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   43871   clinical trials with a EudraCT protocol, of which   7290   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:
    A phase III double-blind, randomized study to evaluate the long-term efficacy and safety of Oxabact® in patients with primary hyperoxaluria

    Summary
    EudraCT number
    		 2017-000684-33
    Trial protocol
    		 DE   GB   NL   ES   BE   FR  
    Global end of trial date
    15 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Oct 2021
    First version publication date
    01 Oct 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    OC5-DB-02
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03116685
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    OxThera Intellectual Property AB
    Sponsor organisation address
    Regeringsgatan 111, Stockholm, Sweden, 11139
    Public contact
    Chief Operating Officer, OxThera Intellectual Property AB, 0046 86600223, elisabeth.lindner@oxthera.com
    Scientific contact
    Chief Operating Officer, OxThera Intellectual Property AB, 0046 86600223, elisabeth.lindner@oxthera.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000370-PIP02-18
    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 Aug 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Apr 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Apr 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of Oxabact® following 52 weeks treatment in patients with primary hyperoxaluria who had maintained kidney function, but below the lower limit of the normal range (eGFR < 90 ml/min/1.73 m2) and a total plasma oxalate concentration ≥ 10 μmol/L at baseline.
    Protection of trial subjects
    Before any study-related examinations were done, patients received detailed patient information, study procedures were explained to them and they had the opportunity to ask questions. Patients (and/or their parents/guardians in case of patients <18 years of age) had to sign an informed consent to be able to participate in the study. The IMP has previously been given to over 130 people without any major side effects but there may be side effects that are unknown at this time. Subjects could get gastrointestinal adverse events such as stomach problems or nausea. Some patients have also reported headache, cough and cold-like symptoms during treatment. There is also a risk of the bacteria getting in the patient’s blood and causing an infection. So far there have been no reports of such infections caused by the bacterium but if this happens it can be treated with antibiotics. To monitor potential adverse events, patients were observed in the clinics during the study visits. Physical exam, vital signs and laboratory safety tests were taken at screening and every study visit. Oxalobacter formigenes metabolises oxalate and forms a substance called formate. There is a theoretical risk that this may enter the patient’s blood and make them ill. So far there have been no reports of such illnesses caused by the bacterium. Since the effects of the study medication on pregnancy are unknown, female patients of child-bearing age had a pregnancy test before taking part to exclude the possibility of pregnancy. All women of childbearing potential needed to use adequate contraceptive precautions during the study. If they became pregnant while taking part in the study, the were asked to immediately tell the doctor. Study related data was collected in electronic Case Report Forms (eCRFs). All data was anonymised and was treated confidentially in line with national requirements and GDPR regulations.
    Background therapy
    		 Patients were allowed to receive Standard of Care, preferably in a stable manner throughout the study. Standard of Care included hyperhydration, avoiding oxalate-rich foods, crystallisation inhibitors (alkali citrates, magnesium or phosphate ions) and Vitamin B6. - Inclusion criteria 6: Subjects receiving vitamin B6 must be receiving a stable dose for at least 3 months prior to screening and must not change the dose during the study. Subjects not receiving vitamin B6 at study entry must be willing to refrain from initiating pyridoxine during study participation. - Prohibited medication in line with exclusion criteria: Exclusion criterion 11: Use of antibiotics to which O. formigenes is sensitive. (This includes current antibiotic use, or antibiotics use within 14 days of initiating study medication.). Exclusion criterion 12: Current treatment with a separate ascorbic acid preparation. (Please note patients were asked to refrain from taking multivitamin supplements throughout the study as these contain ascorbic acid/Vitamin C.)
    Evidence for comparator
    		 No comparator was used in the study; only the investigational drug and a placebo.
    Actual start date of recruitment
    09 Jan 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Tunisia: 4
    Country: Number of subjects enrolled
    United States: 1
    Worldwide total number of subjects
    25
    EEA total number of subjects
    17
    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)
    12
    Adolescents (12-17 years)
    6
    Adults (18-64 years)
    7
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment started on 17 Jan 2018 in Europe (8 sites) and the USA (3 sites) and ended on 07 May 2020. At a late stage in the trial, 3 sites were added in Tunisia and started patients recruiting in Dec 2019. In France, the Netherlands and at two US sites patients were screened but not randomized as they were screen failures.

    Pre-assignment
    Screening details
    		 There were 3 visits over 4-8 weeks to assess if the patient was suitable to receive study medicine (screening/baseline period). Screening was performed to assure eligibility as per inclusion/exclusion criteria especially for eGFR and Pox (these were the main reasons for screen failures). 43 patients were screened (2 re-screened); 25 were enrolled.

    Pre-assignment period milestones
    Number of subjects started
    		 43 [1]
    Number of subjects completed
    		 25

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Consent withdrawn by subject: 2
    Reason: Number of subjects
    		 Failed IC 3 (eGFR) and IC 4 (Pox): 4
    Reason: Number of subjects
    		 Failed IC 6 (Vitamin B6): 1
    Reason: Number of subjects
    		 Met EC 15 (Unable to follow study procedures): 1
    Reason: Number of subjects
    		 Failed IC 4 (Pox): 7
    Reason: Number of subjects
    		 Failed IC 3 (eGFR): 3
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 43 patients were screened in the OC5-DB-02 study. 18 of these patients were considered screen failures and were not eligible for inclusion in the study (15 did not satisfy requisite inclusion criteria, 2 withdrew consent during screening and 1 was unable to follow study procedures). Consequently only 25 patients completed screening and entered the treatment phase of the study.
    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    No blinding during screening/baseline as patients did not yet receive study treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Oxabact OC5
    Arm description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the Oxabact OC5 arm received treatment with Oxabact OC5 twice daily for 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oxabact OC5
    Investigational medicinal product code
    OC5
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The study drug consists of Oxabact® OC5. The dose was administered orally as one enteric-coated size-4 capsule with breakfast and dinner twice daily. The dose was NLT 1E+09 colony forming units (CFU) Oxalobacter formigenes per capsule.

    Arm title
    		 Placebo
    Arm description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the placebo arm received treatment with placebo twice daily for 52 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The placebo capsule was administered orally as one enteric-coated size-4 capsule with breakfast and dinner twice daily. Placebo capsules were of the same size and contained the same bulking agent as the Oxabact® OC5 capsule.

    Number of subjects in period 1
    		Oxabact OC5 Placebo
    Started
    13
    12
    Completed
    13
    12
    Period 2
    Period 2 title
    Treatment period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Oxabact OC5
    Arm description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the Oxabact OC5 arm received treatment with Oxabact OC5 twice daily for 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oxabact OC5
    Investigational medicinal product code
    OC5
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The study drug consists of Oxabact® OC5. The dose was administered orally as one enteric-coated size-4 capsule with breakfast and dinner twice daily. The dose was NLT 1E+09 colony forming units (CFU) Oxalobacter formigenes per capsule.

    Arm title
    		 Placebo
    Arm description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the placebo arm received treatment with placebo twice daily for 52 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    The placebo capsule was administered orally as one enteric-coated size-4 capsule with breakfast and dinner twice daily. Placebo capsules were of the same size and contained the same bulking agent as the Oxabact® OC5 capsule.

    Number of subjects in period 2
    		Oxabact OC5 Placebo
    Started
    13
    12
    Completed
    13
    11
    Not completed
    0
    1
         Physician decision
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Oxabact OC5
    Reporting group description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the Oxabact OC5 arm received treatment with Oxabact OC5 twice daily for 52 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the placebo arm received treatment with placebo twice daily for 52 weeks.

    Reporting group values
    		 Oxabact OC5 Placebo Total
    Number of subjects
    		 13 12 25
    Age categorical
    Patients that were two years of age or older were eligible to participate in the study. The youngest enrolled patient was five years of age at baseline.
    Units: Subjects
        Children (2-11 years)
    		 6 6 12
        Adolescents (12-17 years)
    		 4 2 6
        Adults (18-64 years)
    		 3 4 7
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 12.9 ( 6.4 ) 18.3 ( 16.5 ) -
    Gender categorical
    The study was open to both male and female patients.
    Units: Subjects
        Female
    		 9 5 14
        Male
    		 4 7 11
    Primary Hyperoxaluria Medical History - Type of PH
    Diagnosis of PH and PH type (i.e. PH type I, type II or type III)
    Units: Subjects
        Type I
    		 13 11 24
        Type II
    		 0 1 1
        Type III
    		 0 0 0
    Frequency of kidney stone events 1 yr prior to study start
    Investigator-reported / subject-reported stone events or symptoms of events during the year preceeding study start. Combined PH Medical History and/or Adverse Events reported during screening /baseline.
    Units: Subjects
        None
    		 8 7 15
        One event
    		 2 2 4
        Two events
    		 3 1 4
        Three or more events
    		 0 2 2
    Total plasma oxalate
    Mean value from the 3 screening /baseline visits. Samples for total plasma oxalate were processed at the clinical site and analysed at Academic Medical Centre, Amsterdam, the Netherlands (AMC). Total plasma oxalate was measured using isotope dilution gas chromatography with mass selective detection (GC-MSD).
    Units: micromole(s)/litre
        arithmetic mean (standard deviation)
    		 14.8 ( 5.7 ) 14.4 ( 5.4 ) -
    Kidney function - eGFR
    Mean value of the 3 screening /baseline visits. Kidney function was evaluated based on eGFR calculation using the 2009 creatinine-based “Schwartz bedside” equation (for children below 18 years of age) (Schwartz et al., 2009) and 2009 creatinine-based CKD-EPI equation for adults (Levey et al., 2009). Subjects who turn 18 during the study period were continuously evaluated using the Schwartz equation, ie the equation used at baseline was kept throughout the study.
    Units: millilitres/minute/1.73m2
        arithmetic mean (standard deviation)
    		 70.29 ( 11.58 ) 62.36 ( 16.90 ) -
    Free plasma oxalate
    Mean value of the 3 visits during screening /baseline. Ultrafiltered, acidified plasma samples for free plasma oxalate were processed at the clinical site and analysed at Academic Medical Centre, Amsterdam, the Netherlands (AMC) using isotope dilution gas chromatography with mass selective detection (GC-MSD).
    Units: micromole(s)/litre
        arithmetic mean (standard deviation)
    		 11.3 ( 6.6 ) 10.0 ( 5.2 ) -
    Urinary oxalate excretion /24 hour collection
    Mean of two values during screening /baseline. Twenty-four-hour urine samples for analysis of urinary oxalate were taken at subject´s home and sent to central laboratory TDL, London, UK.
    Units: millimoles/24hours/1.73m2
        arithmetic mean (standard deviation)
    		 2.11 ( 0.93 ) 1.76 ( 0.94 ) -
    Number of Oxalobacter formigenes genotype 1 in stool
    Only one stool sample was collected during screening /baseline. Faecal samples were collected at subject’s home and shipped to central laboratory MVZ Institut für Mikroökologie GmbH, Herborn, Germany. A real-time quantitative PCR assay was used that permits determination of the numbers of both O. formigenes genotype 1 and genotype 2 in faecal samples.
    Units: 1E+06 cells/gram
        median (inter-quartile range (Q1-Q3))
    		 0.0834 (0.0834 to 0.0834) 0.0834 (0.0834 to 0.0834) -
    Number of Oxalobacter formigenes genotype 2 in stool
    Only one stool sample was collected during screening /baseline. Faecal samples were collected at subject’s home and shipped to central laboratory MVZ Institut für Mikroökologie GmbH, Herborn, Germany. A real-time quantitative PCR assay was used that permits determination of the numbers of both O. formigenes genotype 1 and genotype 2 in faecal samples.
    Units: 1E+06 cells/gram
        median (inter-quartile range (Q1-Q3))
    		 0.0268 (0.0268 to 0.0268) 0.0268 (0.0268 to 0.1415) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Oxabact OC5
    Reporting group description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the Oxabact OC5 arm received treatment with Oxabact OC5 twice daily for 52 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the placebo arm received treatment with placebo twice daily for 52 weeks.
    Reporting group title
    Oxabact OC5
    Reporting group description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the Oxabact OC5 arm received treatment with Oxabact OC5 twice daily for 52 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the placebo arm received treatment with placebo twice daily for 52 weeks.

