Trial Outcomes & Findings for A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG (NCT NCT03330197)
NCT ID: NCT03330197
Last Updated: 2025-08-12
Results Overview
Dose Limiting Toxicities are defined as events that occur during the first 28 days (Day 0 - Day 28) that meets one of the following criteria: * Any local reaction that requires operative intervention and is felt to be attributable to study drug * Any local reaction that has life-threatening consequences requiring urgent intervention or results in death and is felt to be attributable to study drug * Any Grade 3 or higher non-hematologic adverse event that is at least possibly related to study drug and lasts ≥ 3 days * Nausea and vomiting will not be considered a DLT unless at least Grade 3 and refractory to antiemetics * Grade 3 or higher thrombocytopenia (\< 50,000/mm3) at least possibly related to study drug * Any Grade 4 hematologic toxicity (except thrombocytopenia) that is at least possibly related to study drug and lasts ≥ 5 days * Transient neurological changes are expected in Arm 2 and will not be considered a DLT unless they last \> 10 days
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
6 participants
Primary outcome timeframe
From Day 0 through Day 56
Results posted on
2025-08-12
Participant Flow
One Arm 2 subject was screened and enrolled but consent was withdrawn prior to Day 0.
All subjects in Arm 1 received 10mg daily of veledimex. A total of three subjects were assigned to Arm 2. One subject withdrew consent prior to any study procedures on Day 0 and received no treatment. A second subject was discontinued from the study due to a Serious Adverse Event (SAE) after the Ad-RTS-hIL-12 injection but prior to receiving veledimex. The third subject received veledimex at a dose of 5 mg/day, which was the body surface area (BSA)-adjusted dose.
Participant milestones
| Measure |
Arm 1 - Closed
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex)
|
Arm 2 - Closed
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE.
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
|
Overall Study
Treated With Ad-RTS-hIL-12 Injection
|
3
|
2
|
|
Overall Study
Treated With Veledimex
|
3
|
1
|
|
Overall Study
Did Not Receive Veledimex Treatment
|
0
|
2
|
|
Overall Study
Received Veledimex Treatment
|
3
|
1
|
|
Overall Study
COMPLETED
|
3
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Arm 1 - Closed
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex)
|
Arm 2 - Closed
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG
Baseline characteristics by cohort
| Measure |
Arm 1 - Closed
n=3 Participants
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex)
|
Arm 2 - Closed
n=2 Participants
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE.
|
Total
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
16.1 years
n=5 Participants
|
5.8 years
n=7 Participants
|
12.1 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 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
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
WHO High Grade at Baseline
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Day 0 through Day 56Population: The Full Analysis Set (FAS) or the OSP includes every subject who received at least one dose of any study drug recorded in the Data Management (DM) database excluding screen failures. • The data analysis for Adverse Events or other Safety variables will be performed on the OSP.
Dose Limiting Toxicities are defined as events that occur during the first 28 days (Day 0 - Day 28) that meets one of the following criteria: * Any local reaction that requires operative intervention and is felt to be attributable to study drug * Any local reaction that has life-threatening consequences requiring urgent intervention or results in death and is felt to be attributable to study drug * Any Grade 3 or higher non-hematologic adverse event that is at least possibly related to study drug and lasts ≥ 3 days * Nausea and vomiting will not be considered a DLT unless at least Grade 3 and refractory to antiemetics * Grade 3 or higher thrombocytopenia (\< 50,000/mm3) at least possibly related to study drug * Any Grade 4 hematologic toxicity (except thrombocytopenia) that is at least possibly related to study drug and lasts ≥ 5 days * Transient neurological changes are expected in Arm 2 and will not be considered a DLT unless they last \> 10 days
Outcome measures
| Measure |
Arm 1 - Closed
n=3 Participants
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex)
|
Arm 2 - Closed
n=2 Participants
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE.
|
|---|---|---|
|
The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance.
DLTs
|
0 Participants
|
1 Participants
|
|
The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance.
AE leading to death
|
0 Participants
|
0 Participants
|
|
The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance.
AEs leading to study discontinuation
|
0 Participants
|
0 Participants
|
|
The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance.
AEs leading to study treatment discontinuation
|
0 Participants
|
1 Participants
|
|
The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance.
AE leading to leading to study treatment dose reduction
|
0 Participants
|
0 Participants
|
|
The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance.
Adverse events leading to study treatment dose interruption
|
1 Participants
|
1 Participants
|
|
The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance.
Treatment emergent adverse events
|
3 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: From Day 0 through Day 15 of veledimex dosingPopulation: Patients with available brain tumor results. Arm 2 patient result was below the level of quantitation (1.8 ng/mL). Arm 1 BLQ was 0.1 ng/mL. One patients was less than BLQ. Arm 2 patient plasma concentrations were not reported due to bioanalytical non-reproducibility. NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
Veledimex brain concentration. Veledimex plasma concentration was below the limit of quantitation for most patients. Given the limited number of subjects enrolled and early closure of the study, complete assessment of veledimex in blood and brain tumor could not be determined.
Outcome measures
| Measure |
Arm 1 - Closed
n=3 Participants
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex)
|
Arm 2 - Closed
n=1 Participants
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE.
|
|---|---|---|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Brain tumor results (Day 0)
|
0.172 ng/mL
Interval 0.1 to 0.211
|
NA ng/mL
For the one patient analyzed in Arm 2, the brain tumor concentration at Day 0 was Below the Quantitation Limit (BQL) of 1.80 ng/mL. All subsequent plasma concentrations for this patient were reported by the laboratory as Non-Reportable Results (NRR) and are therefore not available.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 0 time of resection - veledimex plasma PK
|
1.40 ng/mL
Interval 1.0 to 1.86
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 1 predose- veledimex plasma PK
|
1.02 ng/mL
Interval 1.0 to 1.07
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 1 2 hr postdose- veledimex plasma PK
|
11.64 ng/mL
Interval 8.61 to 13.8
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 1 4 hr postdose- veledimex plasma PK
|
5.66 ng/mL
Interval 3.31 to 9.85
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 1 6 hr postdose- veledimex plasma PK
|
5.64 ng/mL
Interval 2.91 to 11.1
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 2 - veledimex plasma PK
|
2.09 ng/mL
Interval 1.4 to 2.92
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 14 predose- veledimex plasma PK
|
4.39 ng/mL
Interval 2.61 to 6.15
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 14 2 hr postdose - veledimex plasma PK
|
36.83 ng/mL
Interval 14.3 to 66.9
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 14 4 hr postdose - veledimex plasma PK
|
19.80 ng/mL
Interval 9.19 to 30.9
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 14 6 hr postdose - veledimex plasma PK
|
7.63 ng/mL
Interval 7.41 to 8.05
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
|
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Day 15 24 hr postdose - veledimex plasma PK
|
4.35 ng/mL
Interval 3.13 to 5.03
|
NA ng/mL
For the one patient who received veledimex and was analyzed, plasma concentration was reported by the lab as NRR (Non-Reportable Results). NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
|
SECONDARY outcome
Timeframe: 2 YearsPopulation: The Safety Population was defined as all subjects who received at least 1 dose of study drug.
OS is defined as the duration of time from the first dose of the study drug to the date of death. Subjects were followed for up to 2 years.
Outcome measures
| Measure |
Arm 1 - Closed
n=3 Participants
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex)
|
Arm 2 - Closed
n=2 Participants
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE.
|
|---|---|---|
|
Overall Survival (OS)
Deceased
|
2 participants
|
1 participants
|
|
Overall Survival (OS)
Alive
|
0 participants
|
1 participants
|
|
Overall Survival (OS)
Unknown
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Day 0, Day 3, Day 7, Day 14, and Day 28Population: The Biomarker Evaluation Population (BEP) includes all subjects who received Ad-RTS-hIL-12 + at least one dose of their cohort-specific dose of veledimex who have adequate biomarker sample(s) at screening (baseline) and at least one non-missing follow-up biomarker assessment, excluding the disqualified assessments. All biomarker related data presentation will be based on the BEP unless specified otherwise. Note: In Arm 2, only 1 subject met this criteria.
Samples for serum cytokine analysis were collected on Days 0, 3, 7, 14, and 28. For the results, participants who had samples analyzed were included in the "number analyzed" counts; however, values that were below the limit of quantitation (BLQ) were excluded from the calculation of mean and standard deviation.
Outcome measures
| Measure |
Arm 1 - Closed
n=3 Participants
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex)
|
Arm 2 - Closed
n=1 Participants
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE.
|
|---|---|---|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Serum IFN-gamma - Day 0
|
NA pg/mL
Standard Deviation NA
All subjects had BLQ values at this time point. BLQ was reported as \<2.4 pg/mL.
|
NA pg/mL
Standard Deviation NA
Subject's result was BLQ at this time point. BLQ was reported as \<2.4 pg/mL.
|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Serum IFN-gamma - Day 3
|
4.4 pg/mL
Standard Deviation 0
|
11.4 pg/mL
Standard Deviation 0
|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Serum IFN-gamma - Day 7
|
6.4 pg/mL
Standard Deviation 0
|
NA pg/mL
Standard Deviation NA
Subject's result was BLQ at this time point. BLQ was reported as \<2.4 pg/mL.
|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Serum IFN-gamma - Day 14
|
NA pg/mL
Standard Deviation NA
Two subjects had BLQ values at this time point. BLQ was reported as \<2.4 pg/mL.
|
NA pg/mL
Standard Deviation NA
Subject's result was BLQ at this time point. BLQ was reported as \<2.4 pg/mL.
|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Serum IFN-gamma - Day 28
|
NA pg/mL
Standard Deviation NA
Two subjects had BLQ values at this time point. BLQ was reported as \<2.4 pg/mL.
|
NA pg/mL
Standard Deviation NA
Subject's result was BLQ at this time point. BLQ was reported as \<2.4 pg/mL.
|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Serum IL-12 - Day 0
|
12 pg/mL
Standard Deviation 0
|
NA pg/mL
Standard Deviation NA
Subject's result was BLQ at this time point. BLQ was reported as \<1.6 pg/mL.
|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
1.6Serum IL-12 - Day 3
|
11.1 pg/mL
Standard Deviation 2.1
|
NA pg/mL
Standard Deviation NA
Subject's result was BLQ at this time point. BLQ was reported as \<1.6 pg/mL.
|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Serum IL-12 - Day 7
|
6.6 pg/mL
Standard Deviation 4.7
|
NA pg/mL
Standard Deviation NA
Subject's result was BLQ at this time point. BLQ was reported as \<1.6 pg/mL.
|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Serum IL-12 - Day 14
|
NA pg/mL
Standard Deviation NA
Two subjects had BLQ values at this time point. BLQ was reported as \<2.4 pg/mL.
|
NA pg/mL
Standard Deviation NA
Subject's result was BLQ at this time point. BLQ was reported as \<1.6 pg/mL.
|
|
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Serum IL-12 - Day 28
|
1.6 pg/mL
Standard Deviation 0
|
NA pg/mL
Standard Deviation NA
Subject's result was BLQ at this time point. BLQ was reported as \<1.6 pg/mL.
|
SECONDARY outcome
Timeframe: 2 YearsPopulation: The Full Analysis Set (FAS) or the OSP includes every subject who received at least one dose of any study drug recorded in the Data Management (DM) database excluding screen failures. • The data analysis for Adverse Events or other Safety variables will be performed on the OSP.
Subjects with Ad-RTS-hIL-12 and veledimex related adverse events will be assessed for safety by CTCAE v5.0
Outcome measures
| Measure |
Arm 1 - Closed
n=3 Participants
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex)
|
Arm 2 - Closed
n=2 Participants
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE.
|
|---|---|---|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
HEADACHE (NERVOUS SYSTEM DISORDERS)
|
2 participants
|
1 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
WHITE BLOOD CELL COUNT DECREASED (INVESTIGATIONS)
|
2 participants
|
2 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
LYMPHOCYTE COUNT DECREASED (INVESTIGATIONS)
|
2 participants
|
2 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
VOMITING (GASTROINTESTINAL DISORDERS)
|
2 participants
|
1 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
PYREXIA (GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS)
|
1 participants
|
2 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
ANAEMIA (BLOOD AND LYMPHATIC SYSTEM DISORDERS)
|
2 participants
|
0 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
APHASIA (NERVOUS SYSTEM DISORDERS)
|
1 participants
|
1 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
FATIGUE (GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS)
|
1 participants
|
1 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
HYPONATRAEMIA (METABOLISM AND NUTRITION DISORDERS)
|
2 participants
|
0 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
NAUSEA (GASTROINTESTINAL DISORDERS)
|
1 participants
|
1 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
PLATELET COUNT DECREASED (INVESTIGATIONS)
|
2 participants
|
0 participants
|
|
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
TACHYCARDIA (CARDIAC DISORDERS)
|
0 participants
|
2 participants
|
SECONDARY outcome
Timeframe: 2 YearsPopulation: The Efficacy Evaluable population is defined as all subjects who received at least 1 dose of study drug and had at least one post-treatment tumor assessment.
Best Overall Response was assessed using the immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria.
Outcome measures
| Measure |
Arm 1 - Closed
n=3 Participants
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex)
|
Arm 2 - Closed
n=2 Participants
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE.
|
|---|---|---|
|
Best Overall Response by iRANO Criteria
Best Tumor Response SD
|
0 participants
|
2 participants
|
|
Best Overall Response by iRANO Criteria
Best Tumor Response PD
|
3 participants
|
0 participants
|
|
Best Overall Response by iRANO Criteria
Not Evaluable
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: From the time of first response (CR or PR) until progression or deathPopulation: The analysis population for this measure included subjects from the Efficacy Evaluable population who achieved a Complete Response (CR) or Partial Response (PR).
Duration of Response (DOR) was defined as the time from the first documentation of a Complete Response (CR) or Partial Response (PR) to the first documentation of Progressive Disease (PD) or death due to any cause, whichever occurred first.
Outcome measures
Outcome data not reported
Adverse Events
Arm 1
Serious events: 1 serious events
Other events: 3 other events
Deaths: 2 deaths
Arm 2
Serious events: 1 serious events
Other events: 2 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Arm 1
n=3 participants at risk
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor): 1 dose level (10mg/day) 15 oral daily doses of veledimex
|
Arm 2
n=2 participants at risk
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG): 2 dose levels (10mg/day, 20mg/day) 14 oral daily doses of veledimex
|
|---|---|---|
|
Nervous system disorders
Seizure
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
Other adverse events
| Measure |
Arm 1
n=3 participants at risk
Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor): 1 dose level (10mg/day) 15 oral daily doses of veledimex
|
Arm 2
n=2 participants at risk
Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG): 2 dose levels (10mg/day, 20mg/day) 14 oral daily doses of veledimex
|
|---|---|---|
|
Metabolism and nutrition disorders
HYPOCALCAEMIA
|
66.7%
2/3 • Number of events 2 • 2 years
|
100.0%
2/2 • Number of events 4 • 2 years
|
|
Investigations
LYMPHOCYTE COUNT DECREASED
|
66.7%
2/3 • Number of events 4 • 2 years
|
100.0%
2/2 • Number of events 5 • 2 years
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
66.7%
2/3 • Number of events 3 • 2 years
|
100.0%
2/2 • Number of events 3 • 2 years
|
|
Blood and lymphatic system disorders
ANAEMIA
|
100.0%
3/3 • Number of events 5 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
General disorders
PYREXIA
|
33.3%
1/3 • Number of events 1 • 2 years
|
100.0%
2/2 • Number of events 4 • 2 years
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 2 • 2 years
|
|
Metabolism and nutrition disorders
ALKALOSIS
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Investigations
SERUM AMYLASE INCREASED
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Psychiatric disorders
ANXIETY
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Nervous system disorders
APHASIA
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Nervous system disorders
ATAXIA
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Cardiac disorders
BRADYCARDIA
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Infections and infestations
CANDIDA INFECTION
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Nervous system disorders
DIZZINESS
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Eye disorders
DRY EYE
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Nervous system disorders
DYSARTHRIA
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Gastrointestinal disorders
DYSPHAGIA
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Investigations
ELECTROCARDIOGRAM QT PROLONGED
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Nervous system disorders
FACIAL NERVE DISORDER
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Nervous system disorders
FACIAL PARESIS
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
General disorders
FATIGUE
|
33.3%
1/3 • Number of events 1 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
General disorders
GAIT DISTURBANCE
|
33.3%
1/3 • Number of events 1 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Investigations
GAMMA-GLUTAMYLTRANSFERASE INCREASED
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Nervous system disorders
HEADACHE
|
66.7%
2/3 • Number of events 2 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Nervous system disorders
HEMIANOPIA
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Nervous system disorders
HEMIPARESIS
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Nervous system disorders
HEMIPLEGIA
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Nervous system disorders
HYDROCEPHALUS
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 2 • 2 years
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
0.00%
0/3 • 2 years
|
100.0%
2/2 • Number of events 2 • 2 years
|
|
Metabolism and nutrition disorders
HYPERKALAEMIA
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
HYPERNATRAEMIA
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Vascular disorders
HYPERTENSION
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
66.7%
2/3 • Number of events 3 • 2 years
|
50.0%
1/2 • Number of events 3 • 2 years
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
33.3%
1/3 • Number of events 1 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
66.7%
2/3 • Number of events 2 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
HYPOPHOSPHATAEMIA
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Investigations
LIPASE INCREASED
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 4 • 2 years
|
|
Skin and subcutaneous tissue disorders
MADAROSIS
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Nervous system disorders
MEMORY IMPAIRMENT
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Gastrointestinal disorders
NAUSEA
|
33.3%
1/3 • Number of events 1 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Eye disorders
OPTIC NERVE DISORDER
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Investigations
PLATELET COUNT DECREASED
|
66.7%
2/3 • Number of events 2 • 2 years
|
0.00%
0/2 • 2 years
|
|
Investigations
RED BLOOD CELL SEDIMENTATION RATE INCREASED
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
SALIVARY HYPERSECRETION
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Cardiac disorders
TACHYCARDIA
|
0.00%
0/3 • 2 years
|
100.0%
2/2 • Number of events 2 • 2 years
|
|
Injury, poisoning and procedural complications
VESSEL PUNCTURE SITE PAIN
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
|
Eye disorders
VISION BLURRED
|
33.3%
1/3 • Number of events 1 • 2 years
|
0.00%
0/2 • 2 years
|
|
Gastrointestinal disorders
VOMITING
|
66.7%
2/3 • Number of events 2 • 2 years
|
100.0%
2/2 • Number of events 5 • 2 years
|
|
Investigations
WEIGHT DECREASED
|
0.00%
0/3 • 2 years
|
50.0%
1/2 • Number of events 1 • 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place