The Efficacy and Safety of Efsubaglutide Alfa Injection in Overweight and Obese Subjects (ENLIGHT)

NCT06921486 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: YN011-W303YN011-W202
• Study Type: interventional
• Target: 1,003
• Locations: 1 country
• Sites: 41

Brief Summary

This study is a multicenter, randomized, double-blind, placebo-controlled Phase IIb/III 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 of the Phase IIb is the percentage change in body weight from baseline after 18 weeks of treatment. The primary endpoint of the Phase III is the percentage change in body weight from baseline after 30 weeks of treatment, the secondary endpoint is the percentage change in body weight from baseline after a cumulative 48 weeks of treatment.

Conditions

Obesity and Overweight

Outcome Measures

Primary Outcomes (2)

• Percentage change in body weight from baseline

  Phase IIb (18 weeks) , Phase III (30 weeks)

• Proportion of subjects with ≥5% reduction in body weight from baseline

  Phase III (30 weeks)

Secondary Outcomes (15)

• Proportion of subjects with ≥5% reduction in body weight from baseline

  Phase IIb (18 weeks) , Phase III (48 weeks)

• Proportion of subjects with ≥10%, and ≥15% reduction in body weight from baseline

  Phase IIb (18 weeks) , Phase III (30 weeks and 48 weeks)

• Percentage change in body weight from baseline

  Phase III (48 weeks)

• Change in body weight from baseline

  Phase IIb (18 weeks) , Phase III (30 weeks and 48 weeks)

• Change in BMI from baseline

  Phase IIb (18 weeks) , Phase III (30 weeks and 48 weeks)

Other Outcomes (6)

• Change in Total Body Fat Mass from Baseline Measured by Dual-Energy X-ray Absorptiometry

  Phase IIb (18 weeks) , Phase III (30 weeks and 48 weeks)

• Change in Liver Fat Content (LFC) from Baseline Measured by MRI-PDFF

  Phase IIb (18 weeks) , Phase III (30 weeks and 48 weeks)

• Change in Fibrosis-4 (FIB-4) Score from Baseline

  Phase III (30 weeks and 48 weeks)

Study Arms (9)

Phase IIb：Efsubaglutide Alfa 5 mg QW

EXPERIMENTAL

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.

Drug: Phase IIb：Efsubaglutide Alfa 5 mg QW

Phase IIb：Efsubaglutide Alfa 10 mg QW

EXPERIMENTAL

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.

Drug: Phase IIb：Efsubaglutide Alfa 10 mg QW

Phase IIb：Efsubaglutide Alfa 20 mg QW

EXPERIMENTAL

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.

Drug: Phase IIb：Efsubaglutide Alfa 20 mg QW

Phase IIb：Efsubaglutide Alfa 20 mg Q2W

EXPERIMENTAL

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.

Drug: Phase IIb：Efsubaglutide Alfa 20 mg Q2W

Phase IIb：Placebo

PLACEBO COMPARATOR

Once weekly

Drug: Phase IIb：Placebo

Phase III：Recommended Phase 3 Dose (RP3D) Low Dose QW

EXPERIMENTAL

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, The dose escalation continues until reaching the RP3D Low Dose, and then the RP3D is maintained. The total cumulative duration of drug administration (from the first dose to the end of maintenance) is 48 weeks, with the once-weekly administration frequency retained throughout the entire period.

Drug: Phase III：Recommended Phase 3 Dose Low Dose

Phase III：Recommended Phase 3 Dose (RP3D) High Dose QW

EXPERIMENTAL

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, The dose escalation continues until reaching the RP3D High Dose, and then the RP3D is maintained. The total cumulative duration of drug administration (from the first dose to the end of maintenance) is 48 weeks, with the once-weekly administration frequency retained throughout the entire period.

Drug: Phase III：Recommended Phase 3 Dose High Dose

Phase III：Recommended Phase 3 Dose (RP3D) High Dose Q2W

EXPERIMENTAL

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: 1 mg → 5 mg → 10 mg → 20 mg. Dose escalation continues until reaching the RP3D High Dose. Once the RP3D High Dose is achieved, the treatment regimen transitions to alternating weekly between RP3D High Dose and placebo for the remainder of the study. The total cumulative duration of drug administration (from the first dose to the end of the maintenance phase) remains 48 weeks, with the once-weekly administration frequency retained throughout. Blinding is maintained across all treatment groups to ensure unbiased evaluation of efficacy and safety.

Drug: Phase III：Recommended Phase 3 Dose High Dose; Drug: Phase III：Placebo

Phase III：Placebo

PLACEBO COMPARATOR

Once weekly

Drug: Phase III：Placebo

Interventions

Phase IIb：Efsubaglutide Alfa 5 mg QW DRUG

IIb：Efsubaglutide Alfa 5 mg QW

Phase IIb：Efsubaglutide Alfa 5 mg QW

Phase IIb：Efsubaglutide Alfa 10 mg QW DRUG

Efsubaglutide Alfa 10 mg QW

Phase IIb：Efsubaglutide Alfa 10 mg QW

Phase IIb：Efsubaglutide Alfa 20 mg QW DRUG

Efsubaglutide Alfa 20 mg QW

Phase IIb：Efsubaglutide Alfa 20 mg QW

Phase IIb：Efsubaglutide Alfa 20 mg Q2W DRUG

Efsubaglutide Alfa 20 mg Q2W

Phase IIb：Efsubaglutide Alfa 20 mg Q2W

Phase IIb：Placebo DRUG

Placebo

Phase IIb：Placebo

Phase III：Recommended Phase 3 Dose High Dose DRUG

The Recommended Phase 3 Dose High Dose confirmed by the IDMC (Independent Data Monitoring Committee) based on the safety and efficacy data results from the 18-week Phase IIb.

Phase III：Recommended Phase 3 Dose (RP3D) High Dose Q2W; Phase III：Recommended Phase 3 Dose (RP3D) High Dose QW

Phase III：Recommended Phase 3 Dose Low Dose DRUG

The Recommended Phase 3 Dose Low Dose confirmed by the IDMC (Independent Data Monitoring Committee) based on the safety and efficacy data results from the 18-week Phase IIb.

Phase III：Recommended Phase 3 Dose (RP3D) Low Dose QW

Phase III：Placebo DRUG

Placebo

Phase III：Placebo; Phase III：Recommended Phase 3 Dose (RP3D) High Dose Q2W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥ 18 years (including the cutoff value, based on the time of signing the ICF), regardless of gender.
• History of poor weight control through diet and exercise \[defined as weight control failure if the subject has attempted at least 3 months of diet and exercise alone prior to screening without achieving a weight loss of ≥ 5.0% (based on subject self-report)\].
• Willing to follow the recommendations of the investigator regarding medication, diet, and exercise.
• Stable weight within 3 months prior to screening (defined as a weight change \< 5%, based on subject self-report).
• 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.
• 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.

You may not qualify if:

• Allergic constitution or allergic to any component of the investigational drug.
• Previously treated with Efsubaglutide Alfa injection.
• 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.
• 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).
• History of severe hypoglycemia or recurrent symptomatic hypoglycemia (≥ 2 times in the past 6 months).
• 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.
• 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.
• 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.
• 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.
• 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.
• Currently on a weight loss plan and not in the maintenance phase.
• 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).
• 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).
• 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.
• Any disease that could affect HbA1c measurement, such as hemolytic anemia, sickle cell disease, etc.

Sponsors & Collaborators

• Shanghai Yinnuo Pharmaceutical Technology Co., Ltd.: lead

Study Sites (41)

Beijing Friendship Hospital, Capital Medical University

Beijing, China

Location

Beijing Tsinghua Changgung Hospital

Beijing, China

Location

Peking University First Hospital

Beijing, China

Location

Changzhou First People's Hospital

Changzhou, China

Location

Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital

Chengdu, China

Location

Nanfang Hospital Southern Medical University

Guangzhou, China

Location

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, China

Location

The First Affiliateo Hospital of Jinan University

Guangzhou, China

Location

Zhujiang Hospital of Southern Medical University

Guangzhusi, China

Location

The First People'S Hospital of Zunyi

Guizhou, China

Location

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, China

Location

The Fourth Affiliated Hospital of Harbin Medical University

Harbin, China

Location

Anhui Provincial Hospital

Hefei, China

Location

The First Affiliated Hospital of Henan University of Science and Technology

Henan, China

Location

The First Affiliated Hospital of Nanyang Medical College

Henan, China

Location

Pingxiang People's Hospital

Jiangxi, China

Location

Jincheng General Hospital

Jincheng, China

Location

The Third Affiliated Hospital

Jinzhou, China

Location

The First People's Hospital of Yunnan Province

Kunming, China

Location

Luan City People's Hospital

Lu'an, China

Location

Jiangsu Provincial Hospital of Traditional Chinese Medicine

Nanjing, China

Location

Nan Jing First Hospital

Nanjing, China

Location

The Second Hospital of Nanjing Medical University

Nanjing, China

Location

The Affiliated Qingyuan Hospital ,Guangzhou Medical University（Qingyuan People's Hospital）

Qingyuan, China

Location

The First Hospital of Qinhuangdao

Qinhuangdao, China

Location

Shandong Provincial Hospital Affiliated to Shandong First Medical University

Shandong, China

Location

Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University

Shanghai, 200030, China

Location

Shanghai General Hospital

Shanghai, China

Location

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, China

Location

The First Hospital Of China Medical University

Shenyang, China

Location

Shenzhen Second People's Hospital

Shenzhen, China

Location

The First Hospital of Hebei Medical University

Shijiazhuang, China

Location

The Second Hospital of Hebei Medical University

Shijiazhuang, China

Location

Suzhou Municipal Hospital

Suzhou, China

Location

The Second Affiliated Hospital of Soochow University

Suzhou, China

Location

General Hospital of Tianjin Medical University

Tianjin, China

Location

Tianjin Medical University Chu Hsien-I Memorial Hospital

Tianjin, China

Location

Tenth People's Hospital Of Tongji University

Wuhan, China

Location

Wuhan Third Hospital Tongren Hospital of Wuhan University

Wuhan, China

Location

The First Affiliated Hospital of Xi'an Jiao Tong University

Xianian, China

Location

Yueyang Central Hospital

Yueyang, China

Location

MeSH Terms

Conditions

Obesity; Overweight

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Weiping Jia, M.D,Ph. D

  Shanghai Jiao Tong University Affiliated Sixth People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2025
• First Posted: April 10, 2025
• Study Start: March 31, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (41)