Clinical Trial Results:
A phase 2 open-label multi-centre study to evaluate the efficacy and safety of Oxabact® to reduce plasma oxalate in patients with primary hyperoxaluria who are on dialysis
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Summary
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EudraCT number |
2013-004368-74 |
Trial protocol |
DE |
Global end of trial date |
29 Jan 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Aug 2020
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First version publication date |
02 Aug 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
OC5-OL-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02000219 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
OxThera Intellectual Property AB
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Sponsor organisation address |
Regeringsgatan 111, Stockholm, Sweden, 11139
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Public contact |
Director of Regulatory Affairs, OxThera Intellectual Property AB, 0046 86600223, orla.mccallion@oxthera.com
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Scientific contact |
Chief Medical Officer, OxThera Intellectual Property AB, 0046 86600223, bastian.dehmel@oxthera.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Jun 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 Jan 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
29 Jan 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of OC5 to reduce total plasma oxalate levels during OC5 treatment in patients with Primary Hyperoxaluria (PH) who are on dialysis. The study also evaluated the safety of OC5.
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Protection of trial subjects |
The initial 14 weeks phase of the study: Following a 4-week baseline period, patient received OC5 (Oxalobacter formigenes) twice daily for a 6-week treatment period (week 10). Patients were subsequently followed for 4 weeks without study-drug (week 14).
Continued treatment (CT) phase of the study: At the end of the initial 14-week period, patients were offered to continue OC5 treatment for up to 3 years (156 weeks).
Patients were observed in the clinics during the study visits. Physical exam and vital signs were taken at screening and up to last study visit to the clinic. Laboratory safety tests included haematology, chemistry and urinalysis were assessed at weeks 0, 4, 10 and 14 during the initial 14-week study, monthly throughout year 1 and 2, and every third and fourth month throughout year 3 of the continued treatment period. Adverse events (AEs) and concomitant medication were monitored throughout the study during study visits. Patients’ personal data were collected and processed in line with national requirements and subsequent GDPR regulations since 2018.
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Background therapy |
Dialysis | ||
Evidence for comparator |
N/A; only active drug | ||
Actual start date of recruitment |
19 May 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Germany: 11
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Worldwide total number of subjects |
12
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EEA total number of subjects |
12
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
2
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
10
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Open-label study initially conducted at 4 sites (Germany, USA, 2 sites in France). Sites in the USA and France closed during 2017. No patients recruited at US site; subject enrolled in France left study early. First patient enrolled 19 May 2014; last patient completed study 29 Jan 2020. In total: 14 patients screened, 12 patients enrolled. | ||||||||||||||
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Pre-assignment
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Screening details |
Male or female PH patients, ≥2 years, on a stable dialysis regimen with plasma oxalate ≥40 µmol/L were included in the study. Patients should be able to take size-4 capsules twice daily by swallowing or via gastric tube. Inclusion/exclusion criteria were assessed during screening. NB: Baseline characteristics only detailed for enrolled patients. | ||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
14 [1] | ||||||||||||||
Number of subjects completed |
12 | ||||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Screen failure: 2 | ||||||||||||||
| 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: There were 2 screen failures that participated in baseline but were not enrolled into the study. |
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Period 1
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Period 1 title |
Baseline
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
N/A; the study was open-label
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Arms
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Arm title
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Baseline OC5 | ||||||||||||||
Arm description |
- | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Oxabact
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Investigational medicinal product code |
OC5
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
OC5 was provided as enteric-coated size-4 capsule containing at least 1E+09 colony-forming units (CFU) O. formigenes per capsule. After the 4-week baseline period, administration was orally as one capsule twice daily (breakfast and dinner), for 6 weeks in the initial phase of the study and for up to 156 weeks during the continued treatment phase.
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Period 2
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Period 2 title |
Initial 6-wk treatment + 4-wks off drug
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
N/A; the study was open-label
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Arms
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Arm title
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OC5 (initial phase) | ||||||||||||||
Arm description |
Patients received open-label treatment with OC5. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Oxabact
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Investigational medicinal product code |
OC5
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
OC5 was provided as enteric-coated size-4 capsule containing at least 1E+09 colony-forming units (CFU) O. formigenes per capsule. After the 4-week baseline period, administration was orally as one capsule twice daily (breakfast and dinner), for 6 weeks in the initial phase of the study and for up to 156 weeks during the continued treatment phase.
