The Efficacy and Safety of Efsubaglutide Alfa Injection in Overweight and Obese Subjects (LIGHT-2)

Phase 2

Recruiting

• Conditions: Obesity and Overweight
• Interventions: Drug: Efsubaglutide Alfa 5 mg QW; Drug: Efsubaglutide Alfa 10 mg QW; Drug: Efsubaglutide Alfa 20 mg QW; Drug: Efsubaglutide Alfa 20 mg Q2W; Drug: Placebo

• Registration Number: NCT06921486
• Lead Sponsor: Shanghai Yinnuo Pharmaceutical Technology Co., Ltd.

Brief Summary

This study is a multicenter, randomized, double-blind, placebo-controlled Phase IIb clinical trial aimed at evaluating the efficacy, safety, pharmacokinetics (PK), and immunogenicity profile of Efsubaglutide Alfa injection in overweight and obese subjects. The primary endpoint is the percentage change in body weight from baseline after 18 weeks of treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-28
• Study Start: 2025-03-31
• Status Verified: 2025-04
• Study First Submitted QC: 2025-04-08
• Study First Posted: 2025-04-10
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-25
• Primary Completion: 2025-11-30
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Voluntarily participate in the clinical study; fully understand and be informed about the study, and sign the informed consent form (ICF); willing to follow and capable of completing all study procedures.
2. Age ≥ 18 years (including the cutoff value, based on the time of signing the ICF), regardless of gender.
3. History of poor weight control through diet and exercise [defined as weight control failure if the subject has attempted at least 3 months of diet and exercise alone prior to screening without achieving a weight loss of ≥ 5.0% (based on subject self-report)].
4. Willing to follow the recommendations of the investigator regarding medication, diet, and exercise.
5. Stable weight within 3 months prior to screening (defined as a weight change < 5%, based on subject self-report).
6. Obesity: Body Mass Index (BMI) ≥ 28 kg/m² (including the cutoff value) with or without comorbidities; or overweight: BMI ≥ 24 and < 28 kg/m² with at least one weight-related comorbidity, including but not limited to prediabetes (impaired fasting glucose [FPG] and/or abnormal glucose tolerance), hypertension, dyslipidemia, non-alcoholic fatty liver disease, or obstructive sleep apnea syndrome.
7. Women of childbearing potential must have a negative blood pregnancy test during the screening period. Women of childbearing potential or male subjects and their partners must agree not to plan for pregnancy from the time of signing the ICF until 3 months after the last dose of the investigational drug, and voluntarily agree to use effective contraception, with no plans for sperm or egg donation.

Exclusion Criteria

1. Allergic constitution or allergic to any component of the investigational drug.
2. Previously treated with Efsubaglutide Alfa injection.
3. Received glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, insulin, metformin, insulin secretagogues, or thiazolidinediones (TZD) or any other weight-affecting anti-diabetic medication within the past 3 months before screening.
4. HbA1c ≥ 6.5% at screening, or previously diagnosed with Type 1 or Type 2 diabetes (based on the World Health Organization [WHO] 2020 diabetes diagnosis and classification standards).
5. History of severe hypoglycemia or recurrent symptomatic hypoglycemia (≥ 2 times in the past 6 months).
6. Known single-gene mutations, other diseases, or drug-induced obesity, including but not limited to hypothalamic obesity, pituitary obesity, hypothyroid obesity, Cushing's syndrome, insulinoma, growth hormone deficiency, acromegaly, pseudohypoparathyroidism, gonadal dysfunction, etc.
7. Clinically significant gastric emptying abnormalities (e.g., gastric outlet obstruction), severe chronic gastrointestinal diseases (e.g., active ulcers in the past 6 months), long-term use of drugs directly affecting gastrointestinal motility (including but not limited to mosapride, cisapride, etc.), or having undergone gastrointestinal surgery within the past 6 months and deemed unsuitable for participation by the investigator.
8. Use of weight-affecting medications within 3 months prior to screening, including tricyclic antidepressants, psychiatric medications, or sedative drugs (such as imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, sulpiride, clozapine, olanzapine, valproic acid, valproic acid derivatives, lithium salts, etc.). Note: Excluded if cumulative or continuous systemic steroid use is less than 14 days.
9. Use of non-prescription weight loss medications or appetite suppressants (including traditional Chinese medicine weight loss drugs) within 1 month prior to screening, or use of prescription weight loss medications (e.g., phentermine, sibutramine, orlistat) or lipid-dissolving injectables (e.g., lipolytic injections) within 3 months prior to screening.
10. Previously underwent weight-loss surgery (excluding acupuncture, liposuction, and abdominal fat removal within 1 year before screening), or plans to undergo surgery for obesity during the study period, such as gastric bypass surgery or gastric band surgery.
11. Currently on a weight loss plan and not in the maintenance phase.
12. History of hyperthyroidism or hypothyroidism, or thyroid-stimulating hormone (TSH) < 1×LLN (lower limit of normal) or TSH > 1.5×ULN (upper limit of normal).
13. Screening serum calcitonin ≥ 50 ng/L (or ≥ 50 pg/mL), or history of medullary thyroid cancer, multiple endocrine neoplasia (MEN) syndrome type 2A or 2B, or related family history (family history defined as a first-degree relative with the disease).
14. History of acute or chronic pancreatitis, cholecystectomy, or symptomatic gallbladder disease (patients with post-surgery resolved gallstones or cholecystectomy without sequelae can be enrolled), or known history of pancreatic injury or high-risk factors for pancreatitis, or screening with serum amylase or lipase > 2×ULN.
15. Any disease that could affect HbA1c measurement, such as hemolytic anemia, sickle cell disease, etc.
16. Currently receiving or have received chronic (> 14 days) systemic corticosteroid treatment in the past 3 months (excluding local, intraocular, intranasal, intra-articular, or inhaled formulations), or have evidence of severe, active autoimmune disorders (e.g., lupus or rheumatoid arthritis), and, in the opinion of the investigator, require or may require systemic corticosteroid treatment within the next 12 months.
17. History of malignancy within 5 years prior to screening, excluding clinically cured cervical carcinoma in situ, squamous cell carcinoma of the skin, or basal cell carcinoma within the past 5 years.
18. History of major surgery (e.g., thoracic, intracranial, or abdominal surgery) within 6 months prior to screening, or plans to undergo surgery that may affect study completion or adherence.
19. Meets any of the following cardiac function criteria: clinically significant arrhythmias or conduction abnormalities requiring clinical intervention; hereditary long QT syndrome or QTcF > 450 msec or currently taking medications that may prolong the QT interval or cause torsades de pointes; clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina, coronary artery bypass graft surgery, New York Heart Association (NYHA) class III or higher congestive heart failure, left ventricular ejection fraction (LVEF) < 50%, or uncontrolled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg); other clinically significant cardiac abnormalities judged by the investigator.
20. History of hemorrhagic or ischemic stroke or transient ischemic attack within 6 months prior to screening.
21. Known infectious diseases: hepatitis B surface antigen (HBsAg) positive; hepatitis C virus (HCV) antibody positive and HCV RNA above the detection limit; human immunodeficiency virus (HIV) antibody positive; Treponema pallidum antibody positive.
22. Laboratory findings meeting any of the following: alanine aminotransferase (ALT) ≥ 3.0×ULN (subjects diagnosed with non-alcoholic fatty liver disease during screening and within the past 6 months with ALT ≤ 5.0×ULN may be enrolled); aspartate aminotransferase (AST) ≥ 3.0×ULN; total bilirubin (TBIL) ≥ 2.0×ULN; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² (CKD-EPI formula); fasting triglycerides (TG) > 5.65 mmol/L.
23. Known or suspected alcohol abuse within 1 year prior to screening (defined as male subjects consuming > 24 g alcohol per day, female subjects consuming > 12 g alcohol per day; 12 g alcohol is approximately equivalent to 300 mL beer, 100 mL wine, or 25 mL spirits).
24. Known or suspected drug abuse at screening.
25. Pregnant or breastfeeding women.
26. History of moderate to severe depression, anxiety, or serious mental disorders, such as schizophrenia, bipolar disorder, etc., or screening PHQ-9 score ≥ 15.
27. History of suicidal tendencies or suicide attempts.
28. Participation in a clinical trial involving vaccines, medical devices, or other drugs within 3 months prior to screening (except for observational studies).
29. The investigator or treating physician considers that the subject has any factors that may affect the evaluation of the efficacy or safety of the study, and is deemed unsuitable for participation in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Efsubaglutide Alfa 5 mg QW	Efsubaglutide Alfa 5 mg QW	The drug is administered once weekly, starting with a titration dose of 1 mg. The dose is up-titrated every 2 weeks in the sequence of 1 mg → 5 mg, reaching the target dose of 5 mg at Week 3 (W3). From W3 to W18, the treatment is maintained at a 5 mg dose.
Efsubaglutide Alfa 10 mg QW	Efsubaglutide Alfa 10 mg QW	The drug is administered once weekly, starting with a titration dose of 1 mg. The dose is up-titrated every 2 weeks in the sequence of 1 mg → 5 mg → 10 mg, reaching the target dose of 10 mg at Week 5 (W5). From W5 to W18, the treatment is maintained at a 10 mg dose.
Efsubaglutide Alfa 20 mg QW	Efsubaglutide Alfa 20 mg QW	The drug is administered once weekly, starting with a titration dose of 1 mg. The dose is up-titrated every 2 weeks in the sequence of 1 mg → 5 mg → 10 mg → 20 mg, reaching the target dose of 20 mg at Week 7 (W7). From W7 to W18, the treatment is maintained at a 20 mg dose.
Efsubaglutide Alfa 20 mg Q2W	Efsubaglutide Alfa 20 mg Q2W	From Week 1 (W1) to Week 6 (W6), the drug is administered once weekly, starting with a titration dose of 1 mg. The dose is up-titrated every 2 weeks in the sequence of 1 mg → 5 mg → 10 mg → 20 mg, reaching the target dose of 20 mg at Week 7 (W7). From W7 to W18, the drug is administered every two weeks and maintained at a 20 mg dose.
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Percentage change in body weight from baseline after 18 weeks of treatment.	18 weeks

