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This research study involves an investigational product: Ad-RTS-hIL-12 given with veledimex for production of human IL-12. IL-12 is a protein that can improve the body's natural response to disease by enhancing the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor.
The main purpose of this study is to evaluate the safety and tolerability of a single intratumoral injection of Ad-RTS-hIL-12 given with oral veledimex.
Patients who are scheduled for craniotomy and tumor resection will receive one dose of veledimex before the resection procedure. Ad-RTS-hIL-12 will be administered by free-hand injection. Patients will continue on oral veledimex for 14 days.
The study is divided into three periods: the screening period, the treatment period and the follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ad-RTS-hIL-12 + veledimex | Experimental | Intratumoral Ad-RTS-hIL-12 and oral veledimex |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ad-RTS-hIL-12 | Biological |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex in Subjects With Recurrent or Progressive Glioblastoma Based on Evaluation of Adverse Events Summarized by Incidence, Intensity and Type of Adverse Event. | Evaluation of adverse events as assessed by CTCAE v4.03. Adverse events will be summarized based on the incidence, intensity and type of adverse event. | From the first dose of study treatment until 30 days after the last dose of veledimex, lasting approximately 5 months. |
| Tolerability of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex in Subjects With Recurrent or Progressive Glioblastoma Will be Assessed Based on Expected Dose Compliance | The Day 0 (as applicable), and Day 1 doses of veledimex were administered by study personnel at the study center. Thereafter, subjects could self-administer the remaining once daily dose of veledimex. Subjects were instructed to document veledimex dosing compliance in a subject diary, including the time each dose was taken, the time the subject ate the last meal prior to administration of veledimex, the number of capsules taken, whether the subject missed any veledimex doses, and reason for any missed doses. Investigational product container(s) with any remaining capsules were returned to the study staff on Day 15, and staff assessed dose compliance. | Days 1 through 14 of each 21-day treatment cycle, over a total treatment period of up to 6 cycles (approximately 4 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Determine the Overall Survival (OS) of Ad-RTS-hIL-12 + Veledimex | OS is defined as the duration of time from the first dose of study drug (Day 0) to the date of death from any cause in days or months. Subjects are censored based on the last date known to be alive. For example:
|
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Inclusion Criteria:
Male or female subject ≥18 and ≤75 years of age
Provision of written informed consent for tumor resection, tumor biopsy, samples collection, and treatment with investigational products prior to undergoing any study specific procedures
Histologically confirmed glioblastoma
Evidence of supratentorial tumor recurrence/progression by magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria after standard initial therapy
Previous standard-of-care antitumor treatment including surgery and/or biopsy and chemoradiation. At the time of registration, subjects must have recovered from the toxic effects of previous treatments as determined by the treating physician. The washout periods from prior therapies are intended as follows: (windows other than what is listed below should be allowed only after consultation with the Medical Monitor)
Able to undergo standard MRI scans with contrast agent before enrollment and after treatment
Karnofsky Performance Status ≥70
Adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:
Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate <5% per year) from the Screening Visit through 28 days after the last dose of study drug. Women of childbearing potential (perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential) must have a negative pregnancy test at screening
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jaymes Holland | Alaunos Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States | ||
| Northwestern Memorial Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | Ad-RTS-hIL-12 + Veledimex | Intratumoral Ad-RTS-hIL-12 and oral veledimex Ad-RTS-hIL-12: - intratumoral injection of Ad-RTS-hIL-12 veledimex: - 20mg/day - 15 oral daily doses of veledimex |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Full Analysis Set (FAS): Overall Safety Population (OSP) includes all subjects who have received at least one dose of veledimex (pretumor resection and) and/or all subjects who received Ad-RTS-hIL-12.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ad-RTS-hIL-12 + Veledimex | Intratumoral Ad-RTS-hIL-12 and oral veledimex Ad-RTS-hIL-12: - intratumoral injection of Ad-RTS-hIL-12 veledimex: - 20mg/day - 15 oral daily doses of veledimex |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex in Subjects With Recurrent or Progressive Glioblastoma Based on Evaluation of Adverse Events Summarized by Incidence, Intensity and Type of Adverse Event. | Evaluation of adverse events as assessed by CTCAE v4.03. Adverse events will be summarized based on the incidence, intensity and type of adverse event. | The Full Analysis Set (FAS): Overall Safety Population (OSP) includes all subjects who have received at least one dose of veledimex (pretumor resection and) and/or all subjects who received Ad-RTS-hIL-12. | Posted | Number | participants | From the first dose of study treatment until 30 days after the last dose of veledimex, lasting approximately 5 months. |
|
All-cause mortality was assessed from the first dose of study treatment for up to 2 years. All other adverse events were collected from the first dose of study treatment until 30 days after the last dose of veledimex (approximately 5 months).
