Ad26COV2.S Vaccine

Janssen 

ACIP Presentation 

14 April 2021
Agenda

1. Company Statement for thrombosis (particularly CVST) with thrombocytopenia

2. Relevant Janssen clinical and post authorization data

3. Background Epidemiological data

CONFIDENTIAL – FOR INTERNAL USE ONLY 2
Company Statement for thrombosis (particularly CVST) 

with thrombocytopenia

• The safety and well-being of the people who use our products is our 

number one priority. While causality has not been fully established 

between these very rare events and our vaccine, we recognize these 

events could represent an important potential risk with Janssen 

vaccine. We are in the process of updating our CCDS and working 

with Health Authorities to update our labeling appropriately. J&J 

will continue to monitor this potential risk and is committed to efforts 

to ensure vaccinee and HCP awareness of important signs and 

symptoms, as well as appropriate diagnosis and management. 

3
Review of Janssen vaccine data

4
Janssen Phase III Pivotal Trial 

Study 3001 – Venous Thrombosis Events (N=43,783 vaccinated) 

5 Confidential Draft – For Internal Purposes Only. Source: Janssen clinical trial database

TSFAE_VTE_COV3001: Study 3001 AEs

All AEs 

Number of Cases up to 28 Days after 

Vaccination Total Number of Cases 

Ad26.COV2.S Placebo Ad26.COV2.S Placebo 

DVT 4 c 2 11 3 a

PE 2 1 8 4a

CVST 1 b 0 1 1

Venous thrombosis limb 1 0 1 0

embolism venous 0 0 1 0

a One individual in placebo experienced both DVT and PE: This individual had a SARS-CoV-2 PCR (+) nasal swab 4 days after th 

thrombosis

b Only one participant on Ad26 had low platelets (CVST)

c A second individual in Ad26.COV2.S group had multiple SARS-CoV-2 PCR (+) nasal swabs in the 2 weeks preceding the DVT.

[TSFAE_VTE_COV3001.RTF] [VAC31518\Z_ADHOC\DBR_ONESAFETY\RE_ONESAFETY\PDEV\VTE_SUMMARY_OUTPUT.SAS 

08APR2021, 11:1
Janssen Phase III Two-Dose Pivotal Trial

Study 3009 – Venous Thrombosis Events (N=28,277 vaccinated)

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Source: Janssen clinical trial database

TSFAE_VTE_COV3009: Study 3009 AEs (2 Dose Trial): Ongoing Blinded

All AEs 

Number of Cases up to 28 

Days after Vaccination Total Number of Cases 

DVT 0 2

PE 1 4

CVST 0 0

[TSFAE_VTE_COV3009.RTF] 

[VAC31518\Z_ADHOC\DBR_ONESAFETY\RE_ONESAFETY\PDEV\VTE_SUMMARY_OUTPUT.SAS] 08APR2021, 11:10

No CVSTs observed with Janssen adenovirus vaccine program in Ebola and RSV
Sisonke Open Label Study in South African HCPs 

(N=272,438)

As of 09 Apr 2021:

• No CVST cases reported

• One case of PE (no information on platelet or covid status)

• One case of CVA (age: 38 years old, female, 8 days after vaccination) - we are actively 

seeking additional information on this case

• One case of retinal vein thrombosis (age: 68 years old, diabetic, platelet count normal)

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Source: Safety Reporting process - Sisonke Study team

CONFIDENTIAL – FOR INTERNAL USE ONLY
All known cases of CVST and all known cases of thrombosis 

with thrombocytopenia with Janssen COVID vaccine

-

-

summary table on next slide

further individual case details can be found in the appendix section

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208,590 308,181

458,911

638,469

873,726

1,189,207 1,273,958

1,428,465

1,569,675

1,766,131

1,911,052 2,025,349

2,163,681

2,298,614 2,406,337 2,489,153

2,622,182 2,734,367

2,863,246

2,982,453 3,090,712 3,155,418 3,215,657 3,307,113

3,429,880

3,617,377

3,840,647

4,054,089

4,204,015 4,299,901

4,544,552

4,917,225

0

1000000

2000000

3000000

4000000

5000000

6000000

3/5/2021 3/10/2021 3/15/2021 3/20/2021 3/25/2021 3/30/2021 4/4/2021 4/9/2021 4/14/2021

Number of Doses

Date

Janssen Covid-19 Vaccine - Doses Administered in US

As of 14 Apr 2021: Janssen is aware of 6 postauthorization cases of CVST (4 of 6 with low 

platelets, 2 unknown) with 6.8MM individuals 

vaccinated

6,820,188

Vaccinations to date per CDC
As of 14 Apr 2021

As of 12 Apr 2021 10

SOURCE CASE CIOMS # SERIOUS 

ADVERSE EVENT

RISK FACTOR(S) PLATELET COUNT COVID 

STATUS

TTO Treatment Status 

CLINICAL TRIAL CASES

Study 3001 25 YO Male 

on Vaccine

20201017267 CVST with 

hemorrhage

Stenosis of transverse sinus, 

URI suspected

64,000 

(Anti-PF4+)

Negative 8 days Heparin TPA and 

platelets, 

angioplasty and 

thrombectomies

Recovered

Study 3001 24 YO female 

on placebo

20210202793 CVST Newly prescribed OCP Normal

(Anti-PF4-)

Negative >50 

days

N/A Recovered

POST-AUTHORIZATION CASES

VAERS # 

1114806

45 YO female 20210354798 CVST with 

hemorrhage

none “thrombocytopenia” Unknown 11 days Unknown Fatal

VAERS 1133212 38 YO female 20210408478 CVST Unknown Unknown Unknown 10-14 

days

Heparin Not Recovered at 

this time

VAERS 

#1141160-1

59 YO Female 20210407977 Extensive DVTs Coronary artery disease 15,000 Unknown 7 days Vena cava filterIVC, 

thrombectomy

Not Recovered at 

this time

Janssen SAE

Nevada

18 YO female 20210407314 CVST with 

hemorrhage

unknown 16,000 Unknown 14 days Heparin then 

switched to 

“British 

guidelines” and 

thrombectomy

Not Recovered at 

this time

Janssen SAE 

(NEJM -editor 

notification)

Nebraska

48 YO female 20210415297 TTP, splanchnic 

veins thrombosis, 

CVST, then given 

heparin and then 

additional hepatic 

and splanchnic vein 

thrombosis 

Unknown <13,000 (hi d-dimer, AntiPF4+)Negative 14 days Heparin first and 

switched to 

argatroban then 

IVIG 

Not Recovered at 

this time

Janssen SAE

NJ/PA

26 YO female 20210416236 CVST, PE, portal 

vein thrombosis

Obesity 120,000 (hi d-dimer, AntiPF4+)Negative 7 days Heparin and then 

IVIG Discharged from 

hospital 

VAERS 1182133 28 YO female In processing Details pending, FOI 

requested
• 48-year-old woman with unremarkable past medical history to ER after 3 days of malaise and abdominal pain.

• Initial evaluation:

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Mild anemia and severe thrombocytopenia (platelet count 13K) / Smear confirmed marked reduction in platelet count with 

occasional schistocytes.

Hypofibrinogenemia (89 mg/dL); prolonged aPTT (41 sec); markedly elevated D-Dimer.

Extensive splanchnic vein thrombosis on CT

• Transferred to reporting institution, with further evaluation and progression of thrombosis on heparin:

SARS-CoV2 RNA was not detected by RT-PCR

Head CT (for new-onset headaches) showed cerebral venous sinus thrombosis

Thrombosis progressed with hemorrhagic stroke despite treatment with heparin

Repeat CT angiography showed new thrombus involving right hepatic and splenic veins.

Further inquiry revealed patient received the Ad26.COV2.S vaccine 14 days before symptom onset.

• Evidence and management of possible Immune Thrombotic Thrombocytopenia (ITT):

Positive anti-PF4/heparin antibodies by ELISA (3.179 OD) - latex-enhanced immunoassay was negative 

Heparin switched to argatroban

IVIG 1 gm/kg × 2 day

Platelet count increase from 30,000 to 145,000 over 5 days. 

She remains critically ill at last report.

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New England Journal Case (pre-publication of U of Nebraska case) 

Received Thursday 08 Apr 2021
• 26-year-old woman, overweight but active, with no history of clotting disorder and on no medication.

• Initial presentation to ER:

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Severe headache approximately 1 week following vaccination

Discharged home from ER with paracetamol and Benadryl

Headache persisted

• Subsequent hospital admission:

Hospitalized another week later for abdominal pain and rapid heart rate

Covid-19 infection “ruled out” (exact test unknown)

Laboratory evaluation revealed thrombocytopenia (platelet 120K), elevated D-Dimer (level unknow) and normal 

fibrinogen (level unknown)

Diagnostic scan showed CVST, portal vein thrombosis and PE

Initially treated with heparin, switched to IVIG after positive anti-PF4 antibodies result (level 3.0)

Platelet count reportedly started to increase prior to IVIG

• Patient discharged home on oral anticoagulant after 1-1.5 weeks in hospital 12

Direct Report to Janssen, CIOMS # 20210416236

Follow up phone contact with physician Monday, 12 Apr 2021
Clinical Trial (study 3001) Case CIOMS #20201017267

• Healthy 25 year-old male vaccinated on 9/21/2020

• 8 days post-vaccination: feeling progressively unwell, incl. fatigue, faintness, nausea and headache. Took 

NSAIDs

• 11 days post-vaccination: continued fatigue, weakness, nausea; developed abdominal pain and headache; Covid19 swab negative

• Hospitalized 19 days post-vaccination (10/9/2020) after visual disturbance and passing out: 

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Laboratory evaluation: Platelet count was 64K; PT 17.7, INR 1.46; fibrinogen 154, wbc 12.4, hgb 12.7, and hct 36.1

CT/MRI/venogram: CVST and secondary cerebral haemorrhage

Underwent repeated cerebral vascular sinus thrombectomy/venoplasty due to re-occlusion, and noted to have stenosed cerebral sinus.

Also treated with low-molecular weight heparin and IV TPA

• Extensive haematology and infectious disease laboratory evaluation showed inclusive results. Patient discharged 

on treatment with apixaban

• Stored serum tested positive for anti-PF4 antibodies last week

• Recovery after repeat thrombectomy and balloon angioplasty procedures; epiglottitis while in hospital; discharge 

meds include apixiban 13
CVST Background Incidence Rates

• Published Literature from US and EU

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Stam et al. Thrombosis of the Cerebral Veins and Sinuses. N Engl J Med 2005; 352:1791-1798; Janghorbani M et al., 

Cerebral vein and dural sinus thrombosis in adults in Isfahan, Iran: frequency and seasonal variation. Acta Neurol Scand. 

2008 Feb;117(2):117-21. doi: 10.1111/j.1600-0404.2007.00915.x. PMID: 18184347. ; Bousser MG, Ferro JM. Cerebral 

venous thrombosis: an update. Lancet Neurol. 2007 Feb;6(2):162-70. doi: 10.1016/S1474-4422(07)70029-7. PMID: 

17239803.; Coutinho J.M et al, the incidence of cerebral venous thrombosis a cross sectional study, Stroke 

(2012); Devasagayam S et al. Cerebral Venous Sinus Thrombosis Incidence Is Higher Than Previously Thought: A 

Retrospective Population-Based Study. Stroke. 2016 Sep;47(9):2180-2. doi: 10.1161/STROKEAHA.116.013617. Epub 2016 Jul 

19. PMID: 27435401.

• Janssen Analysis of US healthcare claims and EHR databases

meta-analysis across 4 large US healthcare claims and 1 US EHR databases. Persons observed for at least 365 days prior to 1 

January in 2017-2019 were included to generate incidence of the outcome ‘cranial venous sinus thrombosis’.

Methods are similar to those used in the multi-national network cohort study of 15 AESIs shared with FDA and EMA [Xintong

et al., Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across 8 countries: a 

multinational network cohort study. Manuscript under review: 

https://www.medrxiv.org/content/10.1101/2021.03.25.21254315v1]

All specifications and output for this analysis of CVST conducted by JNJ is stored in 

https://epi.jnj.com//atlas/#/iranalysis/548/.

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CVST background incidence rates
• Ongoing review of internal & publicly available data

-Evolving literature on relationship between COVID and 

thrombocytopenic and thrombotic events

- Case reports of association between thromboembolic events 

including CVST with ITP and TTP

- US VAERS data on thrombocytopenic and thrombotic events (and 

other AESIs) for all available vaccines

- European EUDRAVIGILANCE data

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