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    Clinical Trial Results:
    A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE II TRIAL TO EVALUATE THE IMMUNOMODULATORY EFFECT OF RUTI® IN INDIVIDUALS WITH HIGH-RISK NON-MUSCLE-INVASIVE BLADDER CANCER (NMIBC) TREATED WITH INTRAVESICAL BACILLUS CALMETTE-GUÉRIN (BCG)

    Summary
    EudraCT number
    		 2016-004311-12
    Trial protocol
    		 ES  
    Global end of trial date
    22 Dec 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Feb 2026
    First version publication date
    12 Feb 2026
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    RUTIVAC-1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03191578
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ARCHIVEL FARMA, S.L.
    Sponsor organisation address
    Fogars de Tordera, 61 , Badalona, Spain, 08916
    Public contact
    CEO ARCHIVEL FARMA, S.L., ARCHIVEL FARMA, S.L., +34 93 497 24 56, orue@archivelfarma.com
    Scientific contact
    CEO ARCHIVEL FARMA, S.L., ARCHIVEL FARMA, S.L., +34 93 497 24 56, orue@archivelfarma.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
    04 Mar 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Dec 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Dec 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the systemic and mucosal immunological response of RUTI® administration prior to intravesical BCG therapy in individuals with high-risk NMIBC. Immunological changes will be evaluated after completion of intravesical BCG therapy.
    Protection of trial subjects
    The study was performed in accordance with the current version of the declaration of Helsinki, Fortaleza, Brazil, October 2013 and following the Spanish regulations, which required acceptance of the protocol by the sponsor and the coordinating investigator, protocol approval by the Ethics Committee. The trial was conducted in agreement with the International Council on Harmonisation (ICH) guidelines on Good Clinical Practice (GCP). All subjects were guaranteed continued medical and nursing supervision throughout the duration of the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Jun 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 40
    Worldwide total number of subjects
    40
    EEA total number of subjects
    40
    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)
    12
    From 65 to 84 years
    28
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Patients who attend their regular medical visits, confirming compliance criteria and obtaining written Informed Consent Form (ICF) . Four patients declined to participate after randomization due to personal reasons. Forty patients were randomized to receive two doses of either placebo (n=20) or RUTI® (n=20) vaccine.

    Pre-assignment
    Screening details
    		 Four patients declined to participate before randomization due to personal reasons. Forty patients were randomized to receive two doses of either placebo (n=20) or RUTI® (n=20) vaccine

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Clinical investigators, study nurses, and patients were blinded to the treatment allocation. Only pharmacy staff preparing the syringes for administration were not blinded to treatment allocation. Neither the laboratory nor the statistician carrying out the randomization had direct contact with patients. At the end of the Interventional Phase the blind was opened, except for the study physicians who remained blind during the follow-up.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 RUTI
    Arm description
    		 The investigational treatment tested in the trial is RUTI®. It is composed of detoxified, pasteurized and liposomal cellular wall fragments of Mtb (FCMtb).
    Arm type
    		 Experimental

    Investigational medicinal product name
    RUTI®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dose: 25 μg FCMtb Interval: Day 0 (RUTI1) and Day 10 (RUTI2). Method of administration: Two subcutaneous shots of 25 μg RUTI® (subcutaneously into deltoid region of the arm.) After vaccination, individuals will receive the standard induction course of intravesical Bacillus Calmette–Guerin (BCG) therapy (weekly BCG for six weeks).

    Arm title
    		 Placebo
    Arm description
    		 Commercially sterile saline solution (Sodium Chloride 0.9%)
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dose: 0.3mL of 0.9% sterile normal saline solution Interval: Day 0 (RUTI1) and Day 10 (RUTI2). Method of administration: subcutaneously into deltoid region of the arm. After vaccination, individuals will receive the standard induction course of intravesical Bacillus Calmette–Guerin (BCG) therapy (weekly BCG for six weeks). 4 to 8 weeks after the last intravesical BCG administration (BCG6)

    Number of subjects in period 1
    		RUTI Placebo
    Started
    20
    20
    Induction course
    20
    20
    Completed
    18
    16
    Not completed
    2
    4
         Exitus
    1
    2
         Lost to follow-up
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    RUTI
    Reporting group description
    		 The investigational treatment tested in the trial is RUTI®. It is composed of detoxified, pasteurized and liposomal cellular wall fragments of Mtb (FCMtb).

    Reporting group title
    Placebo
    Reporting group description
    		 Commercially sterile saline solution (Sodium Chloride 0.9%)

    Reporting group values
    		 RUTI Placebo Total
    Number of subjects
    		 20 20 40
    Age categorical
    Age (years), Median (IQR) 70 (62-75): There were no significant differences in age, gender, or BMI between groups.
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 4 8 12
        From 65-84 years
    		 16 12 28
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 71 (62 to 77) 67 (59 to 74) -
    Gender categorical
    Gender (male) Total population: 36 (90%)
    Units: Subjects
        Female
    		 3 1 4
        Male
    		 17 19 36

    End points

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    End points reporting groups
    Reporting group title
    RUTI
    Reporting group description
    		 The investigational treatment tested in the trial is RUTI®. It is composed of detoxified, pasteurized and liposomal cellular wall fragments of Mtb (FCMtb).

