Trial Outcomes & Findings for Study of TRC105 With Abiraterone and With Enzalutamide in Prostate Cancer Patients Progressing on Therapy (NCT NCT03418324)

NCT ID: NCT03418324

Last Updated: 2020-12-30

Results Overview

Number of participants with stabilization of disease for at least 2 months or disease improvement at any time from start of combination therapy by radiographic and/or biochemical criteria through treatment completion up to an estimated period of 24 months * radiographic improvement defined as a PR (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum. There can be no appearance of new lesions) or CR (Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions) by RECIST 1.1 or improvement by PCWG3 criteria * Biochemical response will be defined by PCWG3 criteria * Stabilization will be defined as the absence of progression by BOTH radiographic and biochemical criteria

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 11 participants
• Primary outcome timeframe: Through study completion, average 24 months
• Results posted on: 2020-12-30

Participant Flow

Study opened to accrual February 5, 2018 and the first patient on study March 5, 2018. As of November 6, 2019, 12 patients have been consented, 11 were enrolled, and 11 were off-treatment and off-study. Study closed to accrual on May 1, 2019, as drug manufacturer has limited drug supply without plans to increase production.

Early accrual closure due to manufacturer's limited drug supply.

Participant milestones

Measure	Arm A: TRC105 + Abiraterone Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Overall Study STARTED	3	8
Overall Study COMPLETED	2	6
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Arm A: TRC105 + Abiraterone Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Overall Study Death	0	1
Overall Study Physician Decision	1	1

Baseline Characteristics

Study of TRC105 With Abiraterone and With Enzalutamide in Prostate Cancer Patients Progressing on Therapy

Baseline characteristics by cohort

Measure	Arm A: TRC105 + Abiraterone n=2 Participants Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 Participants Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Age, Continuous	76.5 years STANDARD_DEVIATION 3.53 • n=5 Participants	67.83 years STANDARD_DEVIATION 6.97 • n=7 Participants	70 years STANDARD_DEVIATION 7.25 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Through study completion, average 24 months

Number of participants with stabilization of disease for at least 2 months or disease improvement at any time from start of combination therapy by radiographic and/or biochemical criteria through treatment completion up to an estimated period of 24 months

• radiographic improvement defined as a PR (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum. There can be no appearance of new lesions) or CR (Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions) by RECIST 1.1 or improvement by PCWG3 criteria
• Biochemical response will be defined by PCWG3 criteria
• Stabilization will be defined as the absence of progression by BOTH radiographic and biochemical criteria

Outcome measures

Measure	Arm A: TRC105 + Abiraterone n=2 Participants Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 Participants Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Overall Clinical Benefit Overall Clinical Benefit	1 Participants	4 Participants
Overall Clinical Benefit Radiographic Improvement	1 Participants	2 Participants
Overall Clinical Benefit Biochemical Response	1 Participants	1 Participants
Overall Clinical Benefit Stabilization	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 4 months

Number of participants with grade 3/4 Adverse Events Related to investigational therapy as assessed Using CTCAE (v.4) up to 4 months from treatment initiation.

Outcome measures

Measure	Arm A: TRC105 + Abiraterone n=2 Participants Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 Participants Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Adverse Events From TRC105 and Abiraterone or Enzalutamide Grade 3	1 Participants	1 Participants
Adverse Events From TRC105 and Abiraterone or Enzalutamide Grade 4	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 24 months

Population: Median progression free survival (months) (95% confidence interval). Not enough data (insufficient number of participants with events) to establish upper limit.

Time (in Months) from treatment initiation to radiographic and clinical progression over study duration (estimated 24 months)

• radiographic criteria measured by RECIST 1.1 [Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions plus an absolute increase of at least 5 mm, taking as reference the smallest sum recorded since the start of study]

Outcome measures

Measure	Arm A: TRC105 + Abiraterone n=2 Participants Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 Participants Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Progression Free Survival	1.64 months Interval 1.64 to Not enough data (insufficient number of participants with events) to establish upper limit.	4.46 months Interval 1.71 to Not enough data (insufficient number of participants with events) to establish upper limit.

SECONDARY outcome

Timeframe: 2 months

Proportion of participants with stabilization of disease for two months or disease improvement at anytime from start of combination therapy to two months by radiographic and/or biochemical criteria

• radiographic improvement defined as a PR (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum. There can be no appearance of new lesions) or CR (Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions) by RECIST 1.1 or improvement by PCWG3 criteria
• Biochemical response will be defined by PCWG3 criteria
• Stabilization will be defined as the absence of progression by BOTH radiographic and biochemical criteria

Outcome measures

Measure	Arm A: TRC105 + Abiraterone n=2 Participants Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 Participants Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Clinical Benefit at Two Months Clinical Benefit	1 Participants	4 Participants
Clinical Benefit at Two Months Radiographic Improvement	1 Participants	1 Participants
Clinical Benefit at Two Months Biochemical Response	1 Participants	1 Participants
Clinical Benefit at Two Months Stabilization	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 4 months

Proportion of participants with stabilization of disease for at least 4 months or disease improvement at anytime from start of combination therapy to four months by radiographic and/or biochemical criteria

• radiographic improvement defined as a PR (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum. There can be no appearance of new lesions) or CR (Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions) by RECIST 1.1 or improvement by PCWG3 criteria
• Biochemical response will be defined by PCWG3 criteria
• Stabilization will be defined as the absence of progression by BOTH radiographic and biochemical criteria

Outcome measures

Measure	Arm A: TRC105 + Abiraterone n=2 Participants Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 Participants Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Clinical Benefit at Four Months Clinical Benefit	1 Participants	3 Participants
Clinical Benefit at Four Months Radiographic Improvement	1 Participants	2 Participants
Clinical Benefit at Four Months Biochemical Response	1 Participants	1 Participants
Clinical Benefit at Four Months Stabilization	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 2 months

Proportion of participants with stabilization of disease based on PSA serum concentration levels. Stabilization of disease refers to PSA values that do not meet criteria for progression where progression will be defined as a rise in serum PSA that is ≥ 25% and 2 ng/mL above nadir which is confirmed by a second value ≥ 3 weeks later.

Outcome measures

Measure	Arm A: TRC105 + Abiraterone n=2 Participants Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 Participants Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Clinical Benefit From PSA Serum Concentration (2 Months)	1 Participants	4 Participants

SECONDARY outcome

Timeframe: 4 months

Proportion of participants with stabilization of disease based on PSA serum concentration levels. Stabilization of disease refers to PSA values that do not meet criteria for progression where progression will be defined as a rise in serum PSA that is ≥ 25% and 2 ng/mL above nadir which is confirmed by a second value ≥ 3 weeks later.

Outcome measures

Measure	Arm A: TRC105 + Abiraterone n=2 Participants Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 Participants Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Clinical Benefit From PSA Serum Concentration (4 Months)	1 Participants	3 Participants

Adverse Events

Arm A: TRC105 + Abiraterone

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Arm E: TRC105 + Enzalutamide

Serious events: 0 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Measure	Arm A: TRC105 + Abiraterone n=2 participants at risk Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 participants at risk Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Renal and urinary disorders Urinary retention	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Skin and subcutaneous tissue disorders Cellulitis (peri-mandibular)	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Metabolism and nutrition disorders Hyponatremia	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.

