Chinese Covid-19 Vaccine Candidate: Clinical trial begins here this month

Already trailing behind in the race to get a potential Covid-19 vaccine, Bangladesh is all set to start the much-talked-about clinical trial of the Chinese shot by the end of this month.

The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) will run the human trial of the potential vaccine, developed by China's Sinovac Life Sciences Co Ltd, on 4,200 healthcare professionals, maintaining the highest level of safety measures.

Officials at icddr,b say they have almost completed the process of importing the vaccine candidate and are expecting to get the necessary doses for the trial by this month.

"The trial will be conducted among Bangladeshi healthcare workers in order to determine the safety and efficacy of the vaccine. We believe that this trial, if successful, will be a great credit to the people and the government of Bangladesh," Prof John D Clemens, executive director of icddr,b, told The Daily Star on Tuesday.

The government took the final decision of the Chinese vaccine trial in late August, more than a month after approval by the Bangladesh Medical Research Council.

Medical scientists say the trial will help improve Bangladesh's capacity of vaccine research and ensure access to low-cost vaccines, the most sought-after commodity during the pandemic.

According to the agreement with icddr,b, once the vaccine candidate called CoronaVac, already under trial in multiple countries, is proved safe and effective, Sinovac will transfer the technology to a Bangladeshi  manufacturer for local production to ensure affordable price for the people here.

Besides, Sinovac will also provide 1,10,000 free doses to Bangladesh.

Medical scientists said in the history of medicine, rarely a vaccine has been developed in less than five years, but the Covid-19 pandemic has left countries around the world in a fierce race to get a vaccine as early as possible.

Experts say vaccines may be available in the market for mass use within the next four to 10 months. Currently, eight out of over 203 research organisations working to develop a vaccine are going through final stage trials.

The phase-III trial or the final stage means the vaccine is administered on thousands of people to confirm its safety -- including rare side effects -- and effectiveness.

This trial involves a controlled group which is given a placebo -- that has no therapeutic value but is administered to compare with those who get the vaccine.

STRONG MONITORING, REGULATIONS

Like any other final stage trial of a vaccine, icddr,b's 18-month trial involves multiple national and international research and regulatory organisations to complete it step-by-step.

If the vaccine is passed in the clinical trial, it will go through three more stages before its mass use -- regulatory review and approval, manufacturing, and quality control.

For ensuring a rigorous process, icddr,b has engaged a leading South Korea-based contract research organisation -- LSK Global -- for data monitoring and providing other support during the study period.

The study will also be monitored by an independent Data and Safety Monitoring Board (DSMB), consisting of experts from Bangladesh and abroad, organised by LSK Global, according to icddr,b officials.

Additionally, icddr,b will form a National Advisory Committee involving eminent scientists, public health experts and physicians of the country to oversee the clinical trial.

The icddr,b will provide periodic updates to the Directorate General of Drug Administration (DGDA), and relevant authorities of Bangladesh as the trial proceeds, an icddr,b scientist told The Daily Star.

Preliminary findings of the study will also be shared with the Bangladesh Medical and Research Council (BMRC), DGDA, and the Directorate General of Health Services and the study findings will be published in high impact journals and shared with relevant regulatory authorities including the WHO.

If all is well, the WHO will give a prequalification certificate.

Prequalification is a systematic process to determine the capacity of a manufacturer to produce a product of consistent quality in accordance with international standards and WHO/UNFPA specifications, according to the WHO website.

Scientists say the global standard is that any vaccine needs to show 67 percent or more efficacy for approval.

"Considering the Covid-19 pandemic, however, a benchmark has been set that any vaccine will get nod if it shows 50 percent efficacy in the last stage human trial. Also, it has to ensure immunity in human body for at least one year as per the global consensus," Prof Sayedur Rahman, chairman of pharmacology at BSMMU, also a member of the BMRC's ethical committee which evaluated the icddr,b's trial proposal.

He further said any vaccine will need WHO prequalification for its transfer from one country to another for mass use unless there is no bilateral agreement.

Prof Firdausi Qadri, senior scientist at the icddr,b who is in the 11-member Strategic Advisory Group of Experts (SAGE) of WHO, told The Daily Star, "We hope the vaccine will show at least 50 percent efficacy. However, no criterion for approval is fixed yet. Actually, impact of the vaccines or how many people will be benefited from the vaccine will get priority … ."

VOLUNTEERS, OBSERVATION

The trial will enrol literate and well-informed 4,200 healthcare professionals (aged between 18 and 59) including doctors, nurses, ward attendants, who will not carry the virus at the time of vaccination, from seven Covid-19 hospitals. Their participation will be voluntary.

The proposed hospitals are Mugda Medical College and Hospital, two units of the Dhaka Medical College and Hospital (Burn Unit and Unit 2), Kurmitola General Hospital, Holy Family Red Crescent Medical College Hospital, Kuwait Bangladesh Friendship Government Hospital, and Dhaka Mahanagar General Hospital.

Fifty percent of the volunteers will receive CoronaVac and the other 50 percent will receive placebo.

First, the two-dose regimen of vaccine or placebo will be administered in the deltoid region of the upper arm and then again on day 14.

Blood samples will be taken from all participants the day the first dose was administered and on day 28 or two weeks after the second dose. This will allow the study team to determine the level of pathogen as measured in blood serum, an official said.

Only the participants having no virus in their swabs or blood serum during the tests will be included in the primary analysis of vaccine efficacy six to eight months after the vaccination, he added.

Nasopharyngeal and throat swabs will be collected from all participants on the first day in order to determine their infection status upon enrolment in the trial.

Participants will be instructed to call the 24/7 healthcare communication service for any illness. Weekly reminders by SMS will be sent to encourage compliance, icddr,b said.

They will be asked to inform study team members if they have any symptoms suggesting Covid-19 disease, including fever, cough, sore throat, loss of smell, and respiratory distress.

"Anyone with Covid-19 symptoms will get their nasopharyngeal and throat swab samples tested by RT-PCR at the icddr,b," it said.

All participants will be observed for 30 minutes following vaccination.

A randomly selected subsample -- 420 volunteers -- will be advised to record daily any medical events in online diary cards to be provided for seven days after the first and second dose.

Also, a referral system will be established and all serious adverse events (SAEs) will be managed and necessary treatment will be ensured, if needed, according to the National Treatment Guidelines for Covid-19.

All SAEs following vaccination will be reported to LSK Global within 24 hours for onward reporting to Sinovac, DSMB and the ethical review committee of icddr,b.

All suspected unexpected serious adverse reactions will be reported to the DGDA.

The DSMB will review these data according to a schedule outlined in its charter. Safety follow-up will be continued for six months after vaccination.

LIABILITY

Icddr,b said the study participants will not receive any financial benefit for their participation, but in case of any illnesses during the trial, they will be provided with appropriate treatment.

As the sponsor of the trial, Sinovac assumes all liability concerning the investigated vaccine and shall adopt an appropriate liability scheme including insurance, Prof Clemens said.