Sex: F
Vaccine: COVID19
Symptoms: Spinal cord herniation, Vital signs measurement
Clinical narrative: Thoracic cord herniation due to ventral dural defect;   This is a non-Pfizer sponsored interventional study report from License Party for protocol BNT162-21. Other Case identifier(s): US--1646 (UNKNOWN), US-BNTAG-1646.  Sapheus Case No.: Site No.: redacted Country: Patient No.: redacted Initial information received on 30Jun2023: This is a serious case of Cerebral Spinal Fluid Leak (MedDRA PT: Cerebrospinal fluid leakage) from clinical trial BNT162-21. A 48-year-old female patient was diagnosed with Cerebral spinal fluid leak on 10May2023. The patient was treated with BNT162-21 blinded IMP on 05Jan2023. 125 days after start of treatment the patient developed Cerebral Spinal Fluid Leak (MedDRA PT: Cerebrospinal fluid leakage) on 10May2023. Last BNT162-21 blinded IMP administration before start of the event and seriousness was on 05Jan2023. This case is serious due to hospitalization. Relevant medical history was not reported. Relevant concomitant medication was not reported. On 10May2023 the patient experienced Cerebral Spinal Fluid Leak (MedDRA PT: Cerebrospinal fluid leakage) of severe intensity. The patient was hospitalized from 10May2023 until 12May2023. At the time of reporting, the main event has recovered without sequelae. No further information is available at this time. Additional information has been requested and medical records are pending.   BioNTech comments: Initial Medical Assessment 30Jun2023: The reporting investigator considers the event to be serious due to hospitalization. The sponsor agrees to the investigator's assessment. The reporting investigator assessed the event as not related to the treatment with BNT162-21 blinded IMP. The sponsor agrees to the investigator's assessment. In accordance with the sponsor's SOPs, only SARs will be assessed for expectedness. Hence, expectedness for this event is not applicable. The benefit-risk profile of BNT162-21 blinded IMP is not affected by this event and no change in the reference safety information is required at this time.   The investigator and company (BioNTech SE) considered there was not a reasonable possibility that the event "cerebral spinal fluid leak" was related to blinded therapy (BNT162b4, BNT162b5, BNT162b5 omi ba.4-5...).   Follow-up (19Jul2023): This is a non-Pfizer sponsored interventional study follow-up report from License Party (BioNTech SE) for protocol BNT162-21. Other Case identifier(s): US-BNTAG-1646.  Follow-up information received on 19Jul2023 (FU1): The event term was updated to Cerebral spinal fluid leak due to thoracic ventral dural defect (MedDRA PT: Cerebrospinal fluid leakage). The subject was noted to have a history of traumatic brain injury in 2017. In 2022, the subject presented to the primary care physician with acute headaches, dizziness, tinnitus, balance issues, and neck aches. A consulation with an ENT specialist was done in Nov2022. An MRI was performed which revealed bilateral subdural hematomas with concern for CSF hypotension. In Mar2023, computer tomographic angiography and digital subtraction angiography were performed to search for potential vascular lesions, which revealed a ventral spinal fluid leak at the T4-5 level with an associated spinal cord herniation. An attempt was made to repair the herniation with fibrin glue, but this was aborted. The subject was admitted to the hospital on 10May2023 due to persistent intracranial hypotension with debilitating headaches to be treated with a Laminectomy (T4, T5) with a dural sling to address the thoracic cord herniation and repair the ventral dural defect. After the procedure, the subject presented a stable neurological exam and vital signs and was discharged with normal functional and mental status on 12May2023. A diet was prescribed beginning on 10May2023. Wound care instructions were also given including washing, pat drying, and leaving the wound in open air with no lotions, creams, or ointments. Discharge medications include Tylenol (875mg TID), Gabapentin (300mg TID), Lidoderm 5% (1 patch QD), Methocarbamol (500mg TID), Zofran (4mg PRN), and Oxycodone (5mg, 1-2 tablets every 6 hours PRN). Upon discharge, the subject returned home with assistance and a follow-up appointment was planned for 23May2023. There is no further information available at this time. Additional information has been requested.   BioNTech SE Comments: Medical Re-Assessment after follow-up information received on 19Jul2023 (FU1): With the follow-up information received on 19Jul2023, the previous medical assessment provided on 30Jun2023 has not changed. The information in this single case does not change the benefit-risk profile of BNT162-21 blinded IMP or warrant any changes to the conduct of this trial.  The investigator considered there was not a reasonable possibility that the event "cerebral spinal fluid leak due to thoracic ventral dural defect" was related to blinded therapy (BNT162b4, BNT162b5, BNT162b5 omi ba.4-5...).  Follow-up (28Jul2023): This is a non-Pfizer sponsored interventional study follow-up report from License Party(BioNTech SE) for protocol BNT162-21. Other Case identifier(s): US--1646 (UNKNOWN), US-BNTAG-1646.  Follow-up information received on 27Jul2023/28Jul2023 (FU2): The verbatim was updated from Cerebral spinal fluid leak due to thoracic ventral dural defect to CSF leak into Thoracic cord herniation due to ventral dural defect (MedDRA PT: Spinal cord herniation). Per patient report, the subject is improving since the follow-up appointment of 23May2023. Additional information was provided regarding the traumatic brain injury in 2017. The subject fell down the stairs on 23Oct2017 and was treated in the emergency room. Upon diagnosis of traumatic brain injury, subdural hematoma and closed fracture of the occipital bone were noted. No surgical intervention was required at that time. On a follow-up appointment of 07Nov2017, CT scans showed resolution of subdural hematoma and on follow-up with neurology on 20Nov2017, improvement was documented. No further information was provided.  BioNTech SE comments: Initial Medical Assessment 30Jun2023: The reporting investigator considers the event to be serious due to hospitalization. The sponsor agrees to the investigator's assessment. The reporting investigator assessed the event as not related to the treatment with BNT162-21 blinded IMP. The sponsor agrees to the investigator's assessment. In accordance with the sponsor's SOPs, only SARs will be assessed for expectedness. Hence, expectedness for this event is not applicable. The benefit-risk profile of BNT162-21 blinded IMP is not affected by this event and no change in the reference safety information is required at this time. Medical Re-Assessment after follow-up information received on 19Jul2023 (FU1): With the follow-up information received on 19Jul2023, the previous medical assessment provided on 30Jun2023 has not changed. The information in this single case does not change the benefit-risk profile of BNT162-21 blinded IMP or warrant any changes to the conduct of this trial. Medical Re-Assessment after follow-up information received on 27Jul2023/28Jul2023 (FU2): This is a not-related case imported from the former database where expectedness was assessed as not applicable. With the follow-up information received on 27Jul2023 and 28Jul2023, the previous medical assessment provided on 19Jul2023 has not changed. The information in this single case does not change the benefit-risk profile of BNT162-21 blinded IMP or warrant any changes to the conduct of this trial.  The investigator considered there was not a reasonable possibility that the event "csf leak into thoracic cord herniation due to ventral dural defect" was related to blinded therapy (BNT162b4, BNT162b5, BNT162b5 omi ba.4-5...).  Follow-up (22Sep2023): This is a non-Pfizer sponsored interventional study follow-up report from License Party(BioNTech SE) for protocol BNT162-21. Other Case identifier(s): US-BNTAG-1646. Updated information:  Follow-up information received on 22Sep2023 (FU3): Investigator confirmed that the onset date of seriousness 10May2023 and end date of seriousness 12May2023 are correct and the CRF was updated. The event term was updated from CSF leak into Thoracic cord herniation due to ventral dural defect (MedDRA PT: Spinal cord herniation) to Thoracic cord herniation due to ventral dural defect (MedDRA PT: Spinal cord herniation). No further information is available at this time.  BioNTech Sender's comments: Medical Re-Assessment after follow-up information received on 22Sep2023 (FU3): With the follow-up information received on 22Sep2023, the previous medical assessment provided on 19Jul2023 has not changed. The information in this single case does not change the benefit-risk profile of BNT162-21 blinded IMP or warrant any changes to the conduct of this trial.  Follow-up (14Jun2024): This is a non-Pfizer sponsored interventional study follow-up report from License Party (BioNTech SE) for protocol BNT162-21. Other Case identifier(s): US-BNTAG-1646.  Follow-up information received on 14Jun2024 (FU4): The blind has been broken for Protocol BNT162-21 due to the completion of the blinded phase of the study. The participant was randomized to COHORT 1 Expansion and received BNT162b2 bivalent (30 ug) as dose 1. Correction: Cohort was corrected from "Cohort 1 - Sentinel" to "Cohort 1 Expansion".  BioNTech SE comments: Medical re-assessment on 14Jun2024 (FU4): With the study unblinding on 14Jun2024, the previous medical assessment provided on 22Sep2023 has not changed. The information in this single case does not change the benefit-risk profile of BNT162-21 IMP or warrant any changes to the conduct of this trial.  The investigator considered there was not a reasonable possibility that the event "thoracic cord herniation due to ventral dural defect" was related to BNT162b2, BNT162b2 omi ba.4-5, solution for injection. The blind was broken at the end of the study. The patient was found to be treated with BNT162b2, BNT162b2 omi ba.4-5, solution for injection.  BNT162b2 bivalent is under agreement with BioNTech SE.; Sender's Comments: BioNTech comments: Initial Medical Assessment 30Jun2023: The reporting investigator considers the event to be serious due to hospitalization. The sponsor agrees to the investigator's assessment. The reporting investigator assessed the event as not related to the treatment with BNT162-21 blinded IMP. The sponsor agrees to the investigator's assessment. In accordance with the sponsor's SOPs, only SARs will be assessed for expectedness. Hence, expectedness for this event is not applicable. The benefit-risk profile of BNT162-21 blinded IMP is not affected by this event and no change in the reference safety information is required at this time.  The investigator and company (BioNTech SE) considered there was not a reasonable possibility that the event "cerebral spinal fluid leak" was related to blinded therapy (BNT162b4, BNT162b5, BNT162b5 omi ba.4-5...). Medical re-assessment on 14Jun2024 (FU4): With the study unblinding on 14Jun2024, the previous medical assessment provided on 22Sep2023 has not changed. The information in this single case does not change the benefit-risk profile of BNT162-21 IMP or warrant any changes to the conduct of this trial.