Phase II/III Oxabact™ Study
| ISRCTN | ISRCTN63711065 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN63711065 |
| ClinicalTrials.gov number | NCT01037231 |
| Secondary identifying numbers | OC3-DB-02 |
- Submission date
- 07/01/2010
- Registration date
- 22/01/2010
- Last edited
- 20/02/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Dawn Milliner
Scientific
Scientific
Mayo Clinic
Department of Pediatric Nephrology
Rochester
55905
United States of America
Study information
| Study design | Interventional double-blind randomised placebo-controlled multicentre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Can be found at http://www.ohf.org/docs/1009_Oxthera_Study_Announcement.pdf |
| Scientific title | A phase II/III, double-blind, randomised, placebo-controlled, multicentre study to evaluate the efficacy and safety of Oxabact™ to reduce urinary oxalate in subjects with primary hyperoxaluria |
| Study objectives | The purpose of this study is to determine if Oxalobacter formigenes is effective at lowering urinary oxalate levels in patients with primary hyperoxaluria (PH). |
| Ethics approval(s) | 1. Netherlands: Medisch Ethische Commissie AMC approved in December 2009 2. Germany: Ethikkommisssion der Medizinischen Fakulatat zu Koln approved in November 2009 3. United States: Mayo Clinic Institutional Review Board approved in December 2009, ref: 09-006325 |
| Health condition(s) or problem(s) studied | Primary hyperoxaluria |
| Intervention | Active treatment: Oxabact™ - NLT (not less than) 10^7 CFU Oxalobacter formigenes twice daily for 24 weeks and up to 4 weeks follow-up. Control treatment: Placebo twice daily for 24 weeks and up to 4 weeks follow-up. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II/III |
| Drug / device / biological / vaccine name(s) | Oxabact™ |
| Primary outcome measure | Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from baseline to week 24 |
| Secondary outcome measures | 1. Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from baseline to week 8 2. Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from baseline to week 24 in subsets of subjects defined by baseline urinary oxalate level, above and below median at screening 3. Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from baseline to week 24 in subsets of subjects defined by concomitant vitamin B6 therapy and no vitamin B6 therapy, in PH type I 4. Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from baseline to week 24 in subsets of subjects defined by estimated glomerular filtration rate (eGFR) of greater than or equal to 90 mL/min/1.73 m2 and less than 90 mL/min/1.73 m2 5. Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from baseline to week 24 in subsets of subjects defined by PH Type I and PH Type II 6. Percentage change in urinary oxalate levels (expressed as molar oxalate to creatinine ratio) from baseline to week 24 in subsets of subjects defined by age below 18 years and aged 18 years or above 7. Percentage of subjects who have greater than or equal to 20% reduction from Baseline urinary oxalate at week 24 8. Frequency of stone events (i.e. nephrolithiasis or markers thereof) 9. Correlation between percentage change in plasma oxalate levels and percentage change in urinary oxalate levels, from baseline to week 24 10. Adverse events (AEs), haematology, clinical chemistry, urinalysis |
| Overall study start date | 14/01/2010 |
| Completion date | 30/09/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Other |
| Sex | Both |
| Target number of participants | 30 - 35 |
| Key inclusion criteria | 1. Signed informed consent (as applicable for the age of the subject) 2. Male or female subjects greater than or equal to 2 years of age 3. A mean urinary oxalate excretion of greater than 1.0 mmol/1.73 m2/day from eligible urine collections performed during screening 4. A diagnosis of PH I or PH II by one of the following: 4.1. Liver biopsy confirmation of deficient liver specific peroxisomal alanine-glyoxylate aminotransferase (AGT) or mislocalisation of AGT from peroxisomes to mitochondria (PH I) or deficient glyoxylate reductase/hydroxypyruvate reductase (GRHPR) activity (PH II) 4.2. Homozygosity or compound heterozygosity for a known mutation in the causative genes for PH I and PH II 4.3. Increased glycolate excretion for PH I or increased L-glycerate excretion for PH II 5. Subjects receiving pyridoxine must be receiving a stable dose for at least 3 months prior to entry into the study and must remain on the stable dose during the study. Subjects not receiving pyridoxine at study entry must be willing to refrain from initiating pyridoxine during study participation. 6. Renal function defined as an estimated glomerular filtration rate (GFR) greater than or equal to 40 ml/min normalised to 1.73 m2 body surface area, or a creatinine clearance of greater than or equal to 40 ml/min normalised to 1.73 m2 body surface area |
| Key exclusion criteria | 1. Inability to collect two complete 24-hour urine samples 2. Subjects diagnosed as PH I who are pyridoxine naive 3. Subjects that have undergone transplantation (solid organ or bone marrow) 4. The existence of secondary hyperoxaluria, e.g. chronic gastrointestinal diseases such as cystic fibrosis, chronic inflammatory bowel disease and short-bowel syndrome 5. Current systemic (oral, intramuscular [IM], intravenous [IV]) antibiotic use or received systemic antibiotics within 14 days of study enrolment 6. History of a recurrent infection requiring greater than two courses of systemic antibiotics in the past 6 months, or chronic antimicrobial suppression 7. Subjects who require immune suppressive therapy (including prednisone greater than 10 mg daily for more than 2 weeks) 8. Current treatment with a separate ascorbic acid preparation. Ascorbic acid up to 250 mg/day as a component of a multivitamin formulation is not excluded. 9. Known hypersensitivity to esomeprazol (or any of the other ingredients of this medicine), or to any other proton pump inhibitor medicine (Nexium® contraindication) 10. Concomitant treatment with atazanavir (Nexium® contraindication) 11. Pregnancy 12. Women of child-bearing 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, intrauterine devide (IUD), abstinence, use of a condom by the sexual partner or sterile sexual partner) for 30 days prior to the first dose of Oxabact™ and must agree to continue using such precautions during the clinical study. 13. 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. Note: Subjects from correctional facilities or asylums and subjects who are mentally handicapped are not to be included in the study. 14. Participation in any study of an investigational product, biologic, device, or other agent within 30 days prior to randomisation or not willing to forego other forms of investigational treatment during this study |
| Date of first enrolment | 14/01/2010 |
| Date of final enrolment | 30/09/2010 |
Locations
Countries of recruitment
- Germany
- Netherlands
- United States of America
Study participating centre
Mayo Clinic
Rochester
55905
United States of America
55905
United States of America
Sponsor information
OxThera IP AB (Sweden)
Industry
Industry
Dragarbrunnsgatan 45
Uppsala
SE-753 20
Sweden
| Website | http://www.oxthera.com/ |
|---|---|
"ROR" |
https://ror.org/05m0yja37 |
Funders
Funder type
Industry
OxThera IP AB (Sweden)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/08/2018 | 20/02/2019 | Yes | No |
Editorial Notes
20/09/2019: Publication reference added.
