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20-MAR-2019 08:45:01 PM
Case Number: 2017USSYNT0010001
Initial Receipt Date: 08-AUG-2017
Initial Case User: *Kelly McIntosh
Initial Case Site: Cincinnati
General Information
Report Type Country Initial Receipt Date Aware Date: Medically Confirm Case Status
Sponsored Trial UNITED STATES 08-AUG-2017 12-JUL-2018 Closed
Reporter Type
Physician
Report Sent to Regulatory Authority by Reporter? Primary Reporter
Yes No Unk Protect Confidentiality
Reporter Notes
Patient Information
Pat. ID Title Initials
205-001
County
Email Address
Ongoing:
Age:
Units:
Family History
Notes:
Relevant Tests
Substance Information
Substance Name Substance Term ID Version Strength Unit
SYNT001
Product Name Parts Information
Name Part Type Name Part
Dosage Regimens
1 Start Date/Time Stop Date/Time Ongoing
01-AUG-2017 00:00
Duration of Regimen Dose Units 0 0 Frequency
10.00 mg/kg Q Week
Patient Route of Administration Parent Route of Administration Daily Dosage Units Dose Description
Intravenous 10 mg/kg, Q Week
Batch / Lot # Expiration Date Regimen Units
Dosage
Product Details
First Dose Last Dose Duration of Administration Total Dosage Units
01-AUG-2017 00:00
Time Between First Dose/Primary Event Time between Last Dose/Primary Event Total Dose to Gestation Period at Unit
Primary Event Exposure
2 days
Action Taken Taken Previously / Tolerated Dechallenge Results
Dose not changed Unknown / N/A Pos Neg N/A Unk
Rechallenge Results Specialized Product Category
Pos Neg N/A Unk
Batch and lot tested and found within specifications Batch and lot tested and found not within specifications Counterfeit
Drug taken by the father Drug taken beyond expiry date Medication error Misuse
Product Notes
Formulation
Drug Not Administered
Indications
Reported Indication Coded Indication
pemphigus Pemphigus
Preliminary Comments
Malfunction Information
# Reported Malfunction Determined Malfunction Listedness Reportable
Email Address
Product Notes
Formulation
Drug Not Administered
Indications
Reported Indication Coded Indication
premedication Premedication
Preliminary Comments
Malfunction Information
# Reported Malfunction Determined Malfunction Listedness Reportable
Email Address
Product Details
First Dose Last Dose Duration of Administration Total Dosage Units
01-AUG-2017 00:00
Time Between First Dose/Primary Event Time between Last Dose/Primary Event Total Dose to Gestation Period at Unit
Primary Event Exposure
5 days
Action Taken Taken Previously / Tolerated Dechallenge Results
Unknown / N/A Pos Neg N/A Unk
Rechallenge Results Specialized Product Category
Pos Neg N/A Unk
Batch and lot tested and found within specifications Batch and lot tested and found not within specifications Counterfeit
Drug taken by the father Drug taken beyond expiry date Medication error Misuse
Occupational exposure Off label use Overdose
Vaccine History No information present
Quality Control
Product Notes
Formulation
Drug Not Administered
Indications
Reported Indication Coded Indication
premedication Premedication
Preliminary Comments
Malfunction Information
# Reported Malfunction Determined Malfunction Listedness Reportable
Email Address
Product Notes
Description to be Coded
Disease progression
System Organ Class (SOC) General disorders and administration site conditions (10018065)
High Level Group Term General system disorders NEC (10018073)
High Level Term General signs and symptoms NEC (10018072)
Preferred Term Disease progression (10061818)
Details
Action Taken Study Drug
Dose not changed
Hospitalization Details
Hospital Name City State
Hospitalization Prolonged
2 Description as Reported
Acute Kidney Injury (Secondary to Vancomycin and Zosyn)
Original Language
Description to be Coded
Acute Kidney Injury (Secondary to Vancomycin and Zosyn)
System Organ Class (SOC) Renal and urinary disorders (10038359)
High Level Group Term Renal disorders (excl nephropathies) (10038430)
High Level Term Renal failure and impairment (10038443)
Preferred Term Acute kidney injury (10069339)
Lower Level Term Acute kidney injury (10069339)
Synonym
Onset Date/Time Onset From Last Dose Stop Date/Time Duration Onset Latency
09-AUG-2017 00:00 12-AUG-2017 00:00 4 days 9 days
Intensity Medical Confirmation by HCP
Details
Action Taken Study Drug
Dose Not Changed
Hospitalization Details
Hospital Name City State
Hospitalization Prolonged
Event Relationships No information present
Event Assessment
Event (Description as Reported) / NOT USED / License Causality as Reported Causality as Determined Other Causality Source / As Determined Listedness
Source / Method / Result Source / Method / Result Method / Result
Disease progression
(Disease exacerbation (pemphigus vulgaris))
Seriousness: H DIS
Intensity: Grade 3
Duration: 11 days
SYNT001, Infusion - / US (Inv: 132727) / / Not Related (No) / / Not Related (No) Unlisted
SYNT001, Infusion - / US (Inv: 128152) / / Not Related (No) / / Not Related (No) Unlisted
Acute kidney injury
(Acute Kidney Injury (Secondary to Vancomycin
and Zosyn))
Seriousness: H
Intensity: Grade 2
Duration: 4 days
SYNT001, Infusion - / US (Inv: 132727) / / Not Related (No) / / Not Related (No) Unlisted
SYNT001, Infusion - / US (Inv: 128152) / / Not Related (No) / / Not Related (No) Unlisted
Case Analysis
Narrative
Protocol SYNT001-103: A Phase 1b, Multicenter, Open-Label, Safety, Tolerability, and Activity Study of SYNT001 in Subjects with Chronic Pemphigus (Vulgaris or Foliaceus)
Subject 205-001, a 19 year-old African-American male with pemphigus vulgaris (onset date 28-Dec-2016) experienced the serious adverse events of disease exacerbation (pemphigus vulgaris) and acute kidney injury
(secondary to vancomycin and Zosyn). The subject signed informed consent on 18-Jul-2017. The subject began treatment with dose level 1, SYNT001 10 mg/kg/dose on 01-Aug-2017. The subject was in the
treatment phase at the time of the event. Doses were administered weekly for a total of five doses.
The subject's last infusion prior to the onset of event was administered on 01-Aug-2017 (also the first dose). The dose administered was 730 mg intravenous (IV).
On Study Day 01 (02-Aug-2017), the subject was started on Percocet (acetaminophen-oxycodone) for pain in the pemphigus vulgaris lesions. On Study Day 04 (05-Aug-2017), the subject noted that his pemphigus
vulgaris began to worsen with new ocular involvement, drainage from the eyelids bilaterally, and other new lesions on hands, arms, and legs, bilaterally. The patient returned for his infusion on Study Day 07 (08-
Aug-2017) and reported the worsening of lesions. He received the study drug, dose #2 on Study Day 07 per protocol. On Study Day 07 (08-Aug-2017), the subject was admitted to the emergency department after the
infusion, where the subject rated his pain between eight and ten consistently, even following administration of meperidine. Laboratory testing revealed a creatinine result of 0.6-0.7 mg/dL (Normal Range [NR] 0.7 mg/
dL - 1.3 mg/dL). The subject was subsequently admitted to the hospital for further evaluation and treatment. It was determined during hospital admission that the subject failed to notify his physician that he failed to
continue his prescribed prednisone and acyclovir and did not request a refill at his last visit on 01-Aug-2017, which was the likely cause of disease flare. He had previously been prescribed prednisone for his
pemphigus vulgaris, with various dosing regimens and tapers starting December of 2016. Consistent dosing of prednisone was started on 26-May-2017 and the subject had interrupted dosing approximately 31-
Jul-2017. Cultures from the blood were obtained and were negative. Skin cultures returned positive for Methicillin resistant Staphylococcus aureus (MRSA) and Herpes simplex virus (HSV) Type 1 (reported as non-
serious adverse events). The subject was restarted on prednisone and skin lesions showed improvement. Additional treatment included vancomycin, Zosyn, acyclovir, hydromorphone, meperidine, doxycycline,
bacitracin, and oxycodone. On Study Day 08 (09-Aug-2017), laboratory testing revealed a creatinine result of 1.52 mg/dL, and a glomerular filtration rate (GFR) in the normal range (NR >60 mL/min/1.72 m2,
calculation: 175 x [SCr, mg/dL]-1.154 x [Age]-0.203 x [1.210 if African-American]). On Study Day 09 (10-Aug-2017), laboratory testing revealed a creatinine result of 3.23 mg/dL, and a decreased GFR of 30 mL/
min/1.73 m2. That same date, a renal ultrasound showed no evidence of obstruction. The subject was diagnosed with acute kidney injury (AKI). The treating physician considered the vancomycin and Zosyn as the
likely cause of the AKI. Both medications were discontinued, and it was decided to monitor laboratory results for signs of improvement before discharging the subject from the hospital. Treatment for the acute kidney
injury included intravenous sodium chloride. On Study Day 10 (11-Aug-2017), laboratory testing revealed a creatinine of 3.42 mg/dL, and a GFR of 28 mL/min/1.73 m2. On Study Day 11 (12-Aug-2017), laboratory
testing revealed a creatinine of 3.38 mg/dL and GFR of 29 mL/min/1.73 m2. It was reported that the subject had significantly diuresed with no electrolyte imbalances and excellent oral fluid intake, and that kidney
function appeared to be improving. That same day, the events of disease exacerbation (pemphigus vulgaris) and acute kidney injury (secondary to vancomycin and Zosyn) were considered resolved, and the subject
was discharged from the hospital with oral doxycycline, prednisone, acyclovir; artificial tears, ophthalmic bacitracin, and plans to have serum creatinine re-checked at his follow-up appointment to ensure continued
improvement. It was the opinion of the investigator that the AKI had extended the patient's hospitalization. No action was taken with the study drug due to these events. The subject was continued in the study.
Concomitant medications (taken at the time of the event) included prednisone, acetaminophen, and diphenhydramine.
The investigator considered the event of disease exacerbation (pemphigus vulgaris) as Grade 3 intensity and unrelated to SYNT001. The investigator also reported the event of disease exacerbation (pemphigus
Case Comment
MedWatch Info
B. Adverse event or product problem C. Suspect medication(s)
1. Adverse Event and / or Product Problem 9. NDC # :
F. For use by user facility/importer-devices
1. Check one User Facility Importer Suppress Block F Printing
G. All manufacturers
3. Report Source (check all that apply)
Foreign Literature Health Professional Company Representative Study Consumer
User Facility Distributor Other:
5. STN # Pre-1938 OTC product
Contact Log
# Date Due Code / Description Group / User Date Sent
1 25-SEP-2017 Followup02 --Any-- 25-SEP-2017
Follow-up 02 --Any--
2 26-OCT-2017 Followup03 --Any-- 24-OCT-2017
Follow-up 03 --Any--
3 26-JUL-2018 Followup04 --Any-- 26-JUL-2018
Follow-up 04 --Any--
52 17-JUL-2018 15:43 Case routed from Case Repository-Not Expedited by Katie Ahern to Case Processing, (Any)
Katie Ahern
51 17-JUL-2018 15:36 Case Reopened. additional information received
Katie Ahern
50 09-MAR-2018 12:21 Case Closed. re-closed after updates per sponsor request
Katie Ahern
49 09-MAR-2018 12:20 Case routed from Distribution to Sponsor by Katie Ahern to Case Repository-Not Expedited, Any
Katie Ahern
48 09-MAR-2018 11:03 Case Locked. final
Katie Ahern
47 01-MAR-2018 11:06 Case routed from Distribution to Sponsor by Katie Ahern to Distribution to Sponsor, (Any)
Katie Ahern