Phase 3 Trial Data for the Johnson & Johnson COVID-19 Vaccine

These data were presented to the FDA but have not yet been fully published in a peer-reviewed journal. Updates will be provided as further information becomes available. 

This phase 3 trial tested the safety and effectiveness of a booster injection of the Johnson & Johnson COVID-19 given between 2 and 6 months after the original vaccine injection.¹ The dose was the same as in the original trial (50 billion viral vector particles). 

A total of 31,300 participants were enrolled from 9 countries across 3 continents. Detailed data about gender, race/ethnicity, and underlying conditions in the study population were not presented to the FDA but were reported to be similar to the original phase 3 trial. All participants had been in the original phase 3 study and received one vaccine injection in that study. Among the participants, 16,589 were randomly assigned to the booster injection, and 14,711 to the placebo (salt water injection).

At 71 days after the booster injection, the dose was reported to be 94% effective at preventing symptomatic COVID-19 illness in participants from the United States and 75% effective at preventing symptomatic COVID-19 illness in participants from other countries. This is in comparison to the placebo injection.

The investigators also looked at participants’ antibody levels against COVID-19 spike protein. Antibody levels were tested in participants’ blood samples in the vaccine group at 28 days after the booster injection and compared against antibody levels from their blood samples taken 28 days after the vaccine injection given in the original phase 3 trial. They found that antibody levels became 4-fold higher when the booster was given 2 months after the original injection. The difference in levels became even higher (12-fold higher) when the booster was given 6 months after the original injection. 

Side effects were more common among participants under the age of 60 years than in older participants. The most common side effects were fatigue (45% of participants), headache (38%), muscle pain (38%), nausea (15%), fever (5%). The majority of side effects were mild or moderate. There were 2 cases of thrombosis with thrombocytopenia (a life-threatening disorder of having blood clots develop in the deep veins while having low levels of platelets in the blood). One was in the vaccine group and one in the placebo group. There was one case of Bell’s palsy (facial paralysis) in the vaccine group.

Primary Vaccine Phase 3 Safety/Effectiveness Trial for Ages 18+ 

In the phase 3 trial, the researchers investigated the safety and effectiveness of one dose (50 billion viral vector particles) of the COVID-19 vaccine as compared with a placebo injection (salt water).² Participants in the trial were recruited from 213 sites: United States (116 sites); Argentina (11 sites); Brazil (26 sites); Chile (4 sites); Columbia (13 sites); Mexico (4 sites); Peru (8 sites); and South Africa (31 sites). Adults 18 years of age or older could enroll in the study. 

A total of 21,895 participants received the vaccine and 21,888 received placebo. The median age was 52 years. The youngest participants were 18 years old and the oldest was 100 years old. The gender breakdown was 55.0% male, 44.9% female, and 0.1% nonbinary. The racial/ethnic breakdown was: 58.7% white; 45.3% Hispanic/Latino/Latina; 19.4% Black/African-American; 3.3% Asian; 9.4% Native American or Alaskan Native; 0.3% Native Hawaiian or Pacific Islander; 5.6% multiracial; and 3.3% did not report.

About 27% of the participants were obese (had a body mass index of at least 30). About 41% of the participants had at least one chronic condition. The most common chronic medical conditions in the study population were high blood pressure (11.9%), type 2 diabetes (7.7%), HIV positive status (1.6%), serious heart conditions (3.1%), and asthma (1.9%). Other chronic conditions were present in less than 1% each, including cancer, chronic obstructive pulmonary disease, pulmonary fibrosis, liver disease, kidney disease, and neurologic conditions.

The study was designed to look at how well the vaccine prevented moderate COVID-19 cases and severe/critical COVID-19 cases at 2 time points. The first was cases that were diagnosed 14 or more days after vaccination. The second was cases that were diagnosed 28 or more days after vaccination. 

The definition of a “moderate COVID-19 case” that the investigators used in this study was a positive SARS-COV-2 test by polymerase chain reaction (PCR, also called a “molecular test”) plus any of the following: one respiratory symptom, evidence of blood clots in the deep veins, or 2 less serious symptoms (fatigue, sore throat, vomiting, cough, etc.). The definition of a “severe COVID-19 case” was a positive SARS-COV-2 test by PCR plus at least one serious symptom that required hospitalization.

The vaccine was effective in this study for preventing moderate or severe COVID-19 cases. At the 14 or more days after vaccination time point, there were 116 cases of confirmed moderate or severe COVID-19 in the vaccine group and 348 cases in the placebo group. That is an efficacy rate of 66.9%. At the 28 or more days after vaccination time point, there were 66 moderate or severe cases in the vaccine group and 193 in the placebo group. That is an efficacy rate of 66.1%. 

The authors looked at the vaccine efficacy to prevent moderate or severe COVID-19 among subgroups defined by age, sex, and race/ethnicity. The efficacy rate was between 61.0% and 85.4% for these various subgroups. This means that efficacy was generally not affected by age, sex, or race/ethnicity. 

The researchers also looked at how well the vaccine prevents severe COVID-19 disease. The vaccine was very effective at preventing severe disease. At the 14 or more days after vaccination time point, there were 14 severe COVID-19 cases in the vaccine group and 60 in the placebo group. This is an efficacy rate of 76.7%. The efficacy rate was even higher at the 28 or more days after vaccination time point. At that point, there were 5 severe COVID-19 cases in the vaccine group and 34 in the placebo group. That is an efficacy rate of 85.4%.

The researchers next looked at how well the vaccine prevents hospitalization for severe disease, and they found that the vaccine was very effective. At the 14 or more days after vaccination time point, there were 2 hospitalizations in the vaccine group and 29 in the placebo group. This is an efficacy rate of 93.1%. At the 28 or more days after vaccination time point, there were 0 hospitalizations in the vaccine group and 16 in the placebo group. That is an efficacy rate of 100% for preventing hospitalizations.

Six people died during the study from COVID-19 disease. All of those who died were in the placebo group. The vaccine was 100% effective at preventing death from COVID-19 disease. 

Side effects more common in those aged 18 to 59 years and were less common in those 60 years and above. The data summarized here are for those aged 18 to 59 years, where most side effects were seen.

The most common side effect was pain at the injection site in the arm, which 58.6% of the vaccine group and 14% of the placebo group reported. The pain was generally mild to moderate and lasted 1 to 2 days. Only 0.4% of the vaccine group reported the pain as severe. Redness at the injection site was reported by 9.0% of the vaccine group and 4.3% of the placebo group. Swelling at the injection site was reported by 7.0% of the vaccine group and 1.6% of the placebo group. 

Other side effects were fatigue, headache, muscle pain, nausea, and fever. These were more common after the second injection, rather than the first, and were more common in younger participants than in older participants. The information below is about these side effects in younger participants, listed as the rate with vaccine first and the rate with placebo second: fatigue (43.8% and 22.0%); headache (44.4% and 24.8%); muscle pain (39.1% and 12.1%); nausea (15.5% and 8.9%); fever (12.8% and 0.7%). These effects usually lasted 1 to 2 days. Pain relievers were used by 26.4% of the vaccine group and 6.0% of the placebo group.

There were 7 serious adverse events in the vaccine group and 2 in the placebo group. In the vaccine group, there was 1 case of Guillain-Barre syndrome, 1 case of pericarditis (inflammation of the sac around the heart), 1 case of brachial radiculitis (pain and nerve damage to the arm), 1 case of a hypersensitivity reaction, 1 case of severe post-vaccination syndrome (weakness, fever, fatigue), and 2 cases of Bell’s palsy (facial paralysis). In the placebo group, there was 1 case of deep vein thrombosis (blood clot in the deep veins) and 1 case of Epstein-Barr virus infection plus atrial flutter (abnormal heartbeat). There were no deaths related to the vaccine or placebo.