    Reporting group title
    Placebo
    Reporting group description
    		 Commercially sterile saline solution (Sodium Chloride 0.9%)

    Primary: Changes BL Vs w2: CD4 + CD25+

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    End point title
    		 Changes BL Vs w2: CD4 + CD25+
    End point description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    End point type
    Primary
    End point timeframe
    Baseline Vs W2
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: differences (median)
        number (not applicable)
    1.075
    0.9955
    Statistical analysis title
    		 Mann-Whitney U test
    Statistical analysis description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    Comparison groups
    Placebo v RUTI
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 other [1]
    P-value
    		 < 0.05 [2]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [1] - standard non‑parametric comparative analysis, not a specific non-inferiority, equivalence, or superiority design.
    [2] - For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).

    Primary: Changes BL Vs w2: CD4 + CD69+

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    End point title
    		 Changes BL Vs w2: CD4 + CD69+
    End point description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    End point type
    Primary
    End point timeframe
    Baseline (RUTI1) Vs Week2 (BCG1)
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: Differences (Median)
        number (not applicable)
    1.229
    0.9367
    Statistical analysis title
    		 Mann-Whitney U test
    Statistical analysis description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    Comparison groups
    RUTI v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 other [3]
    P-value
    		 < 0.05 [4]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [3] - standard non‑parametric comparative analysis, not a specific non-inferiority, equivalence, or superiority design.
    [4] - For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).

    Primary: Changes BL Vs w2: CD4+CD137+

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    End point title
    		 Changes BL Vs w2: CD4+CD137+
    End point description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    End point type
    Primary
    End point timeframe
    Baseline (RUTI1) Vs Week 2
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: Differences (median)
        number (not applicable)
    1.122
    0.92
    Statistical analysis title
    		 Mann-Whitney U test
    Statistical analysis description
    Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    Comparison groups
    RUTI v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 other [5]
    P-value
    		 < 0.05 [6]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [5] - standard non‑parametric comparative analysis, not a specific non-inferiority, equivalence, or superiority design.
    [6] - For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).

    Primary: Changes BL Vs w2: CD4 +OX40+

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    End point title
    		 Changes BL Vs w2: CD4 +OX40+
    End point description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    End point type
    Primary
    End point timeframe
    Baseline (RUTI1) Vs Week2 (BCG1)
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: Differences (Median)
        number (not applicable)
    1.248
    1.051
    Statistical analysis title
    		 Mann-Whitney U test
    Statistical analysis description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    Comparison groups
    RUTI v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 other [7]
    P-value
    		 < 0.05 [8]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [7] - standard non‑parametric comparative analysis, not a specific non-inferiority, equivalence, or superiority design.
    [8] - Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *

    Primary: Changes BL Vs W6: CD4+CD25+CD27

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    End point title
    		 Changes BL Vs W6: CD4+CD25+CD27
    End point description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    End point type
    Primary
    End point timeframe
    Baseline (RUTI1) Vs W6
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: Differences (Median)
        number (not applicable)
    0.9971
    1.232
    Statistical analysis title
    		 Mann-Whitney U test
    Statistical analysis description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    Comparison groups
    RUTI v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 other [9]
    P-value
    		 < 0.05 [10]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [9] - standard non‑parametric comparative analysis, not a specific non-inferiority, equivalence, or superiority design.
    [10] - For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).

    Primary: Changes BL Vs W16: CD4+CD25+CD27

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    End point title
    		 Changes BL Vs W16: CD4+CD25+CD27
    End point description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    End point type
    Primary
    End point timeframe
    Baseline Vs W16
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: Differences (Median)
        number (not applicable)
    1.002
    1.118
    Statistical analysis title
    		 Mann-Whitney U test
    Statistical analysis description
    For the immunological response analysis, individual-level differences (paired samples) were assessed using Wilcoxon’s matched-pair signed-rank test. Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    Comparison groups
    RUTI v Placebo
    Number of subjects included in analysis
    40
    Analysis specification
    Post-hoc
    Analysis type
    		 other [11]
    P-value
    		 < 0.05 [12]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [11] - Differences between the placebo and RUTI groups (unpaired samples) were evaluated using the Mann-Whitney U test. For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).
    [12] - . For fold-change analyses (compared with a baseline value of 1), the Wilcoxon signed-rank test was applied (* p < 0.05; ** p < 0.01; and *** p < 0.001).

    Secondary: The recurrence-free survival (RFS)

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    End point title
    		 The recurrence-free survival (RFS)
    End point description
    Recurrence (high-grade recurrence) was defined according to the 2024 European Association of Urology (EAU) guidelines as any histology-proven high-grade disease within the bladder occurring during or after BCG therapy. Low-grade recurrence during or after BCG treatment is not considered BCG failure
    End point type
    Secondary
    End point timeframe
    at 5 years of follow up
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: patients
        number (not applicable)
    2
    5
    No statistical analyses for this end point

    Secondary: Disease worsening: events that included diagnosis of T2 or greater

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    End point title
    		 Disease worsening: events that included diagnosis of T2 or greater
    End point description
    Progression to muscle-invasive disease (T2 or greater) occurred in 4 patients (10.8%) in the total population, all of whom were in the placebo group. This resulted in a significant difference in progression-free survival (PFS) between the groups, with rates of 77.7% for placebo and 100% for RUTI (p=0.032).
    End point type
    Secondary
    End point timeframe
    At three years of follow up
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: Patients
        number (not applicable)
    0
    4
    No statistical analyses for this end point

    Secondary: Cancer specific deaths

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    End point title
    		 Cancer specific deaths
    End point description
    End point type
    Secondary
    End point timeframe
    At 5 years of follow up
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: patients
        number (not applicable)
    0
    2
    No statistical analyses for this end point

    Secondary: Cancer specific free survival

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    End point title
    		 Cancer specific free survival
    End point description
    No cancer-associated deaths were observed in the RUTI group during the 5-year follow-up, leading to a higher CSS rate in the RUTIs group (100% vs. 83.3% for placebo; p=0.067).
    End point type
    Secondary
    End point timeframe
    at five years of follow up
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: Percent Patients
        number (not applicable)
    89.5
    50
    No statistical analyses for this end point

    Secondary: Safety of RUTI® will be determined by analysis of local and systemic reactogenicity. The data will be expressed as: o Proportion of patients who develop a Grade 3 or 4 local reactions.

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    End point title
    		 Safety of RUTI® will be determined by analysis of local and systemic reactogenicity. The data will be expressed as: o Proportion of patients who develop a Grade 3 or 4 local reactions.
    End point description
    End point type
    Secondary
    End point timeframe
    At five years of follow up
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: number of AEs
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Secondary: Safety of RUTI® will be determined by analysis of local and systemic reactogenicity. The data will be expressed as: Proportion of patients who develop a Grade 3 or 4 systemic reactions

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    End point title
    		 Safety of RUTI® will be determined by analysis of local and systemic reactogenicity. The data will be expressed as: Proportion of patients who develop a Grade 3 or 4 systemic reactions
    End point description
    End point type
    Secondary
    End point timeframe
    At 5 years of follow up
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: number of AEs
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Secondary: Safety of RUTI® will be determined by analysis of local and systemic reactogenicity. SAEs

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    End point title
    		 Safety of RUTI® will be determined by analysis of local and systemic reactogenicity. SAEs
    End point description
    End point type
    Secondary
    End point timeframe
    At five years of follow up
    End point values
    		 RUTI Placebo
    Number of subjects analysed
    20
    20
    Units: number of SAEs
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Overall Period
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    10
    Reporting groups
    Reporting group title
    RUTI ARM
    Reporting group description
    		 -

    Reporting group title
    Placebo arm
    Reporting group description
    		 -

    Serious adverse events
    		 RUTI ARM Placebo arm
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 20 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 RUTI ARM Placebo arm
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 20 (10.00%)
    8 / 20 (40.00%)
    General disorders and administration site conditions
    Malaise
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 20 (15.00%)
         occurrences all number
    0
    3
    Fatigue
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 20 (10.00%)
         occurrences all number
    1
    2
    Pain
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 20 (10.00%)
         occurrences all number
    1
    2
    Asthenia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 20 (10.00%)
         occurrences all number
    1
    2
    Vomiting
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Hypogastric pain
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Influenza
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Injection site induration
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 20 (5.00%)
         occurrences all number
    1
    1
    Injection site erythema
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Injection site swelling
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Injection site pruritus
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Edema hands and ankles
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Hematuria
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Knee meniscopathy R
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Arthralgia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 20 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Thoracic Herpes Zoster
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 20 (5.00%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Jun 2018
    Modification of exclusion criteria numbers 6 and 10, to allow the inclusion of patients receiving antiplatelet and/or anticoagulant treatment and patients with a clinical history of tuberculosis. Modification in the production process of the investigational product, RUTI®. The investigational medicinal product (IMP), RUTI®, has been manufactured at a dose of 25 µg FCMtb (33.3 µg/vial), incorporating improvements in the manufacturing processes of the active ingredient and the IMP. The collection of biopsy samples and performance of cystoscopy at week 16 will only be carried out if clinically indicated. The European General Data Protection Regulation (GDPR) is incorporated both in the protocol and in the patient information sheet.
    05 Feb 2019
    The principal investigator of the study is changed. The study design is modified to specify that the immunomodulatory effect will be evaluated only after the induction course of intravesical BCG. The intervention period will end at VISIT 1 (4–8 weeks after the last dose of the induction cycle [the 6th dose of intravesical BCG]).

    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.
    Sample size: The study was powered for large effect sizes only; moderate or small effects may not be detected. BCG supply shortage: Some patients did not receive maintenance BCG, which may affect long-term efficacy comparisons.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/41084757
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