Evaluation will be based on the incidence, intensity, and type of Adverse Events (AEs), Clinically significant changes in the subjects' physical examinations, vital signs, and ECG evaluations, and clinical manifestations relevant to abnormal laboratory values will be captured as AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ad-RTS-hIL-12 + Veledimex | Intratumoral Ad-RTS-hIL-12 and oral veledimex Ad-RTS-hIL-12: - intratumoral injection of Ad-RTS-hIL-12 veledimex: - 20mg/day - 15 oral daily doses of veledimex |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Seizure | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jaymes Holland | Alaunos Therapeutics | 6502732627 | jholland@alaunos.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 14, 2018 | Mar 7, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 13, 2021 | Mar 7, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| C000626304 | veledimex |
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| veledimex | Drug |
|
|
| From the first dose of study drug for up to 2 years. |
| Veledimex Pharmacokinetic Profile: Maximum Plasma Concentration (Cmax) | The maximum plasma concentration (Cmax) of veledimex | 15 days |
| Veledimex Pharmacokinetic Profile: Time to Maximum Plasma Concentration (Tmax) | Time to maximum plasma concentration (Tmax) of veledimex. Tmax was estimated based on time of maximum concentration (Cmax) from predose (Day 0 or 14) to predose the following day (Day 1 or 15). | 15 days |
| Veledimex Pharmacokinetic Profile: Half-life (t1/2) | Half-life (t1/2) of veledimex | 15 days |
| Veledimex Pharmacokinetic Profile: Area-under-the-concentration Versus Time Curve (AUC) | Area-under-the-concentration versus time curve (AUC) of veledimex from Day 14 predose to Day 15 predose. AUC was estimated using the elimination rate constant k, where k = ln(Cmax/Ctrough)/time difference and AUC is approximately Cmax/k. | 15 days |
| Veledimex Pharmacokinetic Profile: Volume of Distribution (Vd) | Volume of distribution (Vd) of veledimex. Vd was calculated using AUC approximated as described in the Outcome Measure Description for Outcome Measure 6. | 15 days |
| Veledimex Pharmacokinetic Profile: Clearance (CL) | Clearance (CL) of veledimex. CL was calculated using AUC approximated as described in the Outcome Measure Description for Outcome Measure 6. | 15 days |
| Veledimex Concentration Ratio Between the Brain Tumor and the Blood | Veledimex concentration ratio was calculated based on the Day 0 tumor and plasma PK results. | Day 0 (at the time of tumor resection) |
| Tumor Objective Response Rate (ORR) | For the ORR calculation, responders are defined as those experiencing a confirmed complete response or confirmed partial response. Non-responders are those either with stable or progressive disease. Those subjects that cannot be assessed will be treated as non-responders for the purposes of deriving the percentage of responders and confidence intervals. Overall Response was assessed at multiple timepoints (day 56, week 16, week 24, and week 48) by the study investigators. Changes to the original plan for exploration of estimates of efficacy are summarized below. • The best overall response (BOR) endpoint was added to the efficacy assessment and reported here. | 48 weeks |
| Progression Free Survival (PFS) | PFS (progression free survival) is the time in months from the first treatment (either veledimex or Ad-RTS-hIL-12) to the first assessment on which the overall response is reported as disease progression. Subjects withdrawing from the study will be censored at their last non progressive disease response assessment. If a subject does not have a non-progressive disease response assessment, the subject will be censored on the date of the first treatment as described above. | From the first dose of study drug for up to 2 years. |
| Rate of Pseudo-progression (PSP) | PSP Progression free survival was originally defined for determination of PSP requiring confirmation of progression based on RANO/iRANO criteria guidelines. | From the first dose of study drug for up to 2 years. |
| Changes From Baseline in Cellular Responses Elicited by Ad-RTS-hIL-12 and Veledimex | Evaluation in changes in immune cell population markers, such as CD3 and CD8 in tumor | Baseline and Week 6. |
| Peak Serum Concentration of Interleukin-12 (IL-12) | Serum concentrations of IL-12 were measured at multiple timepoints post-dose. For each participant, the peak (maximum) concentration observed from Day 3 through the 30-day follow-up visit was identified. This measure summarizes the mean of those individual peak concentrations. | Samples were collected at Baseline (Day 1), Day 3, Day 8, and Day 15 of Cycle 1, and at the 30-day follow-up visit. |
| Peak Serum Concentration of Interferon-gamma (IFN-γ) | Serum concentrations of IFN-γ were measured at multiple timepoints post-dose. For each participant, the peak (maximum) concentration observed from Day 3 through the 30-day follow-up visit was identified. This measure summarizes the mean of those individual peak concentrations. | Samples were collected at Baseline (Day 1), Day 3, Day 8, and Day 15 of Cycle 1, and at the 30-day follow-up visit |
| Chicago |
| Illinois |
| 60611 |
| United States |
| NYU - Langone Health | New York | New York | 10016 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Height | Median | Full Range | cm |
|
| Weight | Median | Full Range | kg |
|
|
|
| Primary | Tolerability of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex in Subjects With Recurrent or Progressive Glioblastoma Will be Assessed Based on Expected Dose Compliance | The Day 0 (as applicable), and Day 1 doses of veledimex were administered by study personnel at the study center. Thereafter, subjects could self-administer the remaining once daily dose of veledimex. Subjects were instructed to document veledimex dosing compliance in a subject diary, including the time each dose was taken, the time the subject ate the last meal prior to administration of veledimex, the number of capsules taken, whether the subject missed any veledimex doses, and reason for any missed doses. Investigational product container(s) with any remaining capsules were returned to the study staff on Day 15, and staff assessed dose compliance. | The Full Analysis Set (FAS): Overall Safety Population (OSP) includes all subjects who have received at least one dose of veledimex (pretumor resection and) and/or all subjects who received Ad-RTS-hIL-12. | Posted | Count of Participants | Participants | Days 1 through 14 of each 21-day treatment cycle, over a total treatment period of up to 6 cycles (approximately 4 months) |
|
|
|
| Secondary | Determine the Overall Survival (OS) of Ad-RTS-hIL-12 + Veledimex | OS is defined as the duration of time from the first dose of study drug (Day 0) to the date of death from any cause in days or months. Subjects are censored based on the last date known to be alive. For example:
| The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP is used for analysis of overall survival. | Posted | Median | Inter-Quartile Range | Months | From the first dose of study drug for up to 2 years. |
|
|
|
| Secondary | Veledimex Pharmacokinetic Profile: Maximum Plasma Concentration (Cmax) | The maximum plasma concentration (Cmax) of veledimex | All Subjects with available plasma-time concentration data post dose on Day 14 and predose on Day 15 are included in the PK Population. | Posted | Mean | Standard Deviation | ng/mL | 15 days |
|
|
|
| Secondary | Veledimex Pharmacokinetic Profile: Time to Maximum Plasma Concentration (Tmax) | Time to maximum plasma concentration (Tmax) of veledimex. Tmax was estimated based on time of maximum concentration (Cmax) from predose (Day 0 or 14) to predose the following day (Day 1 or 15). | All Subjects with available plasma-time concentration data post dose on Day 14 and predose on Day 15 are included in the PK Population. | Posted | Mean | Standard Deviation | hr | 15 days |
|
|
|
| Secondary | Veledimex Pharmacokinetic Profile: Half-life (t1/2) | Half-life (t1/2) of veledimex | All subjects with available plasma-time concentration data post dose (steady state) on Day 14 and predose on Day 15 are included in the PK Population. | Posted | Mean | Standard Deviation | hr | 15 days |
|
|
|
| Secondary | Veledimex Pharmacokinetic Profile: Area-under-the-concentration Versus Time Curve (AUC) | Area-under-the-concentration versus time curve (AUC) of veledimex from Day 14 predose to Day 15 predose. AUC was estimated using the elimination rate constant k, where k = ln(Cmax/Ctrough)/time difference and AUC is approximately Cmax/k. | All subjects with available plasma-time concentration data post dose (steady state) on Day 14 and predose on Day 15 are included in the PK Population. | Posted | Mean | Standard Deviation | ng*hr/mL | 15 days |
|
|
|
| Secondary | Veledimex Pharmacokinetic Profile: Volume of Distribution (Vd) | Volume of distribution (Vd) of veledimex. Vd was calculated using AUC approximated as described in the Outcome Measure Description for Outcome Measure 6. | The PK blood sample collection was performed either pre-dose or 3-5 hours post-dose, therefore only Cmax and Ctrough will be summarized and plotted. There will be no parameters including time to maximum plasma concentration (Tmax), half-life (t1/2), area under the curve (AUC), volume of distribution (Vd), and clearance (CL). | Posted | Mean | Standard Deviation | mL | 15 days |
|
|
|
| Secondary | Veledimex Pharmacokinetic Profile: Clearance (CL) | Clearance (CL) of veledimex. CL was calculated using AUC approximated as described in the Outcome Measure Description for Outcome Measure 6. | All Subjects with available plasma-time concentration data post dose on Day 14 and predose on Day 15 are included in the PK Population. | Posted | Mean | Standard Deviation | mL/hr | 15 days |
|
|
|
| Secondary | Veledimex Concentration Ratio Between the Brain Tumor and the Blood | Veledimex concentration ratio was calculated based on the Day 0 tumor and plasma PK results. | All Subjects with available serum-time concentration data are included in the PK Population. | Posted | Mean | Standard Deviation | ratio | Day 0 (at the time of tumor resection) |
|
|
|
| Secondary | Tumor Objective Response Rate (ORR) | For the ORR calculation, responders are defined as those experiencing a confirmed complete response or confirmed partial response. Non-responders are those either with stable or progressive disease. Those subjects that cannot be assessed will be treated as non-responders for the purposes of deriving the percentage of responders and confidence intervals. Overall Response was assessed at multiple timepoints (day 56, week 16, week 24, and week 48) by the study investigators. Changes to the original plan for exploration of estimates of efficacy are summarized below. • The best overall response (BOR) endpoint was added to the efficacy assessment and reported here. | The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP is to be used for analysis of dose limiting toxicities, overall survival and progression free survival and finding the maximum tolerated dose. | Posted | Count of Participants | Participants | 48 weeks |
|
|
|
| Secondary | Progression Free Survival (PFS) | PFS (progression free survival) is the time in months from the first treatment (either veledimex or Ad-RTS-hIL-12) to the first assessment on which the overall response is reported as disease progression. Subjects withdrawing from the study will be censored at their last non progressive disease response assessment. If a subject does not have a non-progressive disease response assessment, the subject will be censored on the date of the first treatment as described above. | The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. | Posted | Mean | Standard Deviation | Days | From the first dose of study drug for up to 2 years. |
|
|
|
| Secondary | Rate of Pseudo-progression (PSP) | PSP Progression free survival was originally defined for determination of PSP requiring confirmation of progression based on RANO/iRANO criteria guidelines. | The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP is denoted as the PP population in this uncontrolled setting. | Posted | Count of Participants | Participants | From the first dose of study drug for up to 2 years. |
|
|
|
| Secondary | Changes From Baseline in Cellular Responses Elicited by Ad-RTS-hIL-12 and Veledimex | Evaluation in changes in immune cell population markers, such as CD3 and CD8 in tumor | Due to the study's early termination and limited enrollment, a decision was made not to perform the planned immunohistochemistry (IHC) analyses on collected tumor biopsies. Therefore, no data are available for this endpoint, and zero subjects were analyzed. These analyses will not be performed in the future, and data for this outcome measure will not be reported. | Posted | Baseline and Week 6. |
|
|
|
| Secondary | Peak Serum Concentration of Interleukin-12 (IL-12) | Serum concentrations of IL-12 were measured at multiple timepoints post-dose. For each participant, the peak (maximum) concentration observed from Day 3 through the 30-day follow-up visit was identified. This measure summarizes the mean of those individual peak concentrations. | The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP is denoted as the Per Protocol population in this uncontrolled setting. | Posted | Mean | Standard Error | pg/mL | Samples were collected at Baseline (Day 1), Day 3, Day 8, and Day 15 of Cycle 1, and at the 30-day follow-up visit. |
|
|
|
| Secondary | Peak Serum Concentration of Interferon-gamma (IFN-γ) | Serum concentrations of IFN-γ were measured at multiple timepoints post-dose. For each participant, the peak (maximum) concentration observed from Day 3 through the 30-day follow-up visit was identified. This measure summarizes the mean of those individual peak concentrations. | The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP is denoted as the Per Protocol population in this uncontrolled setting. | Posted | Mean | Standard Error | pg/mL | Samples were collected at Baseline (Day 1), Day 3, Day 8, and Day 15 of Cycle 1, and at the 30-day follow-up visit |
|
|
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| 4 |
| 36 |
| 10 |
| 36 |
| 36 |
| 36 |
| Aphasia | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Brain Oedema | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Cerebrovascular Accident | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Partial Seizures | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Neutrophil Count Decreased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
|
