Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43870   clinical trials with a EudraCT protocol, of which   7289   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    NGR016: Randomized phase II study evaluating two doses of NGR-hTNF administered either as single agent or in combination with doxorubicin in patients with advanced soft-tissue sarcoma (STS).

    Summary
    EudraCT number
    		 2010-018851-88
    Trial protocol
    		 IT   GB  
    Global end of trial date
    09 May 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Dec 2019
    First version publication date
    21 Dec 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NGR016
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MolMed S.p.A.
    Sponsor organisation address
    Via Olgettina, 58 , Milan, Italy, 20132
    Public contact
    Clinical Operations, MolMed S.p.A., 0039 02212771, clinical.operations@molmed.com
    Scientific contact
    Clinical Operations, MolMed S.p.A., 0039 02212771, clinical.operations@molmed.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Jul 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 May 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the effect on progression-free survival (PFS) of two NGR-hTNF doses administered either as single agent or in combination with doxorubicin
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki. The study was performed in compliance with Good Clinical Practices (CPMP/ICH/135/95), and the essential documents are archived as required by the applicable regulatory requirements. The study and any amendments were reviewed by an Independent Ethics Committees or Institutional Review Boards.
    Background therapy
    		 Patients with locally advanced or metastatic soft-tissue sarcoma untreated or previously treated with one or more systemic regimen. The most commonly used therapies by 3rd level ATC code were: alkylating agents, cytotoxic antibiotics and related substances.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Oct 2010
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 21
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Italy: 42
    Worldwide total number of subjects
    69
    EEA total number of subjects
    69
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    57
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Study period: First patient enrolled: 23 October 2010; Last patient completed: 08 March 2016; End of study: 09 May 2016. 7 investigational study sites: Italy (4 sites), France (2 sites) and United Kingdom (1 site).

    Pre-assignment
    Screening details
    		 Totally 69 consented and screened patients were randomised to the assigned treatment arm. In particular, patients were stratified according to the prior cumulative dose of doxorubicin received.

    Period 1
    Period 1 title
    Overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A: NGR-hTNF low dose
    Arm description
    		 Patients were randomised to receive low-dose NGR-hTNF as single agent. Specifically, patients were treated with: NGR-hTNF 0.8 μg/m2 intravenous infusion over 1 hour once a week until progressive disease.
    Arm type
    		 Experimental

    Investigational medicinal product name
    NGR-hTNF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    NGR-hTNF administered at 0.8 μg/m2 intravenous (iv) infusion over 1 hour once a week until progressive disease.

    Arm title
    		 Arm B: NGR-hTNF high dose
    Arm description
    		 Patients were randomised to receive high-dose NGR-hTNF as single agent. Specifically, patients were treated with: NGR-hTNF 45 μg/m2 intravenous infusion over 1 hour once a week until progressive disease.
    Arm type
    		 Experimental

    Investigational medicinal product name
    NGR-hTNF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    NGR-hTNF administered at 45 μg/m2 iv infusion over 1 hour once a week until progressive disease.

    Arm title
    		 Arm C: NGR-hTNF low dose + Doxorubicin
    Arm description
    		 Patients were randomised to receive low-dose NGR-hTNF + doxorubicin. Specifically, patients were treated with NGR-hTNF 0.8 μg/m2 intravenous infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 intravenous infusion over 15 minutes (starting 1 hour after the end of NGRhTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until a cumulative dose of 550 mg/m2).
    Arm type
    		 Experimental

    Investigational medicinal product name
    NGR-hTNF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    NGR-hTNF administered at 0.8 μg/m2 iv infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 iv infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until cumulative dose of 550 mg/m2)

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    NGR-hTNF administered at 0.8 μg/m2 iv infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 iv infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until cumulative dose of 550 mg/m2)

    Arm title
    		 Arm D: NGR-hTNF high dose + Doxorubicin
    Arm description
    		 Patients were randomised to receive high-dose NGR-hTNF + doxorubicin. Specifically, patients were treated with NGR-hTNF 45 μg/m2 intravenous infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until a cumulative dose of 550 mg/m2).
    Arm type
    		 Experimental

    Investigational medicinal product name
    NGR-hTNF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    NGR-hTNF administered at 45 μg/m2 iv infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 iv infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until cumulative dose of 550 mg/m2).

