V1）时，根据研究者判断，存在维生素B1（硫胺素）或维生素B9（叶酸）的严重缺乏或具有显著的临床意义。
37 接受过器官移植或正在等待接受器官移植。例外情况：允许进行角膜移植或角膜成形术。
38 筛选（V1）时计划在研究期间进行手术，小手术除外。
39 对于IOCBP：正处于妊娠期或哺期乳，或有备孕计划或哺乳计划。
40 与本研究直接相关的研究中心工作人员和/或其直系亲属。直系亲属是指配偶、合法伴侣、父母、子女或兄弟姐妹，无论是生物学意义上的或是合法收养的亲属关系。
41 礼来公司（礼来）员工，或为参与本研究的任何第三方机构的员工需要排除。
42 存在研究者认为可能会干扰研究评估和程序的认知受损，包括但不限于TLFB。
43 既往有惊厥发作（儿童期发热性惊厥的远期病史除外）或其他可能增加参与者惊厥发作风险的疾病，或参与者正在接受抗惊厥药控制惊厥发作。
44 有严重头部损伤（例如颅骨骨折、脑挫伤或导致长时间失去知觉的创伤）、颅内肿瘤或出血史。
45 存在任何未被其他排除标准涵盖的情况、不愿意或无法执行的情形，且经研究者判断，可能危及参与者安全，如急性、严重或不稳定的医疗状况、过敏反应、禁忌症或对方案依从性差。
46 筛选（V1）前30天内或筛选（V1）和随机化（V3）之间正在使用治疗AUD的药物。包括但不限于双硫仑、阿坎酸、纳曲酮以及第6.9.4节中列出的药物列表。注：如果参与者正在使用这些药物中的一种用于治疗非AUD适应症，该参与者也将从研究中排除。
47 存在任何使用GLP-1 RA的禁忌症，如，对含GLP-1 RA活性成分的药物（包括但不限于利拉鲁肽、司美格鲁肽和替尔泊肽等），或对brenipatide或辅料过敏或不耐受。
48 筛选（V1）前90天内或筛选（V1）和随机化（V3）之间，接受了旨在促进减重的其他处方药或非处方药、复合或替代治疗，包括草药或营养补充剂。包括但不限于第6.9.4节中列出的药物。
49 随机化（V3）前30天内调整过，或计划在研究期间开始启动或调整食欲素受体拮抗剂药物，包括但不限于苏沃雷生、莱博雷生和达利雷生。
50 目前入组涉及研究药物的任何其他临床研究或任何其他类型被判定为与本研究在科学或医学上不相容的医学研究。
51 筛选（V1）前90天或5个半衰期内（以较长者为准）参加过临床研究并接受过活性药物治疗，或不确定是否接受过活性药物治疗。
52 此前已完成本研究，，或在接受至少1次活性药物或未知的研究药物后从本研究或其他brenipatide研究中退出。

Exclusion criteria：

1.AUD-related 12. Between screening (V1) and randomization (V3), have initiated cognitive behavioral therapy or other psychotherapy focused on treatment of AUD, or are planning to initiate such therapy during the trial. Exception: Alcoholics Anonymous (AA), self-help groups, supportive psychotherapy, or other general counseling that has already been initiated and has been ongoing for at least 30 days before screening (V1) is permitted; 2. Within 180 days prior to screening (V1) or between screening (V1) and randomization (V3): Have required inpatient management for severe or complicated alcohol withdrawal syndrome, in the opinion of the investigator (Section 10.9 details the categorization of withdrawal severity) Have required a medication to prevent or treat alcohol withdrawal in an outpatient setting, or Are currently at significant risk of suffering an acute (defined as immediately following the cessation of alcohol use) alcohol withdrawal syndrome, for example, seizure and delirium tremens, in the opinion of the investigator, or as determined by CIWA-Ar score >=10 at screening (V1) and randomization (V3); 3. Have a known history of alcoholic ketoacidosis or Mallory-Weiss syndrome (esophageal tears secondary to vomiting); 4. Have evidence of current or within the past 180 days prior to screening (V1), history of any substance use disorder(s) of any severity with a pattern of persistent illicit or nonprescribed substance use as indicated by clinical interview, except alcohol, nicotine, or caffeine; 5. Meet the DSM-5 criteria of moderate-to-severe cannabis use disorder as per SCID-5 at screening (V1). Note: Participants with mild cannabis use disorder are permitted; 6. Cannot agree to refrain from all use of drug(s) of abuse, except for alcohol, nicotine, and cannabis, during the study; 7. Have a positive urine drug screen for drugs of abuse (other than nicotine or cannabis) at screening (V1) and/or randomization (V3). Note: Positive urine drug screen for use of any drugs of abuse will not be considered illicit if it is a prescribed concomitant medication for a known preexisting condition; 8. Have required acute care or inpatient treatment for clinically significant alcohol-related injury or related illness in the 30 days before screening (V1) or between screening (V1) and randomization (V3); 9. Have a lifetime history or current diagnosis of any eating disorder according to the DSM- 5 criteria; 10. Have modified psychoactive medication dosing regimens for a current psychiatric condition or disorder including, but not limited to, antidepressants, antipsychotics, or mood stabilizers, in the past 90 days prior to screening (V1). Exception: Prescription benzodiazepines on a pro re nata (as needed) basis for any symptom relief of anxiety or insomnia is allowed. Note: Use for alcohol withdrawal symptoms is not permitted; 11. Have a history of significant active or unstable DSM-5 major depressive disorder, suicidal ideation, or other severe psychiatric disorder (such as schizophrenia, schizoaffective disorder, or other serious mood disorder) within the past 180 days prior to screening (V1). OR In the investigator’s assessment, have any significant mental health disorder that may put the individual at higher risk of study participation. Note: In the investigator’s assessment, individuals whose disease state is considered stable for the past 180 days prior to screening (V1) and expected to remain stable throughout the course of the study may be considered for inclusion; 12. At screening (V1) OR randomization (V3): have a PHQ-9 score of 15 or more, and are not on stable anti-depressant treatment, defined as having modified psychoactive medication dosing regimens including, but not limited to, antidepressants, antipsychotics, or mood stabilizers within the past 90 days. Exception: Prescription benzodiazepines on a pro re nata basis for any symptom relief is allowed 13. Have a history of a suicide attempt within the past 1 year; 14. Are, in the judgment of the investigator, actively suicidal, and therefore, deemed to be at a significant risk for suicide; 15. Have answered "yes" to either Question 4 or Question 5 on the "Suicidal Ideation" portion of the C-SSRS and the ideation occurred within the past 6 months, or Have answered "yes" to any of the suicide-related behaviors on the "Suicidal Behavior" portion of the C-SSRS and the behavior occurred within the past 6 months Note: Nonsuicidal self-injurious behavior is not considered a suicide-related behavior. Endocrine 16. Have type 1 diabetes mellitus, or a history of ketoacidosis, or hyperosmolar state or coma; 17. Have no prior medical history of diabetes but have HbA1c >=6.5% (48 mmol/mol) or random glucose >=200 mg/dL (>=11.1 mmol/L) at screening (V1); 18. For participants with T2DM: Have HbA1c >8.5% (69 mmol/mol) at screening (V1) or have modified T2DM medication within the last 30 days prior to screening (V1). 19. Within 90 days before screening (V1) or between screening (V1) and randomization (V3), have taken any of the following medications: DPP-4 inhibitors amylin analogues incretins, including but not limited to medications with GLP1-RA activity 60 insulin, or sulfonylureas. Exception: Short-term treatment with insulin for less than 14 days is allowed for certain clinical situations, such as elective surgery, during hospitalization, hyperosmolar states, or acute illness; 20. Participants with T2DM at baseline who have a history of (confirmed by self-report or medical records), or currently have diabetic retinopathy and/or macular edema prior to randomization (V3). Note: For participants with T2DM at screening(V1) with no history or unknown status of diabetic retinopathy and/or macular edema, a screening diabetic retinopathy assessment must be performed to confirm eligibility. The retinopathy assessment must be consistent with local standard of care and must be performed by an ophthalmologist or local eye healthcare professional equivalent. A diabetic retinopathy assessment meeting these same criteria will be acceptable for screening if done within 30 days of the screening visit (V1); 21. Have a calcitonin level of >=35 ng/L (>=35 pg/mL) at screening (V1); 22. Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2; 23. Have, in the opinion of the investigator, evidence of significant, uncontrolled endocrine abnormality, for example uncontrolled hypothyroidism, thyrotoxicosis, or adrenal crisis; 24. Have renal impairment, measured as eGFR <30 mL/min/1.73 m^2, calculated by the Chronic Kidney Disease Epidemiology Collaboration Cystatin-C equation (2012), and determined by the central laboratory during screening (V1).; 25. Have a known history of esophageal varices; 26. Have a history of advanced liver disease (including advanced liver fibrosis or cirrhosis), or alcohol associated hepatitis based on either prior liver histology or imaging studies, such as transient elastography, ultrasound, CT and MRI, or Enhanced Liver Fibrosis score; 27. Have acute or chronic hepatitis, including a history of autoimmune hepatitis, signs, or symptoms of any other liver disease other than metabolic dysfunction-associated steatotic liver disease or metabolic-dysfunction and alcohol associated steatotic liver disease (MetALD), or any of these laboratory values during screening (V1); 28. Have a diagnosis or a history of malignant disease within 5 years before screening (V1), with the following exceptions: 1. basal cell or squamous epithelial carcinomas of the skin that have been resected, with no evidence of metastatic disease for 3 years 2. cervical carcinoma in situ, with no evidence of recurrence within 5 years prior to baseline, or 3. Grade 1 (for example, Gleason 6 or lower) prostate cancer; 29. Have a known clinically significant gastric emptying abnormality, such as severe diabetic gastroparesis or gastric outlet obstruction, have undergone or plan to have during the course of the study either gastric bypass (bariatric) surgery or restrictive bariatric surgery, for example, LAP-BAND® (Apollo Endosurgery US, Inc. Austin, Texas) or, in the opinion of the investigator, have clinically significant GI motility changes related to their current medication regimen; 30. Have a diagnosis of a condition of micro- or macronutrient malabsorption (for example, Crohn’s disease, celiac disease, and small intestine resection) that is of clinical concern in the opinion of the investigator. 42. Have any hematological condition that may interfere with HbA1c measurement, for example, hemolytic anemias, or hemoglobin level of ≤8.0 g/dL; 31. Within 180 days before screening (V1), have had any of the following: acute myocardial infarction cerebrovascular accident (stroke) hospitalization for unstable angina, or hospitalization due to congestive heart failure; 32. Have New York Heart Association Functional Classification Class IV congestive heart failure; 33. Have a 12-lead ECG abnormality at screening (V1) that, in the opinion of the investigator, increases the risks associated with participating in the study or may confound ECG data analysis. Other medical 34. Have a history of chronic or acute pancreatitis; 35. Have a vitamin B1 (thiamine) or vitamin B9 (folate) deficiency that is severe or of significant clinical concern in the opinion of the investigator at screening (V1); 36. Have had a transplanted organ or are awaiting an organ transplant. Exception: Corneal transplants or keratoplasty are allowed; 37. At the time of screening (V1), have a planned surgery, except for minor surgical procedures, to occur during the study; 38. For IOCBP: are pregnant or breastfeeding, or intending to become pregnant or to breastfeed; 39. Are investigative site staff directly affiliated with this study and/or their immediate family. Immediate family is defined as a spouse, legal partner, parent, child, or sibling, whether biological, or legally adopted; 40. Are employees of Eli Lilly and Company (Lilly) or are employees of any third party involved in the study who require exclusion of their employees; 41. Have cognitive impairment that is, in the investigator’s opinion, likely to interfere with the patient’s ability to undergo study assessments and procedures, including but not limited to the TLFB; 42. Have had prior seizures (other than remote history of childhood febrile seizure), or other condition that would place the participant at increased risk of seizures, or participants are receiving anticonvulsants for seizure control; 43. Have a history of serious head injury (for example, skull fracture, cerebral contusion, or trauma resulting in prolonged unconsciousness), intracranial neoplasm, or hemorrhage; 44. Have any condition, unwillingness, or inability, not covered by any of the other exclusion criteria, which in the investigator’s opinion, might jeopardize the participant’s safety, example, acute, serious, or unstable medical condition, hypersensitivity, contraindication, or compliance with the protocol; 45. Are currently taking medications intended to treat AUD within the past 30 days prior to screening (V1) or between screening (V1) and randomization (V3). Examples include, but are not limited to, disulfiram, acamprosate, naltrexone, and the list of medications referenced in Section 6.9.4. Note: If a participant is taking one of these medications for a non-AUD indication, this would still be exclusionary; 46. Have any condition that is a contraindication to GLP-1 RAs, for example, hypersensitivity or intolerance to medications with GLP-1 RA activity (examples include, but are not limited to, liraglutide, semaglutide, and tirzepatide), brenipatide, or excipients; 47. Within 90 days before screening (V1) or between screening (V1) and randomization (V3), received other prescribed or over-the-counter medications, compounded or alternative remedies, including herbal or nutritional supplements, intended to promote body weight reduction. Examples include, but are not limited to, the list of medications referenced in Section 6.9.4. 48. Have modified within the past 30 days prior to randomization (V3), or are planning to initiate or modify during the study, orexin receptor antagonist medications including, but not limited to, suvorexant, lemborexant, and daridorexant. 49. Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study. 50. Have participated in a clinical study and have received active treatment, or unknown if they received active treatment, within 90 days or 5 half-lives (whichever is longer) before screening (V1). 51. Have previously completed or withdrawn from this study or any other study investigating brenipatide after receiving at least 1 dose of active or unknown study intervention.

研究实施时间：

Study execute time：

从 From 2025-11-01 00:00:00至 To 2028-11-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2026-02-02 00:00:00 至 To 2026-06-30 00:00:00

干预措施：

Interventions：

组别：	0.75mg组别	样本量：	200
Group：	0.75mg group	Sample size：	200
干预措施：	第二阶段重新随机分配组别	干预措施代码：
Intervention：	Second stage: random reassignment of groups	Intervention code：

组别：	安慰剂组	样本量：	400
Group：	Placebo group;	Sample size：	400
干预措施：	第二阶段重新随机后接受0.3mg治疗	干预措施代码：
Intervention：	In the second stage, re-randomization was performed to receive 0.3 mg of	Intervention code：

组别：	1.5mg组别	样本量：	300
Group：	1.5mg group	Sample size：	300
干预措施：	第二阶段重新随机分配组别	干预措施代码：
Intervention：	Second stage: random reassignment of groups	Intervention code：

组别：	0.3mg组别	样本量：	200
Group：	0.3mg group	Sample size：	200
干预措施：	第二阶段重新随机分配组别	干预措施代码：
Intervention：	Second stage: random reassignment of groups	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江省	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	杭州市第七人民医院	单位级别：	三级甲等
Institution hospital：	Hangzhou Seventh People's Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	浙江省	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	浙江大学医学院附属邵逸夫医院	单位级别：	三级甲等
Institution hospital：	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	陕西省	市(区县)：
Country：	China	Province：	Shaanxi	City：
单位(医院)：	延安大学咸阳医院	单位级别：	三级甲等
Institution hospital：	Yan'an University Xianyang Hospital	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	河北省	市(区县)：
Country：	China	Province：	Hebei	City：
单位(医院)：	河北医科大学第一医院	单位级别：	三级甲等
Institution hospital：	The first hospital of hebei medical university	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	云南省	市(区县)：
Country：	China	Province：	Yunnan	City：
单位(医院)：	昆明医科大学第一附属医院	单位级别：	三级甲等
Institution hospital：	The First Affiliated Hospital of Kunming Medical University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	无 HDD 的参与者百分比	指标类型：	次要指标
Outcome：	Percentage of participants without HDD	Type：	Secondary indicator
测量时间点：		测量方法：	过TLFB评估
Measure time point of outcome：		Measure method：	Questionnaire scale evaluation

指标中文名：	双重主要终点（饮酒量从基线至终点的总体减少）	指标类型：	主要指标
Outcome：	Dual primary endpoint (overall reduction in alcohol consumption from baseline to endpoint)	Type：	Primary indicator
测量时间点：		测量方法：	过TLFB评估
Measure time point of outcome：		Measure method：	Questionnaire scale evaluation

指标中文名：	每日饮酒量	指标类型：	次要指标
Outcome：	Daily alcohol intake	Type：	Secondary indicator
测量时间点：		测量方法：	过TLFB评估
Measure time point of outcome：		Measure method：	Questionnaire scale evaluation

指标中文名：	饮酒渴求（欲望）	指标类型：	次要指标
Outcome：	Drinking cravings (desires)	Type：	Secondary indicator
测量时间点：		测量方法：	PACS评分
Measure time point of outcome：		Measure method：	PACS evaluation

指标中文名：	戒酒天数	指标类型：	次要指标
Outcome：	Number of days of abstinence	Type：	Secondary indicator
测量时间点：		测量方法：	过TLFB评估
Measure time point of outcome：		Measure method：	Questionnaire scale evaluation

指标中文名：	体重	指标类型：	次要指标
Outcome：	Weight	Type：	Secondary indicator
测量时间点：		测量方法：	体重测量
Measure time point of outcome：		Measure method：	Weight measurement

指标中文名：	对于第I阶段中的brenipatide应答者b：证明brenipatide（不同剂量合并）在减少总饮酒量方面优于安慰剂	指标类型：	主要指标
Outcome：	For brenipatide responders in Phase Ib: Demonstrate that brenipatide (combined doses) is superior to placebo in reducing total alcohol consumption	Type：	Primary indicator
测量时间点：		测量方法：	问卷评估
Measure time point of outcome：		Measure method：	Questionnaire scale evaluation

指标中文名：	戒酒	指标类型：	次要指标
Outcome：	Quit drinking	Type：	Secondary indicator
测量时间点：		测量方法：	过TLFB评估
Measure time point of outcome：		Measure method：	Questionnaire scale evaluation

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	血样	组织：
Sample Name：	Blood	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	75	岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

中央随机系统

Randomization Procedure (please state who generates the random number sequence and by what method)：

Central stochastic system(iwrs)

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：	对研究者、研究参与者设盲
Blinding：	Blinding of researchers and study participants

是否共享原始数据： IPD sharing	否No
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	NA
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	EDC
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2026-02-02 20:34:17