Clinical Data for Johnson & Johnson's Janssen COVID-19 Vaccine
The Janssen COVID-19 Vaccine has not been approved or licensed by the U.S. Food and Drug Administration (FDA), but has been authorized by FDA through an Emergency Use Authorization (EUA) for active immunization to prevent Coronavirus Disease 2019 (COVID-19) in individuals 18 years of age and older for whom other FDA-authorized or approved COVID-19 vaccines are not accessible or clinically appropriate, and in individuals 18 years of age and older who elect to receive the Janssen COVID-19 Vaccine because they would otherwise not receive a COVID-19 vaccine. The emergency use of this product is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of the medical product under Section 564(b)(1) of the FD&C Act, unless the declaration is terminated or authorization revoked sooner.
A primary analysis (cut-off date January 22, 2021) of a multicenter, randomized, double-blind, placebo-controlled phase 3 study (Study 1) was conducted in the United States, South Africa, Brazil, Chile, Argentina, Colombia, Peru, and Mexico to assess the efficacy, safety, and immunogenicity of a single-dose of the Janssen COVID-19 Vaccine for the prevention of COVID-19 in adults aged 18 years and older. Randomization was stratified by age (18-59 years, 60 years and older) and presence or absence of comorbidities associated with an increased risk of progression to severe COVID-19. The study allowed for the inclusion of individuals with stable pre-existing medical conditions, defined as disease not requiring significant change in therapy during the 3 months preceding vaccination, as well as individuals with stable human immunodeficiency virus (HIV) infection.
A total of 44,325 individuals were randomized equally to receive Janssen COVID-19 Vaccine or saline placebo. Individuals are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19.
The primary efficacy analysis population of 39,321 individuals (19,630 in the Janssen COVID-19 Vaccine group and 19,691 in the placebo group) included 38,059 SARS-CoV-2 seronegative individuals at baseline and 1,262 individuals with an unknown serostatus. Demographic and baseline characteristics were similar among individuals who received the Janssen COVID-19 Vaccine and those who received placebo.
In Study 1, up to a cut-off date of January 22, 2021, 54.6% of individuals had follow-up duration of 8 weeks. The median follow-up duration for all individuals was 58 days. SAEs, excluding those related to confirmed COVID-19, were reported by 0.4% (n=83) of individuals who received the Janssen COVID-19 Vaccine (N=21,895) and 0.4% (n=96) of individuals who received placebo (N=21,888).
Additional adverse events of interest, including but not limited to allergic, neurologic, inflammatory, vascular, and autoimmune disorders, were analyzed among all adverse events collected through protocol-specified safety monitoring procedures as well as unsolicited reporting.
Urticaria (all non-serious) was reported in 5 vaccinated individuals and 1 individual who received placebo in the 7 days following vaccination. In addition, an SAE of hypersensitivity, not classified as anaphylaxis, was reported in 1 vaccinated individual with urticaria beginning 2 days following vaccination and angioedema of the lips with no respiratory distress beginning 4 days following vaccination. The event was likely related to the vaccine.
An SAE of severe pain in the injected arm, not responsive to analgesics, with immediate onset at time of vaccination, and that was ongoing 74 days following vaccination was reported in an individual who received the Janssen COVID-19 Vaccine. An SAE of severe generalized weakness, fever, and headache, with onset on the day following vaccination and resolution three days following vaccination was reported in an individual who received the Janssen COVID-19 Vaccine. Both SAEs are likely related to the vaccine.
Numerical imbalances, with more events in vaccine than placebo recipients, were observed for the following serious and other adverse events of interest in individuals receiving the vaccine or placebo, respectively:
- Thromboembolic events:
- Deep vein thrombosis: 6 events (2 serious; 5 within 28 days of vaccination) vs 2 events (1 serious; 2 within 28 days of vaccination)
- Pulmonary embolism: 4 events (3 serious; 2 within 28 days of vaccination) vs 1 event (serious and within 28 days of vaccination)
- Transverse sinus thrombosis with thrombocytopenia: 1 event (serious, with onset of symptoms 8 days post-vaccination) vs 0
- Seizures: 4 events (1 serious; 4 within 28 days of vaccination) vs 1 event (0 serious and 0 within 28 days following vaccination)
- Tinnitus: 6 events (0 serious; 6 within 28 days of vaccination, including 3 within 2 days of vaccination) vs 0
For these events, a causal relationship with the Janssen COVID-19 vaccine could not be determined based on Study 1. The assessment of causality was confounded by the presence of underlying medical conditions that may have predisposed individuals to these events. However, post-authorization experience supports a causal relationship with Janssen COVID-19 Vaccine for the event of transverse sinus thrombosis with thrombocytopenia.
There were no additional notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and cardiovascular events) that would suggest a causal relationship to the Janssen COVID-19 Vaccine.
Overall, in 5 clinical studies conducted in Belgium, Brazil, Colombia, France, Germany, Japan, Netherlands, Philippines, South Africa, Spain, United Kingdom, and the United States, approximately 9,000 participants have received 2 doses of the Janssen COVID‑19 Vaccine, administered at least 2 months apart and approximately 2,700 participants had at least 2 months of safety follow-up after the booster dose.
A randomized, double-blind, placebo-controlled phase 2 study, COV2001 (NCT04535453) (Study 2), evaluated the frequency and severity of local and systemic adverse reactions within 7 days of administration of a booster dose of the Janssen COVID-19 Vaccine administered approximately 2 months after the primary vaccination in healthy adults 18 through 55 years of age and adults 65 years and older in good or stable health. A total of 141 individuals received at least 1 dose of the vaccine and 137 received both the primary vaccination and the booster dose at an interval of 2 months. The median age of individuals was 48 years, and 48 individuals (34%) were 65 years of age and older. Data on solicited adverse reactions after the primary vaccination and after a booster dose are shown in the tables below.
In Study 2, individuals 18 through 55 years of age and 65 years and older received a booster dose of the Janssen COVID-19 Vaccine approximately 2 months after the primary vaccination. Immunogenicity was assessed by measuring neutralizing antibodies to SARS-CoV-2 Victoria/1/2020 strain using a qualified wild-type virus neutralization assay (wtVNA). Immunogenicity data are available from 39 individuals, of whom 15 were 65 years of age and older. Based on a limited number of individuals from this study, a similar fold-rise in neutralizing antibody titers from pre-booster to 14 and 28 days post-booster was observed between individuals 18 through 55 years of age and individuals 65 years of age and older.
For additional information regarding immunogenicity of a booster dose following primary vaccination with another authorized or approved COVID-19 vaccine please see sections 6.1 and 18.3 of our Fact Sheet.