Just hours after an announcement by Justin Trudeau, Prime Minister of Canada, that the nation’s first COVID-19 vaccine clinical trial would commence soon, Canadians sent waves of unsolicited emails offering to volunteer to the Canadian Center for Vaccinology (CCfV) at Dalhousie University in Halifax. TrialSite News reported that Canada’s government selected CanSino Biologics to develop the vaccine in Canada. CCfV’s Dr. Scott Halperin would lead this Phase I/II clinical trial to evaluate the safety and efficacy of the vaccine developed by CanSino Biologics in China. The study team plans on enrolling 696 participants to the study which is scheduled to commence within a few weeks—the study team now awaits approval from the ethics committee board.
Known as Ad5-nCoV, the vaccine has been designed to prevent SARS-CoV-2, the virus behind the COVID-19 pandemic, from actually penetrating the body’s cells. If a virus such as SARS-CoV-2 is effectively blocked from entry, then it cannot exploit the cell’s systems to replicate: this effectively blocks the risk of body-wide infection.
Developed on CanSino Biologics’ adenovirus-based viral vector vaccine technology platform, this candidate has been genetically engineered with the replication-defective adenovirus type 5 as the vector to express SARS-CoV-2 spike protein, reports Precision Vaccines. It was the first COVID-19 vaccine to be tested in humans. By using a weakened common cold virus, the generic product codes for the COVID-19 virus spike protein to the cells. Producing the spike protein, the cells move to the lymph nodes hence triggering the body’s immune system to produce antibodies that actually recognize the spike protein and hence works to block or stop the novel coronavirus from entering the body and expanding.
Positive Results from Phase I Study in China
By May 22, 2020, it was reported from study results (published in The Lancet) that Ad5-nCoV was assessed to be not only tolerable but also immunogenic (can produce an immune response) by the 28th day post-vaccination. Moreover, the Chinese Phase I clinical trial evidenced that humoral responses against SARS-CoV-2 peaked by the 28th day after receiving the vaccination in healthy adults. Also, specific T-cell responses were observed by the clinical investigators starting at day 14 after day of vaccination reports Precision Vaccines. The study team concluded they had seen enough in their words: “Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.”
A Head Start?
Dr. Halperin hasn’t seen anything quite like this as reported locally by Steve McKinley with the Toronto Star, commenting, “We never have trouble getting volunteers for our studies, but they’re not usually pounding our doors.” Because CanSino Biologics has completed a successful Phase I clinical trial in China evaluating initial safety, tolerability and the immunogenicity of the Adenovirus Type 5, non-replicating viral vector platform (Ad5-nCoV) COVID-19 vaccine the Canadian site, led by Halperin, can even enroll elderly participants in this Phase I/II clinical trial. The study is planned to commence within two to three weeks and is now just pending ethical committee board authorization.
Starting within weeks, the randomized, observer-blind, dose-escalating and “adaptive” study, sponsored by CanSino Biologics, the Beijing Institute of Biotechnology and the Canadian Center for Vaccinology, includes two phases. The sponsors seek to investigate the safety, tolerability and the immunogenicity of the vaccine known as Ad5-nCoV in healthy adults from 18 to 55 and those from 65 to <85. It is looking like the start date will be sometime in mid to late June with an estimated primary completion date of March 2021 and estimated completion date of August 2021.
In the first phase of this two-part stepwise study, the Canadian Center for Vaccinology (CCfV) at Dalhousie University will enroll a total of 96 healthy adult volunteers to be vaccinated according to the dose-escalation design from the younger adults (18 to <55) to older adults (65 to <85). This first phase includes two (2) dosage levels including (1) 5E10vp and (2) 10E10vp, as well as two (2) dose schedules including (1) single dose and (2) double dose.
Based on the pre-defined adaptive design standards, the trial will transition from Phase I to Phase II. In the Phase II a total of 600 healthy adult volunteers will be vaccinated based on the dose-escalation design from the younger adults (18 to <55) to the older adults (55 to <85). There are two (2) dosage levels and schedule in this Phase II part of the trial, and will determine a final dose and schedule by the end. Some cohorts in the Phase II trial will be included in a subsequent Phase III clinical trial should the results merit moving forward.
Primary and Secondary Outcome Measures
Primary outcome measures include (1) occurrence of Solicited adverse events (AE) in all groups within the first six days after each vaccination; (2) occurrence of unsolicited adverse events (AE) in all groups within the first 28 days after each vaccination and (3) occurrence of serious adverse events (SAE) in all groups within six months after the final vaccination.
A range of critically important secondary outcome measures can be reviewed at Clinicaltrials.gov, but they include a range of important measures.
A Spirit of Participation and Altruism in Halifax, Nova Scotia
Located in the provincial capital of Nova Scotia, the Canadian Center for Vaccinology (CCfV) has seen major vaccine trials before and Dr. Halperin isn’t surprised by the intense interest to participate among the Canadian people. In 2014 CCfV was the hub of a major Ebola vaccine clinical trials and as reported by Mr. McKinley “they had more volunteers waiting in line than they had spots for.”
Halperin assessed, “We actually did a study of our volunteers in Phase I studies for the Ebola study and an influenza Phase I study to find out what was their primary motivation, and the primary motivation was altruism.”
Intensive Monitoring Limits Geographic Area Participation
Although CCfV is literally getting inundated with offers volunteer participation the center affiliated with Dalhousie University will only be able to accommodate volunteers form the Halifax area due to the requirement for intensive monitoring of volunteers required per the study protocol. Halperin isn’t concerned about what in reality is one of the biggest challenges associated with clinical trials: ensuring that there are enough subjects for a given trial. Dr. Halperin’s experience at least for CCfV has been the opposite—they have always found lots of participants ready and willing to help.
What if a Greenlight to Phase III? The Canadian Immunization Network Testing
Should this study go well the clinical trial could expand to other clinical investigational sites in the Canadian Immunization Network (CIRN). This Canada-wide network of 10 clinical trial sites will ensure opportunity for volunteers throughout the country.
Involving hundreds of participants, a Phase III would also include other countries. In the wonderful scenario that the vaccine works and is approved by Health Canada, the National Research Council is prepared to manufacture the vaccine in Canada “for emergency pandemic use,” reported McKinley from the Toronto Star.
CanSino Biologics Moves Forward with Phase II in China
In the meantime, TrialSite News has commented that the company initiated its Phase II clinical trial assessing Ad5-nCoV vaccine in China. Launched last month (April), the sponsor is evaluating the immunogenicity and safety of the vaccine in a target of 508 participants.
Led by sponsor CanSino Biologics, collaborators include the Institute of Biotechnology and the Academy of Military Medical Sciences (part of the Chinese PLA). Clinical investigational sites include the Hubei Provincial Center for Disease Control and Prevention in Wuhan, Hubei Province. Other participating sites include the Jiangsu Province Centers for Disease Control and the Zhongan Hospital. This study is led by Fengcai Zhu, MD, with the Jiangsu Province Centers for Disease Control and Prevention. For a CanSino Biologics company profile, see a previous TrialSite News article.
Lead Research/Investigator for Halifax Canadian Vaccine Study
Scott A. Halperin, MD, Canadian Center for Vaccinology, Principal Investigator
Joanne M. Langley, MD, Canadian Center for Vaccinology, Principal Investigator
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