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Period 3
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Period 3 title |
Continued treatment (up to 156 weeks)
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
N/A; this was an open-label study
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Arms
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Arm title
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OC5 (continued treatment) | ||||||||||||||
Arm description |
Patients received open-label treatment with OC5. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Oxabact
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Investigational medicinal product code |
OC5
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
OC5 was provided as enteric-coated size-4 capsule containing at least 1E+09 colony-forming units (CFU) O. formigenes per capsule. After the 4-week baseline period, administration was orally as one capsule twice daily (breakfast and dinner), for 6 weeks in the initial phase of the study and for up to 156 weeks during the continued treatment phase.
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| Notes [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: One patient who completed the initial 14-weeks of the study declined participation in the continued treatment phase of the study. |
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Baseline OC5
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Reporting group description |
- | ||
Reporting group title |
OC5 (initial phase)
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Reporting group description |
Patients received open-label treatment with OC5. | ||
Reporting group title |
OC5 (continued treatment)
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Reporting group description |
Patients received open-label treatment with OC5. | ||
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End point title |
Change in total plasma oxalate concentration during OC5 treatment, compared with baseline - week 10 (after 6 weeks of OC5 treatment) [1] | ||||||||
End point description |
For the primary endpoint, the change in total plasma oxalate concentration from baseline during OC5 treatment was calculated using the average from the 2 pre-treatment values as the baseline value. The change from baseline was determined for each post-baseline measurement, i.e., throughout the initial 6-week treatment period, the 4-week off-treatment period and the continued treatment period for up to 3 years (156 weeks). The primary endpoint was evaluated using descriptive statistics.
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End point type |
Primary
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End point timeframe |
Change from baseline after 6 weeks of OC5 treatment (i.e. at week 10 of the initial 14-week phase of the study)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was descriptive and therefore, no formal statistical significance testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in total plasma oxalate concentration during OC5 treatment, compared with baseline - week 14 (after 4 weeks off treatment) [2] | ||||||||
End point description |
For the primary endpoint, the change in total plasma oxalate concentration from baseline during OC5 treatment was calculated using the average from the 2 pre-treatment values as the baseline value. The change from baseline was determined for each post-baseline measurement, i.e., throughout the initial 6-week treatment period, the 4-week off-treatment period and the continued treatment period for up to 3 years (156 weeks). The primary endpoint was evaluated using descriptive statistics.
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End point type |
Primary
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End point timeframe |
Change from baseline after 6 weeks of OC5 treatment + 4 weeks off treatment (i.e. at week 14 of the initial 14-week phase of the study)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was descriptive and therefore, no formal statistical significance testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in total plasma oxalate concentration during OC5 treatment, compared with baseline - week 52 [3] | ||||||||
End point description |
For the primary endpoint, the change in total plasma oxalate concentration from baseline during OC5 treatment was calculated using the average from the 2 pre-treatment values as the baseline value. The change from baseline was determined for each post-baseline measurement, i.e., throughout the initial 6-week treatment period, the 4-week off-treatment period and the continued treatment period for up to 3 years (156 weeks). The primary endpoint was evaluated using descriptive statistics.
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End point type |
Primary
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End point timeframe |
Change from baseline after 52 weeks of continued OC5 treatment
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was descriptive and therefore, no formal statistical significance testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in total plasma oxalate concentration during OC5 treatment, compared with baseline - week 104 [4] | ||||||||
End point description |
For the primary endpoint, the change in total plasma oxalate concentration from baseline during OC5
treatment was calculated using the average from the 2 pre-treatment values as the baseline value. The
change from baseline was determined for each post-baseline measurement, i.e., throughout the initial
6-week treatment period, the 4-week off-treatment period and the continued treatment period for up to
3 years (156 weeks). The primary endpoint was evaluated using descriptive statistics.
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End point type |
Primary
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End point timeframe |
Change from baseline after 104 weeks of continued OC5 treatment
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was descriptive and therefore, no formal statistical significance testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in total plasma oxalate concentration during OC5 treatment, compared with baseline - week 156 [5] | ||||||||
End point description |
For the primary endpoint, the change in total plasma oxalate concentration from baseline during OC5 treatment was calculated using the average from the 2 pre-treatment values as the baseline value. The change from baseline was determined for each post-baseline measurement, i.e., throughout the initial 6-week treatment period, the 4-week off-treatment period and the continued treatment period for up to 3 years (156 weeks). The primary endpoint was evaluated using descriptive statistics.
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End point type |
Primary
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End point timeframe |
Change from baseline after 156 weeks of continued treatment.
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was descriptive and therefore, no formal statistical significance testing was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline - week 10 (after 6 weeks of OC5 treatment) | ||||||||
End point description |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline.
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End point type |
Secondary
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End point timeframe |
Change from baseline after 6 weeks of OC5 treatment (i.e. at week 10 of the initial 14-week phase of the study)
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline - week 14 (after 4 weeks off treatment) | ||||||||
End point description |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline.
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End point type |
Secondary
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End point timeframe |
Change from baseline after 6 weeks of OC5 treatment + 4 weeks off drug (i.e. at week 14 of the initial 14-week phase of the study)
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline - week 52 | ||||||||
End point description |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline.
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End point type |
Secondary
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End point timeframe |
Change from baseline after 52 weeks of continued treatment
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline - week 104 | ||||||||
End point description |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline.
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End point type |
Secondary
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End point timeframe |
Change from baseline after 104 weeks of continued treatment
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline - week 156 | ||||||||
End point description |
Change in free plasma oxalate concentration during OC5 treatment, compared with baseline.
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End point type |
Secondary
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End point timeframe |
Change from baseline after 156 weeks of continued treatment
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| No statistical analyses for this end point | |||||||||
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End point title |
Change in plasma oxalate (total plasma oxalate) values from week 10 to week 14, following the 4-week off-treatment period. | ||||||||
End point description |
Change in total plasma oxalate concentration after 4 weeks off OC5 treatment compared with week 10 (i.e. after 6 weeks of OC5 treatment).
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End point type |
Secondary
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End point timeframe |
Change from week 10 to week 14, i.e. after 4 weeks off-treatment. (Week 10: end of initial 6-week
treatment following 4 weeks baseline period; week 14: end of 4-week wash-out period)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of O. formigenes in faeces during treatment - week 10 (after 6 weeks of OC5 treatment) | ||||||||
End point description |
Number of O. formigenes observed in faeces during treatment.
Measurements provided the number of O. formigenes bacteria (genotypes 1 and 2), and OC5 consists of
O. formigenes derived from the human strain HC-1 of O. formigenes genotype 1. At first baseline, O. formigenes genotype 1 and 2 were not detected in any patients, except for one patient who showed a (low) positive count of genotype 2. Baseline for this assessment was set at 4 weeks. Genotype 1 was observed in all patients during treatment.
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End point type |
Secondary
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End point timeframe |
Number of O. formigenes after 6 weeks of OC5 treatment (i.e. at week 10 of the initial 14-week phase of the study)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of O. formigenes in faeces during treatment - week 14 (after 4 weeks off treatment) | ||||||||
End point description |
Number of O. formigenes observed in faeces during treatment.
Measurements provided the number of O. formigenes bacteria (genotypes 1 and 2), and OC5 consists of
O. formigenes derived from the human strain HC-1 of O. formigenes genotype 1. At first baseline, O. formigenes genotype 1 and 2 were not detected in any patients, except for one patient who showed a (low) positive count of genotype 2. Baseline for this assessment was set at 4 weeks. Genotype 1 was observed in all patients during treatment.
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End point type |
Secondary
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End point timeframe |
Number of O. formigenes after 6 weeks of OC5 treatment + 4 weeks off treatment (i.e. at week 14 of the initial 14-week phase of the study)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of O. formigenes in faeces during treatment - week 56 | ||||||||
End point description |
Number of O. formigenes observed in faeces during treatment.
Measurements provided the number of O. formigenes bacteria (genotypes 1 and 2), and OC5 consists of
O. formigenes derived from the human strain HC-1 of O. formigenes genotype 1. At first baseline, O. formigenes genotype 1 and 2 were not detected in any patients, except for one patient who showed a (low) positive count of genotype 2. Baseline for this assessment was set at 4 weeks. Genotype 1 was observed in all patients during treatment.
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End point type |
Secondary
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End point timeframe |
Number of O. formigenes after 56 weeks of continued OC5 treatment.
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of O. formigenes in faeces during treatment - week 104 | ||||||||
End point description |
Number of O. formigenes observed in faeces during treatment.
