Evaluating ALLN-177 for Reducing Urinary Oxalate Excretion in Calcium Oxalate Kidney Stone Formers With Hyperoxaluria
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ALLN-177 Recurrent Calcium Oxalate Stone Formers with Hyperoxaluria Subjects with Enteric or Idiopathic hyperoxaluria Dosing: 5 capsules of ALLN-177 orally (p.o.) up to 3 times daily (TID) with meals for 4 consecutive days. |
Drug: ALLN-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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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%
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Indiana University Physicians Urology | Indianapolis | Indiana | United States | 46202 |
| 2 | North Shore Long Island Jewish Health System | Lake Success | New York | United States | 11042 |
| 3 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 4 | Omega Clinical Research | Warwick | Rhode Island | United States | 02886 |
Sponsors and Collaborators
- Allena Pharmaceuticals
Investigators
- Study Director: Lee Brettman, MD, FACP, Medical Director
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0000396
Study Results
Participant Flow
| Recruitment Details | Subjects (N = 16) were recruited from 3 centers in the United States between August 2014 and December 2014. |
|---|---|
| Pre-assignment Detail | History of ≥1 calcium oxalate kidney stone within the last 2 years, secondary hyperoxaluria and a mean urinary oxalate of ≥36 mg/day |
| Arm/Group Title | ALLN-177 |
|---|---|
| Arm/Group Description | ALLN-177 (5 capsules; 7,500 units/meal) by mouth 3 times a day with main meals for 4 consecutive days. |
| Period Title: Baseline Period [No Treatment, 3 Days] | |
| STARTED | 16 |
| COMPLETED | 16 |
| NOT COMPLETED | 0 |
| Period Title: Baseline Period [No Treatment, 3 Days] | |
| STARTED | 16 |
| COMPLETED | 16 |
| NOT COMPLETED | 0 |
| Period Title: Baseline Period [No Treatment, 3 Days] | |
| STARTED | 16 |
| COMPLETED | 16 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | ALLN-177 |
|---|---|
| Arm/Group Description | ALLN-177 (5 capsules: 7,500 units/meal), 3 times a day with meals, 4 days |
| Overall Participants | 16 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
13
81.3%
|
| >=65 years |
3
18.8%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
54.1
(14.5)
|
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
58.0
|
| Sex: Female, Male (Count of Participants) | |
| Female |
7
43.8%
|
| Male |
9
56.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
16
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
12.5%
|
| White |
14
87.5%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
16
100%
|
| Glomerular Filtration Rate (GFR) (ml/min/1.73 m^2) [Mean (Full Range) ] | |
| Mean (Full Range) [ml/min/1.73 m^2] |
85.1
|
| Concomitant medications (participants) [Number] | |
| Potassium citrate |
5
31.3%
|
| Chlorthalidone |
2
12.5%
|
| Hydrochlorothiazide |
1
6.3%
|
| Calcium |
5
31.3%
|
| 24-hour Urinary Oxalate (mg/day) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [mg/day] |
77.65
(55.87)
|
Outcome Measures
| Title | Change From Baseline Period to Treatment Period 24-hour Urinary Oxalate Excretion |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Participants (N=16) completed treatment and were included in the analysis population. |
| Arm/Group Title | ALLN-177 |
|---|---|
| Arm/Group Description | ALLN-177 (5 capsules: 7,500 units/meal), 3 times a day with meals, 4 days |
| Measure Participants | 16 |
| Mean (Standard Deviation) [mg/day] |
-13.92
(18.37)
|
| Title | Percent Change From Baseline Period to Treatment Period in 24-hour Urinary Oxalate Excretion |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Participants (N=16) were included in the analysis. |
| Arm/Group Title | ALLN-177 |
|---|---|
| Arm/Group Description | ALLN-177 (5 capsules: 7,500 units/meal), 3 times a day with meals, 4 days |
| Measure Participants | 16 |
| Mean (Standard Deviation) [percentage change] |
-13.28
(16.62)
|
Adverse Events
| Time Frame | Up to 11 days. | |
|---|---|---|
| Adverse Event Reporting Description | Treatment-emergent adverse events = AEs with onset at or after starting study drug through 7 days after the last dose of study drug. | |
| Arm/Group Title | ALLN-177 | |
| Arm/Group Description | ALLN-177 (5 capsules: 7,500 units/meal), 3 times a day with meals, 4 days | |
All Cause Mortality |
||
| ALLN-177 | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| ALLN-177 | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| ALLN-177 | ||
| Affected / at Risk (%) | # Events | |
| Total | 9/16 (56.3%) | |
| Gastrointestinal disorders | ||
| Abdominal discomfort | 1/16 (6.3%) | 1 |
| Abdominal distension | 4/16 (25%) | 4 |
| Diarrhoea | 2/16 (12.5%) | 2 |
| Dyspepsia | 2/16 (12.5%) | 2 |
| Flatulence | 3/16 (18.8%) | 3 |
| Gastroesophageal reflux disease | 1/16 (6.3%) | 1 |
| Nausea | 3/16 (18.8%) | 3 |
| Nervous system disorders | ||
| Headache | 2/16 (12.5%) | 2 |
| Renal and urinary disorders | ||
| Nephrolithiasis | 1/16 (6.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Pruritis | 1/16 (6.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | VP of Clinical Development |
|---|---|
| Organization | Allena Pharmaceuticals |
| Phone | 617-467-4577 ext 314 |
| akausz@allenapharma.com |
- 0000396