Obstructive Sleep Apnea, Obesity
Conditions
Keywords
obstructive sleep apnea, obesity, GLP-1, GIP, GCG
Brief summary
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
Interventions
DRUGUBT251
Administered SC
DRUGPlacebo
Administered SC
Sponsors
The United Bio-Technology (Hengqin) Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in the Apnea-Hypopnea Index (AHI) | Baseline, Week 52 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change from baseline in AHI | Baseline, Week 52 | — |
| Percentage of participants with a reduction in AHI ≥ 50% from baseline | 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 | Baseline, Week 52 | — |
| Percentage change from baseline in body weight | Baseline, Week 52 | — |
| Percentage of participants with a reduction in AHI ≥ 50% from baseline and a reduction in body weight ≥ 10% from baseline | Baseline, Week 20, Week 52 | — |
| Percentage change from baseline in the Sleep Apnea-Specific Hypoxia Burden (SASHB) | 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 | Baseline, Week 20, Week 52 | range: 0 to 100 for both scales; higher scores indicate worse sleep-related impairment and worse sleep disturbance, respectively |
| Percentage of participants with improvement in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire | Baseline, Week 20, Week 52 | range: 0 to 1; higher scores indicate better health-related quality of life |
Contacts
CONTACTLinong Ji, MD
Outcome results
None listed