Secondary Outcome Measures

Name	Time	Method
Change in blood uric acid levels from baseline after 18 weeks of treatment.	18 weeks
Proportion of subjects with ≥5%, ≥10%, and ≥15% reduction in body weight from baseline after 18 weeks of treatment.	18 weeks
Change in body weight from baseline after 18 weeks of treatment.	18 weeks
Change in BMI from baseline after 18 weeks of treatment.	18 weeks
Change in waist circumference from baseline after 18 weeks of treatment.	18 weeks
Change in hip circumference from baseline after 18 weeks of treatment.	18 weeks
Change in blood pressure (diastolic and systolic) from baseline after 18 weeks of treatment.	18 weeks
Change in lipid levels (triglycerides, total cholesterol, low-density lipoprotein cholesterol) from baseline after 18 weeks of treatment, percentage change from baseline, and ratio to baseline.	18 weeks
Change in blood glucose levels (FPG) from baseline after 18 weeks of treatment.	18 weeks
Change in blood glucose levels (HbA1c) from baseline after 18 weeks of treatment.	18 weeks
Change in blood glucose levels (fasting insulin) from baseline after 18 weeks of treatment.	18 weeks
Change in blood glucose levels (insulin resistance index [HOMA-IR]) from baseline after 18 weeks of treatment.	18 weeks

Trial Locations

Locations (13)

Yueyang Central Hospital; 🇨🇳 Yueyang, China

Beijing Tsinghua Changgung Hospital; 🇨🇳 Beijing, China

Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital; 🇨🇳 Chengdu, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, China

Zhujiang Hospital of Southern Medical University; 🇨🇳 Guangzhusi, China

The Fourth Affiliated Hospital of Harbin Medical University; 🇨🇳 Harbin, China

The First People's Hospital of Yunnan Province; 🇨🇳 Kunming, China

The Second Hospital of Nanjing Medical University; 🇨🇳 Nanjing, China

The Affiliated Qingyuan Hospital ,Guangzhou Medical University（Qingyuan People's Hospital）; 🇨🇳 Qingyuan, China

The First Hospital of Qinhuangdao; 🇨🇳 Qinhuangdao, China

Shanghai General Hospital; 🇨🇳 Shanghai, China

Tianjin Medical University Chu Hsien-I Memorial Hospital; 🇨🇳 Tianjin, China

Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University; 🇨🇳 Shanghai, China