Three COVID Vaccine Developers Release Detailed Trial Protocols

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The companies behind three major COVID-19 vaccines in development released the protocols of their trials, outlining their expectations for participant enrollment, benchmarks for vaccine efficacy, and more details about the makeup of each product.

Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the US Food and Drug Administration (FDA) to keep physicians informed of their COVID-19 vaccine review process.

On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.

The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.

Dr Robert Kruse

"I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates," Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.

AstraZeneca Takes a Shot at Transparency

The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.

The projected enrollment is 30,000 participants, and the estimated primary completion date is December 2, 2020, according to information on clinicaltrials.gov.

"Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial," the company said in a statement. "As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.

"AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information," the company added.

Moderna Methodology

The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is October 27, 2022.

A statement that was requested from ModernaTX was not received by press time.

Pfizer Protocol

In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.

Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.

"Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear," Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, "we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients," she said.

"Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial," Castillo said.

If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.

Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. "We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy."

A Positive Move

"COVID-19 vaccines will only be useful if many people are willing to receive them," said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.

"By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy," Kruse said. He noted that information could help inform a potential FDA emergency use authorization.

Kruse has disclosed no relevant financial relationships.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology and neurology. Follow Damian on Twitter: @MedReporter.

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