BIDMC’s COVID-19 vaccine enters phase 3 trials

New York Times – September 23, 2020

Johnson & Johnson begins one-shot vaccine trial

Buoyed by positive results in its earlier studies, Johnson & Johnson has begun the final stage of clinical trials for its coronavirus vaccine.

Although they are a couple of months behind the other so-called Phase 3 trials in the United States, Johnson & Johnson’s trials will be the largest, with plans to enroll 60,000 participants. And the experimental vaccine may have considerable advantages over some of its competitors, experts said. It does not need to be stored in subzero temperatures, and it may require just one dose instead of two.

“It would be fabulous if we had something at a single dose,” said Dr. Judith Feinberg, the vice chairwoman for research in medicine at West Virginia University, who was not involved in the study.

Only a Phase 3 trial, which compares the effects of a vaccine with those of a placebo, could determine if a single dose was indeed effective, Dr. Feinberg said. But if it worked, that could greatly speed efforts to curb the pandemic.

“The real issue here is time,” she said. “We’ve got to vaccinate a lot of people really quickly.”

The trial started on Monday. At a news conference on Tuesday, Dr. Paul Stoffels, chief scientific officer of Johnson & Johnson, said the company might be able to determine by the end of the year if the vaccine is safe and effective. The company will soon be posting a manuscript online with data from the earlier phases of its trials, he said.

Johnson & Johnson’s experimental vaccine uses an adenovirus to carry a gene from the coronavirus into human cells. The cell then produces coronavirus proteins, but not the coronavirus itself. These proteins can potentially prime the immune system to fight off a later infection by the virus.

Adenovirus vaccines must be kept refrigerated but not frozen, unlike the two front-runner vaccines, by Moderna and Pfizer, which depend on bits of genetic material known as mRNA. The freezing requirement could make the distribution of those vaccines difficult, especially to places without advanced medical facilities.

Moderna and Pfizer’s vaccines also require two jabs given a few weeks apart, a significant logistical hurdle.

“I mean, just think about yourself — how much easier would it be for you to go to your local doctor or your local drugstore and be once and done?” said Dr. Daniel Barouch, a virologist at Beth Israel Deaconess Medical Center.

Dr. Barouch led the development of the adenovirus vaccine in the early 2000s. Johnson & Johnson acquired it and used it to make vaccines for Ebola, H.I.V., respiratory syncytial virus and Zika.

All told, 100,000 people have received the adenovirus vaccine in clinical trials for these four diseases, without any serious side effects.

Johnson & Johnson’s Ebola vaccine was licensed in Europe in June. In contrast, the designs for the other three coronavirus vaccines in Phase 3 trials in the United States have not yet been licensed to treat any disease. (A different kind of adenovirus is being used in AstraZeneca’s coronavirus vaccine trials, which have been paused in the United States because of safety concerns.)

Accustomed to the typically slow pace of vaccine research, Dr. Barouch has been astonished by the past eight months of swift work on the coronavirus vaccine.

“It’s pretty amazing,” he said in an interview. “We never would have thought it could be done that quickly.”

Dr. Barouch and his colleagues carried out a number of experiments on animals to learn about how the vaccine stimulates the immune system to fight the virus. In one critical experiment, results of which were published in July, they found that the vaccine gave monkeys enough antibodies to protect them from an infection with the coronavirus.

After these promising results in animals, Johnson & Johnson began small safety studies in people, known as Phase 1/2 trials. Dr. Stoffel said that an analysis of 395 of the volunteers had found no serious side effects. And they produced encouraging levels of antibodies even after just one shot, he said.

“The single dose could be sufficient to protect people for a long time,” he said.

A Phase 1/2 trial measures immune responses but cannot determine if a vaccine actually protects against a virus. Dr. Barouch noted that a single dose of the vaccine produced a level of antibodies in people that his previous experiments showed was enough to protect monkeys.

The company is planning to recruit up to 60,000 people over the age of 18 for its Phase 3 trial in the United States, Argentina, Brazil, Chile, Colombia, Mexico, Peru and South Africa.

The trial is about twice as big as the others begun in the United States so far. (Last week, Pfizer announced it planned to increase its trial to 44,000 people from 30,000.)

Dr. Barouch said the larger size would provide a better sense of the safety of the vaccine and might also reduce the time it takes to determine if the vaccine is effective. “It will provide for a faster readout,” he said.

At the news conference, Dr. Stoffels said that Johnson & Johnson would publicly share its protocol for the Phase 3 trial on its website.

Johnson & Johnson will be testing the single dose in the 60,000-person trial and also run a smaller trial using a double dose.

But Dr. Barouch warned that Phase 3 trials results can’t be pinned to a fixed date. If the trial takes place where there are relatively few cases, it will take longer before enough people get Covid-19, the disease caused by the coronavirus, to know that it works. “It depends on where the epidemic goes,” he said.

Johnson & Johnson is most likely not the last vaccine maker to announce Phase 3 trials in the United States soon. Companies like Novavax and Sanofi are running clinical trials of their own. Their vaccines are based on different designs, such as packaging bits of viral proteins on microscopic scaffolds, which may prove just as good or better than the leading contenders.

“We need multiple vaccines to work,” Dr. Barouch said, “because there are seven billion people in the world, and no single vaccine supplier will be able to manufacture at that scale.”

Additional Coverage:

Boston Globe – Major study to start for COVID-19 vaccine developed by Johnson & Johnson, Beth Israel

Washington Post – A single-shot coronavirus vaccine from Johnson & Johnson will be tested in 60,000 people

Reuters – J&J kicks off final study of single-shot COVID-19 vaccine in 60,000 volunteers

Fox Business – Johnson & Johnson’s COVID-19 candidate enters third trial phase

CBS Boston – Johnson & Johnson’s coronavirus vaccine enters phase 3 trial with Beth Israel

ABC Vaccine Watch – Johnson and Johnson moves forward in vaccine trials

WGBH – COVID-19 vaccine developed in partnership with Beth Israel reaches final stage of testing

Boston Herald – Johnson & Johnson begins large phase 3 study of coronavirus vaccine globally and in Boston

WCVB – Another COVID-19 vaccine developed in Massachusetts entering Phase 3 trial

Yahoo – Johnson & Johnson begins phase 3 trial of single-shot COVID-19 vaccine