Interim analysis from the ongoing Phase 1/2a clinical trial of the Janssen COVID-19 vaccine candidate (JNJ-78436735) was posted today on the pre-print server medRxiv.
The data demonstrate that a single dose of JNJ-78436735 induced a strong neutralizing antibody response in nearly all participants aged 18 years and older and was generally well-tolerated. Immune responses were similar across the age groups studied, including older adults.
The ongoing Phase 1/2a clinical trial is designed to study the safety and immunogenicity of two dose levels of the Janssen COVID-19 vaccine, and as single and two-dose schedules. The interim analysis showed that a single dose induced a robust immune response and was generally well-tolerated. These data are consistent with preclinical studies, published in the scientific journal Nature, which showed that a single dose of the vaccine successfully prevented subsequent infection and provided complete protection in the lungs of nonhuman primates.
Based on these findings, the single dose of the Janssen COVID-19 vaccine candidate of 5x1010 virus particles (vp) has been selected for further evaluation in the Phase 3 ENSEMBLE clinical trial. The Company also plans on running a Phase 3 clinical trial of a two-dose regimen of JNJ-78436735 versus placebo later this year.
The full set of results will be published once the complete Phase 1/2a trial data are available.
Immune Response Data
Seroconversion (the development of detectable antibodies) was observed in 99 percent of participants aged 18-55 years of age. 98 percent of participants were positive for neutralizing antibodies against SARS-CoV-2 at day 29 post-vaccination. The Janssen COVID-19 vaccine candidate elicited strong antibody responses, strong T cell responses, and a Th1 response, believed to be protective against the risk of vaccine-associated enhanced respiratory disease.
Immunogenicity (the ability to trigger an immune response) data from participants aged 65 years of age and above were available for the first 15 participants at the time of this post, with strong humoral and cellular immune responses elicited in all elderly participants who received a single dose of Janssen’s COVID-19 vaccine candidate.
Immune responses were similar across the age groups studied, including older adults.
Safety and Tolerability Data
Interim safety data from the Phase 1/2a trial indicated that the majority of adverse events reported were mild to moderate (grade 1 and grade 2) in severity and generally occurred on the day of vaccination with symptoms generally resolving that day, or the following day. Two serious adverse events were reported, the first for hypotension which the investigator determined to not be vaccine related, and the second was a participant with a fever who was hospitalized due to suspicion of having COVID-19 but recovered within 12 hours. No grade 4 (life-threatening) adverse events, solicited or unsolicited, were reported in any cohort, and no participant discontinued the study due to an adverse event. The analysis showed there was a trend toward higher reactogenicity with the higher vaccine dose and with younger age.
In clinical studies investigating vaccines, it is well known that vaccines often induce local and systemic side-effects that are mild, to moderate, and transient without consequences. In vaccine clinical trials these type of side effects are actively sought (“solicited”). The interim safety data in this Phase 1/2a study is blinded to ensure participants and trial investigators are not made aware which participants received a single dose of Janssen’s COVID-19 vaccine candidate versus a placebo.
Study Design
This Phase 1/2a multi-center, randomized, double-blind, placebo-controlled trial aims to evaluate the safety, reactogenicity, and immunogenicity of Janssen’s COVID-19 vaccine candidate at two dose levels, administered intramuscularly as single-dose or two-dose schedules, eight weeks apart, in healthy adults 18-55 and greater than 65 years of age. The study is ongoing at multiple clinical sites in Belgium and the United States.
For more information on Johnson & Johnson’s multi-pronged approach to helping combat the pandemic, visit: www.jnj.com/coronavirus.
Additional Information
“We are very encouraged by the immunogenicity of our COVID-19 vaccine candidate based on the antibody and T-cell data that was seen after a single dose and reported in the interim analysis of our Phase 1/2a trial,” said Mathai Mammen, M.D., Ph.D., Global Head of Janssen Research & Development, Johnson & Johnson. “Our scientific confidence of strong vaccine efficacy is based on mathematical modelling that relates the antibody levels we have seen in humans to the levels required for disease protection that we observed in non-human primates. We are now evaluating a single-dose of our COVID-19 vaccine candidate versus placebo in the ENSEMBLE Phase 3 study.”
At day 29, 97 percent of participants had detectable wild type SARS-CoV-2 virus neutralizing antibodies, with a titer higher than 1:100 in >80% of participants.
A single dose of a safe and effective vaccine would offer a significant advantage during a global pandemic emergency. However, a two-dose schedule may have potential to offer enhanced durability in some participants. Therefore, Janssen is studying a single-dose of its vaccine candidate in its pivotal ENSEMBLE trial and plans to run a Phase 3 clinical trial with a two-dose regimen of JNJ-78436735 versus placebo later this year.
The Phase 1/2a interim analyses also included data from one set of human convalescent serum (HCS) samples and noted that the geometric mean titers (GMT) in serum of vaccine recipients were lower than the mean titers in this HCS panel. Panels used to assess the immunogenicity of vaccine candidates are not standardized and therefore cannot be directly compared.
As compared to the HCS panel used by the Company to validate the NHP immunogenicity studies, the GMT of neutralizing antibodies induced by a single dose of our vaccine in this study was substantially higher.
In a separate group of participants vaccinated in the Janssen Phase 1/2a COVID-19 vaccine study (data to be published), an alternative human convalescent panel was used. In this panel we have observed the antibody titers induced by our vaccine were higher than this panel.
The Janssen Ad26 vaccine platform (known as AdVac®) has substantial clinical experience and has been used to vaccinate over 100,000 people across its global clinical programs.
For more information on Johnson & Johnson’s multi-pronged approach to helping combat the pandemic, visit: www.jnj.com/coronavirus.
Notice to Investors Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding development of potential preventive and treatment regimens for COVID-19. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of the Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.