UBT251 Injection Phase Ⅲ Study (OSA-NPAP)

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of UBT251 Injection in Obese Participants With Moderate-to-severe Obstructive Sleep Apnea (OSA) Not on Positive Airway Pressure (PAP) Therapy（UNISHAPE-OSA-1）

The objective of this clinical trial is to evaluate the efficacy of investigational drug UBT251 in the treatment of moderate-to-severe obstructive sleep apnea (OSA) with obesity, as well as to assess its safety. The key research question is:

Does UBT251 reduce the Apnea-Hypopnea Index (AHI) in participants?

UBT251 will be compared with placebo (an inactive substance identical in appearance) to determine its efficacy in treating moderate-to-severe OSA.

Participants will:

Receive weekly subcutaneous injections of either UBT251 or placebo for a duration of 52 weeks

Undergo examinations and testing at protocol-specified visit windows

Have their AHI assessed following the 52-week treatment period

Inclusion Criteria:

• Male or female participants aged 18 to 75 years inclusive at the time of signing the informed consent form.
• Confirmed diagnosis of obstructive sleep apnea (OSA) based on the International Classification of Sleep Disorders, 3rd Edition, Text Revision (ICSD-3-TR) criteria, with a polysomnography (PSG) showing an Apnea-Hypopnea Index (AHI) ≥ 15 events/hour at screening.
• Participants who are unwilling or unsuitable to receive positive airway pressure (PAP) therapy, and who have not received PAP therapy within 4 weeks prior to screening.
• Body Mass Index (BMI) ≥ 28 kg/m² at screening.
• Weight has been stable for 3 months prior to screening (body weight change < 5%) (based on self-report).
• Participants of childbearing potential and their partners must have no plan for conception from screening until 6 months after completion of the trial, voluntarily use effective contraceptive measures, and have no plan to donate sperm or oocytes within 6 months after trial completion.
• Willingness to provide written informed consent and strictly comply with the protocol.

Exclusion Criteria:

• Known hypersensitivity to the investigational drug, its excipients, or other drugs with similar pharmacological activity.

• Use of any of the following within 3 months prior to screening:

  1. GLP-1 receptor agonists or similar drugs;
  2. biguanides, SGLT-2 inhibitors, DPP-4 inhibitors, or any other hypoglycemic agents;
  3. weight-influencing medications (including systemic glucocorticoids, tricyclic antidepressants, antipsychotics, mood stabilizers);
  4. over-the-counter weight-loss drugs, prescription weight-loss drugs (e.g., orlistat), or lipolytic injections; stimulants, sedative-hypnotics, opioids, trazodone, or muscle relaxants;
  5. medications that may affect excessive daytime sleepiness assessment.

• History or evidence of:

  1. Diagnosed with type 1 diabetes, type 2 diabetes, or other types of diabetes (except history of gestational diabetes);
  2. History of acute or chronic pancreatitis, or pancreatic surgery;
  3. History of symptomatic gallbladder disease within 1 year prior to screening;
  4. Personal or family history (first-degree relatives, i.e., parents, children, or siblings) of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2);
  5. Presence of endocrine diseases that may significantly affect body weight;
  6. History of bariatric surgery or planned weight-loss procedures (with specific exceptions for procedures >1 year prior);
  7. Previous history of depression, or Patient Health Questionnaire-9 (PHQ-9) score ≥ 15 at screening, or history of severe mental illness;
  8. positive C-SSRS for suicidal ideation/behavior;
  9. History of clinically significant cardiovascular or cerebrovascular disease within 6 months;
  10. History or presence of severe retinal or macular lesions;
  11. History of sleep apnea surgery or major ENT surgery that may still affect breathing;
  12. History or presence at screening of clinically relevant medical conditions (other than OSA) or psychiatric disorders related to insomnia or excessive sleepiness;
  13. Receiving other active device therapies for OSA;
  14. Presence of other sleep disorders besides OSA;
  15. History or diagnosis of obesity hypoventilation syndrome or diurnal hypercapnia;
  16. Requirement for supplemental oxygen therapy;
  17. Severe craniofacial bony deformities or abnormalities significantly affecting the airway;
  18. Presence of gastrointestinal motility disorders, gastrointestinal diseases increasing post-dose risks, or history of major gastrointestinal surgery;
  19. malignancy within 5 years (except cured skin, cervical, or prostate in situ);
  20. Major surgery, severe trauma, or severe infection within 1 month;
  21. Concomitant diseases affecting participant safety, efficacy evaluation, or compliance.

• Abnormal lab results:

  1. HbA1c ≥6.5% or FPG ≥7.0 mmol/L;
  2. ALT/AST ≥3×ULN or total bilirubin ≥1.5×ULN or eGFR <60 mL/min/1.73m²;
  3. calcitonin ≥50 pg/mL;
  4. uncontrolled thyroid dysfunction or TI-RADS ≥4a nodules;
  5. fasting TG ≥5.6 mmol/L;
  6. amylase/lipase >2×ULN;
  7. INR >ULN;
  8. hemoglobin <90 g/L;
  9. untreated hypertension (SBP ≥160 and/or DBP ≥100 mmHg);
  10. clinically significant ECG abnormalities (2nd/3rd degree AV block, QTcF >470ms female/>450ms male, WPW, HR <50 or >110);
  11. positive HBV-DNA, HCV-RNA, HIV, or dual-positive syphilis;
  12. Physical examination, vital signs, laboratory tests, or other assessments showing clinically significant abnormalities that pose a significant risk to the participant or interfere with the evaluation of safety or PK results, rendering the participant unsuitable for the trial.

• Participation in another interventional clinical trial within 3 months prior to screening.

• Blood loss ≥400 mL or blood transfusion within 3 months prior to screening.

• History of drug or alcohol abuse (female >7 or male >14 standard drinks/week).

• Pregnant or lactating women.

• Unable to tolerate venipuncture or history of needle/blood phobia.

• Any other condition deemed unsuitable by the investigator.