    Investigational medicinal product name
    Doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    NGR-hTNF administered at 45 μg/m2 iv infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 iv infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until cumulative dose of 550 mg/m2).

    Number of subjects in period 1
    		Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Started
    14
    14
    28
    13
    Completed
    13
    14
    28
    13
    Not completed
    1
    0
    0
    0
         Death
    1
    -
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Arm A: NGR-hTNF low dose
    Reporting group description
    		 Patients were randomised to receive low-dose NGR-hTNF as single agent. Specifically, patients were treated with: NGR-hTNF 0.8 μg/m2 intravenous infusion over 1 hour once a week until progressive disease.

    Reporting group title
    Arm B: NGR-hTNF high dose
    Reporting group description
    		 Patients were randomised to receive high-dose NGR-hTNF as single agent. Specifically, patients were treated with: NGR-hTNF 45 μg/m2 intravenous infusion over 1 hour once a week until progressive disease.

    Reporting group title
    Arm C: NGR-hTNF low dose + Doxorubicin
    Reporting group description
    		 Patients were randomised to receive low-dose NGR-hTNF + doxorubicin. Specifically, patients were treated with NGR-hTNF 0.8 μg/m2 intravenous infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 intravenous infusion over 15 minutes (starting 1 hour after the end of NGRhTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until a cumulative dose of 550 mg/m2).

    Reporting group title
    Arm D: NGR-hTNF high dose + Doxorubicin
    Reporting group description
    		 Patients were randomised to receive high-dose NGR-hTNF + doxorubicin. Specifically, patients were treated with NGR-hTNF 45 μg/m2 intravenous infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until a cumulative dose of 550 mg/m2).

    Reporting group values
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin Total
    Number of subjects
    		 14 14 28 13 69
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 12 11 24 10 57
        From 65-84 years
    		 2 3 4 3 12
        85 years and over
    		 0 0 0 0 0
    Age continuous
    Units: years
        median (standard deviation)
    		 54.6 ± 10.33 55.6 ± 14.57 50.1 ± 13.00 54.8 ± 13.38 -
    Gender categorical
    Units: Subjects
        Female
    		 5 8 11 7 31
        Male
    		 9 6 17 6 38

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Arm A: NGR-hTNF low dose
    Reporting group description
    		 Patients were randomised to receive low-dose NGR-hTNF as single agent. Specifically, patients were treated with: NGR-hTNF 0.8 μg/m2 intravenous infusion over 1 hour once a week until progressive disease.

    Reporting group title
    Arm B: NGR-hTNF high dose
    Reporting group description
    		 Patients were randomised to receive high-dose NGR-hTNF as single agent. Specifically, patients were treated with: NGR-hTNF 45 μg/m2 intravenous infusion over 1 hour once a week until progressive disease.

    Reporting group title
    Arm C: NGR-hTNF low dose + Doxorubicin
    Reporting group description
    		 Patients were randomised to receive low-dose NGR-hTNF + doxorubicin. Specifically, patients were treated with NGR-hTNF 0.8 μg/m2 intravenous infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 intravenous infusion over 15 minutes (starting 1 hour after the end of NGRhTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until a cumulative dose of 550 mg/m2).

    Reporting group title
    Arm D: NGR-hTNF high dose + Doxorubicin
    Reporting group description
    		 Patients were randomised to receive high-dose NGR-hTNF + doxorubicin. Specifically, patients were treated with NGR-hTNF 45 μg/m2 intravenous infusion over 1 hour once a week until progressive disease, plus Doxorubicin 60 mg/m2 intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles (or until a cumulative dose of 550 mg/m2).

