Primary:- To evaluate the efficacy of Oxabact® following 52 weeks treatment in patients with maintained kidney function but below the lower limit of the normal range (eGFR < 90 ml/min/1.73 m2) and a total plasma oxalate concentration >= 10…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
- Inborn errors of metabolism
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint
* Change from baseline in plasma oxalate concentration after 52 weeks of
treatment (total plasma oxalate concentration).
Secondary outcome
Secondary endpoints:
* Change from baseline in kidney function (eGFR) after 52 weeks of treatment.
* Change from baseline in plasma oxalate concentration (total plasma oxalate
concentration) after 52 weeks of treatment in different subgroups
of patients:
• Patients with a baseline urinary oxalate excretion above and equal to
or below 1.87 mmol/L/24h/1.73 m2 respectively (mean of the two first values
during screening/baseline).
• Patients above or equal toand below 18 years of age.
• Patients with a baseline eGFR above or equal to and below 60
ml/min/1.73m2 respectively (mean of the obtained values during
screening/baseline calculated by the Schwartz/CKD-EPI
equation).
* Change from baseline in kidney function (eGFR) after 52 weeks of treatment in
different subgroups of patients:
• Patients with a baseline urinary oxalate excretion above and equal to
or below 1.87 mmol/L/24h/1.73 m2 respectively (mean of the two
values during screening/baseline).
• Patients above or equal to and below 18 years of age.
• Patients with a baseline eGFR above or equal to and below 60
ml/min/1.73m2 respectively (mean of the obtained values during
screening /baseline calculated by the Schwartz/CKD-EPI
equation).
* Change from baseline in myocardial function as measured by Speckle Tracking
Echocardiography and traditional Echocardiography.
* Change from baseline in score of Quality of Life questionnaire.
* Change from baseline in free plasma oxalate concentration after 52 weeks of
treatment.
* Change from baseline in free plasma oxalate concentration after 52 weeks of
treatment in different subgroups of patients:
• Patients with a baseline urinary oxalate excretion above and equal to
or below 1.87 mmol/L/24h/1.73 m2 respectively (mean of the two
first values during screening/baseline).
• Patients above or equal to and below 18 years of age.
• Patients with a baseline eGFR above or equal to and below 60
ml/min/1.73m2 respectively (mean of the obtained values during
screening/baseline calculated by the Schwartz/CKD-EPI equation.
Background summary
See § 4.1, and § 4.2, and § 4.3 and § 4.5 of the protocol (OC5-DB-02,
version 8, 28-Mar-2018).
Study objective
Primary:
- To evaluate the efficacy of Oxabact® following 52 weeks treatment in patients
with maintained kidney function but below the lower limit of the normal range
(eGFR < 90 ml/min/1.73 m2) and a total plasma oxalate concentration >= 10 µmol/L
at baseline.
Secondary:
- To obtain additional safety data from 52 weeks continuous treatment with
Oxabact®.
Study design
This is a Phase III, double-blind, randomised international multi-center study.
After the baseline period (at visit 3), 18 eligible patients will be randomised
to start on twice daily dosing of Oxabact® or placebo in a 1:1 ratio.
Patients will be stratified in a first step in an attempt to evenly distribute
PH type 2/type 3 patients, if the patient is not PH type 2 or PH type 3, the
patient will be stratified for baseline urinary oxalate excretion above or
below or equal to 1.87 mmol/24h/1.73 m2 (based on the mean of the two values
from screening/baseline).
Intervention
*The active treatment group receives a capsule with study medication (Oxabact®)
twice daily with breakfast and dinner for 52 weeks.*
The control group receives a placebo capsule twice daily with breakfast and
dinner for 52 weeks.*
The randomisation is 1:1.
Study burden and risks
See § 4.6 of the protocol (OC5-DB-02, version 8, 28Mar2018) and § 2.4 of the
IMPD (version 7, 20Mar2017) and §5 "Summary of data and guidance for the
investigator" in the IB (version 7, 26Mar2018).
Patients will be burdened with 10 study visits and all applicable study
procedures as well as 4x stool sampling at home and 6x 24 hour urine collection
at home. There seems a small risk for serious adverse events.
The patient could benefit from the treatment or future PH patients could
benefit from the study results. Patients can be asked to participate in an
open-label, follow-up study compassionate use programme when they have finished
the study.
c /o KLara Papper Box 1062
Stockholm SE-101 39
SE
c /o KLara Papper Box 1062
Stockholm SE-101 39
SE
Listed location countries
Age
Inclusion criteria
1. Signed informed consent (as applicable for the age of the subject).
2. A diagnosis of PH (as determined by standard diagnostic methods).
3. eGFR < 90 ml/min/1.73 m2. The Schwartz formula will be used to estimate GFR for children (age below 18), and CKD-EPI formula will be used for adults (age 18 or above).
4. Plasma oxalate concentration >=10 µmol/L in total plasma oxalate.
5. Male or female patients >= 2 years of age.
6. Patients 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. Patients not receiving vitamin B6 at study entry must be willing to refrain from initiating pyridoxine during study participation.
Exclusion criteria
7. Inability to swallow size 4 capsules.
8. Subjects that have undergone transplantation (solid organ or bone marrow).
9. Patients requiring dialysis or at immediate risk for kidney failure or expected to be in need of dialysis during the study period.
10. 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.
11. Use of antibiotics to which O. formigenes is sensitive, including current antibiotic use, or antibiotics use within 14 days of initiating study medication.
12. Current treatment with a separate ascorbic acid preparation.
13. Pregnant women (or women who are planning to become pregnant) or lactating women.
14. Women of childbearing potential who are not using adequate contraceptive precautions. Please see section 7.3 regarding requirements for contraception.
15. Presence of a medical condition that the Investigator considers likely to make the subject susceptible to adverse effect of study treatment or unable to follow study procedures or any condition that is likely to interfere with the study drug mechanism of action (such as abnormal GI function).
16. Participation in any interventional study of another investigational product, biologic, device, or other agent within 60 days prior to the first dose of OC5 or not willing to forego other forms of investigational treatment during this study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000684-33-NL |
| ClinicalTrials.gov | NCT03116685onClinicalTrials.Gov |
| CCMO | NL60845.018.17 |