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Clinical Trial Data for the Janssen COVID-19 Vaccine

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.

Phase 3 Clinical Trial

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.

The primary analysis of this study has been published in the New England Journal of Medicine. For up-to-date information about study COV3001, please visit ClinicalTrials.gov/ct2/show/NCT04505722

Summary of Demographics and Baseline Characteristics – Primary Efficacy Analysis Population

Janssen COVID-19 Vaccine
(N=19,630)
n (%)
Placebo
(N=19,691)
n (%)
Sex
Male 10,924 (55.6) 10,910 (55.4)
Female 8,702 (44.3) 8,777 (44.6)
Age (years)
Mean (SD) 51.1 (15.0) 51.2 (15.0)
Median 52.0 53.0
Min, max (18; 100) (18; 94)
Age group
≥18 to 59 years of age 12,830 (65.4) 12,881 (65.4)
≥60 years of age 6,800 (34.6) 6,810 (34.6)
≥65 years of age 3,984 (20.3) 4,018 (20.4)
≥75 years of age 755 (3.8) 693 (3.5)
Race*
White 12,200 (62.1) 12,216 (62.0)
Black or African American 3,374 (17.2) 3,390 (17.2)
Asian 720 (3.7) 663 (3.4)
American Indian/Alaska Native 1,643 (8.4) 1,628 (8.3)
Native Hawaiian or other Pacific Islander 54 (0.3) 45 (0.2)
Multiple 1,036 (5.3) 1,087 (5.5)
Unknown 262 (1.3) 272 (1.4)
Not reported 341 (1.7) 390 (2.0)
Ethnicity
Hispanic or Latino 8,793 (44.8) 8,936 (45.4)
Not Hispanic or Latino 10,344 (52.7) 10,259 (52.1)
Unknown 173 (0.9) 162 (0.8)
Not reported 319 (1.6) 333 (1.7)
Region
Northern America (United States) 9,185 (46.8) 9,171 (46.6)
Latin America 7,967 (40.6) 8,014 (40.7)
Southern Africa (South Africa) 2,478 (12.6) 2,506 (12.7)
Comorbidities
Yes 7,830 (39.9) 7,867 (40.0)
No 11,800 (60.1) 11,824 (60.0)

Adverse Reactions

The safety subset of the ongoing phase 3 study (COV3001) includes 6,736 individuals (3,356 from the Janssen COVID-19 Vaccine group, 3,380 from the placebo group). The demographic profile in the safety subset was similar in terms of age and gender compared to the FAS. A larger percentage of individuals in the safety subset were White (83.4%) compared to the FAS (58.7%). Geographically, the safety subset was limited to individuals from the United States (51.4%), Brazil (38.5%), and South Africa (10.2%). Fewer individuals in the safety subset compared to the FAS were SARS-CoV-2 seropositive at baseline, 4.5% vs 9.6%, and had at least 1 comorbidity 34.1% vs 40.8%.

In study COV3001, the most common local solicited adverse reaction (≥10%) reported was injection site pain (48.6%). The most common systemic adverse reactions (≥10%) were headache (38.9%), fatigue (38.2%), myalgia (33.2%), and nausea (14.2%).

Severe allergic reactions, including anaphylaxis, have been reported following administration of the Janssen COVID-19 Vaccine. Severe allergic reactions (including anaphylaxis), thrombosis with thrombocytopenia, Guillain-Barré syndrome, and capillary leak syndrome have been reported following administration of the Janssen COVID-19 Vaccine during mass vaccination outside of clinical trials.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Solicited Local Adverse Reactions Reported in the 7 Days Following Vaccination – Individuals 18 to 59 Years of Age

Adverse Reactions Janssen COVID-19 Vaccine
N=2,036
n (%)
Placebo
N=2,049
n (%)
Injection Site Pain
Any 1,193 (58.6) 357 (17.4)
Grade 3§ 8 (0.4) 0
Injection Site Erythema
Any (≥25 mm) 184 (9.0) 89 (4.3)
Grade 3|| 6 (0.3) 2 (0.1)
Injection Site Swelling
Any (≥25 mm) 142 (7.0) 32 (1.6)
Grade 3|| 5 (0.2) 2 (0.1)

Solicited Local Adverse Reactions Reported in the 7 Days Following Vaccination – Individuals 60 Years of Age and Older

Adverse Reactions Janssen COVID-19 Vaccine
N=1,320
n (%)
Placebo
N=1,331
n (%)
Injection Site Pain
Any 439 (33.3) 207 (15.6)
Grade 3§ 3 (0.2) 2 (0.2)
Injection Site Erythema
Any (≥25 mm) 61 (4.6) 42 (3.2)
Grade 3|| 1 (0.1) 0
Injection Site Swelling
Any (≥25 mm) 36 (2.7) 21 (1.6)
Grade 3|| 2 (0.2) 0

Solicited Systemic Adverse Reactions Reported in the 7 Days Following Vaccination – Individuals 18 to 59 Years of Age

Adverse Reactions Janssen COVID-19 Vaccine
N=2,036
n (%)
Placebo
N=2,049
n (%)
Headache
Any 905 (44.4) 508 (24.8)
Grade 3 18 (0.9) 5 (0.2)
Fatigue
Any 891 (43.8) 451 (22.0)
Grade 3# 25 (1.2) 4 (0.2)
Myalgia
Any 796 (39.1) 248 (12.1)
Grade 3# 29 (1.4) 1 (<0.1)
Nausea
Any 315 (15.5) 183 (8.9)
Grade 3# 3 (0.1) 3 (0.1)
Fever**
Any 261 (12.8) 14 (0.7)
Grade 3 7 (0.3) 0
Use of antipyretic or pain medication 538 (26.4) 123 (6.0)

Solicited Systemic Adverse Reactions Reported in the 7 Days Following Vaccination – Individuals 60 Years of Age and Older

Adverse Reactions Janssen COVID-19 Vaccine
N=1,320
n (%)
Placebo
N=1,331
n (%)
Headache
Any 401 (30.4) 294 (22.1)
Grade 3 5 (0.4) 4 (0.3)
Fatigue
Any 392 (29.7) 277 (20.8)
Grade 3# 10 (0.8) 5 (0.4)
Myalgia
Any 317 (24.0) 182 (13.7)
Grade 3# 3 (0.2) 5 (0.4)
Nausea
Any 162 (12.3) 144 (10.8)
Grade 3# 3 (0.2) 3 (0.2)
Fever**
Any 41 (3.1) 6 (0.5)
Grade 3 1 (0.1) 0
Use of antipyretic or pain medication 130 (9.8) 68 (5.1)

Serious Adverse Events (SAEs) and Other Events of Interest Observed During Clinical Trials

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.

Post Authorization Experience

The following adverse reactions have been identified during post-authorization use of the Janssen COVID-19 Vaccine. Because these reactions are reported voluntarily, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure:


  • Blood and Lymphatic System Disorders: Thrombosis with thrombocytopenia
  • Immune System Disorders: Allergic reactions, including anaphylaxis
  • Nervous System Disorders: Guillain-Barré syndrome
  • Vascular Disorders: Capillary leak syndrome, Thrombosis with thrombocytopenia

Thrombosis with Thrombocytopenia


Reports of adverse events following use of the Janssen COVID-19 Vaccine under Emergency Use Authorization suggest an increased risk of thrombosis involving the cerebral venous sinuses and other sites (including but not limited to the large blood vessels of the abdomen and the veins of the lower extremities) combined with thrombocytopenia and with onset of symptoms approximately 1 to 2 weeks after vaccination. The reporting rate of thrombosis with thrombocytopenia following administration of the Janssen COVID-19 Vaccine has been highest in females ages 18 through 49 years; some cases have been fatal. The clinical course of these events shares features with autoimmune heparin-induced thrombocytopenia. Specific risk factors for thrombosis with thrombocytopenia following administration of the Janssen COVID-19 Vaccine and the level of potential excess risk due to vaccination are under investigation. Based on currently available evidence, a causal relationship between thrombosis with thrombocytopenia and the Janssen COVID-19 Vaccine is plausible.

Healthcare professionals should be alert to the signs and symptoms of thrombosis with thrombocytopenia in individuals who receive the Janssen COVID-19 Vaccine. In individuals with suspected thrombosis with thrombocytopenia following administration of the Janssen COVID-19 Vaccine, the use of heparin may be harmful and alternative treatments may be needed. Consultation with hematology specialists is strongly recommended. The American Society of Hematology has published considerations relevant to the diagnosis and treatment of thrombosis with thrombocytopenia following administration of the Janssen COVID-19 Vaccine (https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia).

