The United Bio-Technology (Hengqin) Co., Ltd.150 enrolled
Overview
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.
Outcomes
Primary Outcomes
Change from baseline in the Apnea-Hypopnea Index (AHI)
Time frame: Baseline, Week 52
Secondary Outcomes
Percentage change from baseline in AHI
Time frame: Baseline, Week 52
Percentage of participants with a reduction in AHI ≥ 50% from baseline
Time frame: Baseline, Week 52
Percentage of participants with an AHI < 5 events/hour or an AHI ≥ 5 and ≤ 14 events/hour with an Epworth Sleepiness Scale (ESS) score ≤ 10
Time frame: Baseline, Week 52
Percentage change from baseline in body weight
Time frame: Baseline, Week 52
Percentage of participants with a reduction in AHI ≥ 50% from baseline and a reduction in body weight ≥ 10% from baseline
Time frame: Baseline, Week 20, Week 52
Percentage change from baseline in the Sleep Apnea-Specific Hypoxia Burden (SASHB)
Time frame: Baseline, Week 20, Week 52
Change from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment Short Form 8a and PROMIS Sleep Disturbance Short Form 8b scores
range: 0 to 100 for both scales; higher scores indicate worse sleep-related impairment and worse sleep disturbance, respectively
Time frame: Baseline, Week 20, Week 52
Percentage of participants with improvement in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire
range: 0 to 1; higher scores indicate better health-related quality of life