Janssen COVID-19 Vaccine: Package Insert and Label Information (Page 3 of 5)

6.2 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, Lymphadenopathy, Immune thrombocytopenia.

Cardiac disorders: Myocarditis, Pericarditis.

Ear and labyrinth disorders: Tinnitus.

Gastrointestinal disorders: Diarrhea, Vomiting.

Immune System Disorders: Allergic reactions, including anaphylaxis.

Nervous System Disorders: Guillain-Barré syndrome, Syncope, Paresthesia, Hypoesthesia.

Vascular Disorders: Capillary leak syndrome, Thrombosis with thrombocytopenia, Venous thromboembolism (with or without thrombocytopenia).

8 REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS

See Overall Safety Summary (Section 6) for additional information.

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):

• Vaccine administration errors whether or not associated with an adverse event,
• Serious adverse events* (irrespective of attribution to vaccination),
• Cases of Multisystem Inflammatory Syndrome (MIS) in adults,
• Cases of COVID-19 that result in hospitalization or death.

* Serious Adverse Events are defined as:

• Death;
• A life-threatening adverse event;
• Inpatient hospitalization or prolongation of existing hospitalization;
• A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
• A congenital anomaly/birth defect;
• An important medical event that based on appropriate medical judgement may jeopardize the individual and may require medical or surgical intervention to prevent one of the outcomes listed above.

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:

• Complete and submit the report online: https://vaers.hhs.gov/reportevent.html, or
• If you are unable to submit this form electronically, you may fax it to VAERS at 1-877-721-0366. If you need additional help submitting a report you may call the VAERS toll-free information line at 1-800-822-7967 or send an email to info@vaers.org.

IMPORTANT: When reporting adverse events or vaccine administration errors to VAERS, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:

• Patient demographics, (e.g., patient name, date of birth),
• Pertinent medical history,
• Pertinent details regarding admission and course of illness,
• Concomitant medications,
• Timing of adverse event(s) in relationship to administration of Janssen COVID-19 vaccine,
• Pertinent laboratory and virology information,
• Outcome of the event and any additional follow-up information if it is available at the time of the VAERS report. Subsequent reporting of follow-up information should be completed if additional details become available.

The following steps are highlighted to provide the necessary information for safety tracking:

1. In Box 17, provide information on Janssen COVID-19 Vaccine and any other vaccines administered on the same day; and in Box 22, provide information on any other vaccines received within one month prior.
2. In Box 18, description of the event:
   1. Write “Janssen COVID-19 Vaccine EUA” as the first line.
   2. Provide a detailed report of vaccine administration error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved vaccine. Please see information to include listed above.
3. Contact information:
   1. In Box 13, provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
   2. In Box 14, provide the name and contact information of the best doctor/healthcare professional to contact about the adverse event.
   3. In Box 15, provide the address of the facility where vaccine was given (NOT the healthcare provider’s office address).

Other Reporting Instructions

Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above.

To the extent feasible, report adverse events to Janssen Biotech, Inc. using the contact information below or by providing a copy of the VAERS form to Janssen Biotech, Inc:

e-mail	Fax number	Telephone numbers
JNJvaccineAE@its.jnj.com	215-293-9955	US Toll Free: 1-800-565-4008 US Toll: (908) 455-9922

10 DRUG INTERACTIONS

There are no data to assess the concomitant administration of the Janssen COVID-19 Vaccine with other vaccines.

11 USE IN SPECIFIC POPULATIONS

11.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Janssen COVID-19 Vaccine during pregnancy. Women who are vaccinated with Janssen COVID-19 Vaccine during pregnancy are encouraged to enroll in the registry by visiting https://c-viper.pregistry.com.

Risk Summary

All Pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Available data on Janssen COVID-19 Vaccine administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

In a reproductive developmental toxicity study female rabbits were administered 1 mL of the Janssen COVID-19 Vaccine (a single human dose is 0.5 mL) by intramuscular injection 7 days prior to mating and on Gestation Days 6 and 20 (i.e., one vaccination during early and late gestation, respectively). No vaccine related adverse effects on female fertility, embryo-fetal or postnatal development up to Postnatal Day 28 were observed.

11.2 Lactation

Risk Summary

Data are not available to assess the effects of Janssen COVID-19 Vaccine on the breastfed infant or on milk production/excretion.

11.3 Pediatric Use

Emergency Use Authorization of the Janssen COVID-19 Vaccine does not include use in individuals younger than 18 years of age.

11.4 Geriatric Use

Clinical studies of Janssen COVID-19 Vaccine included individuals 65 years of age and older and their data contributes to the overall assessment of safety and efficacy [see Overall Safety Summary (6.1) and Clinical Trial Results and Supporting Data for EUA (18)]. Of the 21,895 individuals who received a single-dose of the Janssen COVID-19 Vaccine in COV3001, 19.5% (n=4,259) were 65 years of age and older and 3.7% (n=809) were 75 years of age and older. No overall differences in safety or efficacy were observed between individuals 65 years of age and older and younger individuals.

13 DESCRIPTION

The Janssen COVID-19 Vaccine is a colorless to slightly yellow, clear to very opalescent sterile suspension for intramuscular injection. It contains no visible particulates. The vaccine consists of a replication-incompetent recombinant adenovirus type 26 (Ad26) vector expressing the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike (S) protein in a stabilized conformation.

The Ad26 vector expressing the SARS-CoV-2 S protein is grown in PER.C6 TetR cells, in media containing amino acids and no animal-derived proteins. After propagation, the vaccine is processed through several purification steps, formulated with inactive ingredients and filled into vials.

Each 0.5 mL dose of Janssen COVID-19 Vaccine is formulated to contain 5×10¹⁰ virus particles (VP) and the following inactive ingredients: citric acid monohydrate (0.14 mg), trisodium citrate dihydrate (2.02 mg), ethanol (2.04 mg), 2-hydroxypropyl-β-cyclodextrin (HBCD) (25.50 mg), polysorbate-80 (0.16 mg), sodium chloride (2.19 mg). Each dose may also contain residual amounts of host cell proteins (≤0.15 mcg) and/or host cell DNA (≤3 ng).

Janssen COVID-19 Vaccine does not contain a preservative.

The vial stoppers are not made with natural rubber latex.

14 CLINICAL PHARMACOLOGY

14.1 Mechanism of Action

The Janssen COVID-19 Vaccine is composed of a recombinant, replication-incompetent human adenovirus type 26 vector that, after entering human cells, expresses the SARS-CoV-2 spike (S) antigen without virus propagation. An immune response elicited to the S antigen protects against COVID-19.

18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA

18.1 Efficacy of Primary Vaccination

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 (see Table 9).

Table 9: Summary of Demographics and Baseline Characteristics — Primary Efficacy Analysis Population

	Janssen COVID-19 Vaccine(N=19,630)n (%)	Placebo(N=19,691)n (%)
* 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.
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)

Efficacy Against COVID-19

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.

• 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 any two of the following new or worsening signs or symptoms: fever (≥38.0°C or ≥100.4°F), 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.
• 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, or 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 intensive care unit (ICU), death.

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

Primary analysis

The median length of follow up for efficacy for individuals in the study was 8 weeks post-vaccination. Vaccine Efficacy (VE) 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 (see Table 10).

Table 10: 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

Subgroup	Janssen COVID-19 VaccineN=19,630		PlaceboN=19,691		% Vaccine Efficacy(95% CI)
	COVID-19 Cases(n)	Person-Years	COVID-19 Cases(n)	Person-Years
* Co-primary endpoint. † The adjusted CI implements type I error control for multiple testing and is presented upon meeting the prespecified testing conditions.
14 days post-vaccination
All subjects *	116	3116.6	348	3096.1	66.9(59.0; 73.4)
18 to 59 years of age	95	2106.8	260	2095.0	63.7(53.9; 71.6)
60 years and older	21	1009.8	88	1001.2	76.3(61.6; 86.0)
28 days post-vaccination
All subjects *	66	3102.0	193	3070.7	66.1(55.0; 74.8)†
18 to 59 years of age	52	2097.6	152	2077.0	66.1(53.3; 75.8)
60 years and older	14	1004.4	41	993.6	66.2(36.7; 83.0)

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 (see Table 11).

Table 11: 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

Subgroup	Janssen COVID-19 VaccineN=19,630		PlaceboN=19,691		% Vaccine Efficacy(95% CI)
	COVID-19 Cases(n)	Person-Years	COVID-19 Cases(n)	Person-Years
* The adjusted CI implements type I error control for multiple testing and is presented upon meeting the prespecified testing conditions.
14 days post-vaccination
Severe/critical					76.7
	14	3125.1	60	3122.0	(54.6; 89.1)*
28 days post-vaccination
Severe/critical					85.4
	5	3106.2	34	3082.6	(54.2; 96.9)*

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 (as of January 22, 2021), 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.

Janssen COVID-19 Vaccine 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 (see Table 12). For the subgroup analyses, all COVID-19 cases accrued up to the primary efficacy analysis data cut-off 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%.

Table 12: Summary of Vaccine Efficacy against Moderate to Severe/Critical and Severe/Critical COVID-19 for Countries With >100 Reported Moderate to Severe/Critical Cases

	Onset	Severity
		Moderate to Severe/CriticalPoint estimate (95% CI)	Severe/CriticalPoint estimate (95% CI)
US	at least 14 days after vaccination	74.4% (65.0; 81.6)	78.0% (33.1; 94.6)
	at least 28 days after vaccination	72.0% (58.2;81.7)	85.9% (-9.4; 99.7)
Brazil	at least 14 days after vaccination	66.2% (51.0; 77.1)	81.9% (17.0; 98.1)
	at least 28 days after vaccination	68.1% (48.8; 80.7)	87.6% (7.8; 99.7)
South Africa	at least 14 days after vaccination	52.0% (30.3; 67.4)	73.1% (40.0; 89.4)
	at least 28 days after vaccination	64.0% (41.2; 78.7)	81.7% (46.2; 95.4)

Strain sequencing was conducted on available samples with sufficient viral load from centrally confirmed COVID-19 cases (one 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 B1.1.7 or P.1 lineages were not found in any of the sequenced samples.