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Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02222714
Recruitment Status : Completed
First Posted : August 21, 2014
Results First Posted : November 8, 2018
Last Update Posted : November 8, 2018
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Cedars-Sinai Medical Center
Massachusetts General Hospital
University of Iowa
Information provided by (Responsible Party):
ZZ Biotech, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Ischemic Stroke
Interventions Biological: 3K3A-APC
Drug: Placebo
Enrollment 110
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC Placebo
Hide Arm/Group Description

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

Matching placebo, q12h for up to 5 doses

Placebo: Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion

Period Title: Overall Study
Started 15 24 12 15 44
Completed 15 22 8 11 37
Not Completed 0 2 4 4 7
Reason Not Completed
Death             0             2             3             4             6
Withdrawal by Subject             0             0             1             0             1
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC Placebo Total
Hide Arm/Group Description 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion Matching placebo, q12h for up to 5 doses Placebo: Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion Total of all reporting groups
Overall Number of Baseline Participants 15 24 12 15 44 110
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 15 participants 24 participants 12 participants 15 participants 44 participants 110 participants
63.3
(28 to 84)
61.4
(33 to 88)
65.3
(43 to 89)
66.2
(42 to 89)
63.8
(44 to 83)
63.7
(28 to 89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 24 participants 12 participants 15 participants 44 participants 110 participants
Female
11
  73.3%
12
  50.0%
6
  50.0%
8
  53.3%
20
  45.5%
57
  51.8%
Male
4
  26.7%
12
  50.0%
6
  50.0%
7
  46.7%
24
  54.5%
53
  48.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 24 participants 12 participants 15 participants 44 participants 110 participants
Hispanic or Latino
2
  13.3%
1
   4.2%
0
   0.0%
1
   6.7%
7
  15.9%
11
  10.0%
Not Hispanic or Latino
11
  73.3%
22
  91.7%
12
 100.0%
13
  86.7%
36
  81.8%
94
  85.5%
Unknown or Not Reported
2
  13.3%
1
   4.2%
0
   0.0%
1
   6.7%
1
   2.3%
5
   4.5%
History of Hypertension  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 24 participants 12 participants 15 participants 44 participants 110 participants
11
  73.3%
21
  87.5%
9
  75.0%
11
  73.3%
33
  75.0%
85
  77.3%
History of Diabetes  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 24 participants 12 participants 15 participants 44 participants 110 participants
6
  40.0%
6
  25.0%
2
  16.7%
4
  26.7%
18
  40.9%
36
  32.7%
1.Primary Outcome
Title Number of Participants With Adverse Events That Meet Dose-limiting Toxicity (DLT) Criteria Specified in Protocol
Hide Description Specific AEs in the study were defined in the protocol to be dose-limiting toxicity events. Any given patient was adjudicated in a binary way to either have had a DLT or not to have had a DLT.
Time Frame 48-hours following last dose
Hide Outcome Measure Data
Hide Analysis Population Description
Evaluable participants
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC Placebo
Hide Arm/Group Description:

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

Matching placebo, q12h for up to 5 doses

Placebo: Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion

Overall Number of Participants Analyzed 15 24 12 15 44
Measure Type: Count of Participants
Unit of Measure: Participants
1-hour post dose aPTT out of range
0
   0.0%
1
   4.2%
0
   0.0%
0
   0.0%
1
   2.3%
SICH associated with neuroworsening
0
   0.0%
1
   4.2%
0
   0.0%
0
   0.0%
0
   0.0%
ALT/AST, TBL, ALP, AT values out of range
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Serious bleeding
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Abnormal lab value related to study treatment
0
   0.0%
0
   0.0%
1
   8.3%
0
   0.0%
2
   4.5%
Any other AE leading to cessation of dosing
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.3%
Total
0
   0.0%
2
   8.3%
1
   8.3%
0
   0.0%
4
   9.1%
2.Secondary Outcome
Title Number of Participants With a Presence of Measurable Bleeds in the Brain (Hemorrhage and Microbleeds) as Determined by 1.5T MRI
Hide Description MRI examination to include-at minimum-T1 and T2 weighted images, as well as diffusion weighted imaging (DWI) and susceptibility weighted imaging (SWI) sequences. Post-tPA microbleeds-defined as hypointensities less than 5mm in diameter seen on SWI-will be counted as tPA-related only if found within the ischemic territory. All other areas of hypointensity on SWI larger than 5mm diameter will be counted as tPA-related regardless of the territory in which they are found. All treated subjects (regardless of dose) will be compared to all placebo subjects using a Pearson chi-square test.
Time Frame Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with a Day 30 scan collected.
Arm/Group Title 3K3A-APC Total Placebo
Hide Arm/Group Description:
All 3K3A-APC treated groups combined
Placebo group
Overall Number of Participants Analyzed 43 37
Measure Type: Count of Participants
Unit of Measure: Participants
Hemorrhage (>0.06mL)
24
  55.8%
25
  67.6%
Microbleed (>0)
7
  16.3%
8
  21.6%
3.Secondary Outcome
Title PK of 3K3A-APC by Compartmental Analysis (Clearance)
Hide Description Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Time Frame Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters.
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC
Hide Arm/Group Description:

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

Overall Number of Participants Analyzed 5 3 5 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/hr
20994
(57.1%)
17814
(16.7%)
18504
(49.9%)
24403
(70.5%)
4.Secondary Outcome
Title PK of 3K3A-APC by Compartmental Analysis (Volume of Distribution)
Hide Description Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Time Frame Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters.
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC
Hide Arm/Group Description:

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

Overall Number of Participants Analyzed 5 3 5 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL
8242
(46.9%)
6051
(25.6%)
7164
(79.0%)
11437
(125%)
5.Secondary Outcome
Title PK of 3K3A-APC by Compartmental Analysis (Cmax)
Hide Description Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Time Frame Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters.
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC
Hide Arm/Group Description:

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

Overall Number of Participants Analyzed 5 3 5 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
0.957
(59.1%)
2.37
(11.0%)
2.80
(77.6%)
3.32
(138%)
6.Secondary Outcome
Title PK of 3K3A-APC by Compartmental Analysis (AUC[0-inf])
Hide Description Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Time Frame Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters.
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC
Hide Arm/Group Description:

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

Overall Number of Participants Analyzed 5 3 5 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr▪ng/mL
0.513
(64.7%)
1.16
(6.79%)
1.49
(56.1%)
2.06
(92.7%)
7.Secondary Outcome
Title PK of 3K3A-APC by Compartmental Analysis (λz)
Hide Description Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Time Frame Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters.
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC
Hide Arm/Group Description:

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

Overall Number of Participants Analyzed 5 3 5 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 1/hr
2.55
(13.4%)
2.94
(10.5%)
2.58
(34.9%)
2.13
(45.2%)
8.Secondary Outcome
Title PK of 3K3A-APC by Compartmental Analysis (Half-life)
Hide Description Measured following a single dose; primary parameters (CL, V) were used to fit the model. Secondary parameters (Cmax, AUC(inf), λz, t1/2) were estimated from the primary parameters.
Time Frame Following a single dose, on Day 1, 2 or 3: End of infusion (EOI) and 20, 40, 60 and 80 minutes following EOI
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient data for PK analysis, and who had not been excluded from analysis for protocol deviations that could impact the calculation or interpretation of the PK parameters.
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC
Hide Arm/Group Description:

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

3K3A-APC, q12h for up to 5 doses

3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion

Overall Number of Participants Analyzed 5 3 5 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr
0.272
(13.4%)
0.235
(10.5%)
0.268
(34.9%)
0.325
(45.2%)
Time Frame AEs were collected through Study Day 7 and were followed until resolution or a new baseline was established, up to Study Day 90. SAEs were collected through Study Day 30, and were followed until resolution (or resolution with sequelae), up to Study Day 90.
Adverse Event Reporting Description Standard definitions of adverse events and serious adverse events were used.
 
Arm/Group Title 120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC 3K3A-APC Total Placebo
Hide Arm/Group Description 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion 3K3A-APC, q12h for up to 5 doses 3K3A-APC: 3K3A-APC, diluted in 0.9% sodium chloride in water, given as 100 mL IV infusion All 3K3A-APC treated groups combined Matching placebo, q12h for up to 5 doses Placebo: Matching placebo, 0.9% sodium chloride in water, given as 100 mL IV infusion
All-Cause Mortality
120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC 3K3A-APC Total Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   2/24 (8.33%)   3/12 (25.00%)   4/15 (26.67%)   9/66 (13.64%)   6/44 (13.64%) 
Hide Serious Adverse Events
120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC 3K3A-APC Total Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/15 (53.33%)   9/24 (37.50%)   4/12 (33.33%)   9/15 (60.00%)   30/66 (45.45%)   18/44 (40.91%) 
Blood and lymphatic system disorders             
Anaemia  1  1/15 (6.67%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  2/66 (3.03%)  1/44 (2.27%) 
Leukocytosis  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/66 (0.00%)  1/44 (2.27%) 
Cardiac disorders             
Atrial fibrillation  1  4/15 (26.67%)  0/24 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  5/66 (7.58%)  4/44 (9.09%) 
Bradycardia  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/66 (0.00%)  1/44 (2.27%) 
Cardiac arrest  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  1/66 (1.52%)  1/44 (2.27%) 
Cardiac failure congestive  1  1/15 (6.67%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Intracardiac thrombus  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Myocardial infarction  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Pericarditis  1  0/15 (0.00%)  0/24 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Gastrointestinal disorders             
Duodenal ulcer haemorrhage  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Retroperitoneal haematoma  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
General disorders             
Chest pain  1  0/15 (0.00%)  0/24 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Infections and infestations             
Pneumonia  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/66 (0.00%)  1/44 (2.27%) 
Septic shock  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Staphylococcal infection  1  1/15 (6.67%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Urosepsis  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/66 (0.00%)  1/44 (2.27%) 
Investigations             
Blood fibrinogen decreased  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  2/15 (13.33%)  3/66 (4.55%)  1/44 (2.27%) 
Blood glucose increased  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/66 (0.00%)  1/44 (2.27%) 
Blood potassium decreased  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Blood sodium increased  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Ejection fraction decreased  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  1/66 (1.52%)  0/44 (0.00%) 
Hepatic enzyme increased  1  0/15 (0.00%)  0/24 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Lymphocyte count decreased  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  1/44 (2.27%) 
Troponin increased  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  1/66 (1.52%)  0/44 (0.00%) 
Nervous system disorders             
Brain oedema  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  4/15 (26.67%)  5/66 (7.58%)  3/44 (6.82%) 
Carotid artery stenosis  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Cerebral haemorrhage  1  0/15 (0.00%)  3/24 (12.50%)  0/12 (0.00%)  0/15 (0.00%)  3/66 (4.55%)  2/44 (4.55%) 
Cerebrovascular accident  1  1/15 (6.67%)  3/24 (12.50%)  0/12 (0.00%)  1/15 (6.67%)  5/66 (7.58%)  3/44 (6.82%) 
Convulsion  1  2/15 (13.33%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  2/66 (3.03%)  1/44 (2.27%) 
Haemorrhage intracranial  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  1/66 (1.52%)  1/44 (2.27%) 
Psychiatric disorders             
Agitation  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/66 (0.00%)  1/44 (2.27%) 
Respiratory, thoracic and mediastinal disorders             
Acute respiratory failure  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  1/44 (2.27%) 
Bronchospasm  1  1/15 (6.67%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Pneumonia aspiration  1  1/15 (6.67%)  0/24 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  2/66 (3.03%)  1/44 (2.27%) 
Pneumothorax  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/66 (0.00%)  1/44 (2.27%) 
Pulmonary embolism  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/66 (0.00%)  1/44 (2.27%) 
Pulmonary oedema  1  1/15 (6.67%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  1/44 (2.27%) 
Respiratory distress  1  0/15 (0.00%)  0/24 (0.00%)  1/12 (8.33%)  0/15 (0.00%)  1/66 (1.52%)  0/44 (0.00%) 
Respiratory failure  1  0/15 (0.00%)  1/24 (4.17%)  1/12 (8.33%)  0/15 (0.00%)  2/66 (3.03%)  0/44 (0.00%) 
Surgical and medical procedures             
Aneurysm repair  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  0/66 (0.00%)  1/44 (2.27%) 
Vascular disorders             
Deep vein thrombosis  1  0/15 (0.00%)  0/24 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  1/66 (1.52%)  1/44 (2.27%) 
Hypotension  1  0/15 (0.00%)  1/24 (4.17%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  3/44 (6.82%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
120 µg/kg of 3K3A-APC 240 µg/kg of 3K3A-APC 360 µg/kg of 3K3A-APC 540 µg/kg of 3K3A-APC 3K3A-APC Total Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/15 (66.67%)   18/24 (75.00%)   8/12 (66.67%)   9/15 (60.00%)   45/66 (68.18%)   36/44 (81.82%) 
Blood and lymphatic system disorders             
Anaemia  1  5/15 (33.33%)  4/24 (16.67%)  2/12 (16.67%)  2/15 (13.33%)  13/66 (19.70%)  6/44 (13.64%) 
Leukocytosis  1  0/15 (0.00%)  3/24 (12.50%)  1/12 (8.33%)  2/15 (13.33%)  6/66 (9.09%)  6/44 (13.64%) 
Cardiac disorders             
Bradycardia  1  1/15 (6.67%)  0/24 (0.00%)  0/12 (0.00%)  0/15 (0.00%)  1/66 (1.52%)  5/44 (11.36%) 
Gastrointestinal disorders             
Constipation  1  0/15 (0.00%)  5/24 (20.83%)  1/12 (8.33%)  0/15 (0.00%)  6/66 (9.09%)  4/44 (9.09%) 
General disorders             
Pyrexia  1  1/15 (6.67%)  2/24 (8.33%)  1/12 (8.33%)  0/15 (0.00%)  4/66 (6.06%)  4/44 (9.09%) 
Infections and infestations             
Urinary tract infection  1  1/15 (6.67%)  5/24 (20.83%)  3/12 (25.00%)  1/15 (6.67%)  10/66 (15.15%)  8/44 (18.18%) 
Injury, poisoning and procedural complications             
Contusion  1  0/15 (0.00%)  3/24 (12.50%)  0/12 (0.00%)  0/15 (0.00%)  3/66 (4.55%)  3/44 (6.82%) 
Investigations             
Activated partial thromboplastin time prolonged  1  0/15 (0.00%)  4/24 (16.67%)  0/12 (0.00%)  0/15 (0.00%)  4/66 (6.06%)  2/44 (4.55%) 
Blood calcium decreased  1  1/15 (6.67%)  2/24 (8.33%)  1/12 (8.33%)  1/15 (6.67%)  5/66 (7.58%)  1/44 (2.27%) 
Blood fibrinogen decreased  1  0/15 (0.00%)  3/24 (12.50%)  0/12 (0.00%)  0/15 (0.00%)  3/66 (4.55%)  4/44 (9.09%) 
Lymphocyte count decreased  1  2/15 (13.33%)  0/24 (0.00%)  0/12 (0.00%)  1/15 (6.67%)  3/66 (4.55%)  3/44 (6.82%) 
Prothrombin time prolonged  1  1/15 (6.67%)  3/24 (12.50%)  0/12 (0.00%)  1/15 (6.67%)  5/66 (7.58%)  6/44 (13.64%) 
Nervous system disorders             
Haemorrhage intracranial  1  2/15 (13.33%)  4/24 (16.67%)  4/12 (33.33%)  4/15 (26.67%)  14/66 (21.21%)  16/44 (36.36%) 
Headache  1  1/15 (6.67%)  6/24 (25.00%)  2/12 (16.67%)  3/15 (20.00%)  12/66 (18.18%)  10/44 (22.73%) 
Renal and urinary disorders             
Haematuria  1  1/15 (6.67%)  0/24 (0.00%)  1/12 (8.33%)  1/15 (6.67%)  3/66 (4.55%)  4/44 (9.09%) 
Vascular disorders             
Hypotension  1  0/15 (0.00%)  2/24 (8.33%)  1/12 (8.33%)  0/15 (0.00%)  3/66 (4.55%)  3/44 (6.82%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
The study was designed and powered for evaluating DLTs and identifying a maximum tolerated dose, not for efficacy endpoints.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Patrick Lyden, MD, FAAN, FAHA
Organization: Cedars-Sinai Medical Center
Phone: (310) 423-5166
EMail: Patrick.Lyden@cshs.org
Layout table for additonal information
Responsible Party: ZZ Biotech, LLC
ClinicalTrials.gov Identifier: NCT02222714    
Other Study ID Numbers: ZZ-3K3A-201 (NN104)
1U01NS088312-01 ( U.S. NIH Grant/Contract )
U01NS077352 ( U.S. NIH Grant/Contract )
U01NS077179-01 ( U.S. NIH Grant/Contract )
First Submitted: August 18, 2014
First Posted: August 21, 2014
Results First Submitted: July 27, 2018
Results First Posted: November 8, 2018
Last Update Posted: November 8, 2018