    Primary: Progression-free survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-free survival (PFS)
    End point description
    Progression-free survival (PFS) is defined as the time from the date of randomization until disease progression, or death due to any cause.
    End point type
    Primary
    End point timeframe
    Progression-free survival (PFS) was measured after documented progressive disease (PD), specifically every 12 weeks.
    End point values
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects analysed
    14
    14
    28
    13
    Units: Days
        median (confidence interval 95%)
    42 (36 to 46)
    63 (33 to 107)
    96 (46 to 121)
    58 (41 to 485)
    Statistical analysis title
    		 Progression Free Survival
    Statistical analysis description
    The median PFS was 42 days (95% CI: 36-46 days) in arm A, 63 days (95% CI: 33-107 days) in arm B, 96 days (95% CI: 46-121 days) in arm C and 58 days (95% CI: 41-485 days) in arm D. Two (14.3%) patients in arm A, 1 (7.1%) in arm B, 2 (7.1%) in arm C and 2 (15.4%) in arm D were censored, while events (i.e. failures) were reported in 12 (85.7%) patients in arm A, in 13 (92.9%) in arm B, in 26 (92.9%) in arm C and in 11 (84.6%) in arm D.
    Comparison groups
    Arm A: NGR-hTNF low dose v Arm B: NGR-hTNF high dose v Arm C: NGR-hTNF low dose + Doxorubicin v Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.02
    Method
    		 Logrank
    Confidence interval

    Secondary: Response rate (RR)

    		 Close Top of page
    End point title
    		 Response rate (RR)
    End point description
    Response rate (RR) is defined as the percentage of patients who had a best-response rating of complete or partial response, according to standard RECIST criteria
    End point type
    Secondary
    End point timeframe
    Complete or Partial Response was measured after documented progressive disease (PD), specifically every 12 weeks.
    End point values
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects analysed
    14
    14
    28
    13
    Units: number of patients
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Overall survival

    		 Close Top of page
    End point title
    		 Overall survival
    End point description
    Overall Survival (OS) is defined as the time from the date of randomization until death due to any cause or last contact.
    End point type
    Secondary
    End point timeframe
    Overall survival was measured after documented progressive disease (PD), specifically every 12 weeks.
    End point values
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects analysed
    14
    14
    28
    13
    Units: Days
        median (confidence interval 95%)
    79 (46 to 286)
    151 (48 to 320)
    300 (166 to 707)
    217 (67 to 485)
    Statistical analysis title
    		 Overall survival
    Statistical analysis description
    The median OS was 79 days (95% CI: 46-286 days) in arm A, 151 days (95% CI: 48-320 days) in arm B, 300 days (95% CI: 166-707 days) in arm C and 217 days (95% CI: 67-485 days) in arm D. Two (14.3%) patients in arm A, 2 (14.3%) in arm B, 9 (32.1%) in arm C and 3 (23.1%) in arm D were censored, while events (i.e. deaths) were reported in 12 (85.7%) patients in arm A, in 12 (85.7%) in arm B, in 19 (67.9%) in arm C and in 10 (76.9%) in arm D.
    Comparison groups
    Arm A: NGR-hTNF low dose v Arm B: NGR-hTNF high dose v Arm C: NGR-hTNF low dose + Doxorubicin v Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.011
    Method
    		 Logrank
    Confidence interval

    Secondary: Disease control rate

    		 Close Top of page
    End point title
    		 Disease control rate
    End point description
    Disease Control Rate is defined as the percentage of subjects who have a Best Response of Complete Response, Partial Response or Stable Disease during the whole study.
    End point type
    Secondary
    End point timeframe
    Disease control rate was recovered during the whole study.
    End point values
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects analysed
    14
    14
    28
    13
    Units: number of patients
    1
    4
    16
    5
    Statistical analysis title
    		 Disease Control Rate
    Statistical analysis description
    DCR was reported in 1 (7.1%) patient in arm A, in 4 (28.6%) in arm B, in 16 (57.1%) in arm C and in 5 (38.5%) in arm D.
    Comparison groups
    Arm A: NGR-hTNF low dose v Arm B: NGR-hTNF high dose v Arm C: NGR-hTNF low dose + Doxorubicin v Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0143
    Method
    		 Logrank
    Parameter type
    		 means of Chi-quare tests
    Confidence interval

