This page summarizes findings from the Phase 3 study, ENSEMBLE, testing the efficacy and safety of the Janssen (Johnson & Johnson) COVID-19 vaccine, Ad26.COV2.S (also known as JNJ-78436735). This is a non-replicating viral vector vaccine. Over 40,000 people (age 18 years and older) participated in the study. Half of them received a single dose of the Ad26.COV2.S vaccine, while the other half received a placebo vaccine. A brief summary of the design of this study can be found in Table 1 on this website. More detailed information about the design of the study can be found on ClinicalTrials.Gov and the full protocol for the study can be found here.
Most of the data summarized on this page are from analyses Janssen and the US Food and Drug Administration (FDA) conducted in February 2021. The primary efficacy analyses were limited to data collected before January 22, 2021. A total of 39,321 study participants who had no evidence of a previous SARS-CoV-2 infection were included in the primary analyses examining vaccine efficacy. As of January 22, 2021, these participants had been followed an average of 2 months following vaccination. The safety analyses included an additional 4,462 people who had evidence of a previous SARS-CoV-2 infection, bringing the total number of people included in the safety analyses up to 43,783. The study is continuing and the findings may change somewhat as more data are collected. At the bottom of this page, we provide links to more detailed information reporting study findings prepared by Janssen, the FDA, and the Centers for Disease Control and Prevention (CDC).
The table below show characteristics of study participants. These characteristics did not differ between people who received the Ad26.COV2.S vaccine and those who received the placebo vaccine.
|Participant Characteristic (N=43,783)||# (%)|
|Black or African American||8,515 (19.4%)|
|American Indian or Alaska Native||4,143 (9.5%)|
|Other or Unknown||2,980 (6.8%)|
|United States||19,302 (44.1%)|
|Latin America||17,905 (40.9%)|
|South Africa||6,576 (15.0%)|
|Had at least one chronic health problem at start of study||17,858 (40.8%)|
The figure below shows when the cases of COVID-19 occurred in the groups that received the placebo vaccine (brown line) and the Ad26.COV2.S vaccine (blue line). This figure is from the Briefing Document prepared by the FDA for the advisory committee meeting on February 26, 2021. The figure suggests that the Ad26.COV2.S vaccine starts to provide protection around 2 to 3 weeks following administration and continues to provide protection for at least 2 to 3 months. As participants in the study are followed longer, this type of figure will give us an idea of the extent to which vaccine efficacy may decrease over time. (You can click on the figure to enlarge it.)
To assess vaccine safety, a subset of 6,376 participants completed an electronic diary each day for seven days after receiving either the placebo or Ad26.COV2.S vaccine. The diary included a list of possible vaccine side effects. Participants were asked to check any side effects they were having that day and to provide information about the severity of the side effect. The list included both local (e.g., pain at the injection site) and systemic side effects (e.g., fever). Information reported in these diaries is presented in the figures below.
Local Side Effects: Any Severity
The figure below shows the percentage of participants who had local side effects of any severity. On average, these side effects started within two days of the the injection and lasted 2 to 3 days. Participants age 60 and older were somewhat less likely to report local side effects than younger participants.
Local Side Effects: Severe
A side effect was considered severe if it prevented a participant from performing his/her usual daily activities (including social activities) or required medical care. A total of 29 people experienced at least one severe local side effect; 23 (0.7%) people who received the Ad26.COV2.S vaccine and 6 (0.2%) people who received the placebo vaccine. None of the study participants had a local side effect that caused them to visit the emergency room or required hospitalization.
Systemic Side Effects: Any Severity
The figure below shows the percentage of participants who had systemic side effects of any severity. Most of these side effects started within two days of the the injection and lasted 1 to 2 days. All of the systemic side effects were reported less often by participants age 60 and older than younger participants.
Systemic Side Effects: Severe
As described above, a side effect was considered severe if it prevented a participant from performing his/her usual daily activities (including social activities) or required medical care. A total of 82 people experienced at least one severe systemic side effect; 61 (1.8%) people who received the Ad26.COV2.S vaccine and 21 (0.6%) people who received the placebo vaccine. None of the study participants had a systemic side effect that caused them to visit the emergency room or required hospitalization.
Other Potential Side Effects
All 43,783 study participants are being followed for two years to determine if they experience any serious adverse events following vaccination. The safety findings summarized below are based on data collected before January 22, 2021. At that time, participants had been followed for an average of 2 months following vaccination.
- 153 participants (91 in the Ad26.COV2.S group and 62 in the placebo group) reported joint pain following vaccination. The FDA concluded that these events were probably caused by vaccine reactogencity (the immune response the vaccine is designed to stimulate).
- 50 participants (31 in the Ad26.COV2.S group and 18 in the placebo group) reported muscle weakness following vaccination. The FDA concluded that these events were probably caused by vaccine reactogencity (the immune response the vaccine is designed to stimulate).
- 24 participants (14 in the Ad26.COV2.S group and 10 in the placebo group) experienced a thromboembolic event; most involved either a deep vein thrombosis or pulmonary embolism. Many of these participants had health conditions that increased their risk of having a thromboembolic event, making if difficult to determine any role the vaccine may have played. After reviewing all of the individual cases, the FDA concluded that they could not rule out the possibility that the Ad26.COV2.S vaccine may have been a contributing factor. They recommended continued surveillance of thromboembolic events as the vaccine is used in more people.
- 6 participants (all in the Ad26.COV2.S group) developed tinnitis (ringing in the ears) after receiving the vaccine. All of these participants had health conditions that increased their risk of tinnitis. After reviewing all of the individual cases, the FDA concluded that they could not determine whether the vaccine had been a contributing factor.
- 6 participants (5 in the Ad26.COV2.S group and 1 in the placebo group) experienced urticaria (a rash with intense itching) within 7 days following vaccination. All 6 cases were considered non-serious. However, one person in the Ad26.COV2.S group also reported a hypersensitivity reaction that was rated as serious. This participant experienced lip swelling that began four days after vaccination. The FDA concluded that the Ad26.COV2.S vaccine likely caused these adverse events.
- 5 participants (4 in the AD26.COV2.S group and 1 in the placebo group) experienced a seizure following vaccination. After reviewing all of the individual cases, the FDA concluded that they could not determine whether the vaccine had been a contributing factor.
- 1 person experienced severe pain in the arm where the Ad26.COV2.S vaccine was administered. The pain began at the time of vaccination, was ongoing 10 weeks following vaccination, and did not respond to pain medication. The FDA considered this a serious adverse event likely related to the vaccine.
Questions That Remain
Unknown Benefits/Data Gaps
- Duration of protection. Currently, only about 1,000 study participants have been followed more than 90 days after receiving the Ad26.COV2.S vaccine. Therefore, at this point in time, it is not possible to determine how long protection from COVID-19 is likely to last.
- Vaccine effectiveness against asymptomatic infection and transmission. More data are needed to determine if the Ad26.COV2.S vaccine helps prevent asymptomatic COVID-19 and virus shedding and transmission, particularly among people with asymptomatic infections.
- Vaccine effectiveness against mortality and long-term health effects of COVID-19. It is reasonable to expect that the Ad26.COV2.S vaccine will reduce the risk of dying from COVID-19 or experiencing long-term health problems (e.g., organ damage) as a result of the disease. However, more data are needed to confirm these potential benefits. It is likely that answers to these questions will come from observational studies involving millions of people. People in observational studies are not randomized to receive a particular type of treatment. Therefore, no one would be required to get the Ad26.COV2.S vaccine and no one would be denied the vaccine. Nonetheless, researchers can use data from observational studies to see if there are differences in health outcomes (e.g., death, hospitalization) between people who received a certain type of treatment (for example, the Ad26.COV2.S vaccine) and those who did not.
- Effectiveness in specific population subgroups: Currently, not enough data are available to assess vaccine efficacy in certain population subgroups such as people who are immunocompromised, including those with HIV/AIDS.
- Effectiveness of the vaccine going forward: As the SARS-CoV-2 virus continues to evolve, it is not clear that the vaccine will retain a high level of efficacy against emerging variants. Janssen plans to conduct large observational studies using health insurance claims and electronic health records to estimate vaccine effectiveness as it is made available to millions of people in the general public over the coming months.
Unknown Risks/Data Gaps
- Pregnancy and Lactation: The Phase 3 trial excluded women who were pregnant or breastfeeding at the start of the trial and female participants of child-bearing potential agreed to practice adequate conception for 3 months following vaccination. Most clinical trials of investigational drugs do not include pregnant women, so this is not unusual. If you would like more information about the inclusion of pregnant women in clinical trials, see this FDA Guidance document.
In spite of the exclusion of pregnant women from the Phase 3 trial, 8 study participants (4 in the Ad26.COV2.S group and 4 in the placebo group) have reporting pregnancies since receiving the vaccine/placebo. As of January 22, 2021, one woman in the Ad26.COV2.S group reported a miscarriage and another reported an ectopic pregnancy. In the placebo group, one woman reported a miscarriage and two women reported elective abortions. The FDA concluded that not enough data were available to make conclusions about the safety of the vaccine in pregnant and lactating women and their babies. However, they noted that a study conducted in animals found no evidence of harmful effects on reproduction, fetal development, or development after birth.
The FDA advises women who are pregnant or breastfeeding to discuss their options for vaccination with their healthcare provider.
Why might a woman who is pregnant consider getting the Ad26.COV2.S vaccine? First, among women with COVID-19, research suggests that pregnancy may increase the risk of severe disease. (See these two reports from CDC for more information 1, 2.) Second, among pregnant women, getting COVID-19 may increase the risk of preterm birth. Being vaccinated against COVID-19 may lower these risks. Finally, certain medical conditions increase the risk of developing severe COVID-19. Therefore, it is especially important for women with any of these conditions to discuss their options for vaccination with their healthcare provider.
The information in the box below is taken directly from the FDA-approved Fact Sheet for Healthcare Providers (pages 15-16) dated 2/27/2021
Pregnancy Exposure Registry
In a reproductive developmental toxicity study female rabbits were administered 1 mL of the
- Adverse reactions that are very uncommon or that require longer follow-up to detect. In the Phase 3 trial, about 20,000 people received the Ad26.COV2.S vaccine. This may not be enough to discover uncommon (and potentially serious) side effects. In addition, when the FDA issued the emergency use authorization (EUA) for the Ad26.COV2.S vaccine in February 2021, study participants had only been followed for an average of 8 weeks. The FDA considered this an adequate length of follow-up for the purpose of issuing the EUA because historical data indicate that most adverse events from vaccines occur within 6 weeks following vaccination. Nonetheless, surveillance systems (including, the Vaccine Adverse Event Reporting System, VAERS, and v-safe) are in place to detect uncommon or delayed adverse events as soon as possible under the EUA.
- Vaccine-enhanced disease. Data from the Phase 3 trial suggest that the Ad26.COV2.S vaccine helps protect against severe COVID-19. However, it is still unknown if the risk of more severe disease following vaccination may increase over time, especially if immunity decreases over time. Study participants continue to be followed to assess this potential risk.
- Individuals who are immunocompromised. The FDA concluded that there is not enough information to draw conclusions about the safety and efficacy of the Ad26.COV2.S vaccine in individuals who are immunocompromised. Individuals who are immunocompromised or on a medication that affects the immune system are advised to talk to their health care provider. More information about vaccination decisions for people with underlying medical conditions is available from the CDC.
- 119-page report and an 8-page addendum to the report prepared by Janssen (Johnson & Johnson) when requesting an emergency use authorization for the Ad26.COV2.S vaccine
- 62-page briefing document prepared by the FDA after reviewing the materials submitted by Janssen
- Fact Sheets for (1) Healthcare Providers Administering Vaccine and (2) Recipients and Caregivers can be downloaded in multiple languages from the Janssen website