| Mental Status Changes | Psychiatric disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Aphasia | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Hemiparesis | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Brain oedema | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Ataxia | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Cerebrovascular Accident | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Cognitive Disorder | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Dysarthria | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Haemorrhage Intracranial | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Speech Disorder | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Cerebral Haemorrhage | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Facial Paralysis | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Cerebrospinal Fluid Retention | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Facial Paresis | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Neuralgia | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Pyramidal Tract Syndrome | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Subdural Hygroma | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Dry Mouth | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Hypoaesthesia Oral | Gastrointestinal disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Lymphocyte Count Decreased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Platelet Count Decreased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| White Blood Cell Count Decreased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Aspartate Aminotransferase Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Alanine Aminotransferase Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Neutrophil Count Decreased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Blood Lactate Dehydrogenase Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Amylase Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| C-Reactive Protein Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Activated Partial Thromboplastin Time Prolonged | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Blood Albumin Decreased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Blood Alkaline Phosphatase Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| International Normalised Ratio Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Blood Calcium Decreased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Blood Potassium Decreased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Blood Bilirubin Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Heart Rate Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Vitamin D Decreased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| White Blood Cell Count Increased | Investigations | MedDRA Version 23.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Hypernatraemia | Metabolism and nutrition disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Decreased Appetite | Metabolism and nutrition disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Gait Disturbance | General disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Influenza Like Illness | General disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA Version 23.0 | Systematic Assessment |
|
| Oral Candidiasis | Infections and infestations | MedDRA Version 23.0 | Systematic Assessment |
|
| Lower Respiratory Tract Infection | Infections and infestations | MedDRA Version 23.0 | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 23.0 | Systematic Assessment |
|
| Wound Infection | Infections and infestations | MedDRA Version 23.0 | Systematic Assessment |
|
| Incision site pain | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Systematic Assessment |
|
| Procedural Pain | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Systematic Assessment |
|
| Pseudomeningocele | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Systematic Assessment |
|
| Thermal Burn | Injury, poisoning and procedural complications | MedDRA Version 23.0 | Systematic Assessment |
|
| Confusional State | Psychiatric disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Abulia | Psychiatric disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Hot Flush | Vascular disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Respiratory Tract Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Periorbital Oedema | Eye disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Vision Blurred | Eye disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Blepharospasm | Eye disorders | MedDRA Version 23.0 | Systematic Assessment |
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| Retinal Exudates | Eye disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Retinal Tear | Eye disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Urinary Retention | Renal and urinary disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Spinal Muscular Atrophy | Congenital, familial and genetic disorders | MedDRA Version 23.0 | Systematic Assessment |
|
| Hepatic Lesion | Hepatobiliary disorders | MedDRA Version 23.0 | Systematic Assessment |
|
Disclosure shall not occur until (i) twenty-four (24) months have elapsed since Sponsor has notified Institution of the completion of the multi-center Study in order for Sponsor to comply with its obligations under 21 CFR 312.53(c)(4), or (ii) after the publication of the multi-center Study data, if the Study is a multi-center Study or Sponsor confirms in writing there will be no multi-center publication.
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| Progressive Disease |
|
| Not Evaluable |
|
| No Response |
|
| Missing |
|