HONG KONG – Cambridge, U.K.-based Astrazeneca plc has resumed phase I/II trials in Japan for AZD-1222, the experimental, adenovirus vector-based candidate coronavirus vaccine that it is co-developing with the University of Oxford.

Japan’s Pharmaceuticals and Medical Devices Agency was the latest health authority to greenlight the resumption of the trials, after an unexplained illness in one of the U.K. phase III trials participants triggered a halt for all global trials on Sept. 6.

“A standard review process allowed for the review of safety data by an independent committee,” an Astrazeneca spokesperson told BioWorld. The data and safety monitoring committee concluded in its review that the illness was unlikely to be related to the vaccination process. Astrazeneca declined to provide further details of the process to restart the trials.

The company also did not provide further details of the trial participant’s illness. However, a participant information sheet for a phase II/III study of the vaccine, with a version date of July 12, noted that while neither allergic reactions nor Guillain-Barré syndrome had been seen in the study, “one volunteer in the trials of ChAdOx1 nCoV-19 (alternate name for AZD-1222) developed symptoms of transverse myelitis (inflammation in the spinal cord), which has not required medical treatment and is being investigated, though the cause is uncertain.”

It took a week for the trials across the U.K. to resume on Sept. 12 after the Medicines Health Regulatory Authority deemed it safe to do so. Authorities in Brazil, South Africa and India have also allowed trials to resume in their countries. In Brazil, the Brazilian National Health Surveillance Agency and the National Council for Research Ethics allowed trials resumed on Sept. 14. The South African Health Products Regulatory Authority allowed trials to resume in that country on Sept. 17. Regarding the timeline, “regulators in each individual country determine when trials can start and they do this in their own time frame,” the Astrazeneca spokesperson said.

In the U.S., “we are continuing to work with the FDA to facilitate review of the information needed to make a decision regarding resumption of the U.S. trial,” the spokesperson said. Phase III trials began in the country on Aug. 31, less than a week before the halt.

The U.S. Astrazeneca-led trial, is funded by the Biomedical Advanced Development Authority, an arm of the office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services, as well as the National Institute of Allergy and Infectious Diseases (NIAID). The NIAID-backed COVID-19 Prevention Network will participate in the trial.

The U.S. trial aims to recruit up to 30,000 adults aged 18 and over, from a variety of ethnic and geographic backgrounds who are either healthy or have stable underlying medical conditions, including HIV, and are thus at higher risk of contracting the virus. The participants are randomized to receive two doses of either AZD-1222 or a saline control, four weeks apart, to test the vaccine’s efficacy and safety in all the participants. The trial will also assess the local and systemic reactions and immune responses in 3,000 participants, the company said.

Astrazeneca reported positive interim data for a phase I/II blinded, multicenter, randomized, controlled clinical trial of 1,077 healthy adults in late July. The data showed that the vaccine was tolerated and generated a robust immune response against the SARS-CoV-2 virus. Antibodies to the virus spike protein increased fourfold in 95% of the patients a month after injection, while the T-cell response, peaking by day 14, was also induced and maintained for two months afterward, the data showed.

Albany, N.Y.-based Albany Molecular Research Inc. (AMRI) signed a supply agreement with Astrazeneca in September to support the vaccine’s manufacture. Under the agreement, AMRI is responsible for the sterile fill and finish at its Albuquerque, N.M. drug product manufacturing facility.

In Asia, Astrazenca signed a trilateral memorandum of understanding with South Korea’s SK Bioscience Co. Ltd., the vaccine business arm of SK Group, and the Ministry of Health and Welfare on July 21 to produce AZD-1222 in the country. The company also inked a deal with Shenzhen-based Kangtai Biological Products Co. Ltd. in August to produce the vaccine in China. Kangtai requested the production of at least 100 million doses by the end of 2020, and at least 200 million doses by the end of 2021 at the time of the agreement.

Despite the setback from the trials halt, “we anticipate that efficacy results from phase II/III trials will come later this year, but this will depend on the rate of infection within the clinical trial communities,” the spokesperson said. With the number of COVID-19 cases topping 35.6 million as of Oct. 6, according to Johns Hopkins University data, the need for a viable COVID-19 vaccine is ever more urgent.

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