Hyperoxaluria, Nephrolithiasis
Conditions
Keywords
Urine Oxalate, Nephrolithiasis, Kidney Stones, Hyperoxaluria, Enteric Hyperoxaluria, Idiopathic Hyperoxaluria, Urological Diseases, Kidney Diseases
Brief summary
The purpose of this study is to evaluate the effect of ALLN-177 to reduce urinary oxalate excretion in patients with recurring kidney stones and enteric or idiopathic hyperoxaluria.
Detailed description
A multi-center, open-label, single arm study to evaluate the safety and the effect of ALLN-177 to reduce urinary oxalate excretion in recurrent kidney stone formers with associated hyperoxaluria. The study design includes a screening period to confirm eligibility, followed by a 3-day baseline period, 4-day open label treatment period with ALLN-177 and 4-day follow up period.
Interventions
DRUGALLN-177
ALLN-177 is orally administered oxalate decarboxylase (OxDc). The goal of oral therapy with ALLN-177 is to enzymatically degrade both dietary oxalate and endogenously produced oxalate secreted in the gastrointestinal tract resulting in decreased absorption and reduced urinary oxalate excretion.
Sponsors
Allena Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Able to provide informed consent * Able to comply with study procedures * History of enteric or idiopathic hyperoxaluria and at least one calcium oxalate kidney stone * Hyperoxaluria \>36mg of oxalate/24-hr * May be taking drugs for the prevention of stone disease as long as there have been no changes in these medications for at least 3 months
Exclusion criteria
* Uric acid ≥1.5g/24-hr * Estimated glomerular filtration rate of \< 60 mL/min * Positive results from drug urine screen * Requires daily vitamin C (defined as \>10 days of \>300 mg/day) * Diagnosis of hypercalcemia or hypothyroidism * Obstructive uropathy, chronic urosepsis, renal failure, renal tubular acidosis, primary hyperparathyroidism, primary hyperoxaluria, pure uric acid and cystine stones, and/or medullary sponge kidney. * Auto-immune disorder requiring high dose steroids or other immunosuppressant drugs. * Subjects who are pregnant. Women of childbearing potential must have a negative pregnancy test prior to enrollment and must practice approved methods of birth control during the trial * History of cancer diagnosis except for within the past 5 years excluding dermal squamous and/or basal cell carcinoma or cervical carcinoma in situ. * Taken investigational compound within 30 days prior to the first day of the study * Treatment with cholestyramine * Average daily dietary intake of \<75 mg oxalate per day calculated from diet recalls
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Period to Treatment Period 24-hour Urinary Oxalate Excretion | 7 days | Change from Baseline is defined as Baseline value (average of Days 2 and 3) minus ALLN-177 treatment value (mean of Days 5, 6, and 7). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline Period to Treatment Period in 24-hour Urinary Oxalate Excretion | 7 days | Percent Change from Baseline is defined as baseline value (average of Days 2 and 3) minus ALLN-177 treatment value (mean of Days 5, 6, and 7) divided by baseline value times 100% |
Countries
United States
Participant flow
Recruitment details
Subjects (N = 16) were recruited from 3 centers in the United States between August 2014 and December 2014.
Pre-assignment details
History of ≥1 calcium oxalate kidney stone within the last 2 years, secondary hyperoxaluria and a mean urinary oxalate of ≥36 mg/day
Participants by arm
| Arm | Count |
|---|---|
| ALLN-177 ALLN-177 (5 capsules: 7,500 units/meal), 3 times a day with meals, 4 days | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | ALLN-177 |
|---|---|
| 24-hour Urinary Oxalate | 77.65 mg/day STANDARD_DEVIATION 55.87 |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 54.1 years STANDARD_DEVIATION 14.5 |
| Concomitant medications Calcium | 5 participants |
| Concomitant medications Chlorthalidone | 2 participants |
| Concomitant medications Hydrochlorothiazide | 1 participants |
| Concomitant medications Potassium citrate | 5 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Glomerular Filtration Rate (GFR) | 85.1 ml/min/1.73 m^2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Change From Baseline Period to Treatment Period 24-hour Urinary Oxalate Excretion
Change from Baseline is defined as Baseline value (average of Days 2 and 3) minus ALLN-177 treatment value (mean of Days 5, 6, and 7).
Time frame: 7 days
Population: All Participants (N=16) completed treatment and were included in the analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALLN-177 | Change From Baseline Period to Treatment Period 24-hour Urinary Oxalate Excretion | -13.92 mg/day | Standard Deviation 18.37 |
Secondary
Percent Change From Baseline Period to Treatment Period in 24-hour Urinary Oxalate Excretion
Percent Change from Baseline is defined as baseline value (average of Days 2 and 3) minus ALLN-177 treatment value (mean of Days 5, 6, and 7) divided by baseline value times 100%
Time frame: 7 days
Population: All Participants (N=16) were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALLN-177 | Percent Change From Baseline Period to Treatment Period in 24-hour Urinary Oxalate Excretion | -13.28 percentage change | Standard Deviation 16.62 |