Interim phase 1/2a study results for Johnson & Johnson’s experimental COVID-19 vaccine JNJ-78436735 have been published online on the preprint server medRxiv, with researchers saying that a single dose was “well tolerated and highly immunogenic,” and that the findings warrant further development at the lower dose level of 5×1010 viral particles (vp). The release of the early-stage data follows Johnson & Johnson’s recent announcement that it was advancing the vaccine into a phase 3 study targeting enrollment of 60,000 volunteers to test a single-dose regimen versus placebo.
The company said it is also planning to run a parallel phase 3 trial of a two-dose regimen of JNJ-78436735 versus placebo later this year. “The [interim analysis] data demonstrate that a single dose of JNJ-78436735 induced a strong neutralizing antibody response in nearly all participants,” Johnson & Johnson stated, adding that “immune responses were similar across the age groups studied, including older adults.”
Johnson & Johnson initiated the phase 1/2a placebo-controlled study of JNJ-78436735, also known as Ad26.COV2.S, at the end of July. The vaccine, a non-replicating adenovirus 26 vector expressing the stabilised pre-fusion spike (S) protein of SARS-CoV-2, was administered at a dose level of 5×1010 vp or 1×1011 vp per vaccination, either as a single dose or as a two-dose schedule spaced by 56 days in healthy adults.
Cohorts 1a and 1b included 402 participants from 18 to 55 years old, while cohort 3 enrolled 394 elderly participants over 65. The interim analyses were performed after the first dose of blinded safety data from cohorts 1a, 1b and 3, and group unblinded immunogenicity data from cohort 1a and 3.
SARS-CoV-2 neutralizing antibody titers were measured by wild-type virus neutralization assay (wtVNA). Researchers reported that after a single dose, the seroconversion rate in wtVNA at day 29 in cohort 1a already reached 92% with geometric mean titers (GMT) of 214, and 92% with GMTs of 243, for the lower and higher dose levels, respectively. Similar results were seen in the first 15 participants of cohort 3, where 100% seroconversion with GMTs of 196 were observed for the 5×1010 vp dose group, and 83% seroconversion with GMTs of 127 were seen at the 1×1011 vp dose level.
Seroconversion for S antibodies was observed in 99% of cohort 1a participants, with GMTs of 528 and 695 for the lower and higher doses, respectively, and in 100% of cohort 3 subjects, with GMTs of 507 and 248, respectively. Further, on day 14 post immunization, CD4+ Th1 immune responses were measured in 80% and 83% of a subset of participants in cohort 1a and 3, respectively, with no or very low Th2 responses. The researchers noted that CD8+ T cell responses were also “robust” in cohorts 1a and 3, at both dose levels.
As some participants have not yet received the planned second dose, the safety data included in this analysis were presented without disclosing the assignment of vaccine versus placebo.
In cohorts 1 and 3, solicited systemic adverse events were reported in 64% and 36% of participants, respectively. Fevers occurred in both cohorts 1 and 3 at rates of 19% and 4%, respectively, and were mostly mild or moderate, resolving within one to two days. The most frequent local adverse event (AE) was injection-site pain, while the most frequent solicited AEs were fatigue, headache and myalgia. No grade 4 AEs, either solicited or unsolicited, were reported in any cohort, and no one discontinued the study due to an AE.
There were two serious AEs, including one case of hypotension judged by the investigator not to be vaccine-related because of a past history of recurrent hypotension. Meanwhile, another participant with fever was hospitalized overnight because of suspicion of COVID-19, but the individual recovered within 12 hours, and the fever was subsequently judged by the investigator to be vaccine-related.
The researchers noted that while reactogenicity was acceptable in all groups, “there was a trend for higher reactogenicity with the higher vaccine dose and with younger age.”