Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adults With COVID-19 at Increased Risk of Progressing to Severe Illness

Официальное название

A Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adult Participants With COVID-19 Who Are at Increased Risk of Progressing to Severe Illness

Обзор

To investigate whether treatment with Azvudine reduces the risk of severe illness or death in patients who are at a potential risk of progressing to severe COVID-19 infection.

Подробное описание

The study is designed as a randomized, parallel, double-blind, placebo-controlled trial, in which all participants will be randomized to a test group or control group in a 1:1 ratio.

The test group will be given Azvudine in combination with conventional therapy excluding anti-viral therapy and observed for efficacy. The control group will be given placebo in combination with conventional therapy excluding anti-viral therapy and observed for efficacy.

Test Group will recruit 548 participants who will be given Azvudine + conventional therapy other than antiviral\*5 mg/day, oral, up to 7 days (1 mg/tablet).

Control Group will recruit 548 who will be given Placebo + conventional therapy other than antiviral\* 5 tablets/day, oral, up to 7 days.

Вмешательства

• Препарат Azvudine
  Azvudine po. 5mg daily for 7 days
• Препарат Placebo
  Placebo po. 5 tablets daily for 7 days

Первичные конечные точки

• Proportion of COVID-19-related critical illness or all-cause death within 28 days. [Срок оценки: 28 days]

Вторичные конечные точки (5)

• Incidence rates of Azvudine-related adverse events and serious adverse events [Срок оценки: 28 days]
• Duration of COVID-19-related symptoms [Срок оценки: 14 days]
• All-cause death [Срок оценки: 6 months]
• COVID-19 viral load in pharyngeal swabs [Срок оценки: D1, D3, D7]
• Days of hospitalization and ICU stay [Срок оценки: 28 days]

Критерии участия

Критерии включения

• (1) An age of 18 years or over (inclusive); (2) Not more than five days since the development of COVID-19 symptoms, and positive for nucleic acid or antigen test for COVID-19 within five days before enrollment; (3) Presence of at least one symptom related to COVID-19 infection at the time of enrollment; (4) Agreement to practice effective birth control (for females of child-bearing potential); (5) Presence of at least one high risk factor for severe COVID-19 infection:

• Age ≥ 60 years;

• BMI>25；

• Fever (body temperature ≥ 38℃) for ≥ 3 days;

• Current smokers (still being smoking within 30 days before enrollment and have used at least 100 cigarettes up to date);

• Immunosuppressive diseases, including but not limited to: myelosuppression or organ transplantation or primary immunodeficiency disease; prolonged use of immunosuppressive agents (≥ 20 mg/d for at least 14 days in the case of prednisone within the last 30 days); biologic therapy (such as infliximab, etc.); use of immunomodulators (including but not limited to methotrexate, azathioprine, etc.); radiotherapy and/or chemotherapy for any malignancies within 90 days (for chest radiotherapy, this time interval should be more than 6 months);

• Chronic lung disease (such as asthma requiring intervention daily, bronchiectasis, COPD, pulmonary hypertension, OSAS, interstitial lung disease, etc.);

• Hypertension; ⑧ Cardiovascular diseases (previously diagnosed as myocardial infarction or stroke, TIA (transient ischemic attack), cardiac insufficiency, angina pectoris requiring nitrate therapy, CABG, post-PCI, post-carotid endarterectomy and aortic bypass surgery, etc.);

⑨ Type 1 or type 2 diabetes;

⑩ Neurodevelopmental abnormalities (such as cerebral palsy, Down's syndrome) or other genetic or metabolic syndromes and severe congenital malformations;

⑪ Active tumors (excluding localized skin cancer);

⑫ No vaccination against COVID-19

Критерии исключения

• (1) Known or suspected allergy to the components of Azvudine Tablets; (2) Patients diagnosed as severe or critical COVID-19 infection (Severe: 1. shortness of breath with RR ≥ 30 breaths/min; 2. oxygen saturation ≤ 93% when inhaling air at rest; 3. partial pressure of arterial oxygen (PaO2) / fraction of inspired oxygen (FiO2) ≤ 300 mmHg; 4. progressive worsening of clinical symptoms, and obvious lesion progression > 50% on lung images within 24 to 48 hours. Critical: 1. respiratory failure, requiring mechanical ventilation; 2. shock; 3. concomitant organ failure, requiring care in ICU); (3) Patients with severe liver disease (total bilirubin \[TBIL\] ≥ 2 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3 × ULN; (4) Patients with severe renal insufficiency (glomerular filtration rate ≤ 60 mL/min/1.73 m2) or currently on continuous renal replacement therapy, hemodialysis, and/or peritoneal dialysis; (5) Patients with malabsorption syndrome or any other condition compromising gastrointestinal absorption, or patients requiring parenteral nutrition or with difficulty in taking the investigational product orally; (6) Known HIV infection; (7) Presence of diabetic ketosis or hyperosmolar hyperglycemic state (HHS); (8) Total neutrophil count < 750 cells/L; (9) Pregnant or lactating women or those who plan to have a child during participation in this study and within six months after the end of this study; (10) Currently participating in another clinical trial or currently using another investigational product; (11) Presence of other active infections (must be etiologically confirmed) in addition to COVID-19 infection; (12) Presence of any comorbidities requiring hospitalization and/or a surgical procedure within 7 days prior to the start of this study or a comorbidity considered life-threatening within 30 days prior to the start of this study; (13) Patients who have received or are expected to receive convalescent plasma for COVID-19; (14) Previous treatment with anti-viral agents that have been proved to be effective against COVID-19, including but not limited to Nirmatrelvir/Ritonavir or Molnupiravir (this criterion does not apply to use of glucocorticoids for reasons other than COVID-19); (15) Other conditions that make it inappropriate for the participant to take part in this trial at the investigator's discretion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospita — Пекин

Публикации

• Tian X, Xu Y, Wang L, Dong C, Yan X, Fan J, Xie H, Zhang H, Wang J, Liu Y, Wang Y, Pan S, Wu A, Liu X, Yao C, Wang M. Efficacy and safety of azvudine in symptomatic adult COVID-19 participants who are at increased risk of progressing to critical illness: a study protocol for a multicentre randomized double-blind placebo-controlled phase III trial. Trials. 2024 Jan 22;25(1):77. doi: 10.1186/s13063- PMID 38254211

Идентификаторы

NCT: NCT05689034 · FNC-K3482

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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