Primary Hyperoxaluria
Conditions
Keywords
hyperoxaluria, oxalate, PH
Brief summary
The purpose of this study is to determine if Oxalobacter formigenes is effective at lowering urinary oxalate levels in patients with primary hyperoxaluria.
Interventions
BIOLOGICALOxabact OC5 capsules
The dose will be not less than (NLT) 1E+09 colony forming units (CFU) twice daily for 8 to 10 weeks. The dose (an enteric-coated size 4 capsule) will be administered orally with breakfast and dinner.
DRUGPlacebo capsules
An enteric-coated placebo capsule manufactured to mimic the OC5 capsule. The capsule will be administered orally with breakfast and dinner twice daily for 8 to 10 weeks.
Sponsors
FP7-SME-2013 Research for the benefit of SMEs program
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
* Signed informed consent (as applicable for the age of the subject). * Male or female subjects ≥ 2 years of age (Germany & France) / Male or female subjects ≥ 5 years of age (United Kingdom) * A diagnosis of PH type I, II or III (as determined by standard diagnostic methods). * A mean urinary oxalate excretion of \> 1.0 mmol/24h/1.73m2, based on at least three eligible urine collections performed during baseline (weeks 1-4). * Renal function defined as an estimated GFR ≥ 40 ml/min normalised to 1.73m2 body surface area, or a creatinine clearance of ≥ 40 ml/min normalised to 1.73m2 body surface area. * 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.
Exclusion criteria
* Inability to collect complete 24-hour urine samples. Each urine collection will be evaluated for completeness based on urine qualitative criteria. * Inability to swallow size 4 capsules twice daily for 8 to 10 weeks. * Subjects that have undergone transplantation (solid organ or bone marrow). * 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. * Use of antibiotics to which O. formigenes is sensitive, including chronic use, a history of more than two courses of antibiotic use during the past 6 months, current antibiotic use, or antibiotics use within 14 days of initiating study medication. * Subjects who require immune suppressive therapy. * Current treatment with ascorbic acid preparation. * Pregnancy. * Women of child-bearing potential who are not using adequate contraceptive precautions such as oral, transdermal, injectable, or implanted contraceptives, IUD, complete abstinence, use of a condom by the sexual partner, or sterile sexual partner. * Presence of a medical condition that the Principal Investigator considers likely to make the subject susceptible to adverse effect of study treatment or unable to follow study procedures. * Participation in any study of an investigational product, biologic, device, or other agent within 30 days prior to screening or not willing to forego other forms of investigational treatment during this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in urinary oxalate levels from Baseline to week 8 of treatment. | 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects who reach urinary oxalate levels below 0.5, 0.7 and 1.0 mmol/24h/1.73m2 respectively from Baseline to week 8 of treatment. | 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study) | — |
| Change in plasma oxalate levels from Baseline to week 8 of treatment. | 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study) | — |
| Change in urinary oxalate levels from Baseline to week 4 of treatment. | 8 weeks of active treatment (i.e. between Weeks 7 and 10 of the study) | — |
| Correlation between change in plasma oxalate levels and change in urinary oxalate levels, from Baseline to week 8 of treatment. | 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study) | — |
| Change in urinary oxalate levels from Baseline to week 8 of treatment in subsets of subjects | 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study) | Change in urinary oxalate levels from Baseline to week 8 of treatment in subsets of subjects defined by: * baseline urinary oxalate level, above and below 1.5 mmol/24h/1.73m2 * concomitant vitamin B6 therapy and no vitamin B6 therapy * eGFR of ≥90 mL/min/1.73m2 (normal renal function) and \< 90 mL/min/1.73m2 (mild to moderate reduction in renal function) * age below 18 and age 18 or above |
| Adverse events | 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study) | — |
| Haematology | 14 weeks (Throughout the study) | Blood samples taken for hematology at weeks 0, 5, 10 and 14. Complete blood count with differential and platelet count evaluated. |
| Clinical Chemistry | 14 weeks (Throughout the study) | Blood samples taken for clinical chemistry at weeks 0, 5, 10 and 14. Blood Urea Nitrogen, creatinine, electrolytes (Na+, K+, Mg++, Ca++, HCO3+, Cl), glucose, pH, albumin, alkaline phosphatase, ALT, AST, total bilirubin and total protein evaluated. |
| Urinalysis | 14 weeks (Throughout the study) | Urine samples will be taken at weeks 0, 5, 10 and 14 of the study. Protein, glucose and pH evaluated. |
| Change in number of O. formigenes in faeces from Baseline to week 8 of treatment. | 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study) | — |
Countries
France, Germany, United Kingdom
Outcome results
None listed