Hepatocellular Carcinoma Study Comparing Vaccinia Virus B... | NCT02562755

NCT02562755

Status Module

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pexa-Vec followed by Sorafenib	Experimental	Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 1e9 pfu at day 1 and weeks 2 and 4, followed by sorafenib at Week 6.	Biological: Pexastimogene Devacirepvec (Pexa Vec) Drug: Sorafenib
Sorafenib	Active Comparator	Sorafenib (400 mg twice daily) begins on Day 1.	Drug: Sorafenib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pexastimogene Devacirepvec (Pexa Vec)	Biological	Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR)	Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), >=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR.	From date of randomization to the date of first documented radiographic tumor progression up to 53 months

Eligibility Module

Name	Affiliation	Role
SillaJen Medical	SillaJen, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama		Birmingham	Alabama	35294	United States
Mayo Clinic Arizona

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pexa-Vec Followed by Sorafenib	Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 1e9 pfu at day 1 and weeks 2 and 4, followed by sorafenib at Week 6. Pexastimogene Devacirepvec (Pexa Vec): Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells. Sorafenib: Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 26, 2019	Sep 22, 2020

Arm/Group Information

ID	Title	Description
BG000	Pexa-Vec Followed by Sorafenib	Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 1e9 pfu at day 1 and weeks 2 and 4, followed by sorafenib at Week 6. Pexastimogene Devacirepvec (Pexa Vec): Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells. Sorafenib: Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.
BG001	Sorafenib	Sorafenib (400 mg twice daily) begins on Day 1. Sorafenib: Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00061.3± 10.05 BG00160.5± 11.06 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00030 BG00143 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0005 BG0016 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Singapore

Title	Measurements
	BG0008 BG0013 BG002

ECOG performance status

The ECOG Performance Status describes a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.): Grade 0, Fully active, able to carry on all pre-disease performance without restriction; Grade 1, Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
0	BG000146 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response Rate (ORR)

Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), >=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR.

Posted

Number

percentage of participants

From date of randomization to the date of first documented radiographic tumor progression up to 53 months

ID	Title	Description
OG000	Pexa-Vec Followed by Sorafenib	Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 1e9 pfu at day 1 and weeks 2 and 4, followed by sorafenib at Week 6. Pexastimogene Devacirepvec (Pexa Vec): Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells. Sorafenib: Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.
OG001	Sorafenib	Sorafenib (400 mg twice daily) begins on Day 1. Sorafenib: Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.

Units	Counts
Participants	OG000234 OG001225

Title

Denominators

Categories

Title	Measurements
	OG00019.2 OG00120.9

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pexa-Vec Followed by Sorafenib	Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 1e9 pfu at day 1 and weeks 2 and 4, followed by sorafenib at Week 6. Pexastimogene Devacirepvec (Pexa Vec): Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells. Sorafenib: Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.	33	218	117	218	218	218
EG001	Sorafenib	Sorafenib (400 mg twice daily) begins on Day 1. Sorafenib: Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.	25	217	77	217	214	217

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hypotension	Vascular disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Shock haemorrhagic	Vascular disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Hypertension	Vascular disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Orthostatic hypotension	Vascular disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0004 affected218 at risk EG0014 affected217 at risk
Liver carcinoma ruptured	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0003 affected218 at risk EG0012 affected217 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0011 affected217 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Tumour rupture	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Metastases to spine	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Cholangiocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Anaphylactic Reaction	Immune system disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Pyrexia	General disorders	MedDRA Version 22.0	Systematic Assessment		EG0008 affected218 at risk EG0011 affected217 at risk
Asthenia	General disorders	MedDRA Version 22.0	Systematic Assessment		EG0003 affected218 at risk EG0015 affected217 at risk
General physical health deterioration	General disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0011 affected217 at risk
Fatigue	General disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Malaise	General disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Pain	General disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Chills	General disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0011 affected217 at risk
Non-cardiac chest pain	General disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Death NOS	General disorders	MedDRA Version 22.0	Systematic Assessment	Death Not Otherwise Specified	EG0001 affected218 at risk EG0010 affected217 at risk
Confusional state	Psychiatric disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Hepatic rupture	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0003 affected218 at risk EG0010 affected217 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Blood bilirubin increased	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0014 affected217 at risk
Aspartate aminotransferase increased	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Blood creatinine increased	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Angina pectoris	Cardiac disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Myocardial infarction	Cardiac disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Aortic valve disease	Cardiac disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Atrial flutter	Cardiac disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Cardiac arrest	Cardiac disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Atrial thrombosis	Cardiac disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA Version 22.0	Systematic Assessment		EG0004 affected218 at risk EG0011 affected217 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0003 affected218 at risk EG0010 affected217 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0011 affected217 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0011 affected217 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0005 affected218 at risk EG0014 affected217 at risk
Ischaemic stroke	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0012 affected217 at risk
Headache	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Paraesthesia	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Seizure	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Alcoholic seizure	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Presyncope	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Syncope	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Spinal cord compression	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Facial paralysis	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Vertigo	Ear and labyrinth disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0007 affected218 at risk EG0013 affected217 at risk
Ascites	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0008 affected218 at risk EG0014 affected217 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0004 affected218 at risk EG0015 affected217 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0003 affected218 at risk EG0013 affected217 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0004 affected218 at risk EG0011 affected217 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0004 affected218 at risk EG0011 affected217 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0012 affected217 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0011 affected217 at risk
Haematemesis	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Gastric varices haemorrhage	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Colitis	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Diverticular perforation	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Gastritis erosive	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Gastric antral vascular ectasia	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Dieulafoy's vascular malformation	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Proctalgia	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Peritoneal haemorrhage	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0004 affected218 at risk EG0013 affected217 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Dental caries	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Faecaloma	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Melaena	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Renal failure	Renal and urinary disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG00011 affected218 at risk EG0018 affected217 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0003 affected218 at risk EG0010 affected217 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0003 affected218 at risk EG0010 affected217 at risk
Bile duct stenosis	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Cholangitis	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Cholangitis acute	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Biliary dilatation	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Hepatorenal syndrome	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Cholestasis	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Hepatic haemorrhage	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Acute hepatic failure	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Hepatic pain	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Hepatocellular injury	Hepatobiliary disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0012 affected217 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Hypersensitivity vasculitis	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Toxic skin eruption	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Dermatitis exfoliative generalised	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0003 affected218 at risk EG0010 affected217 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Arthritis reactive	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Gout	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Pneumonia	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0003 affected218 at risk EG0014 affected217 at risk
Sepsis	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0014 affected217 at risk
Peritonitis bacterial	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0004 affected218 at risk EG0010 affected217 at risk
Liver abscess	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0002 affected218 at risk EG0010 affected217 at risk
Urinary tract infection	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Bacteraemia	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Abdominal abscess	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Pneumonia necrotising	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Mycobacterial infection	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Peritonitis	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Tonsillitis	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Rectal abscess	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Post procedural infection	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0011 affected217 at risk
Gastroenteritis viral	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Rhinitis	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Infection	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk
Influenza	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Escherichia infection	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Device related infection	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Hepatitis viral	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Dengue fever	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Pneumonia bacterial	Infections and infestations	MedDRA Version 22.0	Systematic Assessment		EG0000 affected218 at risk EG0011 affected217 at risk
Paraplegia	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment		EG0001 affected218 at risk EG0010 affected217 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA Version 22.0	Systematic Assessment	EG00044 affected218 at risk EG00139 affected217 at risk
Hypotension	Vascular disorders	MedDRA Version 22.0	Systematic Assessment	EG00035 affected218 at risk EG0012 affected217 at risk
Pyrexia	General disorders	MedDRA Version 22.0	Systematic Assessment	EG000184 affected218 at risk EG00128 affected217 at risk
Fatigue	General disorders	MedDRA Version 22.0	Systematic Assessment	EG00065 affected218 at risk EG00164 affected217 at risk
Chills	General disorders	MedDRA Version 22.0	Systematic Assessment	EG00071 affected218 at risk EG0014 affected217 at risk
Asthenia	General disorders	MedDRA Version 22.0	Systematic Assessment	EG00022 affected218 at risk EG00121 affected217 at risk
Influenza like illness	General disorders	MedDRA Version 22.0	Systematic Assessment	EG00037 affected218 at risk EG0015 affected217 at risk
Injection site pain	General disorders	MedDRA Version 22.0	Systematic Assessment	EG00027 affected218 at risk EG0010 affected217 at risk
Insomnia	Psychiatric disorders	MedDRA Version 22.0	Systematic Assessment	EG00016 affected218 at risk EG00120 affected217 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA Version 22.0	Systematic Assessment	EG00012 affected218 at risk EG0012 affected217 at risk
Weight decreased	Investigations	MedDRA Version 22.0	Systematic Assessment	EG00058 affected218 at risk EG00149 affected217 at risk
Aspartate aminotransferase increased	Investigations	MedDRA Version 22.0	Systematic Assessment	EG00030 affected218 at risk EG00139 affected217 at risk
Blood bilirubin increased	Investigations	MedDRA Version 22.0	Systematic Assessment	EG00022 affected218 at risk EG00133 affected217 at risk
Alanine aminotransferase increased	Investigations	MedDRA Version 22.0	Systematic Assessment	EG00017 affected218 at risk EG00129 affected217 at risk
Platelet count decreased	Investigations	MedDRA Version 22.0	Systematic Assessment	EG00015 affected218 at risk EG00115 affected217 at risk
Sinus tachycardia	Cardiac disorders	MedDRA Version 22.0	Systematic Assessment	EG00013 affected218 at risk EG0013 affected217 at risk
Tachycardia	Cardiac disorders	MedDRA Version 22.0	Systematic Assessment	EG00016 affected218 at risk EG0010 affected217 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00031 affected218 at risk EG00125 affected217 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00018 affected218 at risk EG00111 affected217 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00016 affected218 at risk EG00110 affected217 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00010 affected218 at risk EG00112 affected217 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00013 affected218 at risk EG0019 affected217 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA Version 22.0	Systematic Assessment	EG00033 affected218 at risk EG00123 affected217 at risk
Headache	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment	EG00033 affected218 at risk EG00123 affected217 at risk
Dizziness	Nervous system disorders	MedDRA Version 22.0	Systematic Assessment	EG00020 affected218 at risk EG00113 affected217 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG000107 affected218 at risk EG001116 affected217 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00074 affected218 at risk EG00163 affected217 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00062 affected218 at risk EG00160 affected217 at risk
Constipation	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00052 affected218 at risk EG00151 affected217 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00056 affected218 at risk EG00127 affected217 at risk
Ascites	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00046 affected218 at risk EG00136 affected217 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00043 affected218 at risk EG00130 affected217 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00026 affected218 at risk EG00126 affected217 at risk
Stomatitis	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00017 affected218 at risk EG00124 affected217 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 22.0	Systematic Assessment	EG00015 affected218 at risk EG00113 affected217 at risk
Palmar plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00073 affected218 at risk EG00199 affected217 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00032 affected218 at risk EG00146 affected217 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00023 affected218 at risk EG00128 affected217 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00016 affected218 at risk EG00117 affected217 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00029 affected218 at risk EG00117 affected217 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00020 affected218 at risk EG00115 affected217 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00019 affected218 at risk EG00112 affected217 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00014 affected218 at risk EG00112 affected217 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00010 affected218 at risk EG00112 affected217 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Systematic Assessment	EG00011 affected218 at risk EG0018 affected217 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment	EG00085 affected218 at risk EG00164 affected217 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment	EG00018 affected218 at risk EG00119 affected217 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment	EG00015 affected218 at risk EG00111 affected217 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment	EG00016 affected218 at risk EG00110 affected217 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA Version 22.0	Systematic Assessment	EG00014 affected218 at risk EG0014 affected217 at risk
Rash pustular	Infections and infestations	MedDRA Version 22.0	Systematic Assessment	EG00039 affected218 at risk EG0012 affected217 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA Version 22.0	Systematic Assessment	EG00017 affected218 at risk EG00123 affected217 at risk
edema peripheral	General disorders	MedDRA Version 22.0	Systematic Assessment	EG00027 affected218 at risk EG00121 affected217 at risk

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D008113	Liver Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D004066	Digestive System Diseases
D008107	Liver Diseases
D011213	Poxviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D007239	Infections

ID	Term
D010671	Phenylurea Compounds
D014508	Urea
D000577	Amides
D009930	Organic Chemicals
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009536	Niacinamide
D009539	Nicotinic Acids
D000147	Acids, Heterocyclic
D006571	Heterocyclic Compounds
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring

ID	Term
D006528	Carcinoma, Hepatocellular
D009369	Neoplasms
D014615	Vaccinia