Evaluation of Ganovo （Danoprevir ） Combined With Ritonavir in the Treatment of SARS-CoV-2 Infection

• ClinicalTrials.gov Identifier: NCT04291729
• Recruitment Status: Completed
• First Posted: March 2, 2020
• Last Update Posted: April 13, 2020
• Sponsor: The Ninth Hospital of Nanchang
• Collaborator: Ascletis Pharmaceuticals Co., Ltd.
• Information provided by (Responsible Party): The Ninth Hospital of Nanchang

Study Description

Brief Summary:

Evaluation of the efficacy and safety of Ganovo combined with ritonavir for patients infected with SARS-CoV-2.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Ganovo+ritonavir+/-Interferon nebulization	Phase 4

Detailed Description:

Given no specific antiviral therapies for new coronavirus pneumonia approved yet and Ganovo, an oral Hepatitis C virus protease inhibitor, approved in China in June 2018 , this open, controlled trial will evaluate the efficacy and safety of Ganovo in hospitalized patients infected with SARS-CoV-2.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Clinical Trial to Evaluate Ganovo（Danoprevir ） Combined With Ritonavir in the Treatment of SARS-CoV-2 Infection
• Actual Study Start Date: February 17, 2020
• Actual Primary Completion Date: March 19, 2020
• Actual Study Completion Date: March 19, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ganovo+ritonavir with or without interferon nebulization	Drug: Ganovo+ritonavir+/-Interferon nebulization; Ganovo one tablet (100mg / tablet) at a time, twice a day, up to 14 days. Ritonavir one tablet(100mg / tablet) at a time, twice a day, up to 14 days.With or without spray inhalation of interferon, 50μg / time for adults, twice a day up to 14 days.

Outcome Measures

Primary Outcome Measures :

1. Rate of composite adverse outcomes [ Time Frame: 14 days ]
   Defined as SPO2≤ 93% without oxygen supplementation, PaO2/FiO2 ≤300mmHg or a respiratory rate ≥30 breaths per min without supplemental oxygen

Secondary Outcome Measures :

1. Time to recovery [ Time Frame: 14 days ]
   Clinical recovery was defined as sustained (48 hours) alleviation of illness based on symptom scores (fever, cough, diarrhea, myalgia, dyspnea) all being absent and no evidence for progression (newly-presented dyspnea, SpO2 decline ≥3%, respiratory rate ≥ 24 breaths per min without supplemental oxygen).
2. Rate of no fever [ Time Frame: 14 days ]
   Rate of no fever
3. Rate of no cough [ Time Frame: 14 days ]
   Rate of no cough
4. Rate of no dyspnea [ Time Frame: 14 days ]
   Rate of no dyspnea
5. Rate of no requiring supplemental oxygen [ Time Frame: 14 days ]
   Rate of no requiring supplemental oxygen
6. Rate of undetectable New coronavirus pathogen nucleic acid [ Time Frame: 14 days ]
   Rate of undetectable New coronavirus pathogen nucleic acid
7. Rate of mechanical ventilation [ Time Frame: 14 days ]
   Rate of mechanical ventilation
8. Rate of ICU admission [ Time Frame: 14 days ]
   Rate of ICU admission
9. Rate of serious adverse event [ Time Frame: 14 days ]
   Rate of serious adverse event

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Aged 18-75 years old;
• Pneumonia patients with new coronavirus infection were confirmed to be positive by RT-PCR and clinical manifestations. The diagnosis standard refers to the diagnosis and treatment plan for pneumonia with new coronavirus infection (Current Trial Version);
• Patients with newly diagnosed respiratory system discomfort who have been hospitalized (the diagnosis time of respiratory system discomfort shall not exceed 7 days);
• Women and their partners who have no planned pregnancy for nearly half a year and are willing to take effective contraceptive measures within 30 days from the first administration of the study drug to the last administration;
• Agree not to participate in other clinical research within 30 days from the first administration of the study drug to the last administration;
• Patients who voluntarily sign informed consent.

Exclusion Criteria:

• The pneumonia patients with severe new coronavirus infection met one of the following conditions: respiratory distress, RR >= 30 times / min; or SaO2 / SpO2 <93% in resting state; or arterial partial pressure of oxygen (PaO2) / concentration of oxygen (FiO2) <300MMHG (1mmhg = 0.133kpa);
• Pneumonia patients with severe new coronavirus infection meet one of the following conditions: respiratory failure and need mechanical ventilation; or shock; or other organ failure combined with ICU monitoring treatment;
• Severe liver disease (such as child Pugh score >=C, AST > 5 times upper limit);
• Patients with contraindications specified in the instructions of ritonavir tablets;
• The pregnancy test of female subjects in the screening period was positive;
• The researchers judged that it was not suitable to participate in this clinical trial (for example, patients who may be transferred to another hospital during the study period; patients with multiple basic diseases, etc.).

Contacts and Locations

Locations

China, Jiangxi

The Ninth Hospital of Nanchang

Nanchang, Jiangxi, China, 330000

Sponsors and Collaborators

The Ninth Hospital of Nanchang

Ascletis Pharmaceuticals Co., Ltd.

Investigators

• Study Director: Yahong Chen, MD; Ascletis Pharmaceuticals Co., Ltd.

More Information

• Responsible Party: The Ninth Hospital of Nanchang
• ClinicalTrials.gov Identifier: NCT04291729
• Other Study ID Numbers: ASC-CTP-NC-01
• First Posted: March 2, 2020
• Last Update Posted: April 13, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Interferons; Ritonavir; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors