Assessing the safety and effectiveness of sofosbuvir plus daclatasvir or ravidasvir in Egyptian adults with COVID-19

Plain English Summary

Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.

In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of March 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.

Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.

The aim of this study is to evaluate the safety and efficacy of Sofosbuvir plus Daclatasvir (SOF+DCV) or Sofosbuvir plus Ravidasvir (SOF+RVD) in COVID-19.

Who can participate?
Patients with laboratory-confirmed Symptomatic COVID-19

What does the study involve?
Participants will be randomly allocated to receive:
Group 1: the standard of care therapy (as per the Egyptian MOH protocol) together with a daily dose of [SOF+RVD] for 10 days.
Group2: the standard of care therapy (as the Egyptian MOH protocol) together with a daily dose of [SOF+DCV] for 10 days.
Group 3: the standard of care therapy (as the Egyptian MOH protocol) without any of the experimental drugs or other direct-acting antiviral therapies.
Participants will be closely monitored in hospital for 10 days, and there is a follow up visit at home 7 days later.

What are the possible benefits and risks of participating?
It is possible that no direct health benefits may result during or following the completion of this study. However, the overall conclusion drawn from the results of this study might lead to better care and future treatment for subjects who will suffer from such a condition. Side effects may be caused by Sofosbuvir

Where is the study run from?
National Liver Institute, Menufia, Egypt

When is the study starting and how long is it expected to run for?
March 2020 to March 2021

Who is funding the study?
European Egyptian Pharmaceutical Industries (Egypt)

Who is the main contact?
Mostafa Salah, mostafa.salah@tcdmena.com

Study website

Type

Scientific

Contact name

Mr Mostafa Salah

ORCID ID

Contact details

Third Floor
112B Ammar Ibn Yasser Street
Heliopolis
Cairo
-
Egypt
+20 (0)1062256804
mostafa.salah@tcdmena.com

Type

Public

Contact name

Mr Mostafa Salah

ORCID ID

Contact details

Third Floor
112B Ammar Ibn Yasser Street
Heliopolis
Cairo
-
Egypt
+20 (0)1062256804
mostafa.salah@tcdmena.com

EudraCT/CTIS number

Nil known

IRAS number

ClinicalTrials.gov number

Nil known

Protocol/serial number

PHA-SDR-002

Scientific title

Randomized, open-label, prospective study to evaluate the safety and efficacy of sofosbuvir plus daclatasvir or ravidasvir in Egyptian adults with COVID-19

Acronym

SAVE

Study hypothesis

Sofosbuvir plus daclatasvir or sofosbuvir plus ravidasvir effectively treat COVID-19 infection.

Ethics approval(s)

1. Approved 20/04/2020, Menoufia University National Liver Institute IRB (Shebin Elkom, Menoufia, Egypt, NLI IRB 00003413; +20 (0)482222740; gamalelsaidmousa@gmail.com), ref: NLI IRB 00003413
2. Approved 05/08/2020, Research Ethics Committee, Egyptian Ministry of Health (Saad Zaglool Street, Kasr Elainy, Cairo, Egypt; +202 27946369; mohp.rec@gmail.com), ref: IRB 0000687

Study design

Multicenter randomized open-label prospective interventional controlled parallel-group study

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

COVID-19 (SARS-CoV-2 infection)

Intervention

Upon entry into the study (screening visit), each patient will be allocated to a Subject Identifier (Subject ID) number. This will be a 6 digit number where the first 3 digits identify the study center and the last 3 digits, which increase incrementally, will identify each subject at a given study center. The subject ID will be retained throughout the study and will be used to uniquely identify each patient.

For patients eligible to receive study treatment, a randomization number will be allocated at the time of randomization. This randomization number will be used to identify and dispense the drug kits allocated to each subject.
Note that the subject identifier number (Subject ID) which uniquely identifies the subject is different to the randomization number (uniquely identifies a drug kit).

Patients will be randomized within each site to three groups:
Group 1 (Experimental 1, n=40): Patients will continue the standard of care therapy (as per the Egyptian Ministry of Health [MOH] protocol) together with a daily oral dose of one gratisovir (sofosbuvir) 400 mg tablet combined with one ravidasvir 200 mg tablet orally [SOF+RVD] for 10 days, OR
Group 2 (Experimental 2, n=40): Patients will continue the standard of care therapy (as per the Egyptian MOH protocol) together with a daily oral dose of one gratisovir (sofosbuvir) 400 mg tablet combined with one daktavera (daclatasvir) 60 mg tablet [SOF+DCV] for 10 days, OR
Group 3 (Control, n=40): Patients will continue the standard of care therapy (as per the Egyptian MOH protocol) without any of the experimental drugs or other direct-acting antiviral therapy.

The study duration will be as follows:
Pre-treatment: 1 day for screening and baseline data collection.
On treatment: 10 days of daily treatment.
Post-treatment: One follow-up visit after end of treatment within 7 days.

Intervention type

Drug

Pharmaceutical study type(s)

Phase

Phase II/III

Drug/device/biological/vaccine name(s)

Sofosbuvir, daclatasvir, ravidasvir

Primary outcome measure

Measured using case report forms unless otherwise indicated
1. Sum of the counted symptoms (fever, headache, generalized aches (myalgia/arthralgia), respiratory distress combined with no evidence of deterioration (ICU admission and mechanical ventilation) at days3, 7 and 10
2. Mean Oxygen saturation from day 1 to day 10 (based on daily recording as per CRF)

Secondary outcome measures

1. The percentage of patients with undetectable plasma SARS-CoV-2 RNA for two consecutive nasopharyngeal swabs at day 7 and day 10
2. Percentage of reported AEs/SAEs at any time point from day 1 to day 10, and follow up visit on week 1 measured using patient records
3. The percentage of patients who need ICU admission at any time point from day 1 to day 10, and follow up visit on week 1, measured using patient records

Overall study start date

15/03/2020

Overall study end date

10/03/2021

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Written informed consent signed and dated by the study subject or their legal representatives
2. Age ≥18 years old
3. Female or male patients with laboratory-confirmed symptomatic COVID-19 (SARS-CoV-2 infection) as determined by polymerase chain reaction (PCR) assay in any specimen collected <72 hours before randomization
4. Patients with any category of the following disease severity:
4.1. Moderate:
4.1.1. Symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion
4.1.2. Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate ≥20 breaths per minute, saturation of oxygen (SpO₂) ˃90% on room air at sea level, heart rate ≥90 beats per minute
4.1.3. No clinical signs indicative of severe or critical illness severity
4.2. Severe (not critical): meeting the following criteria:
4.2.1 Symptoms suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress
4.2.2. Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory rate ≥30 per minute, heart rate ≥125 per minute, SpO₂ ≤90% on room air at sea level or PaO₂/FiO₂ <300
4.2.3. No criteria for critical severity
5. Radiographic evidence of pulmonary infiltrate

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

120

Total final enrolment

120

Participant exclusion criteria

1. Critically severe COVID-19 acute respiratory distress syndrome (ARDS) cases requiring invasive mechanical ventilation at screening
2. Patients who have a severe concomitant illness that affects survival, including uncontrolled malignant tumor, blood dyscrasia, active bleeding, or patients with shock/or multiple organ failure at screening
3. Hypersensitivity or contraindication to any of the drugs used in the study
4. Patients with liver disease or cirrhosis (Child-Pugh >9 for ravidasvir and ˃12 for daclatasvir) or abnormal liver enzyme tests above three times the upper limit values (alanine aminotransferase [ALT] and aspartate aminotransferase [AST])
5. Cardiac ischemia with history of recurrent angina, clinically symptomatic cardiac abnormalities, or requirement for cardiac pacemaker
6. History of any malignancy within the last 5 years
7. History of solid organ or bone marrow transplantation
8. Patients who received treatment with any other investigational drug/device or involved in another clinical trial within 6 months prior to Screening
9. People living with HIV
10. Pregnant or breastfeeding subjects
11. Patients unable to comply with the procedures described in the protocol
12. Mentally or neurologically disabled patients not able to consent to their participation in the study

Recruitment start date

29/09/2020

Recruitment end date

29/12/2021

Countries of recruitment

Egypt

Study participating centre

National Liver Institute
Shebin Elkom
Menoufia
32511
Egypt

Organisation

European Egyptian Pharmaceutical Industries (EEPI)

Sponsor details

Km 25 Alex-Cairo Desert Road
Alexandria
21500
Egypt
+20 1006006992
amr.fahmy@pharco-corp.com

Sponsor type

Industry

Website

https://www.pharco.org/companies.html#:~:text=European%20Egyptian%20Pharmaceutical%20Industries%20(EEPI,export%20to%20the%20regulated%20markets.

Funder type

Industry

Funder name

European Egyptian Pharmaceutical Industries (EEPI)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

Intention to publish date

01/05/2021

Individual participant data (IPD) sharing plan

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

IPD sharing plan summary

Available on request

Study outputs