Trial Outcomes & Findings for A Study of Sipuleucel-T With Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer (NCT NCT01981122)

NCT ID: NCT01981122

Last Updated: 2018-10-24

Results Overview

PA2024-specific T cell proliferation responses over time will be compared between the concurrent arm and sequential arm using a repeated measurement mixed model analysis. The unit of analysis for the T cell proliferation data is the stimulation index, defined as the median 3H uptake of 3 wells exposed to antigen divided by the median 3H thymidine uptake of 3 wells exposed to media. The stimulation index will be log-transformed prior to analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

52 participants

Primary outcome timeframe

Each patient was followed for up to 52 weeks after the first dose of sipuleucel-T. Immune sample draws during the treatment period (Week 0 through Week 4) were to be performed at the patient's pre-leukapheresis visits (Pre-Leuk 2 and Pre-Leuk 3).

Results posted on

2018-10-24

Participant Flow

Participant milestones

Participant milestones
Measure	Concurrent Arm Subjects will receive sipuleucel-T concurrently with enzalutamide (160 mg orally once daily). Enzalutamide treatment will start 2 weeks prior to the first leukapheresis and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.	Sequential Arm Subjects will receive sipuleucel-T followed by enzalutamide (160 mg orally once daily). Enzalutamide treatment will start approximately 10 weeks after the first infusion of sipuleucel-T and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.
Overall Study STARTED	25	27
Overall Study COMPLETED	11	7
Overall Study NOT COMPLETED	14	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Concurrent Arm Subjects will receive sipuleucel-T concurrently with enzalutamide (160 mg orally once daily). Enzalutamide treatment will start 2 weeks prior to the first leukapheresis and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.	Sequential Arm Subjects will receive sipuleucel-T followed by enzalutamide (160 mg orally once daily). Enzalutamide treatment will start approximately 10 weeks after the first infusion of sipuleucel-T and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.
Overall Study Withdrawal by Subject	0	2
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Investigator Or Dendreon Discretion	0	1
Overall Study Death	14	15

Baseline Characteristics

A Study of Sipuleucel-T With Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Concurrent Arm n=25 Participants Subjects will receive sipuleucel-T concurrently with enzalutamide (160 mg orally once daily). Enzalutamide treatment will start 2 weeks prior to the first leukapheresis and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.	Sequential Arm n=27 Participants Subjects will receive sipuleucel-T followed by enzalutamide (160 mg orally once daily). Enzalutamide treatment will start approximately 10 weeks after the first infusion of sipuleucel-T and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.	Total n=52 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=93 Participants	4 Participants n=4 Participants	14 Participants n=27 Participants
Age, Categorical >=65 years	15 Participants n=93 Participants	23 Participants n=4 Participants	38 Participants n=27 Participants
Age, Continuous	66.4 Years STANDARD_DEVIATION 10.6 • n=93 Participants	73.3 Years STANDARD_DEVIATION 9.0 • n=4 Participants	70.0 Years STANDARD_DEVIATION 10.3 • n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	25 Participants n=93 Participants	27 Participants n=4 Participants	52 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) White	25 Participants n=93 Participants	25 Participants n=4 Participants	50 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	25 Participants n=93 Participants	27 Participants n=4 Participants	52 Participants n=27 Participants
Height	177.0 Centimeters STANDARD_DEVIATION 8.0 • n=93 Participants	177.2 Centimeters STANDARD_DEVIATION 6.0 • n=4 Participants	177.1 Centimeters STANDARD_DEVIATION 6.9 • n=27 Participants
Weight	94.6 Kg STANDARD_DEVIATION 19.4 • n=93 Participants	91.2 Kg STANDARD_DEVIATION 13.9 • n=4 Participants	92.8 Kg STANDARD_DEVIATION 16.6 • n=27 Participants
Body Mass Index	30.3 Kg/m^2 STANDARD_DEVIATION 5.1 • n=93 Participants	29.0 Kg/m^2 STANDARD_DEVIATION 4.2 • n=4 Participants	29.6 Kg/m^2 STANDARD_DEVIATION 4.6 • n=27 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 0=Fully Active; No restrictions	22 Participants n=93 Participants	19 Participants n=4 Participants	41 Participants n=27 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 1=Restricted Strenuous Activity	3 Participants n=93 Participants	8 Participants n=4 Participants	11 Participants n=27 Participants
Gleason Score Gleason Score ≤6	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Gleason Score Gleason Score 7	4 Participants n=93 Participants	8 Participants n=4 Participants	12 Participants n=27 Participants
Gleason Score Gleason Score ≥8	19 Participants n=93 Participants	16 Participants n=4 Participants	35 Participants n=27 Participants
Gleason Score Missing	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Time from Diagnosis to Randomization	5.1 Years STANDARD_DEVIATION 5.3 • n=93 Participants	6.5 Years STANDARD_DEVIATION 5.6 • n=4 Participants	5.8 Years STANDARD_DEVIATION 5.5 • n=27 Participants
Time in Years 0-5	16 years n=93 Participants	14 years n=4 Participants	30 years n=27 Participants
Time in Years 6-10	5 years n=93 Participants	5 years n=4 Participants	10 years n=27 Participants
Time in Years 11-15	3 years n=93 Participants	6 years n=4 Participants	9 years n=27 Participants
Time in Years 16-20	0 years n=93 Participants	1 years n=4 Participants	1 years n=27 Participants
Time in Years 21-25	1 years n=93 Participants	1 years n=4 Participants	2 years n=27 Participants

PRIMARY outcome

Timeframe: Each patient was followed for up to 52 weeks after the first dose of sipuleucel-T. Immune sample draws during the treatment period (Week 0 through Week 4) were to be performed at the patient's pre-leukapheresis visits (Pre-Leuk 2 and Pre-Leuk 3).

Population: Summary of Cellular Proliferation Data Through Week 52. All patients with reported data at a specified time-point were analyzed. Number of patients at each time-point differed across the time-points resulting in patient numbers at each time-point that are not equal to the total number of patients analyzed.

Outcome measures

Outcome measures
Measure	Concurrent Arm n=23 Participants Subjects will receive sipuleucel-T concurrently with enzalutamide (160 mg orally once daily). Enzalutamide treatment will start 2 weeks prior to the first leukapheresis and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.	Sequential Arm n=26 Participants Subjects will receive sipuleucel-T followed by enzalutamide (160 mg orally once daily). Enzalutamide treatment will start approximately 10 weeks after the first infusion of sipuleucel-T and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Week 26	27.07 10^3 cells/mL Standard Deviation 18.26	15.39 10^3 cells/mL Standard Deviation 10.58
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Week 40	18.64 10^3 cells/mL Standard Deviation 15.48	13.70 10^3 cells/mL Standard Deviation 11.28
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Week 52	16.67 10^3 cells/mL Standard Deviation 13.13	25.43 10^3 cells/mL Standard Deviation 18.72
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Baseline	2.48 10^3 cells/mL Standard Deviation 4.76	1.48 10^3 cells/mL Standard Deviation .92
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Pre-leuk 2	8.76 10^3 cells/mL Standard Deviation 13.40	5.08 10^3 cells/mL Standard Deviation 7.07
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Pre-leuk 3	23.33 10^3 cells/mL Standard Deviation 16.98	13.96 10^3 cells/mL Standard Deviation 11.90
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Week 6	17.36 10^3 cells/mL Standard Deviation 14.39	12.72 10^3 cells/mL Standard Deviation 11.83
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Week 10	15.48 10^3 cells/mL Standard Deviation 9.53	10.90 10^3 cells/mL Standard Deviation 9.07
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Week 14	17.05 10^3 cells/mL Standard Deviation 18.72	13.05 10^3 cells/mL Standard Deviation 13.28
To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). PA2024 Week 20	22.33 10^3 cells/mL Standard Deviation 20.23	17.83 10^3 cells/mL Standard Deviation 13.80

Adverse Events

Concurrent Arm

Serious events: 2 serious events

Other events: 23 other events

Deaths: 14 deaths

Sequential Arm

Serious events: 9 serious events

Other events: 27 other events

Deaths: 15 deaths

Serious adverse events

Other adverse events

Additional Information

Shabnam Vaziri

Dendreon

Phone: 206.455.2323

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The results of the Study will be published and/or presented in an integrated manner reflecting the results observed across all participating centers. Accordingly, decisions on timing and content of publications and presentations relating to the Study will be coordinated by Dendreon in communication with institutions contributing patients to the Study.
Publication restrictions are in place

Restriction type: OTHER

Measure	Concurrent Arm n=25 participants at risk Subjects will receive sipuleucel-T concurrently with enzalutamide (160 mg orally once daily). Enzalutamide treatment will start 2 weeks prior to the first leukapheresis and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.	Sequential Arm n=27 participants at risk Subjects will receive sipuleucel-T followed by enzalutamide (160 mg orally once daily). Enzalutamide treatment will start approximately 10 weeks after the first infusion of sipuleucel-T and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. sipuleucel-T: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). enzalutamide: Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.
Blood and lymphatic system disorders Anaemia	0.00% 0/25 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	3.7% 1/27 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Cardiac disorders Atrial Flutter	0.00% 0/25 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	3.7% 1/27 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Cardiac disorders Cardiac Failure Congestive	0.00% 0/25 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	3.7% 1/27 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Eye disorders Conjunctival Haemorrhage	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Gastrointestinal disorders Vomiting	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
General disorders Thrombosis In Device	0.00% 0/25 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	3.7% 1/27 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Infections and infestations Sepsis	0.00% 0/25 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	3.7% 1/27 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Infections and infestations Urinary Tract Infection	0.00% 0/25 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	3.7% 1/27 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Injury, poisoning and procedural complications Eye Injury	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Injury, poisoning and procedural complications Face Injury	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Injury, poisoning and procedural complications Fall	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Injury, poisoning and procedural complications Femur Fracture	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Injury, poisoning and procedural complications Laceration	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Injury, poisoning and procedural complications Road Traffic Accident	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Nervous system disorders Dizziness	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Nervous system disorders Dysarthria	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Nervous system disorders Headache	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Nervous system disorders Loss of Consciousness	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Nervous system disorders Spinal Cord Compression	0.00% 0/25 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	7.4% 2/27 • Number of events 2 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Renal and urinary disorders Urinary Incotinence	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Respiratory, thoracic and mediastinal disorders Sinus Disorder	4.0% 1/25 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	0.00% 0/27 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.
Vascular disorders Deep Vein Thrombosis	0.00% 0/25 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.	3.7% 1/27 • Number of events 1 • All SAEs reported or observed during or following the first infusion through 60 days post final infusion were recorded in subject's medical record and reported on an electronic case report form (eCRF). Data collection continued until every subject had been followed for minimum 3 years, had died, or had otherwise gone off study.