Investigating Azvudine for treating symptomatic COVID-19 in high-risk adults

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

This study is testing if a new medication called Azvudine can help high-risk adults with COVID-19 feel better and avoid severe illness or death.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 1096 (estimated)
• Ages: 18 Years to 120 Years
• Sex: All
• Sponsor: Peking Union Medical College Hospital (other)
• Drugs / interventions: infliximab, chemotherapy, methotrexate, prednisone
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT05689034 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of Azvudine in reducing the risk of severe illness or death in symptomatic adults with COVID-19 who are at increased risk of progressing to severe disease. Participants will be randomly assigned to receive either Azvudine combined with conventional therapy or a placebo with conventional therapy, both administered for up to seven days. The study will include 1,096 participants across multiple centers, with a focus on those who have developed COVID-19 symptoms within the last five days and have at least one risk factor for severe illness.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and over who have developed COVID-19 symptoms within the last five days and have at least one risk factor for severe illness.

Not a fit: Patients who do not have COVID-19 symptoms or who are not at increased risk for severe illness may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the severity of COVID-19 in high-risk patients, potentially saving lives.

How similar studies have performed: While there have been various studies on COVID-19 treatments, the specific use of Azvudine in this context is novel and has not been extensively tested in similar trials.

Eligibility criteria

Inclusion Criteria:

* (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

Exclusion Criteria:

* (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.

Where this trial is running

Beijing, Beijing Municipality

• Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Xinlun Tian

Conditions: COVID-19 Respiratory Infection