Recipients of the Janssen COVID-19 Vaccine should be instructed to seek immediate medical attention if they develop shortness of breath, chest pain, leg swelling, persistent abdominal pain, neurological symptoms (including severe or persistent headaches or blurred vision), or petechiae beyond the site of vaccination.

Guillain-Barré Syndrome


Reports of adverse events following use of the Janssen COVID-19 Vaccine under Emergency Use Authorization suggest an increased risk of Guillain-Barré syndrome during the 42 days following vaccination.

Primary Endpoint

The co-primary endpoints evaluated the first occurrence of moderate to severe/critical COVID-19 with onset of symptoms at least 14 days and at least 28 days after vaccination. Moderate to severe/critical COVID-19 was molecularly confirmed by a central laboratory based on a positive SARS-CoV-2 viral RNA result using a polymerase chain reaction (PCR)-based test.

Definition of Moderate COVID‑19

Moderate COVID-19 was defined based on the following criteria: the individual must have experienced any one of the following new or worsening signs or symptoms:

  • Respiratory rate ≥20 breaths/minute
  • Abnormal saturation of oxygen (SpO2) but still >93% on room air at sea level
  • Clinical or radiologic evidence of pneumonia
  • Radiologic evidence of deep vein thrombosis (DVT)
  • Shortness of breath or difficulty breathing OR or any 2 of the following new or worsening signs or symptoms:
    • Fever (≥100.4°F or ≥38°C)
    • Heart rate ≥90 beats/minute
    • Shaking chills or rigors
    • Sore throat
    • Cough
    • Malaise
    • Headache
    • Muscle pain (myalgia)
    • Gastrointestinal symptoms
    • New or changing olfactory or taste disorders
    • Red or bruised-appearing feet or toes

Definition of Severe/Critical COVID‑19

Severe/critical COVID-19 was defined based on the following criteria: the individual must have experienced any one of the following at any time during the course of observation:

  • Clinical signs at rest indicative of severe systemic illness
    • Respiratory rate ≥30 breaths/minute
    • Heart rate ≥125 beats/minute
    • Oxygen saturation (SpO2) ≤93% on room air at sea level
    • Partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <300 mmHg
  • Respiratory failure (defined as needing high-flow oxygen, non-invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation [ECMO])
  • Evidence of shock (defined as systolic blood pressure <90 mmHg, diastolic blood pressure <60 mmHg, or requiring vasopressors)
  • Significant acute renal, hepatic, or neurologic dysfunction
  • Admission to ICU
  • Death

Final determination of severe/critical COVID-19 cases were made by an independent adjudication committee.


Efficacy in Adults 18 Years of Age and Older

Vaccine efficacy for the co-primary endpoints against moderate to severe/critical COVID-19 in individuals who were seronegative or who had an unknown serostatus at baseline was 66.9% (95% CI: 59.0; 73.4) at least 14 days after vaccination and 66.1% (95% CI: 55.0; 74.8) at least 28 days after vaccination.

Analyses of Vaccine Efficacy Against Centrally Confirmed Moderate to Severe/Critical COVID-19 – With Onset at Least 14 Days and at Least 28 Days Post-Vaccination – Primary Efficacy Analysis Population

Solicited Systemic Adverse Reactions Reported in the 7 Days Following Vaccination – Individuals 60 Years of Age and Older

Secondary Endpoints

Vaccine efficacy against severe/critical COVID-19 at least 14 days after vaccination was 76.7% (95% CI: 54.6; 89.1) and 85.4% (95% CI: 54.2; 96.9) at least 28 days after vaccination.

Among all COVID-19 cases with onset at least 14 days post vaccination, including cases diagnosed by a positive PCR from a local laboratory and still awaiting confirmation at the central laboratory, there were 2 COVID-19–related hospitalizations in the vaccine group (with none after 28 days) and 29 in the placebo group (with 16 after 28 days).

As of the primary analysis cut-off date of January 22, 2021, there were no COVID-19–related deaths reported in Janssen COVID-19 Vaccine recipients compared to 5 COVID-19–related deaths reported in placebo recipients, who were SARS-CoV-2 PCR negative at baseline.

No overall differences in safety or efficacy were observed between individuals 65 years of age and older and younger individuals.

Analyses of Vaccine Efficacy: Secondary Endpoints of Centrally Confirmed Severe/Critical COVID-19 – in Adults 18 Years of Age and Older With Onset at Least 14 Days and at Least 28 Days Post-Vaccination – Primary Efficacy Analysis Population

Solicited Systemic Adverse Reactions Reported in the 7 Days Following Vaccination – Individuals 60 Years of Age and Older

Efficacy in Countries With Different Circulating SARS-CoV-2 Variants

Exploratory subgroup analyses of vaccine efficacy against moderate to severe/critical COVID-19 and severe/critical COVID-19 for Brazil, South Africa, and the United States were conducted. For the subgroup analyses, all COVID-19 cases accrued up to the primary efficacy analysis data cutoff date, including cases confirmed by the central laboratory and cases with documented positive SARS-CoV-2 PCR from a local laboratory which are still awaiting confirmation by the central laboratory, were included. The concordance rate observed up to the data cut-off date between the PCR results from the local laboratory and the central laboratory was 90.3%.

Summary of Vaccine Efficacy Against Moderate to Severe/Critical and Severe/Critical COVID-19 for Countries With >100 Reported Moderate to Severe/Critical Cases

Solicited Systemic Adverse Reactions Reported in the 7 Days Following Vaccination – Individuals 60 Years of Age and Older

Strain sequencing was conducted on available samples with sufficient viral load from centrally confirmed COVID-19 cases (1 sequence per case). As of February 12, 2021, samples from 71.7% of central laboratory confirmed primary analysis cases had been sequenced [United States (73.5%), South Africa (66.9%), and Brazil (69.3%)]. In the United States, 96.4% of strains were identified as the Wuhan-H1 variant D614G; in South Africa, 94.5% of strains were identified as the 20H/501Y.V2 variant (B.1.351 lineage); in Brazil, 69.4% of strains were identified to be a variant of the P.2 lineage and 30.6% of strains were identified as the Wuhan-H1 variant D614G. As of February 12, 2021, SARS-CoV-2 variants from the B.1.1.7 or P.1 lineages were not found in any of the sequenced samples.

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).

Co-primary endpoint.

The adjusted CI implements type I error control for multiple testing and is presented upon meeting the prespecified testing conditions.

Important safety information

CONTRAINDICATIONS

Do not administer the Janssen COVID-19 Vaccine to individuals with a known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Janssen COVID-19 Vaccine.

WARNINGS AND PRECAUTIONS

Monitor Janssen COVID-19 Vaccine recipients for the occurrence of immediate adverse reactions according to the Centers for Disease Control and Prevention guidelines (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html).

ADVERSE REACTIONS

Adverse reactions reported in a clinical trial following administration of the Janssen COVID-19 Vaccine include injection site pain, headache, fatigue, myalgia, nausea, fever, injection site erythema and injection site swelling. In clinical studies, severe allergic reactions, including anaphylaxis, have been reported following the administration of the Janssen COVID-19 Vaccine.

Additional adverse reactions, some of which may be serious, may become apparent with more widespread use of the Janssen COVID-19 Vaccine.

Reporting Adverse Events and Vaccine Administration Error

The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for mandatory reporting of the listed events following Janssen COVID-19 Vaccine administration to the Vaccine Adverse Event Reporting System (VAERS):

Instructions for Reporting to VAERS

The vaccination provider enrolled in the federal COVID-19 Vaccination Program should complete and submit a VAERS form to FDA using one of the following methods below. Reports should include the words “Janssen COVID-19 Vaccine EUA” in the description section of the report as the first line.

Report adverse events to Janssen Biotech, Inc. by calling 1-800-565-40081-800-565-4008 or provide a copy of the VAERS form by faxing 1-215-293-9955.

PREGNANCY AND LACTATION

DOSING AND SCHEDULE

The Janssen COVID-19 Vaccine is administered intramuscularly as a single dose (0.5 mL).

There are no data available on the use of the Janssen COVID-19 Vaccine to complete a vaccination series initiated with another COVID-19 vaccine.

Please read Emergency Use Authorization (EUA) Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers) including full EUA Prescribing Information available at www.JanssenCOVID19Vaccine.com/EUA-factsheet.

cp-213942v1

Important safety information