Primary Objective:To evaluate the Safety of OxabactTM with continued exposure.Secondary Objectives:To obtain additional efficacy data with up to 48 weeks continuous exposure to Oxabact*.
ID
Source
Brief title
Condition
- Inborn errors of metabolism
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety
* Frequency of AEs and SAEs
* Abnormal Laboratory Values
* Clinically relevant changes in Physical Exams and Vital Signs
Secondary outcome
Efficacy
* Percentage of subjects who received either placebo or Oxabact* in the
qualifying study (OC3-DB-01) and have
*30% reduction in urinary oxalate at 24 weeks from Screening
* Percentage of subjects who received placebo in the qualifying study
(OC3-DB-01) and have *20% reduction in
urinary oxalate at 24 weeks from Screening
* Percentage of subjects randomized to the treatment arm of DB trial that
demonstrate continued reduction
(*20%) in urinary oxalate at 48 weeks from screening.
* Reduction in urinary Ca-oxalate super-saturation
* Stabilization or change in GFR
* Incidence of renal stones and/or signs and symptoms of renal stones
* Reduction in burden of Ca-oxalate stones
Other endpoints (not for the Dutch Participants):
Quality of Life assessment will be done using the Kidney Disease and Quality of
Life (KDQOL* -36) survey at weeks 12 and 24 in adults.
The Quality of Life assessment in children and adolescents will be done using
the Child Health Questionnaire (CHQ), at weeks 12 and 24.
Background summary
Primary Hyperoxaluria is a metabolic disorder, characterized by excess
endogenous oxalate synthesis and excretion in the urine. Raised oxalate
excretion leads to calcifications in the kidneys. Primary Hyperoxaluria is an
inborn error of metabolism, and symptoms occur as early as the first month of
age. Calcification in the urinary tract can lead to decreased kidney function,
and 50% of patients need dialysis by 25 years.
The use of OxabactTM is supposed to lead to increased degradation of oxalate in
the intestine. This generates a suitable trans-epithelial gradient to promote
the removal of endogenously produced plasma oxalate by enteric elimination.
Animal studies have shown that enteric elimination of oxalate occurs both by
the passive flow of oxalate across the gut epithelia in response to a
concentration gradient, as well as by its active flux mediated by specific
transporters. Enteric elimination is expected to reduce the levels of urinary
oxalate in both PH1 and PH2 patient populations
Study objective
Primary Objective:
To evaluate the Safety of OxabactTM with continued exposure.
Secondary Objectives:
To obtain additional efficacy data with up to 48 weeks continuous exposure to
Oxabact*.
Study design
This study is an Open-label extension, single-arm, multicenter, international,
extension study of 6-months, evaluating the safety of OxabactTM with long term
exposure in subjects who complete participation in the phase 2/3 double-blind,
placebo-controlled efficacy study. This open-label extension study also allows
subjects randomized to placebo in the qualifying study (OC3-DB-01) to receive
OxabactTM. Participation in this study is voluntary and eligible participants
will have to sign an Informed Consent form for the open-label study.
After consenting (and assent for subjects * 12 years and < 18 years or country
specific age as appropriate) and meeting the inclusion/exclusion criteria,
subjects will receive one OxabactTM capsule twice daily after meals by mouth,
for up to 24 weeks.
Urinary and plasma oxalate levels will be measured at Weeks 12 and 24.
Laboratory safety assessments will be performed at Weeks 12 and 24.
All subjects in the open-label study will be monitored for safety (AE) and
concomitant medications every 2 weeks by telephone interview and diary records
for the first 12 weeks and then monthly for the remainder of the open-label
treatment period.
Subjects with less than 20% reduction in urinary oxalate levels at Week 12 from
Screening values (i.e. at entry into the qualifying study # OC3-DB-01) will
exit the study with final safety assessment completed at Week 12. All others
will continue in the study and be monitored for safety throughout the study
period.
Intervention
All included patients receives during 24 weeks twice daily a capsule with
Lyophilized O. formigenes (strain HC-1)
Oral administration.
Strength: NLT 10exp7 CFU/capsule
Study burden and risks
The treatment may harm the unborn child. Therefore, pregnancy is ruled out at
the start of the study. Male participants must be advise not to be enrolled in
the study if their partner wishes to become pregnant during the study time.
There may be side effects that are unknown at this time, such as stomach
problems, diarrhea, bloating, or flatus. Any stomach problems that are
currently present may worsen. The bacteria present in OxabactTM may cause
infection in blood. However, no such infections have been reported by the use
of OxabactTM to date.
Taking blood from the arm may cause discomfort and can leave a bruise. The
consequences related to the drawing of blood are usually considered to be of
minimal discomfort.
13709 Progress oulevard
Alachua, Florida 32615
United States
13709 Progress oulevard
Alachua, Florida 32615
United States
Listed location countries
Age
Inclusion criteria
1. The subject (or legally acceptable representative) must give informed consent (and assent for subjects * 12 years or country specific age as appropriate). For subjects less than 18 years of age, parent or guardian will provide informed consent and the subject will provide witnessed verbal assent. (This is the text in the protocol, in the Netherlands no signature from subjects younger than 12 is needed, see text D4b.);2. All subjects completing the qualifying study (OC3-DB-01) will be eligible for open-label extension study;3. Subjects receiving pyridoxine during the qualifying study (OC3-DB-01) must be willing to remain on the stable dose at entry and during the OL study
Exclusion criteria
1. Pregnant, lactating, or actively menstruating women and 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, IUD, abstinence, use of a condom by the sexual partner, or sterile sexual partner) and must agree to continue using such precautions during the OL extension study.;2. Positive serum pregnancy test;3. Any other abnormal finding such as physical examination or laboratory evaluation, in the opinion of the investigator, is indicative of a disease that would compromise the safety of the subject;4. Subjects not willing to forego other forms of investigational treatment during the OL study;5. Chronic immune suppressive therapy including prednisone at doses greater than 10 mg daily for more than 2 weeks
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 | EUCTR2007-006187-30-NL |
| CCMO | NL22120.018.08 |