Measurements provided the number of O. formigenes bacteria (genotypes 1 and 2), and OC5 consists of
O. formigenes derived from the human strain HC-1 of O. formigenes genotype 1. At first baseline, O. formigenes genotype 1 and 2 were not detected in any patients, except for one patient who showed a (low) positive count of genotype 2. Baseline for this assessment was set at 4 weeks. Genotype 1 was observed in all patients during treatment.
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End point type |
Secondary
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End point timeframe |
Number of O. formigenes after 104 weeks of continued OC5 treatment.
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of O. formigenes in faeces during treatment - week 156 | ||||||||
End point description |
Number of O. formigenes observed in faeces during treatment.
Measurements provided the number of O. formigenes bacteria (genotypes 1 and 2), and OC5 consists of
O. formigenes derived from the human strain HC-1 of O. formigenes genotype 1. At first baseline, O. formigenes genotype 1 and 2 were not detected in any patients, except for one patient who showed a (low) positive count of genotype 2. Baseline for this assessment was set at 4 weeks. Genotype 1 was observed in all patients during treatment.
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End point type |
Secondary
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End point timeframe |
Number of O. formigenes after 156 weeks of continued OC5 treatment.
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| No statistical analyses for this end point | |||||||||
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End point title |
To evaluate results from Speckle tracking echocardiography - week 52 | ||||||||
End point description |
Change in Global Longitudinal Strain - GLS (%, assessed by Speckle-tracking echocardiography) during treatment compared with baseline.
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End point type |
Secondary
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End point timeframe |
Change from baseline after 52 weeks of OC5 treatment. (No post-treatment data for the initial 14 weeks of the study.)
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| No statistical analyses for this end point | |||||||||
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End point title |
To evaluate results from Speckle tracking echocardiography - week 104 | ||||||||
End point description |
Change in Global Longitudinal Strain - GLS (%, assessed by Speckle-tracking echocardiography) during treatment compared with baseline.
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End point type |
Secondary
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End point timeframe |
Change from baseline after 104 weeks of OC5 treatment. (No post-treatment data for the initial 14 weeks of the study.)
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| No statistical analyses for this end point | |||||||||
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End point title |
To evaluate results from Speckle tracking echocardiography - week 156 | ||||||||
End point description |
Change in Global Longitudinal Strain - GLS (%, assessed by Speckle-tracking echocardiography) during treatment compared with baseline
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End point type |
Secondary
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End point timeframe |
Change from baseline after 156 weeks of OC5 treatment. (No post-treatment data for the initial 14 weeks of the study.)
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| No statistical analyses for this end point | |||||||||
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End point title |
To evaluate results from traditional echocardiography - week 52 | ||||||||
End point description |
Change in Left Ventricular Ejection Fraction - LVEF (%, assessed by traditional echocardiography) during treatment compared with baseline.
|
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End point type |
Secondary
|
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End point timeframe |
Change from baseline after 52 weeks of OC5 treatment. (No post-treatment data for the initial 14 weeks of the study.)
|
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|
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| No statistical analyses for this end point | |||||||||
|
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End point title |
To evaluate results from traditional echocardiography - week 104 | ||||||||
End point description |
Change in Left Ventricular Ejection Fraction - LVEF (%, assessed by traditional echocardiography) during treatment compared with baseline.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Change from baseline after 104 weeks of OC5 treatment. (No post-treatment data for the initial 14 weeks of the study.)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
To evaluate results from traditional echocardiography - week 156 | ||||||||
End point description |
Change in Left Ventricular Ejection Fraction - LVEF (%, assessed by traditional echocardiography) during treatment compared with baseline.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Change from baseline after 156 weeks of OC5 treatment. (No post-treatment data for the initial 14 weeks of the study.)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Each subject was questioned about AEs at each clinic visit/telephone follow-up following initiation of treatment.
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Adverse event reporting additional description |
Each subject was asked the question "Since your last clinic visit have you had any health problems?" The information could also be obtained from signs and symptoms detected during each examination, observed by the study personnel or spontaneous reports from the study subjects or by laboratory results.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
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Reporting groups
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Reporting group title |
OC5 group
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
|||||||
| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
14 Feb 2014 |
Amendment 1 (which related to Version 1 of the Protocol in Germany and France):
This amendment added a new inclusion criterion; this detailed the minimum age of the patients (≥ 2 years) and that they had to be able to swallow the capsules or could use a gastric tube that allowed for administration of the capsules. A new exclusion criterion concerning inability to take study medication was also added. This amendment further clarified that children would not be treated with Oxabact OC5 until the 4-week safety data from at least two adult patients in the earlier OC5-DB-01 study had been reviewed and raised no safety concerns.
|
||||||
26 Mar 2014 |
Amendment 2 (which related to Version 2 of the Protocol in US):
This amendment only concerned US (which did not enroll any subjects).
This amendment clarified the exclusion criteria no. 8 and detailed that transplanted patients or patients requiring ongoing immunosuppressive treatment during the study were excluded. Moreover, the following was added:
• Clarification of evaluation of infections during the study,
• Change of recommended first-line antibiotics for treatment of unexpected infections caused by the study medication
• Subjects experiencing a systemic infection with unknown origin or suspected to be caused by Oxalobacter formigenes will be taken off treatment.
|
||||||
09 May 2014 |
Amendment 3 (which related to Version 3 of the Protocol in US):
This amendment only concerned US (which did not enroll any subjects).
This amendment clarified that patients with elevated numbers of Oxalobacter formigenes at week 14 would be followed until values return to baseline levels or until they stabilise over two consecutive samples.
|
||||||
21 Oct 2014 |
Amendment 4 (which related to Version 4 of the Protocol in Germany):
This amendment only concerned Germany.
This amendment processed the following: after the end of the 4 weeks follow-up, patients would be offered to receive study drug until transplantation (continued treatment period). Moreover, the following additions were made:
• Addition of a secondary endpoint to evaluate the efficacy and safety of long-term treatment for patients who would continue on study drug after the follow-up period,
• Addition that Speckle Tracking Echocardiography would be performed at screening or week 14 visit and repeated every 6 months during the continued treatment period.
|
||||||
14 Dec 2014 |
Amendment 5 (which related to Version 5 of the Protocol in Germany).
This amendment only concerned Germany.
This amendment clarified that the length of the continued treatment had been prolonged to a maximum of 12 months.
|
||||||
20 Feb 2015 |
Amendment 6 (which related to Version 6 of the Protocol in France).
This amendment only concerned France.
This amendment clarified a new administration process for patients who would not be able to swallow capsules.
|
||||||
08 Mar 2016 |
Amendment 7 (which related to Version 7 of the Protocol in Germany).
This Amendment only concerned Germany.
This amendment clarified that the length of the continued treatment period had been extended by an additional 12-month period, i.e. to a maximum of 24 months. The timeline for evaluation of the primary endpoint (change in plasma oxalate from baseline) was also revised.
|
||||||
31 May 2016 |
Amendment 8 (which related to Version 8 of the Protocol).
This amendment was submitted to Germany as a notification only, and included non-substantial amendments (administrative modifications).
|
||||||
20 Sep 2016 |
Amendment 9 (which related to Version 8 of the Protocol).
This amendment was submitted to Germany as a notification only.
The amendment included non-substantial amendments (administrative modifications).
|
||||||
04 Apr 2017 |
Amendment 10 (which related to Version 9 of the Protocol in Germany).
This amendment only concerned Germany.
This amendment clarified that the length of the continued treatment period had been extended by an additional 12-month period (i.e. to a maximum of 36 months).
|
||||||
27 Nov 2017 |
Amendment 11 (which related to Version 10 of the Protocol).
This amendment was an internal document only, and not submitted to any authority.
This amendment clarified that the primary endpoint will evaluate total plasma oxalate values, added analysis of change in free plasma oxalate values as a secondary endpoint, and further specified that an interim analysis of data would be performed after 12 months of continued treatment.
|
||||||
18 Jan 2018 |
Amendment 12 (which related to Version 11 of the Protocol in Germany).
This amendment only concerned Germany.
In addition to the revisions detailed in Version 10 of the protocol, this amendment clarified that final visit date after completion of 3 years was corrected from week 152 to week 156.
|
||||||
14 Oct 2019 |
Amendment 13 (which related to Version 12 of the Protocol in Germany).
This amendment only concerned Germany.
This amendment clarified transplantation as an explicit reason for withdrawal. It further defined events that would not be reported as Adverse Events, and detailed that an interim analysis of data would be performed after 24 months of continued treatment.
|
||||||
Interruptions (globally) |
|||||||
| Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
