Condition category
Nutritional, Metabolic, Endocrine
Date applied
07/01/2010
Date assigned
22/01/2010
Last edited
22/01/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Dawn Milliner

ORCID ID

Contact details

Mayo Clinic
Department of Pediatric Nephrology
Rochester
55905
United States of America

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01037231

Protocol/serial number

OC3-DB-02

Study information

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

Acronym

Study hypothesis

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

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)

Study design

Interventional double-blind randomised placebo controlled multicentre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Can be found at http://www.ohf.org/docs/1009_Oxthera_Study_Announcement.pdf

Condition

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

Phase

Phase II/III

Drug names

Oxabact™

Primary outcome measures

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 trial start date

14/01/2010

Overall trial end date

30/09/2010

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Other

Gender

Both

Target number of participants

30 - 35

Participant 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

Recruitment start date

14/01/2010

Recruitment end date

30/09/2010

Locations

Countries of recruitment

Germany, Netherlands, United States of America

Trial participating centre

Mayo Clinic
Rochester
55905
United States of America

Sponsor information

Organisation

OxThera IP AB (Sweden)

Sponsor details

Dragarbrunnsgatan 45
Uppsala
SE-753 20
Sweden

Sponsor type

Industry

Website

http://www.oxthera.com/

Funders

Funder type

Industry

Funder name

OxThera IP AB (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes