Clinical Trial Results:
An open Phase II study to assess the clinical activity and safety of recMAGE-A3 + AS15 cancer immunotherapeutic in patients with metastatic cutaneous melanoma, and to explore its immunogenic properties, including their relation to tumor infiltration, genomics and proteomics
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Summary
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EudraCT number |
2008-001301-42 |
Trial protocol |
FR BE |
Global end of trial date |
03 Nov 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
28 Apr 2021
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First version publication date |
03 Mar 2016
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
111473
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT00896480 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline Biologicals
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Sponsor organisation address |
Rue de l’Institut 89, Rixensart, Belgium, B-1330
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Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Aug 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Nov 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Nov 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Clinical Activity - To characterize in patients with MAGE-A3-positive metastatic cutaneous melanoma:
The clinical activity of the MAGE-A3 ASCI study treatment in terms of objective response (OR), stable disease (SD) and mixed response (MR)*
The clinical activity of the MAGE-A3 ASCI study treatment in terms of time to treatment failure (TTF)*
The safety of the MAGE-A3 ASCI study treatment.
Immunogenicity - To document the humoral and cellular immune response induced by the MAGE-A3 ASCI study treatment.
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Protection of trial subjects |
The patients will be observed closely for at least 30 minutes following the administration of treatments, with appropriate medical treatment readily available in case of a rare anaphylactic reaction. VMAGE-A3 ASCI/placebo were administered by qualified and trained personnel, only to eligible subjects with no contraindications to any components of these products. During treatment, the following was checked to assess need to postpone treatment: acute disease at time of administration; any systemic grade ≥ 2 Common Terminology Criteria Adverse Event related or possibly related to treatment; fever, defined as an oral, axillary or tympanic temperature =< 38°C; need for influenza vaccine, immunoglobulins and/or any blood products; any medical reason exposing the patient to unacceptable risk. Patients were required to discontinue treatment in case of evidence of disease relapse/occurrence of second primary lung cancer; treatment with either investigational or non-registered product other than MAGE-A3 ASCI study product or other anticancer treatments; anaphylactic reaction following treatment administration; any intolerable adverse event; clinical signs or symptoms indicative of any autoimmune disorder, except vitiligo; appearance of any confirmed or suspected immunosuppressive or immunodeficient condition, or any condition requiring use of any immunosuppressive agent or systemic corticosteroids prescribed for chronic use; inability of the patient to complete study evaluations due to unforeseen circumstances; other conditions indicating the patient’s best interest to be withdrawn from treatment. In addition, between the end of the 120-weeks treatment phase, the following follow-up (FU) of patients was also planned: 1) an active FU for survival, recurrence, serious adverse events related to treatment & SAEs related to study participation and concurrent GSK medication of up to 5 years from the 1st treatment, and 2) annual contacts up to 10 years after 1st treatment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 May 2009
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 9
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Country: Number of subjects enrolled |
France: 15
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Worldwide total number of subjects |
24
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EEA total number of subjects |
24
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
11
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From 65 to 84 years |
13
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
During the screening the following steps occurred: check for inclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms. | ||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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MAGE-A3 Group | ||||||||||
Arm description |
Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
recMAGE-A3 recombinant protein formulated in AS15 adjuvant
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Investigational medicinal product code |
GSK2132231A
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Other name |
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Pharmaceutical forms |
Powder and suspension for suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Administration as follows:
-Cycle 1 (ending Week 11): 6 doses at 2-week intervals (Weeks 1, 3, 5, 7, 9 and11)
-Cycle 2 (ending Week 30): 6 doses at 3-week intervals (Weeks 15, 18, 21, 24, 27 and 30)
-Cycle 3 (ending Week 52): 4 doses at 6-week intervals (Weeks 34, 40, 46 and 52)
-Cycle 4: 4 doses at 12-week intervals, starting 12 weeks after end of Cycle 3, followed by, after an interruption of treatment of 6 months, 4 doses at 24-week intervals. All analyses were performed on the overall study population (MAGE3 Group) as well as in the subsets of patients with or without the pre-specified gene signature (GS+ or GS- groups) and in one patient with unknown status as regards GS signature (Unknown Group).
