Adjunctive Therapeutic Treatment With Human Monoclonal An... | NCT03027609

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

Label	Type	Description	Intervention Names
AR-105	Experimental	One intravenous infusion of AR-105 20mg/'kg	Drug: AR-105
Control	Placebo Comparator	Matching placebo	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
AR-105	Drug	monoclonal antibody	AR-105	Aerubumab Aerucin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Clinical Cure on Day 21	A summary of the number (%) of patients who were cured on or before Day 21 (micro-ITT population) is provided, by treatment group	21 days following dosing

Secondary Outcomes

Measure	Description	Time Frame
Clinical Cure on Day 7	A summary of the number (%) of patients who were cured on or before Day 7 (micro-ITT population) is provided, by treatment group	7 days following dosing
Clinical Cure on Day 14

Eligibility Module

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Research Site 1		Sacramento	California	95814	United States
Research Site 2

IPD Sharing Statement Module

Results Section

Participant Flow Module

ID	Title	Description
FG000	AR-105	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody
FG001	Control	Matching placebo placebo: matching placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 9, 2018	Oct 23, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
BG000	AR-105	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody
BG001	Control	Matching placebo placebo: matching placebo
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, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00063.5± 13.83 BG00161.2± 15.58 BG00262.3± 14.73

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Age </= 64 years

Title	Measurements
	BG00040 BG00139 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00017 BG00121 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number of participants per Country

Number

participants

Title

Denominators

Categories

Hungary

Title	Measurements
	BG00010 BG0018 BG002

World Regions

Actual Regions of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Americas	BG0003 BG0014 BG002

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

Clinical Cure on Day 21

A summary of the number (%) of patients who were cured on or before Day 21 (micro-ITT population) is provided, by treatment group

Posted

Count of Participants

Participants

21 days following dosing

ID	Title	Description
OG000	AR-105	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody
OG001	Control	Matching placebo placebo: matching placebo

Units	Counts
Participants	OG00070 OG00167

Title

Denominators

Categories

Observed Cured

Title	Measurements
	OG00034 OG00137

Imputed Cured

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		0.6154	P-value was obtained with the stratified CMH test adjusted for baseline randomization strata	Risk Difference (RD)	-5.54			2-Sided	95	-21.9	10.8					Superiority	comparison between the treatment and placebo

Secondary

Clinical Cure on Day 7

A summary of the number (%) of patients who were cured on or before Day 7 (micro-ITT population) is provided, by treatment group

Posted

Count of Participants

Participants

7 days following dosing

ID	Title	Description
OG000	AR-105	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody
OG001	Control	Matching placebo placebo: matching placebo

Units	Counts
Participants	OG000

Secondary

Clinical Cure on Day 14

A summary of the number (%) of patients who were cured on or before Day 14 (micro-ITT population) is provided by treatment group

Posted

Count of Participants

Participants

14 days following dosing

ID	Title	Description
OG000	AR-105	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody
OG001	Control	Matching placebo placebo: matching placebo

Units	Counts
Participants	OG000

Secondary

Clinical Cure on Day 28

A summary of the number (%) of patients who were cured on or before Day 28 (micro-ITT population) is provided by treatment group

Posted

Count of Participants

Participants

28 days following dosing

ID	Title	Description
OG000	AR-105	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody
OG001	Control	Matching placebo placebo: matching placebo

Units	Counts
Participants	OG000

Post-Hoc

Absolute Difference Clinical Cure at Day 14 and 21 for Study 1

Difference in percentage of clinical cure rates between the two treatment groups

Posted

Count of Participants

Participants

Up to Day 21

ID	Title	Description
OG000	Subset AR-105 Study1	Using the appropriate clinical severity, level of CRP and adequate antibiotic criteria, patients were subdivided into subgroups to identify a pattern in the clinical cure rates in both treatment groups. The results suggest the presence of heterogeneity of factors influencing the clinical cure rates, where only a quite small sample is evaluable. A subset of patients had the following characteristics and were found to belong to appropriate clinical Severity inadequate antibiotic regimen and lower 3rd quartile of level of CRP
OG001	Subset Placebo Study1	Using the appropriate clinical severity, level of CRP and adequate antibiotic criteria, patients were subdivided into subgroups to identify a pattern in the clinical cure rates in both treatment groups. The results suggest the presence of heterogeneity of factors influencing the clinical cure rates, where only a quite small sample is evaluable. A subset of patients had the following characteristics and were found to belong to appropriate clinical Severity inadequate antibiotic regimen and lower 3rd quartile of level of CRP

Post-Hoc

Absolute Difference Clinical Cure at Day 14 and 21 for Study 2

Difference in percentage of clinical cure rates between the two treatment groups

Posted

Count of Participants

Participants

Up to Day 21

ID	Title	Description
OG000	Subset AR-105 Study2	Using the appropriate clinical severity, level of CRP and adequate antibiotic criteria, patients were subdivided into subgroups to identify a pattern in the clinical cure rates in both treatment groups. The results suggest the presence of heterogeneity of factors influencing the clinical cure rates, where only a quite small sample is evaluable. A subset of patients had the following characteristics and were found to belong to appropriate clinical Severity inadequate antibiotic regimen and lower 3rd quartile of level of CRP
OG001	Subset Placebo Study2	Using the appropriate clinical severity, level of CRP and adequate antibiotic criteria, patients were subdivided into subgroups to identify a pattern in the clinical cure rates in both treatment groups. The results suggest the presence of heterogeneity of factors influencing the clinical cure rates, where only a quite small sample is evaluable. A subset of patients had the following characteristics and were found to belong to appropriate clinical Severity inadequate antibiotic regimen and lower 3rd quartile of level of CRP

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	AR-105	One intravenous infusion of AR-105 20mg/'kg AR-105: monoclonal antibody	25	79	36	79	73	79
EG001	Control	Matching placebo placebo: matching placebo	13	79	22	79	73	79

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Circulatory Collapse	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Haemodynamic instability	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Shock	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Shock haemorrhagic	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Cardiac death	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (19.1)	Systematic Assessment	EG0007 affected79 at risk EG0014 affected79 at risk
Systemic inflammatory response syndrome	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Brain herniation	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0003 affected79 at risk EG0010 affected79 at risk
Gastrointestinal stoma complication	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Transaminases increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Acute left ventricular failure	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Cardiac arrest	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected79 at risk EG0011 affected79 at risk
Cardiac failure	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected79 at risk EG0011 affected79 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0011 affected79 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0011 affected79 at risk
Cardiovascular insufficiency	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Myocardial infarction	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0011 affected79 at risk
Rhythm idioventricular	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Tracheo-oesophageal fistula	Congenital, familial and genetic disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected79 at risk EG0010 affected79 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0011 affected79 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected79 at risk EG0012 affected79 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0012 affected79 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected79 at risk EG0010 affected79 at risk
Brain oedema	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected79 at risk EG0010 affected79 at risk
Coma	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0012 affected79 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Oesophageal ulcer	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected79 at risk EG0010 affected79 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Abdominal abscess	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0012 affected79 at risk
Bacteraemia	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Cholecystitis infective	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Fungal sepsis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Lung abscess	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Pneumonia	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0003 affected79 at risk EG0011 affected79 at risk
Pneumonia bacterial	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Pneumonia cytomegaloviral	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Pneumonia pseudomonal	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Postoperative wound infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Sepsis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0003 affected79 at risk EG0010 affected79 at risk
Septic shock	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0005 affected79 at risk EG0013 affected79 at risk
Systemic candida	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0011 affected79 at risk
Arterial rupture	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0010 affected79 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypotension	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG00014 affected79 at risk EG0019 affected79 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (19.1)	Systematic Assessment	EG00010 affected79 at risk EG0014 affected79 at risk
Oedema peripheral	General disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0014 affected79 at risk
Pyrexia	General disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected79 at risk EG0013 affected79 at risk
Agitation	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0012 affected79 at risk
Alanine aminotransferase increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0016 affected79 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (19.1)	Systematic Assessment	EG0000 affected79 at risk EG0016 affected79 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0006 affected79 at risk EG0017 affected79 at risk
Bradycardia	Cardiac disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected79 at risk EG0014 affected79 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG00016 affected79 at risk EG00113 affected79 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0006 affected79 at risk EG0011 affected79 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected79 at risk EG0013 affected79 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0012 affected79 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected79 at risk EG0010 affected79 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0013 affected79 at risk
Brain oedema	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected79 at risk EG0010 affected79 at risk
Delirium	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0012 affected79 at risk
Insomnia	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0013 affected79 at risk
Constipation	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0006 affected79 at risk EG0012 affected79 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected79 at risk EG00113 affected79 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected79 at risk EG0014 affected79 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0014 affected79 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0006 affected79 at risk EG0019 affected79 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0006 affected79 at risk EG0014 affected79 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0011 affected79 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG00012 affected79 at risk EG0016 affected79 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0013 affected79 at risk
Cystitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0014 affected79 at risk
Pneumonia	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0005 affected79 at risk EG0015 affected79 at risk
Sepsis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0005 affected79 at risk EG0010 affected79 at risk
Septic shock	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0006 affected79 at risk EG0015 affected79 at risk
Tracheobronchitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0004 affected79 at risk EG0012 affected79 at risk
Urinary tract infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected79 at risk EG0016 affected79 at risk

A post-hoc analysis was performed on the data reviewed by the AC, using the appropriate clinical severity, adequate antibiotic criteria and the inflammatory status of the patient (level of C-reactive protein [CRP]).

Certain Agreements

Ancestor Terms

ID	Term
D016905	Gram-Negative Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections
D012141	Respiratory Tract Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases