Primary Hyperoxaluria
Conditions
Brief summary
This study will evaluate the efficacy and safety of OC5 in patients with PH.
Detailed description
To evaluate the efficacy of Oxabact following 52 weeks treatment in subjects with maintained kidney function, but below the lower limit of the normal range (estimated glomerular filtration rate \[eGFR\] \< 90 ml/min/1.73 m2) and a total plasma oxalate (Pox) concentration ≥ 10 μmol/L. Parameters to be evaluated include the ability to stabilise/reduce Pox concentration, to stabilise/improve kidney function and to reduce oxalate deposits in primary hyperoxaluria (PH) subjects.
Interventions
BIOLOGICALOxabact OC5 - Oxalobacter formigenes HC-1
Active study drug
OTHERPlacebo
Placebo
Sponsors
OxThera
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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) 2. A diagnosis of PH (as determined by standard diagnostic methods). 3. eGFR \< 90 ml/min/1.73 m2. The Schwartz formula will be used to estimate GFR for children (age below 18), and CKD-EPI formula will be used for adults (age 18 or above). 4. Plasma oxalate concentration ≥10 μmol/L in total plasma oxalate. 5. Male or female patients ≥ 2 years of age. 6. Patients 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. Patients not receiving vitamin B6 at study entry must be willing to refrain from initiating pyridoxine during study participation.
Exclusion criteria
1. Inability to swallow size 4 capsules. 2. Subjects that have undergone transplantation (solid organ or bone marrow). 3. Patients requiring dialysis or at immediate risk for kidney failure or expected to be in need of dialysis during the study period. 4. 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. 5. Use of antibiotics to which O. formigenes is sensitive. (This includes current antibiotic use, or antibiotics use within 14 days of initiating study medication). 6. Current treatment with a separate ascorbic acid preparation. 7. Pregnant women (or women who are planning to become pregnant) or lactating women. 8. Women of childbearing potential who are not using adequate contraceptive precautions. Please see section 7.3 regarding requirements for contraception. 9. 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 or any condition that is likely to interfere with the study drug mechanism of action (such as abnormal GI function). 10. Participation in any interventional study of another investigational product, biologic, device, or other agent within 60 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 From Baseline in Plasma Oxalate Concentration After 52 Weeks of Treatment | 52 weeks | Change from baseline in total plasma oxalate concentration after 52 weeks of treatment in micromole/liter |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Kidney Function | 52 weeks | Evaluation 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. |
| Frequency of Kidney Stone Events | Through week 48 | Number of kidney stone events for each patient |
Countries
Belgium, France, Germany, Spain, Tunisia, United Kingdom, United States
Participant flow
Recruitment details
Recruitment began 09 January 2018. Primary study completion 15 April 2021
Participants by arm
| Arm | Count |
|---|---|
| Oxabact OC5 Capsules Oxabact OC5 - Oxalobacter formigenes HC-1
Oxabact OC5 - Oxalobacter formigenes HC-1: Active study drug | 13 |
| Placebo Capsules Placebo
Placebo: Placebo | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Oxabact OC5 Capsules | Total | Placebo Capsules |
|---|---|---|---|
| Age, Categorical <=18 years | 10 Participants | 18 Participants | 8 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 7 Participants | 4 Participants |
| Age, Continuous | 12.9 years STANDARD_DEVIATION 6.4 | 15.5 years STANDARD_DEVIATION 12.4 | 18.3 years STANDARD_DEVIATION 16.5 |
| Primary Hyperoxaluria Type PH Type I | 13 Participants | 24 Participants | 11 Participants |
| Primary Hyperoxaluria Type PH Type II | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 24 Participants | 12 Participants |
| Region of Enrollment Belgium | 1 participants | 3 participants | 2 participants |
| Region of Enrollment Germany | 2 participants | 6 participants | 4 participants |
| Region of Enrollment Spain | 6 participants | 8 participants | 2 participants |
| Region of Enrollment Tunisia | 3 participants | 4 participants | 1 participants |
| Region of Enrollment United Kingdom | 1 participants | 3 participants | 2 participants |
| Region of Enrollment United States | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 9 Participants | 14 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 7 Participants |
| Stage of Chronic Kidney Disease Stage I | 1 Participants | 3 Participants | 2 Participants |
| Stage of Chronic Kidney Disease Stage II | 11 Participants | 16 Participants | 5 Participants |
| Stage of Chronic Kidney Disease Stage III | 1 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 13 / 13 | 11 / 12 |
| serious Total, serious adverse events | 3 / 13 | 4 / 12 |
Outcome results
Primary
Change From Baseline in Plasma Oxalate Concentration After 52 Weeks of Treatment
Change from baseline in total plasma oxalate concentration after 52 weeks of treatment in micromole/liter
Time frame: 52 weeks
Population: Full analysis set using a mixed repeated measures model for change for missing data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxabact OC5 Capsules | Change From Baseline in Plasma Oxalate Concentration After 52 Weeks of Treatment | Baseline value | 14.8 micromole/liter | Standard Deviation 5.7 |
| Oxabact OC5 Capsules | Change From Baseline in Plasma Oxalate Concentration After 52 Weeks of Treatment | Change from baseline to 52 weeks | -0.71 micromole/liter | Standard Deviation 1.34 |
| Placebo Capsules | Change From Baseline in Plasma Oxalate Concentration After 52 Weeks of Treatment | Baseline value | 14.4 micromole/liter | Standard Deviation 5.4 |
| Placebo Capsules | Change From Baseline in Plasma Oxalate Concentration After 52 Weeks of Treatment | Change from baseline to 52 weeks | 2.35 micromole/liter | Standard Deviation 1.46 |
Secondary
Change From Baseline in Kidney Function
Evaluation 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.
Time frame: 52 weeks
Population: Patients with baseline and week 52 assessments
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Oxabact OC5 Capsules | Change From Baseline in Kidney Function | -1.35 millilitres/minute/1.73m2 | Standard Error 2.68 |
| Placebo Capsules | Change From Baseline in Kidney Function | -0.06 millilitres/minute/1.73m2 | Standard Error 3.12 |
Secondary
Frequency of Kidney Stone Events
Number of kidney stone events for each patient
Time frame: Through week 48
Population: Number of events
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxabact OC5 Capsules | Frequency of Kidney Stone Events | 7 Number of kidney stone events |
| Placebo Capsules | Frequency of Kidney Stone Events | 8 Number of kidney stone events |