Primary Hyperoxaluria
Conditions
Keywords
hyperoxaluria, oxalate, PH, dialysis
Brief summary
The purpose of this study is to determine if Oxalobacter formigenes is effective at lowering plasma oxalate levels in patients with primary hyperoxaluria who are on dialysis.
Interventions
BIOLOGICALOxalobacter formigenes
The dose will be (not less than) NLT ≥1E+09 colony forming units (CFU) twice daily. The dose (an enteric-coated capsule) will be administered orally with breakfast and dinner.
Sponsors
FP7-SME-2013 Research for the benefit of SMEs program
OxThera
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent (as applicable for the age of the subject). An appendix to the informed consent will be signed by patients continuing on treatment after week 14. 2. Male or female subjects ≥ 2 years of age. Subjects have to be able to swallow size 4 capsules twice daily for 6 weeks, or use a gastric tube that allows for administration of size 4 capsules. 3. A diagnosis of PH (as determined by standard diagnostic methods). 4. Patient should be on a stable dialysis regimen for at least two weeks before baseline. 5. Pre-dialysis plasma oxalate ≥40 micromole/L. 6. Patients receiving vitamin B6 must be receiving a stable dose for at least 3 months prior to screening and must remain on the stable dose during the study. Patients not receiving vitamin B6 at study entry must be willing to refrain from initiating vitamin B6 during study participation.
Exclusion criteria
7. Inability to swallow size 4 capsules twice daily for 6 weeks or using a gastric tube not suited for administration of size 4 capsules via the tube. 8. Ongoing treatment with immunosuppressive medication. 9. The existence of secondary hyperoxaluria, e.g. hyperoxaluria due to bariatric surgery or chronic gastrointestinal diseases such as cystic fibrosis, chronic inflammatory bowel disease and short-bowel syndrome. 10. Use of antibiotics to which O. formigenes is sensitive, including current antibiotic use, or antibiotics use within 14 days of initiating study medication. 11. Current treatment with a separate ascorbic acid preparation. Standard of care vitamin supplement for patients on dialysis is allowed. 12. Pregnancy. 13. Women of childbearing potential who are not using adequate contraceptive precautions. Sexually active females, unless surgically sterile or at least 2 years post-menopausal, must be using a highly effective contraception (including oral, transdermal, injectable, or implanted contraceptives, IUD, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 30 days prior to the first dose of OC5 and must agree to continue using such precautions during the clinical study. 14. Presence of a medical condition that the Investigator considers likely to make the subject susceptible to adverse effect of study treatment or unable to follow study procedures. 15. Participation in any study of an investigational product, biologic, device, or other agent within 30 days prior to the first dose of OC5 or not willing to forego other forms of investigational treatment during this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | Baseline (average of week 2 & 4 pretreatment); treatment weeks 6, 8 & 10 (on treatment 2, 4, & 6 weeks); off treatment weeks 12 & 14 (2 & 4 weeks off treatment); patients were then eligible for treatment up to 3 years & oxalate was measured every 6 months | Total plasma oxalate measured in umol/L |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Left Ventricular Ejection Fraction From Baseline. | At baseline and approximately every 6 months throughout the 3 year continued treatment. | Mean left ventricular ejection fraction measured as a percentage. Reference range 55-70%. |
| Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Baseline (average of week 2 & 4 pretreatment); treatment weeks 6, 8 & 10 (on treatment 2, 4, & 6 weeks); off treatment weeks 12 & 14 (2 & 4 weeks off treatment); patients were then eligible for treatment up to 3 years & oxalate was measured every 6 months | Comparison of free plasma oxalate compared to the four week baseline period. |
| Speckle Tracking Echocardiography | At baseline and approximately every 6 months throughout the 3 year continued treatment. | Global longitudinal strain (GLS), which measures the maximal shortening of myocardial longitudinal length during systole compared to the resting length in diastole. The normal range for GLS is considered to be \< -18%. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxabact OC5 Capsule This is an open-label study so all patients will receive the active drug product, Oxalobacter formigenes, OC5. This will be administered as an enteric-coated capsules twice daily for 6 weeks of treatment.
In Germany, the protocol has been amended such that patients can receive OC5 for a further 3 year of continued treatment after the initial part of the study.
Oxalobacter formigenes: The dose will be (not less than) NLT ≥1E+09 colony forming units (CFU) twice daily. The dose (an enteric-coated capsule) will be administered orally with breakfast and dinner. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 14-Week Study Period | Adverse Event | 1 |
| 14-Week Study Period | Physician Decision | 1 |
| 14-Week Study Period | Underwent transplantation | 1 |
| Continuation Period | Had liver transplant | 2 |
| Continuation Period | Non-compliance with study drug | 2 |
| Continuation Period | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Oxabact OC5 Capsule |
|---|---|
| Age, Continuous | 29.3 years STANDARD_DEVIATION 17 |
| Primary hyperoxaluria Type I | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment France | 1 participants |
| Region of Enrollment Germany | 11 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 10 / 12 |
| serious Total, serious adverse events | 7 / 12 |
Outcome results
Primary
Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline.
Total plasma oxalate measured in umol/L
Time frame: Baseline (average of week 2 & 4 pretreatment); treatment weeks 6, 8 & 10 (on treatment 2, 4, & 6 weeks); off treatment weeks 12 & 14 (2 & 4 weeks off treatment); patients were then eligible for treatment up to 3 years & oxalate was measured every 6 months
Population: Data presented by visit for patients completing each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | Baseline value (average of week 2 and 4 pretreatment) | 147.57 μmol/L | Standard Deviation 39.63 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | 2 week treatment change from baseline | 11.34 μmol/L | Standard Deviation 2.68 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | 4 week treatment change from baseline | 7.46 μmol/L | Standard Deviation 26.93 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | 6 week treatment change from baseline | -5.68 μmol/L | Standard Deviation 21.02 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | 2 week off treatment change from baseline | -4.56 μmol/L | Standard Deviation 18.23 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | 4 week off treatment change from baseline | -8.41 μmol/L | Standard Deviation 19.26 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | continued treatment 24 weeks change from baseline | -35.99 μmol/L | Standard Deviation 42.6 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | continued treatment 52 weeks change from baseline | -33.99 μmol/L | Standard Deviation 34.78 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | continued treatment 76 weeks change from baseline | -28.04 μmol/L | Standard Deviation 38.45 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | continued treatment 104 weeks change from baseline | -67.36 μmol/L | Standard Deviation 47.77 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | continued treatment 128 weeks change from baseline | -46.25 μmol/L | Standard Deviation 26.9 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Total Plasma Oxalate) Level During Treatment With OC5 Compared With Baseline. | continued treatment 156 weeks change from baseline | -44.65 μmol/L | Standard Deviation 54.75 |
Secondary
Change in Left Ventricular Ejection Fraction From Baseline.
Mean left ventricular ejection fraction measured as a percentage. Reference range 55-70%.
Time frame: At baseline and approximately every 6 months throughout the 3 year continued treatment.
Population: Data presented for patients with baseline and visit values recorded
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxabact OC5 Capsule | Change in Left Ventricular Ejection Fraction From Baseline. | Week 156 | 58.67 Percent | Standard Deviation 7.57 |
| Oxabact OC5 Capsule | Change in Left Ventricular Ejection Fraction From Baseline. | Baseline | 50.20 Percent | Standard Deviation 10.26 |
| Oxabact OC5 Capsule | Change in Left Ventricular Ejection Fraction From Baseline. | Week 24 | 59.43 Percent | Standard Deviation 4.08 |
| Oxabact OC5 Capsule | Change in Left Ventricular Ejection Fraction From Baseline. | Week 52 | 59.83 Percent | Standard Deviation 5.85 |
| Oxabact OC5 Capsule | Change in Left Ventricular Ejection Fraction From Baseline. | Week 80 | 59.60 Percent | Standard Deviation 5.18 |
| Oxabact OC5 Capsule | Change in Left Ventricular Ejection Fraction From Baseline. | Week 104 | 59.40 Percent | Standard Deviation 5.94 |
| Oxabact OC5 Capsule | Change in Left Ventricular Ejection Fraction From Baseline. | Week 128 | 58.00 Percent | Standard Deviation 2.16 |
Secondary
Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline.
Comparison of free plasma oxalate compared to the four week baseline period.
Time frame: Baseline (average of week 2 & 4 pretreatment); treatment weeks 6, 8 & 10 (on treatment 2, 4, & 6 weeks); off treatment weeks 12 & 14 (2 & 4 weeks off treatment); patients were then eligible for treatment up to 3 years & oxalate was measured every 6 months
Population: Patients completing each study visit are included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Baseline | 106.91 μmol/L | Standard Deviation 35.5 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Change from baseline at the end of six weeks of treatment | 1.59 μmol/L | Standard Deviation 18.77 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Change from baseline 4 weeks after treatment for 6 weeks | -6.50 μmol/L | Standard Deviation 17.31 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Change from baseline at 24 weeks | -10.17 μmol/L | Standard Deviation 15.27 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Change from baseline at 52 weeks | 2.52 μmol/L | Standard Deviation 13.79 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Change from baseline at 76 weeks | -17.47 μmol/L | Standard Deviation 13.71 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Change from baseline at 104 weeks | -47.29 μmol/L | Standard Deviation 30.46 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Change from baseline at 128 weeks | -38.54 μmol/L | Standard Deviation 10.59 |
| Oxabact OC5 Capsule | Change in Pre Dialysis Plasma Oxalate (Free Plasma Oxalate) Level During Study Compared With Baseline. | Change from baseline at 156 weeks | -5.36 μmol/L | Standard Deviation 20.99 |
Secondary
Speckle Tracking Echocardiography
Global longitudinal strain (GLS), which measures the maximal shortening of myocardial longitudinal length during systole compared to the resting length in diastole. The normal range for GLS is considered to be \< -18%.
Time frame: At baseline and approximately every 6 months throughout the 3 year continued treatment.
Population: Data presented for patients completing analyses
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxabact OC5 Capsule | Speckle Tracking Echocardiography | Baseline value | -17.37 percentage of myocardial length change | Standard Deviation 5.3 |
| Oxabact OC5 Capsule | Speckle Tracking Echocardiography | Week 24 | -19.15 percentage of myocardial length change | Standard Deviation 2.52 |
| Oxabact OC5 Capsule | Speckle Tracking Echocardiography | Week 52 | -18.29 percentage of myocardial length change | Standard Deviation 3.27 |
| Oxabact OC5 Capsule | Speckle Tracking Echocardiography | Week 80 | -19.53 percentage of myocardial length change | Standard Deviation 1.65 |
| Oxabact OC5 Capsule | Speckle Tracking Echocardiography | Week 104 | -19.99 percentage of myocardial length change | Standard Deviation 2.96 |
| Oxabact OC5 Capsule | Speckle Tracking Echocardiography | Week 128 | -19.60 percentage of myocardial length change | Standard Deviation 1.73 |
| Oxabact OC5 Capsule | Speckle Tracking Echocardiography | Week 156 | -18.52 percentage of myocardial length change | Standard Deviation 1.65 |