    Primary: Change from baseline in total plasma oxalate concentration after 52 weeks of treatment

    		 Close Top of page
    End point title
    		 Change from baseline in total plasma oxalate concentration after 52 weeks of treatment
    End point description
    Samples for total plasma oxalate were processed at the clinical site and analysed at Academic Medical Centre, Amsterdam, the Netherlands (AMC). Total plasma oxalate was measured using isotope dilution gas chromatography with mass selective detection (GC-MSD).
    End point type
    Primary
    End point timeframe
    Every 8 weeks starting from randomisation and until /including week 52. Change from baseline in total plasma oxalate concentration was calculated at each visit as the visit value minus the mean of the three measurements during baseline.
    End point values
    		 Oxabact OC5 Placebo
    Number of subjects analysed
    13 [1]
    12 [2]
    Units: micromole(s)/litre
        least squares mean (standard error)
    -0.78 ( 1.37 )
    3.01 ( 1.61 )
    Notes
    [1] - 13 patients started Oxabact OC5. 12 patients were analysed for total plasma oxalate at wk 52.
    [2] - 12 patients started treatment with placebo. 8 of them reported total plasma oxalate values at wk 52.
    Statistical analysis title
    		 Mixed-effect Repeated Measures Model - MRMM
    Statistical analysis description
    The primary statistical analysis was performed using a mixed-effect repeated measures model (MRMM) on the change from baseline value at 52 weeks, with the following independent variables: treatment group, baseline total plasma oxalate concentration value, week and week*treatment interaction. First order autoregressive covariance structure, AR(1) was used. This analysis is considered the first analysis in the hierarchical approach.
    Comparison groups
    Oxabact OC5 v Placebo
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.064
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Change from baseline in kidney function (eGFR) after 52 weeks of treatment.

    		 Close Top of page
    End point title
    		 Change from baseline in kidney function (eGFR) after 52 weeks of treatment.
    End point description
    Change in kidney function was evaluated based on eGFR calculation using the 2009 creatinine-based “Schwartz bedside” equation (for children below 18 years of age) (Schwartz et al., 2009) and 2009 creatinine-based CKD-EPI equation for adults (Levey et al., 2009). Subjects who turn 18 during the study period were continuously evaluated using the Schwartz equation, ie the equation used at baseline was kept throughout the study.
    End point type
    Secondary
    End point timeframe
    eGFR was determined every 8 weeks during the treatment phase. Change from baseline in kidney function (eGFR) was evaluated after 52 weeks treatment.
    End point values
    		 Oxabact OC5 Placebo
    Number of subjects analysed
    13 [3]
    12 [4]
    Units: millilitres/minute/1.73m2
        least squares mean (standard error)
    -1.35 ( 2.68 )
    -0.06 ( 3.12 )
    Notes
    [3] - 13 patients started Oxabact OC5. 12 of these patients were analysed for eGFR at week 52.
    [4] - 13 patients started treatment with placebo. 8 of these patients reported eGFR values at week 52.
    Statistical analysis title
    		 Mixed-effect Repeated Measures Model - MRMM
    Statistical analysis description
    A similar MRMM as for the primary endpoint was performed. A fixed order autoregressive covariance structure, AR(1) was used. The model provided a test of difference in slopes using the proposed time-by-treatment interaction, treatment slopes and slope differences on change through time. LS means were determined for each visit.
    Comparison groups
    Placebo v Oxabact OC5
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.744
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Frequency of kidney stone events - Adjudicated assessment

    		 Close Top of page
    End point title
    		 Frequency of kidney stone events - Adjudicated assessment
    End point description
    The kidney stone data, including adverse events and renal ultrasound at week 48, were assessed by an independent adjudicator. A composite number of kidney stone events was provided for each patient.
    End point type
    Secondary
    End point timeframe
    Stone event data collected throughout the 52-week treatment period.
    End point values
    		 Oxabact OC5 Placebo
    Number of subjects analysed
    13
    12
    Units: Number of kidney stone events
    7
    8
    Statistical analysis title
    		 Analysis for adjudicated stone data
    Statistical analysis description
    For comparison between treatments on the total number of kidney stone events as per adjudicated data, a zero-inflated Poisson model was used.
    Comparison groups
    Placebo v Oxabact OC5
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.117
    Method
    		 Poisson model
    Confidence interval

    Other pre-specified: Percent change from baseline in total plasma oxalate concentration after 52 weeks of treatment

