A Safety and Efficacy Study of Hymecromone Tablets for the Treatment of Patients With COVID-19.

A Single-center, Randomized, Parallel Controlled, Double-blind Clinical Trial Designed to Evaluate the Efficacy and Safety of Hymecromone Tablets in Subjects Diagnosed With COVID-19 Infection.

The coronavirus (SARS-CoV-2) is a new strain of coronavirus found in human in 2019, which causes epidemic worldwide. A study found that the increase in hyaluronic acid levels is closely related to the clinical symptoms of COVID-19, including pulmonary ground glass lesions, lymphocytopenia, immune response and cytokine storms, systemic vascular diseases, thrombotic coagulation disorders, which suggests that hyaluronic acid could be an important target for COVID-19 treatment and could improve the clinical symptoms of COVID-19 patients.

The results from a recent clinical trial recruited 144 patients with COVID-19 show that the inhibitor of hyaluronic acid synthesis, hymecromone, can significantly improve clinical symptoms, such as lung lesions and lymphocytopenia in COVID-19 patients. Therefore, hymecromone has the potential to become one of the options of COVID-19 treatment.

This study is a single-center, randomized, parallel controlled, double-blind clinical trial designed to evaluate the efficacy and safety of Hymecromone tablets in subjects aged 18-90 years (with boundary values) with a confirmed mild or moderate form of COVID-19 infection. The aim of this study is to optimize the program of the combination of hymecromone in the treatment of COVID-19 to improve the therapeutic effect.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Hymecromone tablets; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 304
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hao Fang; Phone Number: +86 21-64041990; Email: fang.hao@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Zhong Shan Hospital affiliated to Fudan University
      • Contact: Hao Fang, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants who have a positive SARS-CoV-2 test result ;
2. Participants who have been diagnosed with mild or ordinary type of COVID-19 infection;
3. Participants whose serum hyaluronic acid level was higher than the upper limit of normal value;
4. Participants who must agree to adhere to contraception restrictions;
5. Participants who understand and agree to comply with planned study procedures;
6. Participants who give signed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

1. Participants who have any of the following conditions when screening:

   1. ALT or AST > 5 ULN;
   2. Scr > 1.5 ULN or Ccr < 50 mL/min;
   3. TBIL > 2ULN ;
   4. HGB ≤ 90 g/ L;
   5. PLT ≤ 75×10^9/ L;
2. Participants who have suspected/active infections during the screening period including uncontrolled active bacterial, viral or fungal infections that require systemic treatment, except COVID-19 virus infections;
3. Participants who have any active autoimmune diseases during the screening period and need to be treated with immunosuppressants, including biological agents;
4. Participants who have a medical history of organ transplantation, or plan for organ transplantation including liver transplantation;
5. Participants who need a loading dose of anti-platelet drugs, such as aspirin (>300 mg/day) and clopidogrel (>300 mg/day);
6. Participants who have a medical history of central nervous system and digestive system bleeding, or a tendency of gastrointestinal bleeding, local active ulcer lesions included, in the last three months;
7. Participants who have biliary obstruction;
8. Female participants who are pregnant or breast-feeding or plan to be pregnant within this study period;
9. Male participants whose wife or partner plan to be pregnant within this study period.
10. Participants who have taken the drugs containing coumarin compounds, such as warfarin, within 3 days before screening;
11. Participants who have other diseases requiring hospitalization and/or in a need of surgical treatment within 7 days before screening, or have suffered from life-threatening diseases within 30 days before screening;
12. Participants who have known allergies to any of the components used in the formulation of the interventions;
13. Participants who have taken a part in a clinical study of an investigational intervention in the last 28 days. After 5 half-lives or 28 days, whichever is longer, can be allowed for screening;
14. Participants who are not suitable for this trial, and with any medical condition will compromise their own safety.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Conventional treatment combined with Hymecromone tablets, 0.4g , tid ac, 7 days.	Drug: Hymecromone tablets; Conventional treatment combined with Hymecromone tablets, 0.4g , tid ac, 7 days.
Placebo Comparator: Control group; Conventional treatment combined with placebo.	Other: Placebo; Conventional treatment combined with Placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects who developed disease progression.	To compare the proportion of subjects in the experimental group and the control group who developed disease progression within 28 days after initial treatment.	Within 28 days after initial treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of adverse events and serious adverse events.	To compare the incidence of adverse events and serious adverse events related to the study treatment in the experimental group and the control group.	The whole test process.
The time gap of COVID-19 virus clearance.	To compare the time of virus clearance by COVID-19 virus tests in the experimental group and the control group.	From the beginning of the research to the negative report of COVID-19 nucleic acid.
The clinical recovery time of the COVID-19 virus infection-related symptoms.	To compare the clinical recovery time of the COVID-19 virus infection-related symptoms in the experimental group with the control group.	From the beginning of the research to the disappearance of clinical symptoms.
The change of the serum hyaluronic acid.	To compare the serum hyaluronic acid level between baseline and the end of study observation of all subjects in the experimental group and the control group.	Between baseline and the end of study observation.

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Hao Fang, Zhong Shan Hospital affiliated to Fudan University

Publications and helpful links

General Publications

• Yang S, Ling Y, Zhao F, Li W, Song Z, Wang L, Li Q, Liu M, Tong Y, Chen L, Ru D, Zhang T, Zhou K, Zhang B, Xu P, Yang Z, Li W, Song Y, Xu J, Zhu T, Shan F, Yu W, Lu H. Hymecromone: a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression. Signal Transduct Target Ther. 2022 Mar 18;7(1):91. doi: 10.1038/s41392-022-00952-w.
• Li W, Yang S, Xu P, Zhang D, Tong Y, Chen L, Jia B, Li A, Lian C, Ru D, Zhang B, Liu M, Chen C, Fu W, Yuan S, Gu C, Wang L, Li W, Liang Y, Yang Z, Ren X, Wang S, Zhang X, Song Y, Xie Y, Lu H, Xu J, Wang H, Yu W. SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network. EBioMedicine. 2022 Feb;76:103861. doi: 10.1016/j.ebiom.2022.103861. Epub 2022 Feb 3.
• Nagy N, Kuipers HF, Frymoyer AR, Ishak HD, Bollyky JB, Wight TN, Bollyky PL. 4-methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer. Front Immunol. 2015 Mar 23;6:123. doi: 10.3389/fimmu.2015.00123. eCollection 2015.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2022
• Primary Completion (Anticipated): August 15, 2022
• Study Completion (Anticipated): November 15, 2022

Study Registration Dates

• First Submitted: May 20, 2022
• First Submitted That Met QC Criteria: May 20, 2022
• First Posted (Actual): May 23, 2022

Study Record Updates

• Last Update Posted (Actual): June 9, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Hymecromone
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: QJXDS-22-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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