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Baseline characteristics reporting groups
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Reporting group title |
MAGE-A3 Group
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Reporting group description |
Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
GS+/+ Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subset of patients with the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a gene signature positive for two biopsies, as assessed at screening.
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Subject analysis set title |
GS+/- Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subset of patients the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a gene signature positive for only one biopsies, as assessed at screening.
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Subject analysis set title |
GS- Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subset of patients the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a gene signature negative for both biopsies, as assessed at screening.
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End points reporting groups
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Reporting group title |
MAGE-A3 Group
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Reporting group description |
Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles. | ||
Subject analysis set title |
GS+/+ Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of patients with the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a gene signature positive for two biopsies, as assessed at screening.
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Subject analysis set title |
GS+/- Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of patients the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a gene signature positive for only one biopsies, as assessed at screening.
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Subject analysis set title |
GS- Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of patients the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a gene signature negative for both biopsies, as assessed at screening.
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End point title |
Number of patients with mixed response (MxR) to MAGE-A3 ASCI study treatment [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Assessment was done based on a set of measurable lesions(MLs) identified at baseline as target lesions(TLs) and non-target lesions(NTLs) followed up until disease progression.MLs were assessed as regards matching below MR definitions. If Evaluability per RECIST: a)MR Type 1= at least (a.l.) 30% decrease in longest diameter(LD) in a.l. 1 TL measured at baseline.Such response occurring in SD/PD status of LD of TL and without appearance of 1 or more new lesions (= SD/PD with TL regression); b)MR Type 2: appearance of 1 or more new lesions occurring in SD/PR status of LD of TL(= SD/PR with new lesion).If Non-evaluability per RECIST (due to LD<20mm): a)MR Type 1 = clear decrease in diameters occurring in a.l. 1 TL measured at baseline.Such response occurring in SD/PD status of LD of (baseline) TL and without appearance of 1 or more new lesions (= SD/PD with TL regression); b)MR Type 2 = appearance of 1 or more new lesions occurring in SD/PR status of LD of TL (= SD/PR with new lesion)
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End point type |
Primary
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End point timeframe |
From Pre-treatment (up to 4 weeks before first treatment) to study end (Year 4), each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of patients with best objective tumor response (OR) to MAGE-A3 ASCI study treatment [2] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Response assessment was done based on a set of MLs identified at baseline as TLs, and followed up until disease progression. OR was defined as the best Overall Response (OR) in a patient. OR = Complete Response (CR) + Partial Response (PR). Responses were categorized as CR, PR, stable disease (SD), SD/PR, progressive disease (PD) and non-evaluable (NE). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic-resonance imaging: Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = ≥30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) = neither sufficient shrinkage to be PR, not sufficient increase to qualify for Progressive Disease (PD); PD = ≥20% increase in the sum of largest diameter for target lesions. Best objective response = PR or CR. Disease control = CR, or PR, or SD, or SD/PR.
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End point type |
Primary
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End point timeframe |
From Pre-treatment (up to 4 weeks before first treatment) to study end (Year 4), each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Time to treatment failure (TTF), by Gene Signature [3] | ||||||||||||||||||||
End point description |
TTF was defined as withdrawal from treatment with the MAGE-A3 ASCI study product due to disease progression or death. TTF analysis was performed using the non-parametric Kaplan-Meier method. “9999” as placeholder value for confidence interval result being not applicable/missing: upper limit not calculated as 1 patient (among 8) still under treatment at the time of the analysis.
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End point type |
Primary
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End point timeframe |
From Pre-treatment (up to 4 weeks before first treatment) to study end (Year 4), each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number of seroconverted patients for anti-MAGE-A3 [4] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Seroconversion was defined as a concentration of antibodies assessed that was greater than the cut-off value for a patient whose concentration of such antibodies was below the cut-off level before the initiation of treatment. Seroconverted patients were those patients with anti-MAGE-A3 antibody concentrations ≥ 27 EL.U/mL.
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End point type |
Primary
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End point timeframe |
From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Anti-MAGE-A3 antibody concentrations [5] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per millilitre (EL.U/mL). A seropositive patient was defined as a patient whose anti-MAGE-A3 antibody concentration greater than or equal to 27 EL.U/mL. D=Day, W=Week. Limits of the CI were entered = to the GMC when not available: limits are not available, as there is only one subject analyzed in the group, at this time point.
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End point type |
Primary
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End point timeframe |
From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of patients with treatment response for anti-MAGE-A3 antibodies [6] | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
For initially seronegative patients: post-administration antibody concentration ≥ 27 EL.U/mL
For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration
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End point type |
Primary
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End point timeframe |
From Day 2 to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of patients with CD4+ and CD8+ T cell frequency ≥ 1.24 cut-off [7] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
A patient was considered as a cellular mediated immune (CMI) responder if there was an increased amount of antigen-specific T-cells after immunization as compared to the patient’s baseline value. These specific T-cells included the CD4+ or CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).
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End point type |
Primary
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End point timeframe |
From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of patients with a cellular response (Anti-MAGE-A3 specific CD4+ and CD8+ T-cells concentrations after immunization) [8] | ||||||||||||||||||||||||||||||||||||||
End point description |
A patient was considered as a cellular mediated immune (CMI) responder if there was an increased amount of antigen-specific T-cells after immunization as compared to the patient’s baseline value. These specific T-cells included the CD4+ or CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).
|
||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Week 5 to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
|
||||||||||||||||||||||||||||||||||||||
| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
|
|||||||||||
End point title |
Number of patients reported with ASCI-related grade3/4 adverse events (AEs) according to the Common Terminology Criteria (CTCAE) version 3.0. [9] | ||||||||||
End point description |
The assessed AEs were ASCI-related grade 3/4 adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. An unsolicited AE covers any untoward medical occurrence in a clinical investigation patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. AEs may include pre- or post-treatment events that occur as a result of protocol-mandated procedures (i.e. invasive procedures, modification of patient’s previous therapeutic regimen).
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
Within the 31-day (Days 0-30) post-administration periods.
|
||||||||||
| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||
End point title |
Number of patients reported with serious adverse events (SAEs) [10] | ||||||||
End point description |
Serious adverse events (SAEs) include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a patient, is a Grade 4 AE according to the CTCAE, version3.0. Events which were part of the natural course of the disease under study were captured as part of the clinical activity outcome variables in this study; therefore did not need to be reported as SAEs. Progression/recurrence of the tumor was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. However, if the investigator considered that there was a causal relationship between treatment or protocol design/procedures and the disease progression/recurrence, then the event was reported as an SAE. Any new primary cancer (non-related to the cancer under study) was reported as an SAE.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
During the entire study period (from Day 0 to CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion
|
||||||||
| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||
End point title |
Number of patients with abnormal Alanine aminotransferase (ALT) values by maximum grade [11] | ||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality(UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. ALT – SCR G0; SE G3 = ALT with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||
| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with abnormal Aspartate aminotransferase (AST) values by maximum grade [12] | ||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. AST – SCR G0; SE G3 = AST with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||
| Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Alkaline Phosphatase (ALK) values by maximum grade [13] | ||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. ALK – SCR G0; SE G3 = ALK with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||
| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with abnormal Bilirubine (BIL) values by maximum grade [14] | ||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. BIL – SCR G0; SE G3 = BIL with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||
| Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Creatinine (CREA) values by maximum grade [15] | ||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. CREA – SCR G0; SE G3 = CREA with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||
| Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal gamma-glutamyl transpeptidase (GGT) values by maximum grade [16] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. GGT – SCR G0; SE G3 = GGT with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||||||||||||||
| Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Hemoglobin (HGB) values by maximum grade [17] | ||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HGB – SCR G0; SE G3 = HGB with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||
| Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Hypercalcemia (HCA) values by maximum grade [18] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HCA – SCR G0; SE G3 = HCA with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||||||||||||||
| Notes [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Hyperkalemia (HKA) values by maximum grade [19] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HKA – SCR G0; SE G3 = HKA with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||||||||||||||
| Notes [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Hypernatremia (HNA) values by maximum grade [20] | ||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HNA – SCR G0; SE G3 = HNA with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||
| Notes [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal hypoalbuminemia(hAL) values by maximum grade [21] | ||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hAL – SCR G0; SE G3 = hAL with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||
| Notes [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal hypocalcemia(hCA) values by maximum grade [22] | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hCA – SCR G0; SE G3 = hCA with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||||||||||||||
| Notes [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal hypokalemia (hKA) values by maximum grade [23] | ||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hKA – SCR G0; SE G3 = hKA with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||
| Notes [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal hyponatremia (hNA) values by maximum grade [24] | ||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hNA – SCR G0; SE G3 = hNA with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||
| Notes [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Leukocytes (LEU) values by maximum grade [25] | ||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. LEU – SCR G0; SE G3 = LEU with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||
| Notes [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Lymphopenia (LYM) values by maximum grade [26] | ||||||||||||||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. LYM – SCR G0; SE G3 = LYM with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||||||||||||||
| Notes [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with abnormal Neutrophils (NEU) values by maximum grade [27] | ||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. NEU – SCR G0; SE G3 = NEU with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||
| Notes [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with abnormal Platelets(PLT) values by maximum grade [28] | ||||||||||||||||||
End point description |
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK). The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. PLT – SCR G0; SE G3 = PLT with no abnormality/normal value at screening and with Severe abnormality at study end].
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
|
||||||||||||||||||
| Notes [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with any AE(s) and with AEs by maximum grade, related to treatment administration [29] | ||||||||||||||||||
End point description |
An AE was any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) – Mild AE, G2 – Moderate AE, G3 – Severe AE, G4 – Life threatening/Disabling AE and G5 – Death related to AE.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Within the 31-day follow-up period post treatment administration.
|
||||||||||||||||||
| Notes [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with any adverse events (AEs) and with AEs by maximum grade [30] | ||||||||||||||||||
End point description |
An AE was any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the CTC Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) – Mild AE, G2 – Moderate AE, G3 – Severe AE, G4 – Life threatening/Disabling AE and G5 – Death related to AE.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Within the 31-day follow-up period post treatment administration.
|
||||||||||||||||||
| Notes [30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with any serious adverse events (SAEs) and with SAEs by maximum grade [31] | ||||||||||||||||||
End point description |
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a patient. Events which were part of the natural course of the disease under study were captured as part of the clinical activity outcome variables in this study; therefore did not need to be reported as SAEs. Progression/recurrence of the tumor was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. SAEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the CTC Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) – Mild SAE, G2 – Moderate SAE, G3 – Severe SAE, G4 – Life threatening/Disabling SAE and G5 – Death related to SAE.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Within the 31-day follow-up period post treatment administration.
|
||||||||||||||||||
| Notes [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with any serious adverse events (SAEs) and with SAEs by maximum grade, related to treatment administration [32] | ||||||||||||||||||
End point description |
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a patient. Events which were part of the natural course of the disease under study were captured as part of the clinical activity outcome variables in this study; therefore did not need to be reported as SAEs. Progression/recurrence of the tumor was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. SAEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the CTC Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) – Mild SAE, G2 – Moderate SAE, G3 – Severe SAE, G4 – Life threatening/Disabling SAE and G5 – Death related to SAE.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Within the 31-day follow-up period post treatment administration.
|
||||||||||||||||||
| Notes [32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean titers of Anti-MAGE-A3 specific CD4+ and CD8+ T-cells concentrations after immunization [33] | ||||||||||||||||||||||||||||||||||||||||
End point description |
This endpoint presents the geometric mean concentration, expressed in titers, of anti-MAGE-A3 specific CD4+ and CD8+ T-cells. These specific T-cells included the cluster of differentiation 4+ (CD4+) and CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
|
||||||||||||||||||||||||||||||||||||||||
| Notes [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This outcome was descriptive, hence no statistical analyses were performed. |
|||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
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Timeframe for reporting adverse events |
Unsolicited AEs during the 31-day post-vaccination (Days 0-30), SAEs during the entire study period (Day 0 - Year 4).
|
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
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|
Reporting groups
|
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Reporting group title |
MAGE-A3 Group
|
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Reporting group description |
Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
02 Mar 2009 |
The changes following this amendment concern:
• The possibility of taking a new tumor biopsy in case the results of the analysis of the biopsies originally taken are inconclusive.
• The description of the AJCC staging system for cutaneous melanoma
• The AJCC staging system for cutaneous melanoma
• The time window for tumor imaging at screening
• The expected time for completing patient recruitment
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