    		 Close Top of page
    End point title
    		 Percent change from baseline in total plasma oxalate concentration after 52 weeks of treatment
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Plasma oxalate was measured every 8 weeks throughout the treatment phase.
    End point values
    		 Oxabact OC5 Placebo
    Number of subjects analysed
    13 [5]
    12 [6]
    Units: Percent
        arithmetic mean (standard deviation)
    -0.57 ( 27.42 )
    15.27 ( 16.36 )
    Notes
    [5] - 13 patients started treatment with Oxabact OC5. 12 of them were analysed for % Pox at week 52
    [6] - 12 patients started placebo. 8 of them were analysed for percentage plasma oxalate at wk 52.
    Statistical analysis title
    		 ANOVA
    Statistical analysis description
    Percent change from baseline in total plasma oxalate concentration after 52 weeks of treatment was analysed statistically using an ANOVA model.
    Comparison groups
    Oxabact OC5 v Placebo
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.146
    Method
    		 ANOVA
    Confidence interval

    Other pre-specified: Subjects achieving ‘near-normalisation’ of total plasma oxalate concentration (<10 µmol/L) at least twice during weeks 24 to 52 of treatment

    		 Close Top of page
    End point title
    		 Subjects achieving ‘near-normalisation’ of total plasma oxalate concentration (<10 µmol/L) at least twice during weeks 24 to 52 of treatment
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Plasma oxalate was measured every 8 weeks throughout the treatment phase.
    End point values
    		 Oxabact OC5 Placebo
    Number of subjects analysed
    13
    12
    Units: Number of subjects
    2
    3
    Statistical analysis title
    		 Cochran-Mantel-Haenszel test
    Statistical analysis description
    Statistical analysis to compare the treatment arms was done using a Cochran-Mantel-Haenszel test controlling for the stratification as applied in the randomisation.
    Comparison groups
    Oxabact OC5 v Placebo
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.582
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Other pre-specified: Change from baseline in free plasma oxalate concentration after 52 weeks of treatment

    		 Close Top of page
    End point title
    		 Change from baseline in free plasma oxalate concentration after 52 weeks of treatment
    End point description
    Ultrafiltered, acidified plasma samples for free plasma oxalate were processed at the clinical site and analysed at Academic Medical Centre, Amsterdam, the Netherlands (AMC) using isotope dilution gas chromatography with mass selective detection (GC-MSD).
    End point type
    Other pre-specified
    End point timeframe
    Plasma oxalate was measured every 8 weeks during the treatment period.
    End point values
    		 Oxabact OC5 Placebo
    Number of subjects analysed
    13 [7]
    12 [8]
    Units: micromole(s)/litre
        least squares mean (standard error)
    2.88 ( 1.87 )
    1.46 ( 2.06 )
    Notes
    [7] - 13 patients started Oxabact OC5. 10 patients were analysed for free plasma oxalate at wk 52.
    [8] - 12 patients started placebo. 8 of them were analysed for free plasma oxalate at wk 52.
    Statistical analysis title
    		 Mixed-effect Repeated Measures Model - MRMM
    Statistical analysis description
    See Primary endpoint. A first order autoregressive covariance structure, AR(1) was used.
    Comparison groups
    Oxabact OC5 v Placebo
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6
    Method
    		 Mixed models analysis
    Confidence interval

    Other pre-specified: Change from baseline in urinary oxalate excretion after 52 weeks of treatment

    		 Close Top of page
    End point title
    		 Change from baseline in urinary oxalate excretion after 52 weeks of treatment
    End point description
    24-hour urine collection for analysis of urinary oxalate were taken at subject´s home and sent to central laboratory TDL, London, UK.
    End point type
    Other pre-specified
    End point timeframe
    24-hour urine collection was done at weeks 8, 24, 40 and 52 of the treatment phase.
    End point values
    		 Oxabact OC5 Placebo
    Number of subjects analysed
    13 [9]
    12 [10]
    Units: millimoles/24hours/1.73m2
        least squares mean (standard error)
    0.082 ( 0.247 )
    -0.320 ( 0.263 )
    Notes
    [9] - 13 patients started Oxabact OC5. 12 patients were analysed for Uox at wk 52.
    [10] - 12 patients started placebo. 10 of them were analysed for Uox at wk 52.
    Statistical analysis title
    		 Mixed-effect Repeated Measures Model - MRMM
    Statistical analysis description
    A first order autoregressive covariance structure, AR(1) was used.
    Comparison groups
    Oxabact OC5 v Placebo
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.232
    Method
    		 Mixed models analysis
    Confidence interval

    Other pre-specified: Change in number of Oxalobacter formigenes in stool - genotype 1

    		 Close Top of page
    End point title
    		 Change in number of Oxalobacter formigenes in stool - genotype 1
    End point description
    Faecal samples were collected at subject’s home and shipped to central laboratory MVZ Institut für Mikroökologie GmbH, Herborn, Germany. A real-time quantitative PCR assay was used that permits determination of the numbers of both O. formigenes genotype 1 and genotype 2 in faecal samples.
    End point type
    Other pre-specified
    End point timeframe
    Stool samples were collected at weeks 24, 40 and 52 of the treatment period.
    End point values
    		 Oxabact OC5 Placebo
    Number of subjects analysed
    13 [11]
    12 [12]
    Units: x 1E+06 cells/g
        median (inter-quartile range (Q1-Q3))
    0.6906 (-0.0025 to 3.1566)
    0.000 (0.0000 to 0.0000)
    Notes
    [11] - 13 patients started Oxabact OC5. 11 patients were analysed for O. formigenes genotype 1 at wk 52.
    [12] - 12 patients started placebo. 10 of them were analysed for O. formigenes genotype 1 at wk 52.
    No statistical analyses for this end point

    Other pre-specified: Change in number of Oxalobacter formigenes in stool - genotype 2

    		 Close Top of page
    End point title
    		 Change in number of Oxalobacter formigenes in stool - genotype 2
    End point description
    Faecal samples were collected at subject’s home and shipped to central laboratory MVZ Institut für Mikroökologie GmbH, Herborn, Germany. A real-time quantitative PCR assay was used that permits determination of the numbers of both O. formigenes genotype 1 and genotype 2 in faecal samples.
    End point type
    Other pre-specified
    End point timeframe
    Stool samples were collected at weeks 24, 40 and 52 of the treatment period.
    End point values
    		 Oxabact OC5 Placebo
    Number of subjects analysed
    13 [13]
    12 [14]
    Units: x 1E+06 cells/g
        median (inter-quartile range (Q1-Q3))
    0.0000 (0.0000 to 0.0000)
    0.0000 (0.0000 to 0.0000)
    Notes
    [13] - 13 patients started Oxabact OC5. 11 patients were analysed for O. formigenes genotype 2 at wk 52.
    [14] - 12 patients started placebo. 10 of them were analysed for O. formigenes genotype 2 at wk 52.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse Event reporting for each subject started at the initiation of study treatment, (i.e. from First Dose Date). The reporting continued during the course of the study (i.e. until End Of Study).
    Adverse event reporting additional description
    Patients were asked about adverse events at least at each visit, and these were reported in the eCRF by the investigator. Serious AEs were reported within 24 hours of awareness directly to the sponsor's safety vendor. End of Study was defined as End of Treatment (i.e. last dose date) + maximum 14 days of safety follow-up.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Oxabact OC5
    Reporting group description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the Oxabact OC5 arm received treatment with Oxabact OC5 twice daily for 52 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 During the baseline period, subjects did not receive any study treatment. Randomization (1:1 to Oxabact OC5:Placebo) was done after completion of the baseline period. Disposition information at baseline is provided as by subsequent treatment arm. Subjects in the placebo arm received treatment with placebo twice daily for 52 weeks.

    Serious adverse events
    		 Oxabact OC5 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 13 (23.08%)
    4 / 12 (33.33%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Renal and urinary disorders
    Calculus urinary
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Flank pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial pyelonephritis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Oxabact OC5 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 13 (100.00%)
    11 / 12 (91.67%)
    Surgical and medical procedures
    Bladder catheterisation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Renal stone removal
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Catheter placement
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 12 (16.67%)
         occurrences all number
    3
    4
    Chest pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Asthma
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Cough
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Eosinophilia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Hand fracture
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Cardiac disorders
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Eye disorders
    Myopia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Optic disc drusen
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    1 / 13 (7.69%)
    4 / 12 (33.33%)
         occurrences all number
    1
    6
    Abdominal pain
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 12 (8.33%)
         occurrences all number
    2
    1
    Abdominal distension
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Calculus urinary
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Renal colic
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 12 (0.00%)
         occurrences all number
    5
    0
    Nephrolithiasis
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Flank pain
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 12 (8.33%)
         occurrences all number
    3
    1
    Back pain
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Arthralgia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Foot deformity
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Infections and infestations
    Tonsillitis
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 12 (16.67%)
         occurrences all number
    2
    2
    Nasopharyngitis
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 12 (16.67%)
         occurrences all number
    2
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 12 (16.67%)
         occurrences all number
    1
    3
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 12 (8.33%)
         occurrences all number
    2
    2
    COVID-19
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Dientamoeba infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    Infected bite
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Iron deficiency
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Jun 2017
    Amendment 1: UK specific amendment • Added information on the process for emergency unblinding • Clarified that separate regulatory approval would be sought for the open-label follow up study
    21 Sep 2017
    Amendment 2: • Spain and Belgium added to list of participating countries. • Clarified that a separate Clinical Trial Application would be issued for the follow-up study. • Safety analyses performed at a central lab instead of at the local lab. • Clarified process for patients with AKI during baseline. • Clarified that in the event there is a need to know the identity of the drug given to a patient, the decision to unblind the treatment resides solely with the investigator.
    28 Mar 2018
    Amendment 3: • Reporting of Pregnancy during the study added to the Safety section. • Information added about the Data and Safety Monitoring Board. • Sample size section updated. • Schedule of assessments updated. • The previous numbering of references (superscription format) have been replaced by Author name and year. • Reference list corrected and updated in alphabetical order. • Minor corrections and clarifications.
    15 Oct 2018
    Amendment 4: • Secondary and exploratory endpoints were reorganised. • Frequency of kidney stone events was added under key secondary endpoints. • Information added that kidney stone events and related symptoms were to be captured throughout the study. • Clarified that if an acute kidney injury/stone event occurred close to a scheduled visit, the visit would be rescheduled once the AKI/stone event was resolved. • Tunisia added to list of participating countries. • Statistical sections updated in line with revised endpoints. • Minor corrections and clarifications
    06 Sep 2019
    Amendment 5: • Clarification that for determination of eligibility, estimated Glomerular Filtration Rate (eGFR) could be calculated using Schwartz or CKD-EPI equations that include serum creatinine and/or cystatin C. Please note, that this amendment was a country-specific Amendment for Spain and the US.
    19 Dec 2019
    Amendment 6: • Included revisions made in Amendment 5 of 06 Sep 2019. • Implementation of post-treatment safety follow-up (mainly addressed in sections 6.2 and 6.3). Consequently, the definition of “End-of-Study” was updated and “End-of-Treatment” was defined. • Updated section 7.4. Withdrawal criteria to include “The subject requires dialysis”. • Updated list of blind data and added clarifications in section 8.4. • Updated section 11.4 Reporting of Adverse Events to harmonise with the Safety Management plan for this study (Vs 4.0 dated 24 Jun 2019). • Updated section 11.5.3 to refer to Investigator Brochure; this was to harmonise with the protocol of the OC5-OL-01 and OC5-OL-02 studies. • Added updates and clarifications in section 12 Statistical Methods including tests of hypotheses and significance levels, information on methods used to analyse endpoints and definition of treatment-emergent AEs. Added additional subgroups. • Minor updates, corrections and clarifications throughout the protocol.
    08 Jan 2021
    Amendment 7: • Added clinical success criteria in section 5.3 • Updated section 7.4. Withdrawal criteria to clarify which assessments were to be done for early withdrawal. • Added 2 new other endpoints (Percent change from baseline in total plasma oxalate concentration and Subjects achieving ‘near-normalisation’ in total plasma oxalate concentration) in section 10. • Added updates and clarifications in section 12 relating to hierarchical testing. • Updated OC5-OL-01 study information throughout the protocol. • Minor updates, corrections and clarifications throughout the protocol. (N.B. “Patient” was replaced with “subject” throughout the protocol as appropriate).

    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-Thu May 02 16:20:49 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA