E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038140 |
E.1.2 | Term | Recurrent urinary tract infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of this study is to obtain the prevention of recurrent Urinary Tract Infections in women immunized with multivalent bacterial vaccine, MV140 after treatment for three or six months, compared with placebo group.
Primary efficacy variable is reduction in the average number of episodes of UTIs in immunized women, after active treatment of 3 to 6 months, at 12 months follow up. For this, the number of episodes of UTIs will be assessed during follow-up period. - Reduction in the average number of episodes of UTIs in women treated with MV140 for 3 months compared to placebo. - Reduction in the average number of episodes of UTIs in women treated with MV140 for 6 months compared to placebo. - Reduction in the average number of episodes of UTIs in women treated with MV140 for 6 months compared to women treated with MV140 for 3 months.
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E.2.2 | Secondary objectives of the trial |
• To compare the event rate, during the time of the study, between the treatment groups against placebo. • To compare by a cost-benefit ratio the three treatment groups. • Time elapsed from start of treatment until the appearance of the first UTI • Use of antibiotics for treatment of infections Treatments to be permitted will be graded on a scale of 1-3 points according to the need of treatment required, according to the established medical history. Point 1: Use of one of these two treatment options, considering the possibility of allergies, when only lower urinary tract infection without fever is suspected: Rule A: Septrim forte® (Trimetoprim 160mg+sulfamethoxazol 800mg) 1 tablet orally every 12 hours for 6 days. Rule A in the UK: Trimetoprim 200mg twice daily for 7 days. Rule B: Fosfomycin 1 gram orally every 8 hours for 6 days. Rule B in the UK: Nitrofurontoin 100mg twice daily for 7 days Point 2: Use of one of these two patterns, considering the possibility of allergies, |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
The individuals to be included in the study will meet the following criteria: Women who have given their informed consent. Age between 18 and 75 years. Must be able to meet the dosage regimen Individuals who have had at least 5 episodes of cystitis in the last 12 months. Individuals who have not responded to hygienic-sanitary measures and / or suppressive treatment and / or postcoital prophylaxis. Individuals who are free of urinary tract infections at the time of inclusion in the study.
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E.4 | Principal exclusion criteria |
Non- included individuals will be those who/whose: Have not given their informed consent. Age is not within the established age range. Cannot offer cooperation and/or have severe psychiatric disorders Present a pathologic post-micturition residue. Present moderate to severe incontinence Present genital tumors. Presents Urinary tract tumors. Present lithiasis Present alterations in the immune system Present complicated UTIs
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E.5 End points |
E.5.1 | Primary end point(s) |
The main objective of this study is to achieve the prevention of Recurrent Urinary Tract Infections in women immunized with multivalent bacterial vaccine after treatment for three or six months, compared with placebo group.
- Primary variable: mean number of episodes of urinary tract infections. - Primary efficacy variable is reduction in the average number of episodes of UTIs in immunized women, after active treatment of 3 to 6 months, at 12 months follow up. For this, the number of episodes of UTIs will be assessed during follow-up period. Reduction in the average number of episodes of UTIs in women treated with MV140 for 3 months compared to placebo. Reduction in the average number of episodes of UTIs in women treated with MV140 for 6 months compared to placebo. Reduction in the average number of episodes of UTIs in women treated with MV140 for 6 months compared to women treated with MV140 for 3 months. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary and secondary variables including adverse events will be evaluated at baseline, 3 months, 6 months, 9 months and 12 months follow up time points in Phase I of the study.
In phase II Primary and secondary variables including adverse events will be evaluated at 15 months, 18 months, 21 months and 24 months follow up time points. |
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E.5.2 | Secondary end point(s) |
• To compare the event rate, during the time of the study, between the treatment groups against placebo. • To compare by a cost-benefit ratio the three treatment groups. • Time elapsed from start of treatment until the appearance of the first UTI • Use of antibiotics for treatment of infections Treatments to be permitted will be graded on a scale of 1-3 points according to the need of treatment required, according to the established medical history. Point 1: Use of one of these two treatment options, considering the possibility of allergies, when only lower urinary tract infection without fever is suspected: Rule A: Septrim forte® (Trimetoprim 160mg+sulfamethoxazol 800mg) 1 tablet orally every 12 hours for 6 days. Rule A in the UK: Trimetoprim 200mg twice daily for 7 days. Rule B: Fosfomycin 1 gram orally every 8 hours for 6 days. Rule B in the UK: Nitrofurontoin 100mg twice daily for 7 days Point 2: Use of one of these two patterns, considering the possibility of allergies, one or another treatment modality for intercurrent ITU when renal parenchymal damage is suspected by the presence of fever, but with uncomplicated pyelonephritis criteria, which can be treated on an out-patient basis: Rule A: Septrim forte® (Trimetoprim 160mg+sulfamethoxazol 800mg) 1 tablet orally every 12 hours for 14 days plus intramuscular injection of gentamicin 2 mg / kg / day in a single daily dose for 4 days. Rule A in the UK: Ciprofloxacin 500mg for 14 days Rule B: Levofloxacin 500mg every 24 hours orally for 14 days. Point 3: Need for hospital admission for intravenous treatment when an UTI is suspected with risk of sepsis or complicated pyelonephritis: intravenous treatment will be carried out at least 3 days until the event is controlled, fever has decreased and complicated infection blood parameters evolve favourably (leukocytosis): Rule A: Third-generation cephalosporin: Cefotaxime 1 g intravenously every 8 hours at least for 3 days, then switch to oral administration according to dosing described in “2 points” section. Rule A in the UK: Gentamicin dose determined by weight as per local treatment guidelines Rule B: Amoxicillin (1000 mg) / clavulanate (200 mg) endovenously every 8 hours plus 100 mg of tobramycin intravenously every 12 hours at least for 3 days, then switch to oral administration according to dosing described in “2 points” section. Rule B in the UK: Targeted treatments as recommended by microbiologist. • Use of health resources: Emergency Hospital visits/consultations as follows: Hospitalization: 3 points Emergency Hospital visit: 2 points Unscheduled medical consultation due to a UTI: 1 point. • Health expenditure: expenses derived from consumption of health resources will be accounted according to the rates of that hospital. • Quality of life through the questionnaire SF36 • Satisfaction questionnaire with investigational medicinal product. • Family Resources (absenteeism) • Change from specific cell proliferation baseline against antigens of the vaccine. • Safety Variables Overall rate, severity and relationship of any adverse event (AE) per administration and per patient. Evaluation of local tolerance - reactions at the site of administration (and due to any medication administered for the treatment of AE).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary variables will be evaluated at baseline, 3 months, 6 months, 9 months, 12 months, 15th months, 18 months, 21 months and 24 months follow up time points. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 0 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 30 |