Study to Evaluate the Efficacy and Safety of Oxabact (OC5) in Patients With Primary Hyperoxaluria

Primary Hyperoxaluria Clinical Trial

Official title:

A Phase 1/2, Randomised, Placebo-controlled, Double-blind, Multi-centre Study to Evaluate the Efficacy and Safety of OC5 to Reduce Urinary Oxalate in Subjects With Primary Hyperoxaluria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02012985
• Other study ID #: OC5-DB-01
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 11, 2013
• Last updated: October 14, 2015
• Start date: December 2013
• Est. completion date: January 2015

Study information

• Verified date: October 2015
• Source: OxThera
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesFrance: Agence Nationale de Sécurité du Médicament et des produits de santéUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if Oxalobacter formigenes is effective at lowering urinary oxalate levels in patients with primary hyperoxaluria.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyperoxaluria, Primary
• Primary Hyperoxaluria

Intervention

Biological:
• Oxabact 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.

Drug:
• Placebo 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.

Locations

Country	Name	City	State
France	Hôpital des Enfants, Centre de référence maladies rénales rares du Sud-Ouest (SORARE), CHU de Bordeaux	Bordeaux
France	Hôpital Femme Mère Enfant, Lyon - Paediatric Dept	Lyon
France	Hôpital Necker-Enfants Malades,Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA)	Paris
France	Hôpital Robert-Debré, Néphrologie Pédiatrique	Paris	Cedex 19
Germany	Universitätsklinikum Bonn, Dept of Paediatric Nephrology	Bonn
United Kingdom	Birmingham Children's Hospital NHS Foundation Trust - Dept of Nephrology	Birmingham
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London
United Kingdom	Royal Free Hospital -UCL Centre for Nephrology	London

Sponsors (2)

Lead Sponsor	Collaborator
OxThera	FP7-SME-2013 Research for the benefit of SMEs program

Countries where clinical trial is conducted

France,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Change in urinary oxalate levels from Baseline to week 8 of treatment in subsets of subjects	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	8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	Adverse events		8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study)	Yes
Secondary	Haematology	Blood samples taken for hematology at weeks 0, 5, 10 and 14. Complete blood count with differential and platelet count evaluated.	14 weeks (Throughout the study)	Yes
Secondary	Clinical Chemistry	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.	14 weeks (Throughout the study)	Yes
Secondary	Urinalysis	Urine samples will be taken at weeks 0, 5, 10 and 14 of the study. Protein, glucose and pH evaluated.	14 weeks (Throughout the study)	Yes