Clinical Data for the 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. 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.
An ongoing, multicenter, randomized, double-blind, placebo-controlled phase 3 study (COV3001) (NCT04505722) is being 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 the 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.
In study COV3001, 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 COV3001. The assessment of causality was confounded by the presence of underlying medical conditions that may have predisposed individuals to these events. However, taking into consideration post authorization experience, a causal relationship with the Janssen COVID-19 Vaccine is plausible for 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.
COVID-19=coronavirus disease 2019; EUA=Emergency Use Authorization; FAS=full analysis set; FD&C Act=Federal Food, Drug, and Cosmetic Act; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2; vp=virus particles.
Some individuals could be classified in more than one category.
Including 175 individuals in the United States, which represents 1% of the population recruited in the United States.
Number of individuals who have 1 or more comorbidities at baseline that increase the risk of progression to severe/critical COVID-19: Obesity defined as BMI ≥30 kg/m2 (27.5%), hypertension (10.3%), type 2 diabetes (7.2%), stable/well-controlled HIV infection (2.5%), serious heart conditions (2.4%), asthma (1.3%), and in ≤1% of individuals: cancer, cerebrovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, cystic fibrosis, immunocompromised state (weakened immune system) from blood or organ transplant, liver disease, neurologic conditions, pulmonary fibrosis, sickle cell disease, thalassemia, and type 1 diabetes, regardless of age.
Grade 3 injection site pain: Defined as incapacitating symptoms; inability to do work, school, or usual activities; use of narcotic pain reliever.
Grade 3 injection site swelling and erythema: Defined as >100 mm.
Grade 3 headache: Defined as incapacitating symptoms; requires bed rest and/or results in loss of work, school, or cancellation of social activities; use of narcotic pain reliever.
Grade 3 fatigue, myalgia, nausea: Defined as incapacitating symptoms; requires bed rest and/or results in loss of work, school, or cancellation of social activities; use of narcotic pain reliever.
Fever of any grade: Defined as body temperature ≥100.4°F/38°C. Grade 3 fever: Defined as 102.1°F to 104°F (39°C to 40°C).
The adjusted CI implements type I error control for multiple testing and is presented upon meeting the prespecified testing conditions.