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Efficacy and Safety of AP 12009 in Patients With Recurrent or Refractory Anaplastic Astrocytoma or Secondary Glioblastoma (SAPPHIRE)

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ClinicalTrials.gov Identifier: NCT00761280
Recruitment Status : Terminated (Unable to recruit the projected patient number. All analyses are descriptive, only.)
First Posted : September 29, 2008
Results First Posted : August 22, 2014
Last Update Posted : November 14, 2014
Sponsor:
Information provided by (Responsible Party):
Isarna Therapeutics GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Anaplastic Astrocytoma
Glioblastoma
Interventions Drug: trabedersen
Drug: temozolomide
Device: Drug delivery system for administration of AP 12009
Procedure: Placement of Drug Delivery System
Drug: carmustine
Drug: lomustine
Enrollment 27

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Period Title: Randomization to First Dose
Started 14 13
Catheter Surgery 13 [1] 0 [2]
First Dose of Study Drug / Chemotherapy 12 11 [1]
Completed 12 11
Not Completed 2 2
Reason Not Completed
Withdrawal by Subject             0             2
Sponsor decision             1             0
Other             1             0
[1]
Safety population
[2]
Not applicable to control group
Period Title: First Dose to End of Study
Started 12 11
Completed 0 [1] 0 [1]
Not Completed 12 11
Reason Not Completed
End of trial             5             5
Progressive disease             5             3
Sponsor decision             1             2
Death             1             0
Lost to Follow-up             0             1
[1]
Study was discontinued early due to the inability to recruit a sufficient number of participants.
Arm/Group Title Trabedersen 10 µM Chemotherapy Total
Hide Arm/Group Description

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Total of all reporting groups
Overall Number of Baseline Participants 14 13 27
Hide Baseline Analysis Population Description
The Intent-to-treat population includes all participants randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 13 participants 27 participants
38.2  (12.72) 40.8  (11.63) 39.5  (12.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
Female
5
  35.7%
5
  38.5%
10
  37.0%
Male
9
  64.3%
8
  61.5%
17
  63.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
White 8 10 18
Black 0 0 0
Asian 6 2 8
Hispanic or Latino 0 1 1
American Indian or Native Alaskan 0 0 0
Native Hawaiian or Other Pacific Islander 0 0 0
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
Spain 1 1 2
Austria 0 1 1
Russian Federation 4 4 8
India 6 2 8
Mexico 0 1 1
Canada 0 1 1
Germany 1 2 3
Israel 0 1 1
Poland 2 0 2
[1]
Measure Description: Study was discontinued early because of the inability to recruit a sufficient number of suitable participants within the planned recruitment period, therefore not all planned sites recruited participants. Only those regions that recruited at least one participant are listed.
Height (cm) (Descriptive analysis, only)   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 14 participants 13 participants 27 participants
172.57  (9.913) 170.29  (10.019) 171.52  (9.829)
[1]
Measure Description: Height is missing for one participant in the Chemotherapy group.
Weight (kg) (Descriptive analysis, only)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 14 participants 13 participants 27 participants
75.34  (17.265) 71.62  (14.213) 73.62  (15.731)
[1]
Measure Description: Weight is missing for one participant in the Chemotherapy group.
Diagnosis of Anaplastic Astrocytoma (AA) World Health Organization (WHO) Grade III   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
Refractory 3 2 5
Recurrent 11 10 21
[1]
Measure Description: Twenty-six participants were diagnosed with Anaplastic Astrocytoma, and one participant was diagnosed with Secondary Glioblastoma Multiforme.
Time of first diagnosis of AA WHO Grade III (years) (Descriptive analysis, only)   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 13 participants 27 participants
1.71  (1.110) 1.81  (1.194) 1.75  (1.124)
[1]
Measure Description: Time of first diagnosis (in years before study entry) is available for all 14 participants in the Trabedersen group and 11 participants in the chemotherapy group.
Diagnosis of other brain tumor prior to diagnosis of Anaplastic Astrocytoma WHO Grade III   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
AA WHO Grade I 0 0 0
AA WHO Grade II 1 0 1
Not diagnosed with Other Brain Tumor 12 12 24
Other diagnosis 1 0 1
[1]
Measure Description: Twenty-six participants were diagnosed with Anaplastic Astrocytoma, and one participant was diagnosed with Secondary Glioblastoma Multiforme.
Diagnosis of Secondary Glioblastoma Multiforme (GBM) (WHO Grade IV)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
0 1 1
Time to first diagnosis of Secondary GBM (years) (Descriptive analysis, only)   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 13 participants 27 participants
NA [2]   (NA) 0.03 [3]   (NA) 0.03 [3]   (NA)
[1]
Measure Description: Time of first diagnosis (in years before study entry) of Secondary Glioblastoma Multiforme. One participant in the Chemotherapy group was diagnosed with Secondary Glioblastoma Multiforme (GBM); all other participants were diagnosed with Anaplastic Astrocytoma (AA).
[2]
No participants in this group were diagnosed with Secondary Glioblastoma Multiforme.
[3]
One participant in this group was diagnosed with Secondary Glioblastoma Multiforme.
Previous diagnosis of Astrocytoma or AA before diagnosis of Secondary Glioblastoma Multiforme  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
Previous diagnosis of Astrocytoma 0 0 0
Previous diagnosis of Anaplastic Astrocytoma 0 1 1
One or more Prior Surgical Treatments  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
Yes 14 12 26
No 0 1 1
One or more Prior Radiotherapy Regimens  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
14 13 27
One or more Prior Chemotherapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
Yes 10 9 19
No 4 4 8
One or more Prior Immunotherapy  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 27 participants
Yes 1 1 2
No 13 12 25
1.Primary Outcome
Title Survival Rate at 24 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
Hide Description Survival rate was defined as the proportion of participants known to be alive at 24 months from randomization. If a participant's status was unknown and there was no follow-up information available, they were categorized as 'Died' for the purposes of the analysis.
Time Frame 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.6
(11.7 to 54.6)
15.4
(4.3 to 42.2)
2.Primary Outcome
Title Survival at 24 Months in the Intent-to-treat Population - Number of Participants
Hide Description Survival status was assessed at 24 months from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. The category "Lost to / insufficient follow-up" includes participants who were alive at last data collection point but did not yet have enough follow-up time to reach the 24 month time point.
Time Frame 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Measure Type: Number
Unit of Measure: participants
Alive 4 2
Died 7 5
Lost to/insufficient follow-up 3 6
3.Secondary Outcome
Title Survival Rate at 12, 18, and 21 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
Hide Description Survival rate was defined as the proportion of participants known to be alive at each time-point from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead.
Time Frame 12, 18, and 21 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Survival rates at 12 months
57.1
(32.6 to 78.6)
53.8
(29.1 to 76.8)
Survival rates at 18 months
42.9
(21.4 to 67.4)
38.5
(17.7 to 64.5)
Survival rates at 21 months
35.7
(16.3 to 61.2)
23.1
(8.2 to 50.3)
4.Secondary Outcome
Title Survival at 12, 18, and 21 Months in the Intent-to-treat Population - Number of Participants
Hide Description Survival status was assessed at each time-point from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. The category "Lost to follow-up" for each time-point includes participants who were alive at the last data collection point but did not yet have enough follow-up time to reach the time point.
Time Frame 12, 18, and 21 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Measure Type: Number
Unit of Measure: participants
Alive at 12 months 8 7
Died at 12 months 5 1
Lost to follow-up at 12 months 1 5
Alive at 18 months 6 5
Died at 18 months 7 3
Lost to follow-up at 18 months 1 5
Alive at 21 months 5 3
Died at 21 months 7 5
Lost to follow-up at 21 months 2 5
5.Secondary Outcome
Title Median Overall Survival (Days) From Randomization in the Intent-to-treat Population (Descriptive Analysis, Only)
Hide Description Median overall survival was defined as the date of randomization to the date of death. If a participant's status was unknown and there was no follow-up information available, they were categorized as 'Died' for the purposes of the analysis. Analysis was by Kaplan-Meier estimation.
Time Frame Up to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized. Early study discontinuation with site closures led to a high proportion of participants being censored or lost to follow-up in the initial analysis. Additional survival data were collected in a post-hoc fashion under a protocol amendment. These data are presented.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Median (95% Confidence Interval)
Unit of Measure: days
458.0 [1] 
(193.0 to NA)
584.5 [1] 
(426.0 to NA)
[1]
The upper limit of the 95% confidence interval could not be calculated because of insufficient data.
6.Secondary Outcome
Title Response Category by Independent Review in the Intent-to-treat Population - Number of Participants
Hide Description

Tumor response was classified based on the (neuro-)radiologist’s evaluation according to the Macdonald Response Criteria for bidimensionally measurable disease as outlined below:

  • Complete Response (CR): Disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off steroids, neurologically stable or improved.
  • Partial Response (PR): ≥50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, neurologically stable or improved.
  • Progressive Disease (PD): ≥25% increase in size of enhancing tumor or any new tumor on MRI scans, steroids stable or increased, neurologically worse.
  • Stable Disease (SD): all other situations.

Two qualified neuro-radiologists reviewed scans at each MRI time point, with adjudication of discrepancies by a third reviewer. Their findings and clinical information were independently reviewed by a neuro-oncologist, who made the assessment of overall response.

Time Frame Up to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 0 0
Partial Response (PR) 2 1
Stable Disease (SD) 2 6
Progressive Disease (PD) 7 1
Unknown 1 3
Missing 2 2
7.Secondary Outcome
Title Overall Response Rate (CR+PR) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
Hide Description Overall response rate was the proportion of participants with a best response of Complete Response (CR) or Partial Response (PR) observed from the start of treatment until disease progression.
Time Frame Up to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.3
(4.0 to 39.9)
7.7
(1.4 to 33.3)
8.Secondary Outcome
Title Tumor Control Rate (CR+PR+SD) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
Hide Description Tumor control rate was defined as the proportion of participants assessed as having Complete Response (CR), Partial Response (PR), or Stable Disease (SD). Participants with unknown or missing response were treated as non-responders.
Time Frame Up to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.6
(11.7 to 54.6)
53.8
(29.1 to 76.8)
9.Secondary Outcome
Title Median Duration of Response (Days) by Independent Review (Descriptive Analysis, Only)
Hide Description

Duration of response was defined as the time from the first documentation of confirmed response (Complete Response, CR, or Partial Response, PR) to the first signs of Progressive Disease (PD), as assessed by the study neuro-oncologist. Median Duration of Response was calculated by Kaplan-Meier estimate.

Censoring rules were:

  • at the date of randomization -- participants without baseline assessments, or for those with no post-baseline timor assessments who were discontinued for other than progressive disease or death.
  • at the date of last tumor assessment -- discontinuation other than PD or death, or if a new treatment was started prior to disease progression
  • at the date of death or last tumor assessment -- death or PD after one missed tumor assessment
  • at the date of last tumor assessment -- death or PD after more than one missed tumor assessment
  • at the date of last tumor assessment -- participants on ongoing treatment at data cut-off
Time Frame Up to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Due to early discontinuation of study, an insufficient number of patients reached this endpoint for estimation.
10.Secondary Outcome
Title Disease Progression at 10, 12, 14, 16, 18, 21, and 24 Months by Independent Review in the Intent-to-treat Population - Number of Participants
Hide Description

Tumor response was classified based on the (neuro-)radiologist’s evaluation:

  • Complete Response (CR): Disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off steroids, neurologically stable or improved.
  • Partial Response (PR): ≥50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, neurologically stable or improved.
  • Progressive Disease (PD): ≥25% increase in size of enhancing tumor or any new tumor on MRI scans, steroids stable or increased, neurologically worse.
  • Stable Disease (SD): all other situations.

Based on clinical and imaging data, an independent neuro-oncologist made the final assessment of "Progressed" versus "Not Progressed". Participants who had MRI assessment results missing or unknown were "UNK or missing", and were treated as "Progressed" for the purposes of the calculation.

Time Frame 10, 12, 14, 16, 18, 21, and 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Measure Type: Number
Unit of Measure: participants
Progressed at 10 months 7 5
Not progressed at 10 months 3 0
Status unknown / missing at 10 months 4 7
Lost to follow-up at 10 months 0 1
Progressed at 12 months 7 5
Not progressed at 12 months 2 0
Status unknown / missing at 12 months 5 7
Lost to follow-up at 12 months 0 1
Progressed at 14 months 7 5
Not progressed at 14 months 2 0
Status unknown / missing at 14 months 5 7
Lost to follow-up at 14 months 0 1
Progressed at 16 months 7 5
Not progressed at 16 months 2 0
Status unknown / missing at 16 months 5 7
Lost to follow-up at 16 months 0 1
Progressed at 18 months 7 5
Not progressed at 18 months 2 0
Status unknown / missing at 18 months 5 7
Lost to follow-up at 18 months 0 1
Progressed at 21 months 7 5
Not progressed at 21 months 1 0
Status unknown / missing at 21 months 6 7
Lost to follow-up at 21 months 0 1
Progressed at 24 months 7 5
Not progressed at 24 months 1 0
Status unknown / missing at 24 months 6 7
Lost to follow-up at 24 months 0 1
11.Secondary Outcome
Title Disease Progression Rate at 10, 12, 14, 16, 18, 21, and 24 Months by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
Hide Description

Tumor response was classified based on the (neuro-)radiologist’s evaluation:

  • Complete Response (CR): Disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off steroids, neurologically stable or improved.
  • Partial Response (PR): ≥50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, neurologically stable or improved.
  • Progressive Disease (PD): ≥25% increase in size of enhancing tumor or any new tumor on MRI scans, steroids stable or increased, neurologically worse.
  • Stable Disease (SD): all other situations.

Based on clinical and imaging data, an independent neuro-oncologist made the final assessment of "Progressed" versus "Not Progressed". Participants who had MRI assessment results missing or unknown were "UNK or missing", and were treated as "Progressed" for the purposes of the calculation.

Time Frame 10, 12, 14, 16, 18, 21 and 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Progression rate at 10 months
78.6
(52.4 to 92.4)
100.0
(77.2 to 100.0)
Progression rate at 12 months
85.7
(60.1 to 96.0)
100.0
(77.2 to 100.0)
Progression rate at 14 months
85.7
(60.1 to 96.0)
100.0
(77.2 to 100.0)
Progression rate at 16 months
85.7
(60.1 to 96.0)
100.0
(77.2 to 100.0)
Progression rate at 18 months
85.7
(60.1 to 96.0)
100.0
(77.2 to 100.0)
Progression rate at 21 months
92.9
(68.5 to 98.7)
100.0
(77.2 to 100.0)
Progression rate at 24 months
92.9
(68.5 to 98.7)
100.0
(77.2 to 100.0)
12.Secondary Outcome
Title Median Time to Progression (Days) by Independent Review for the Intent-to-treat Population (Descriptive Analysis, Only)
Hide Description Time to progression was calculated from the date of randomization to the date of the first documented tumor progression. Participants who did not progress or died were censored at the last tumor assessment date or the date of start of a new anti-tumor treatment or death.
Time Frame Up to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Intent-to-treat population includes all participants randomized.
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description:

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

Overall Number of Participants Analyzed 14 13
Median (95% Confidence Interval)
Unit of Measure: days
57.0 [1] 
(57.0 to NA)
153.5
(65.0 to 209.0)
[1]
The upper limit of the 95% confidence interval was not calculable because of insufficient data.
Time Frame Safety monitoring (including adverse events) started from the signature of the informed consent and continued until 28 days after the last administration of study drug, up to 24 months.
Adverse Event Reporting Description Only treatment-emergent adverse events are listed, defined as any AE whose onset occurred or intensity worsened after undertaking the first study procedure or first dose of study drug (whichever occurred first) but less than 28 days after medication/procedures had stopped. Adverse events (including lab tests) were assessed at study visits.
 
Arm/Group Title Trabedersen 10 µM Chemotherapy
Hide Arm/Group Description

10 µM trabedersen (AP 12009), intratumoral infusion, every other week, 11 cycles, maximum 21 weeks.

Drug delivery system for administration of AP 12009: Drug delivery system for Convection Enhanced Delivery consists of a portable pump (Pegasus vario or Pega vario) with drug reservoir (Pega Bag) and infusion line (Pega Line). Main implanted parts are the port access system (PORT-A-CATH) and the intratumoral catheter (Medtronic ventricular catheter).

Placement of Drug Delivery System: Surgery for placement of intratumoral catheter and subcutaneous port access system as per routine clinical practice. Stereotactical catheter placement controlled by CT.

Temozolomide: capsules, up to 200 mg/sqm/day, 5 days per cycle, up to 26 cycles.

OR carmustine: i.v. administration, up to 200 mg/sqm/day, 1 day per cycle, up to 8 cycles;

OR lomustine: capsules, 110 mg/sqm/day, 1 day per cycle, up to 8 cycles.

Only 1 of these 3 drugs/interventions is administered per patient in the comparator arm.

All-Cause Mortality
Trabedersen 10 µM Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Trabedersen 10 µM Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/13 (46.15%)      0/11 (0.00%)    
Blood and lymphatic system disorders     
Pancytopenia  1  1/13 (7.69%)  0/11 (0.00%) 
Gastrointestinal disorders     
Haematemesis  1  1/13 (7.69%)  0/11 (0.00%) 
General disorders     
Device malfunction  1  1/13 (7.69%)  0/11 (0.00%) 
Device occlusion  1  1/13 (7.69%)  0/11 (0.00%) 
Infections and infestations     
Meningitis  1  2/13 (15.38%)  0/11 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasm progression  1  2/13 (15.38%)  0/11 (0.00%) 
Nervous system disorders     
Grand mal convulsion  1  2/13 (15.38%)  0/11 (0.00%) 
Nervous system disorder  1  1/13 (7.69%)  0/11 (0.00%) 
Partial seizures  1  1/13 (7.69%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  1/13 (7.69%)  0/11 (0.00%) 
Pulmonary embolism  1  1/13 (7.69%)  0/11 (0.00%) 
Surgical and medical procedures     
Neurosurgery  1  1/13 (7.69%)  0/11 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trabedersen 10 µM Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/13 (92.31%)      9/11 (81.82%)    
Blood and lymphatic system disorders     
Pancytopenia  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Ear and labyrinth disorders     
Ear discomfort  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Eye disorders     
Blepharospasm  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Hippus  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Gastrointestinal disorders     
Nausea  1  3/13 (23.08%)  3 2/11 (18.18%)  2
Diarrhoea  1  2/13 (15.38%)  2 2/11 (18.18%)  2
Vomiting  1  2/13 (15.38%)  2 2/11 (18.18%)  2
Abdominal pain upper  1  0/13 (0.00%)  0 2/11 (18.18%)  2
Constipation  1  1/13 (7.69%)  1 1/11 (9.09%)  1
Dyspepsia  1  1/13 (7.69%)  1 1/11 (9.09%)  1
Abdominal distention  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Abdominal tenderness  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Gastrointestinal haemorrhage  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Haematemesis  1  1/13 (7.69%)  1 0/11 (0.00%)  0
General disorders     
Asthenia  1  2/13 (15.38%)  2 3/11 (27.27%)  3
Pyrexia  1  5/13 (38.46%)  5 0/11 (0.00%)  0
Chills  1  3/13 (23.08%)  3 0/11 (0.00%)  0
Device occlusion  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Fatigue  1  1/13 (7.69%)  1 1/11 (9.09%)  1
Gait disturbance  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Administration site reaction  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Device alarm issue  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Device malfunction  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Medical device pain  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Medical device site reaction  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Pain  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Vessel puncture site haemorrhage  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Infections and infestations     
Meningitis  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Bronchitis  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Nasopharyngitis  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Oral herpes  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Pneumonia  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Skin bacterial infection  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Urinary tract infection  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Injury, poisoning and procedural complications     
Incorrect dose administered  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Meningitis chemical  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Overdose  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Investigations     
White blood cell count decreased  1  0/13 (0.00%)  0 4/11 (36.36%)  4
Platelet count decreased  1  0/13 (0.00%)  0 3/11 (27.27%)  3
Neutrophil count  1  0/13 (0.00%)  0 2/11 (18.18%)  2
White blood cell count  1  0/13 (0.00%)  0 2/11 (18.18%)  2
Alanine aminotransferase increased  1  1/13 (7.69%)  1 0/11 (0.00%)  0
CSF protein increased  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Haemoglobin  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Pseudomonas test positive  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Staphylococcus test postivie  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Weight increased  1  1/13 (7.69%)  1 0/11 (0.00%)  0
White blood cell count increased  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  1/13 (7.69%)  1 1/11 (9.09%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Back pain  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Muscular weakness  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasm progression  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Metastases to spine  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Nervous system disorders     
Headache  1  7/13 (53.85%)  7 2/11 (18.18%)  2
Partial seizures  1  4/13 (30.77%)  4 0/11 (0.00%)  0
Brain oedema  1  3/13 (23.08%)  3 0/11 (0.00%)  0
Dizziness  1  2/13 (15.38%)  2 1/11 (9.09%)  1
Hemiparesis  1  2/13 (15.38%)  2 1/11 (9.09%)  1
Convulsion  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Epilepsy  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Facial palsy  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Grand mal convulsion  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Memory impairment  1  1/13 (7.69%)  1 1/11 (9.09%)  1
Somnolence  1  2/13 (15.38%)  2 0/11 (0.00%) 
Speech disorder  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Acquired epileptic aphasia  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Aphasia  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Burning sensation  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Complex partial seizures  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Dysgeusia  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Hydrocephalus  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Hyperaesthesia  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Hypoaesthesia  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Loss of consciousness  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Monoplegia  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Nervous system disorder  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Paralysis  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Simple partial seizures  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Tremor  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Psychiatric disorders     
Depression  1  1/13 (7.69%)  1 1/11 (9.09%)  1
Confusional state  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Disorientation  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Insomnia  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Restlessness  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Renal and urinary disorders     
Urethral pain  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Urinary retention  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Hiccups  1  1/13 (7.69%)  1 1/11 (9.09%)  1
Acute respiratory failure  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Cough  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Pulmonary embolism  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Scar pain  1  2/13 (15.38%)  2 0/11 (0.00%)  0
Acne  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Dermatitis contact  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Dry skin  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Rash pruritic  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Surgical and medical procedures     
Neurosurgery  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Vascular disorders     
Hypotension  1  0/13 (0.00%)  0 1/11 (9.09%)  1
Varicose veins  1  1/13 (7.69%)  1 0/11 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.0)
Early termination of the study leading to recruitment of 27 of 180 planned subjects and incomplete collection of data. Survival results are based on post-study collection of additional survival data under a protocol amendment.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Investigator and Sponsor both have publication / presentation privileges. Investigator abstracts or publications had to be reviewed and approved by the Sponsor prior to submission or presentation. The Clinic/Investigator agrees to delete information or defer publication or presentation, if (i) publication would hinder or delay the development of the investigational product or (ii) necessary to permit the filing of any desired patent applications by the Sponsor.
Results Point of Contact
Name/Title: Medical Officer
Organization: Isarna Therapeutics GmbH, formerly Antisense Pharma GmbH
Phone: +49-89-890831 ext 0
Responsible Party: Isarna Therapeutics GmbH
ClinicalTrials.gov Identifier: NCT00761280     History of Changes
Other Study ID Numbers: AP 12009-G005
First Submitted: September 26, 2008
First Posted: September 29, 2008
Results First Submitted: August 7, 2014
Results First Posted: August 22, 2014
Last Update Posted: November 14, 2014