Other adverse events

Measure	Arm A: TRC105 + Abiraterone n=2 participants at risk Patients progressing on Abiraterone will undergo a washout period and then continue treatment with TRC105 + Abiraterone TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Abiraterone: Patients who are progressing on Abiraterone will undergo a washout period and then continue treatment with standard dosing of Abiraterone plus TRC105.	Arm E: TRC105 + Enzalutamide n=6 participants at risk Patients progressing on Enzalutamide will undergo a washout period and then continue treatment with TRC105 + Enzalutamide TRC105: Patients will receive TRC105 10mg weekly x 4, and then 15 mg/kg every 2 weeks Enzalutamide: Patients who are progressing on Enzalutamide will undergo a washout period and then continue standard treatment with Enzalutamide plus TRC105.
Immune system disorders Allergic reaction	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	50.0% 1/2 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Blood and lymphatic system disorders Anemia Hemoglobin (Hgb)	100.0% 2/2 • Number of events 7 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	33.3% 2/6 • Number of events 8 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Metabolism and nutrition disorders Anorexia	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Musculoskeletal and connective tissue disorders Back pain	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 3 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Respiratory, thoracic and mediastinal disorders Cough	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Nervous system disorders Dizziness	50.0% 1/2 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Nervous system disorders Dysphasia	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
General disorders Edema limbs	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Respiratory, thoracic and mediastinal disorders Epistaxis	50.0% 1/2 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	100.0% 6/6 • Number of events 10 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Injury, poisoning and procedural complications Fall	100.0% 2/2 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
General disorders Fatigue	100.0% 2/2 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
General disorders Flu like symptoms	50.0% 1/2 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	33.3% 2/6 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
General disorders Generalized weakness	50.0% 1/2 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Gastrointestinal disorders Gingival bleeding	100.0% 2/2 • Number of events 3 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	83.3% 5/6 • Number of events 6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Gastrointestinal disorders Guaiac + Stool	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Metabolism and nutrition disorders Hyponatremia	50.0% 1/2 • Number of events 5 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Musculoskeletal and connective tissue disorders Myalgia	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Gastrointestinal disorders Nausea	50.0% 1/2 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	50.0% 3/6 • Number of events 4 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
General disorders Non-cardiac chest pain	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Blood and lymphatic system disorders Petechiae	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Respiratory, thoracic and mediastinal disorders Pleural effusion	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Infections and infestations Urinary tract infection	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Investigations Weight loss	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 3 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Nervous system disorders Cauda equina	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Skin and subcutaneous tissue disorders Cellulitis (peri-mandibular)	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Nervous system disorders Right leg sciatica	50.0% 1/2 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	0.00% 0/6 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Skin and subcutaneous tissue disorders Acne	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Injury, poisoning and procedural complications Bruising	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Eye disorders Cataract	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Psychiatric disorders Confusion	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Metabolism and nutrition disorders Dehydration	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	33.3% 2/6 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Gastrointestinal disorders Geographic Tongue	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Eye disorders Glaucoma	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 3 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Nervous system disorders Headache	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	50.0% 3/6 • Number of events 3 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
General disorders Infusion related reaction	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Infections and infestations Laryngitis	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Gastrointestinal disorders Lip pain	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
General disorders Localized edema	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	33.3% 2/6 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Infections and infestations MRSA	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Nervous system disorders Memory impairment	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	33.3% 2/6 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Gastrointestinal disorders Oral pain	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
General disorders Pain	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Investigations Platelet count decreased	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Nervous system disorders Recurrent laryngeal nerve palsy	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Eye disorders Redness sclera left eye	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Infections and infestations Rhinitis infective	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Infections and infestations Tooth infection	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Eye disorders Vision decrease (binocular)	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.
Gastrointestinal disorders Vomiting	0.00% 0/2 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.	16.7% 1/6 • Number of events 1 • 2 years 3 patients consented to Arm A, but only 2 were considered evaluable (1 patient considered unevaluable per physician decision prior to treatment start). 8 patients consented to Arm E, but 6 were considered evaluable. Of the 2 patients not included in Arm E, 1 patient was deemed unevaluable by physician decision prior to starting study treatment, and the other died prior to starting study treatment. Therefore, this number is reflected in All-Cause Mortality, and differs from SAEs and Other.

Additional Information

Edwin Posadas, MD

Cedars-Sinai Medical Center

Phone: 310-423-7600

Email: Edwin.Posadas@cshs.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place