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

NCT02012985 | Completed Phase 1

• 1 other identifier: OC5-DB-01
• Study Type: interventional
• Target: 28
• Locations: 3 countries
• Sites: 8

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.

Conditions

Primary Hyperoxaluria

Keywords

hyperoxaluria; oxalate; PH

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• 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)

• 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)

Study Arms (2)

Oxabact OC5 capsules

EXPERIMENTAL

The active study drug consists of Oxalobacter formigenes OC5 in enteric-coated size-4 capsules. The dose (not less than (NLT) 1E+09 colony forming units (CFU)) will be administrated orally with breakfast and dinner as one capsule two times per day for 8 to 10 weeks.

Biological: Oxabact OC5 capsules

Placebo capsules

PLACEBO COMPARATOR

The placebo study drug consists of microcrystalline cellulose in enteric-coated size-4 capsules. It has been manufactured to mimic the OC5 capsule. The dose will be administrated orally with breakfast and dinner as one capsule two times per day for 8 to 10 weeks.

Drug: Placebo capsules

Interventions

Oxabact OC5 capsules BIOLOGICAL

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.

Also known as: Oxalobacter formigenes

Oxabact OC5 capsules

Placebo capsules DRUG

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.

Placebo capsules

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• OxThera: lead
• FP7-SME-2013 Research for the benefit of SMEs program: collaborator

Study Sites (8)

Hôpital Robert-Debré, Néphrologie Pédiatrique

Paris, Cedex 19, 75945, France

Location

Hôpital des Enfants, Centre de référence maladies rénales rares du Sud-Ouest (SORARE), CHU de Bordeaux

Bordeaux, 33076, France

Location

Hôpital Femme Mère Enfant, Lyon - Paediatric Dept

Lyon, 69677 Bron, France

Location

Hôpital Necker-Enfants Malades,Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA)

Paris, 75015, France

Location

Universitätsklinikum Bonn, Dept of Paediatric Nephrology

Bonn, DE-53113, Germany

Location

Birmingham Children's Hospital NHS Foundation Trust - Dept of Nephrology

Birmingham, B4 6NH, United Kingdom

Location

Royal Free Hospital -UCL Centre for Nephrology

London, NW3 2QG, United Kingdom

Location

Great Ormond Street Hospital for Children NHS Trust

London, WCIN 3JH, United Kingdom

Location

MeSH Terms

Conditions

Hyperoxaluria, Primary; Hyperoxaluria

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Bernd Hoppe, MD PhD

  Universitätsklinikum Bonn, Dept of Paediatric Nephrology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2013
• First Posted: December 17, 2013
• Study Start: December 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: October 16, 2015

Record last verified: 2015-10

Locations

GB (3); DE (1); FR (4)