    Secondary: Metabolic response rate (MRR)

    		 Close Top of page
    End point title
    		 Metabolic response rate (MRR)
    End point description
    A complete metabolic response (CMR) was defined as the complete resolution of 18F-fluorodeoxyglucose (FDG) uptake within the tumor volume so that it was indistinguishable from surrounding normal tissue. A partial metabolic response (PMR) was defined as a 25% or more reduction in tumor FDG uptake. An increase in tumor standardised uptake value (SUV) 25% or more within the ROI defined on the baseline scan, or the appearance of new FDG uptake in another region, was classified as progressive metabolic disease (PMD). Stable metabolic disease (SMD) was defined as an increase in tumor SUV of less than 25% or a decrease of less than 25%.
    End point type
    Secondary
    End point timeframe
    Metabolic response rate (MRR) was measured after first cycle (day 1) and at the time of documented progression.
    End point values
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects analysed
    14
    14
    28
    13
    Units: number of patients
        Cycle 1: Complete metabolic response
    0
    0
    0
    0
        Cycle 1: Partial metabolic response
    1
    0
    4
    1
        Cycle 1: Stable metabolic disease
    7
    8
    11
    4
        Cycle 1: Progressive metabolic disease
    1
    1
    3
    2
        Cycle 1: Inevaluable
    5
    5
    10
    6
        At Progression: Complete metabolic response
    0
    0
    0
    0
        At Progression: Partial metabolic response
    0
    0
    1
    0
        At Progression: Stable metabolic disease
    0
    0
    1
    0
        At Progression: Progressive metabolic disease
    0
    3
    1
    0
        At Progression: Inevaluable
    14
    11
    25
    13
    Statistical analysis title
    		 Metabolic response rate: cycle 1
    Statistical analysis description
    At cycle 1, none (0.0%) of patients in any arm had CMR. PMR was reported in 1 (7.1%) patient in arm A, in none (0.0%) in arm B, in 4 (14.3%) in arm C and in 1 (7.7%) in arm D. SMD was reported in 7 (50.0%) patients in arm A, in 8 (57.1%) in arm B, in 11 (39.3%) in arm C and in 4 (30.8%) in arm D. PMD was reported in 1 (7.1%) patient in arm A, in 1 (7.1%) in arm B, in 3 (10.7%) in arm C and in 2 (15.4%) in arm D.
    Comparison groups
    Arm B: NGR-hTNF high dose v Arm C: NGR-hTNF low dose + Doxorubicin v Arm D: NGR-hTNF high dose + Doxorubicin v Arm A: NGR-hTNF low dose
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8735
    Method
    		 Logrank
    Parameter type
    		 means of Chi-quare tests
    Confidence interval
    Statistical analysis title
    		 Metabolic response rate: at Progression
    Statistical analysis description
    At progression, none (0.0%) of patients in any arm had CMR. PMR and SMD were reported in none (0.0%) of patients in arms A, C and D, and in 1 (3.6%) patient in arm C. PMD was reported in none (0.0%) of patients in arms A and D, in 3 (21.4%) patients in arm B and in 1 (3.6%) in arm C.
    Comparison groups
    Arm A: NGR-hTNF low dose v Arm B: NGR-hTNF high dose v Arm C: NGR-hTNF low dose + Doxorubicin v Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.2677
    Method
    		 Logrank
    Parameter type
    		 means of Chi-quare tests
    Confidence interval

    Secondary: Duration of stable disease

    		 Close Top of page
    End point title
    		 Duration of stable disease
    End point description
    Duration of stable disease was measured from the date of randomization until the criteria for disease progression was met.
    End point type
    Secondary
    End point timeframe
    Duration of stable disease is measured until the criterion for disease progression is met, up to 24 months
    End point values
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects analysed
    14
    14
    28
    13
    Units: Days
        median (confidence interval 95%)
    42 (36 to 46)
    90 (37 to 168)
    114 (85 to 138)
    58 (41 to 502)
    Statistical analysis title
    		 Duration of stable disease
    Statistical analysis description
    The median duration of stable disease was 42 days (95% CI: 36-46 days) in arm A, 90 days (95% CI: 37-NE days) in arm B, 114 days (95% CI: 85-138 days) in arm C and 58 days (95% CI: 41-502 days) in arm D. Two (14.3%) patients in arm A, 6 (42.9%) in arm B, 5 (17.9%) in arm C and 4 (30.8%) in arm D were censored, while events (i.e. disease progression) were reported in 12 (85.7%) patients in arm A, in 8 (57.1%) in arm B, in 23 (82.1%) in arm C and in 9 (69.2%) in arm D.
    Comparison groups
    Arm A: NGR-hTNF low dose v Arm B: NGR-hTNF high dose v Arm C: NGR-hTNF low dose + Doxorubicin v Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.009
    Method
    		 Logrank
    Confidence interval

    Secondary: Duration of response

    		 Close Top of page
    End point title
    		 Duration of response
    End point description
    Duration of response (DR) was measured from the time that measurement criteria were met for complete response or partial response (whichever status was recorded first) until the progressive disease was objectively documented.
    End point type
    Secondary
    End point timeframe
    Duration of response was measured until the progressive disease was objectively documented.
    End point values
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Number of subjects analysed
    14
    14
    28
    13
    Units: number of patients
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All adverse events occurring after initiation of trial treatment will be recorded for 28 days after completion of the last treatment administration. All serious adverse events related to the study drug will be recorded indefinitely.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Arm A: NGR-hTNF low dose
    Reporting group description
    		 -

    Reporting group title
    Arm B: NGR-hTNF high dose
    Reporting group description
    		 -

    Reporting group title
    Arm C: NGR-hTNF low dose + Doxorubicin
    Reporting group description
    		 -

    Reporting group title
    Arm D: NGR-hTNF high dose + Doxorubicin
    Reporting group description
    		 -

    Serious adverse events
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    3 / 28 (10.71%)
    2 / 13 (15.38%)
         number of deaths (all causes)
    11
    12
    19
    10
         number of deaths resulting from adverse events
    Blood and lymphatic system disorders
    Pancytopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile Neutropenia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary Retention
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Localised Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm A: NGR-hTNF low dose Arm B: NGR-hTNF high dose Arm C: NGR-hTNF low dose + Doxorubicin Arm D: NGR-hTNF high dose + Doxorubicin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 13 (76.92%)
    14 / 14 (100.00%)
    28 / 28 (100.00%)
    13 / 13 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    1
    Flushing
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    2
    0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    5 / 13 (38.46%)
    11 / 14 (78.57%)
    7 / 28 (25.00%)
    10 / 13 (76.92%)
         occurrences all number
    5
    36
    14
    32
    Pyrexia
         subjects affected / exposed
    4 / 13 (30.77%)
    4 / 14 (28.57%)
    6 / 28 (21.43%)
    3 / 13 (23.08%)
         occurrences all number
    5
    4
    8
    8
    Chest Pain
         subjects affected / exposed
    3 / 13 (23.08%)
    2 / 14 (14.29%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    3
    3
    1
    1
    Asthenia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    5 / 28 (17.86%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    5
    1
    Chest Discomfort
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    11 / 28 (39.29%)
    7 / 13 (53.85%)
         occurrences all number
    2
    0
    14
    10
    Oedema Peripheral
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    4 / 28 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    5
    0
    Influenza Like Illness
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    3 / 28 (10.71%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    3
    3
    Peripheral Swelling
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Mucosal Inflammation
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Drug Hypersensitivity
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 14 (14.29%)
    3 / 28 (10.71%)
    5 / 13 (38.46%)
         occurrences all number
    2
    2
    4
    9
    Bronchospasm
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    0
    1
    Cough
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    6 / 28 (21.43%)
    3 / 13 (23.08%)
         occurrences all number
    1
    0
    6
    9
    Oropharyngeal Pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    4 / 28 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    5
    0
    Productive Cough
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Haemoptysis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Nasal Congestion
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Sinus Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Mood Altered
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Investigations
    Breath Sounds Abnormal
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Weight Decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    4 / 28 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    4
    0
    Ejection Fraction Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Gamma-Glutamyltransferase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    1
    0
    2
    Platelet Count Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Neutrophil Count Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    7
    1
    Activated Partial Thromboplastin Time Prolonged
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Lymphocyte Count Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    7
    1
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    0
    0
    2
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Blood Bilirubin Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    2
    Oxygen Saturation Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    White Blood Cell Count Decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    10
    Injury, poisoning and procedural complications
    Tooth Avulsion
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac disorders
    Extrasystoles
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Cyanosis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    3 / 28 (10.71%)
    2 / 13 (15.38%)
         occurrences all number
    0
    0
    3
    4
    Pericardial Effusion
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 14 (7.14%)
    4 / 28 (14.29%)
    2 / 13 (15.38%)
         occurrences all number
    1
    11
    5
    5
    Presyncope
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Seizure
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Syncope
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dysgeusia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    2 / 13 (15.38%)
         occurrences all number
    0
    0
    2
    2
    Paraesthesia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Somnolence
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Dizziness
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Amputation Stump Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Epilepsy
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    11 / 28 (39.29%)
    5 / 13 (38.46%)
         occurrences all number
    0
    0
    21
    11
    Anaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    6 / 28 (21.43%)
    3 / 13 (23.08%)
         occurrences all number
    0
    0
    10
    5
    Thrombocytopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    3 / 13 (23.08%)
         occurrences all number
    0
    0
    2
    3
    Leukopenia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Febrile Neutropenia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Eye disorders
    Lacrimation Increased
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Dry Eye
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    1
    Eyelid Irritation
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 14 (0.00%)
    11 / 28 (39.29%)
    3 / 13 (23.08%)
         occurrences all number
    2
    0
    19
    6
    Nausea
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 14 (7.14%)
    18 / 28 (64.29%)
    7 / 13 (53.85%)
         occurrences all number
    1
    1
    25
    10
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 14 (21.43%)
    2 / 28 (7.14%)
    1 / 13 (7.69%)
         occurrences all number
    0
    4
    3
    1
    Constipation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    11 / 28 (39.29%)
    2 / 13 (15.38%)
         occurrences all number
    0
    1
    15
    2
    Diarrhoea
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    4 / 28 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    5
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    5 / 28 (17.86%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    5
    1
    Abdominal Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    4 / 28 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    4
    0
    Stomatitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    3 / 28 (10.71%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Anorectal Discomfort
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    2
    Gingival Disorder
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Lip Oedema
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Hepatobiliary disorders
    Hepatomegaly
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    13 / 28 (46.43%)
    4 / 13 (30.77%)
         occurrences all number
    0
    0
    13
    4
    Hyperhidrosis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Skin Reaction
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal Pain
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    1
    2
    2
    1
    Back Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    2 / 13 (15.38%)
         occurrences all number
    0
    1
    4
    5
    Musculoskeletal Chest Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    2 / 28 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    4
    0
    Pain In Extremity
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    0
    1
    Spinal Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    3
    0
    1
    Arthralgia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    2
    3
    Neck Pain
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    2
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 14 (0.00%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Influenza
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    7 / 28 (25.00%)
    1 / 13 (7.69%)
         occurrences all number
    2
    0
    9
    2
    Fungal Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    1 / 28 (3.57%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Localised Infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    2
    Gingivitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Oral Candidiasis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    2
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 14 (0.00%)
    6 / 28 (21.43%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    8
    1
    Glucose Tolerance Impaired
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 14 (7.14%)
    0 / 28 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dehydration
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 14 (0.00%)
    0 / 28 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue Apr 30 17:57:23 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA