Clinical trial NCT02012985: Study to Evaluate the Efficacy and Safety of Oxabact (OC5) in Patients With Primary Hyperoxaluria
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Primary Hyperoxaluria
Keywords: hyperoxaluria
oxalate
PH
Lead sponsor: OxThera
Sponsor class: INDUSTRY
Collaborators: name: FP7-SME-2013 Research for the benefit of SMEs program
First posted: 2013-12-17
Enrollment: 28
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in urinary oxalate levels from Baseline to week 8 of treatment.
timeFrame: 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study)
Secondary outcomes:
measure: Change in urinary oxalate levels from Baseline to week 8 of treatment in subsets of subjects
timeFrame: 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study)
measure: 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.
timeFrame: 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study)
measure: Change in plasma oxalate levels from Baseline to week 8 of treatment.
timeFrame: 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study)
measure: Change in urinary oxalate levels from Baseline to week 4 of treatment.
timeFrame: 8 weeks of active treatment (i.e. between Weeks 7 and 10 of the study)
measure: Correlation between change in plasma oxalate levels and change in urinary oxalate levels, from Baseline to week 8 of treatment.
timeFrame: 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study)
measure: Change in number of O. formigenes in faeces from Baseline to week 8 of treatment.
timeFrame: 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study)
measure: Adverse events
timeFrame: 8 weeks of active treatment (i.e. between Weeks 7 and 14 of the study)
measure: Haematology
timeFrame: 14 weeks (Throughout the study)
measure: Clinical Chemistry
timeFrame: 14 weeks (Throughout the study)
measure: Urinalysis
timeFrame: 14 weeks (Throughout the study)
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Robert-Debré, Néphrologie Pédiatrique
state: Cedex 19
city: Bordeaux
country: France
facility: Hôpital des Enfants, Centre de référence maladies rénales rares du Sud-Ouest (SORARE), CHU de Bordeaux
city: Lyon
country: France
facility: Hôpital Femme Mère Enfant, Lyon - Paediatric Dept
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades,Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA)
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Dept of Paediatric Nephrology
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital NHS Foundation Trust - Dept of Nephrology
city: London
country: United Kingdom
facility: Royal Free Hospital -UCL Centre for Nephrology
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
Study officials:
affiliation: Universitätsklinikum Bonn, Dept of Paediatric Nephrology
name: Bernd Hoppe, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: