Three weeks into its Phase III trial of its COVID-19 vaccine candidate, Johnson & Johnson (J&J) said last night that a participant’s “unexplained illness” compelled it to temporarily pause the 60,000-participant ENSEMBLE study (NCT04505722)—as well as all other clinical trials of the vaccine candidate sponsored by J&J’s Janssen Pharmaceutical Cos.

“Following our guidelines, the participant’s illness is being reviewed and evaluated by the ENSEMBLE independent Data Safety Monitoring Board (DSMB) as well as our internal clinical and safety physicians,” J&J stated last night.

JNJ-78436735 (Ad26.COV2.S) is one of nine COVID-19 vaccine candidates in late-stage clinical trials—and is one of about 200 vaccine candidates in development against SARS-CoV-2 as of October 2, according to the World Health Organization.

The J&J vaccine candidate dosed its first volunteer participant on September 23. JNJ-78436735 is among 19 “front runner” candidates among the 230+ COVID-19 therapeutics detailed in GEN’s updated “COVID-19 Drug & Vaccine Candidate Tracker.”

In addition to the ENSEMBLE trial, J&J’s pause also extends to at least three other clinical trials of JNJ-78436735 that were reported to be recruiting patients according to

  • A Phase II study (NCT04535453) evaluating humoral immune responses of three dose levels of the J&J vaccine administered intramuscularly (IM) as a two-dose schedule (56 days apart) and as a single vaccination; and testing both compressed and expanded two-dose schedules of the vaccine 28 and 84 days apart, in up to 550 participants.
  • A Phase I/II study (NCT04436276) assessing the safety, reactogenicity, and immunogenicity of the J&J vaccine candidate at two dose levels, administered IM as a single-dose or 2-dose schedule, with a single booster vaccination administered in one cohort, in up to 1,045 participants in groups of adults ages 18–55 and ages 65 and older.
  • A Phase I study (NCT04509947) evaluating the safety and reactogenicity of the J&J vaccine candidate IM at two-dose levels, and as a two-dose schedule in up to 250 healthy participants in groups of adults ages 20–55 and ages 65 and older.

No details on illness

It is not known—and “is not always immediately apparent,” J&J added—if the ill participant was among participants randomized to JNJ-78436735, or to placebo. The company offered no details about the participant’s illness.

“We must respect this participant’s privacy,” J&J stated. “We’re also learning more about this participant’s illness, and it’s important to have all the facts before we share additional information.”

J&J said its studies may be paused if an unexpected serious adverse event (SAE) that might be related to a vaccine or study drug is reported, “so there can be a careful review of all of the medical information before deciding whether to restart the study.”

“SAEs are not uncommon in clinical trials, and the number of SAEs can reasonably be expected to increase in trials involving large numbers of participants,” J&J added. “We are committed to providing transparent updates throughout the clinical development process of our vaccine candidate, in compliance with regulatory standards and our own high ethical and scientific principles.”

Investors responded to the pause by sending J&J’s share price down nearly 3% or $4 from yesterday’s close of $151.84, to $147.84 as of 2:30 p.m.

“This event could have significant negative impact (increased regulatory scrutiny, less consumer confidence etc.) for all other viral vector vaccines if proven to be associated with vaccination, in our view,” wrote Geoffrey C. Porges, MBBS, director of therapeutics research and a senior research analyst with SVB Leerink, in a research note.

The ENSEMBLE trial will enroll volunteers at up to nearly 215 clinical research sites in the U.S. and worldwide. Janssen is funding the trial along with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedical Advanced Research and Development Authority (BARDA).

$1.5B committed by BARDA

BARDA has committed up to nearly $1.5 billion toward supporting JNJ-78436735, from development through licensure—an award of more than $456.2 million in February, followed August 5 by approximately $1 billion to support a manufacturing demonstration project including the ability to deliver vaccine doses to government-designated locations nationwide.

ENSEMBLE is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of a single vaccine dose versus placebo in up to 60,000 adults ages 18 years old and older, including what J&J said would be “significant” representation from participants over age 60. The trial will include participants both with and without comorbidities associated with an increased risk for progression to severe COVID-19.

J&J has said it aims to enroll participants in the U.S. as well as in Argentina, Brazil, Chile, Colombia, Mexico, Peru, and South Africa—countries and clinical trial sites which according to the company have a high incidence of COVID-19 and the ability to achieve rapid initiation.

JNJ-78436735 is the second Phase III candidate to temporarily stop enrollment in recent weeks. Last month, AstraZeneca briefly paused enrollment in its up-to-30,000-patient Phase III trial of AZD1222 (NCT04516746), the vaccine it is co-developing with the University of Oxford and a spinout company, following a “potentially unexplained illness” involving a participant from the U.K.

While the trial has resumed in the U.K., it remains on hold in the U.S. pending “answers to important questions” over the vaccine’s safety for patients being sought by the FDA, U.S. Secretary of Health and Human Services, Alex Azar II, told CNBC last month. In its statement yesterday, J&J pointedly noted that its company-initiated pause differed from a clinical hold.

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