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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19 Respiratory Infection
• Intervention / Treatment: Drug: Azvudine; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1096
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: nlun Tian; Phone Number: +8613911204657; Email: tianxl@pumch.cn
• Study Contact Backup: Name: Mengzhao Wang; Email: wangmengzhao@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Azvudine; Azvudine in Patients at Potential Risk of Progressing to Severe COVID-19 Infection	Drug: Azvudine; Azvudine po. 5mg daily for 7 days
Placebo Comparator: Placebo; Placebo in Patients at Potential Risk of Progressing to Severe COVID-19 Infection	Drug: Placebo; Placebo po. 5 tablets daily for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of COVID-19-related critical illness or all-cause death within 28 days.	Proportion of COVID-19-related critical illness or all-cause death within 28 days. COVID-19-related critical illness is defined as: a patient with an SpO2 of 90% to 95% requiring high-flow oxygen inhalation with a fraction of inspired oxygen (FiO2) not less than 60% or requiring non-invasive ventilation with a FiO2 not less than 60%; or requiring mechanical ventilation or ECMO for organ support.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rates of Azvudine-related adverse events and serious adverse events	Incidence rates of Azvudine-related adverse events and serious adverse events	28 days
Duration of COVID-19-related symptoms	Duration of COVID-19-related symptoms	14 days
All-cause death	All-cause death	6 months
COVID-19 viral load in pharyngeal swabs	COVID-19 viral load in pharyngeal swabs	D1, D3, D7
Days of hospitalization and ICU stay	Days of hospitalization and ICU stay	28 days

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 20, 2023
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: January 17, 2023
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 18, 2023

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Respiratory Tract Infections
• Other Study ID Numbers: FNC-K3482

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No