Evaluating ALLN-177 for Reducing Urinary Oxalate Excretion in Calcium Oxalate Kidney Stone Formers With Hyperoxaluria
Primary Purpose
Hyperoxaluria, Nephrolithiasis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ALLN-177
Sponsored by
About this trial
This is an interventional treatment trial for Hyperoxaluria focused on measuring Urine Oxalate, Nephrolithiasis, Kidney Stones, Hyperoxaluria, Enteric Hyperoxaluria, Idiopathic Hyperoxaluria, Urological Diseases, Kidney Diseases
Eligibility 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
Sites / Locations
- Indiana University Physicians Urology
- North Shore Long Island Jewish Health System
- Cleveland Clinic
- Omega Clinical Research
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ALLN-177
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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%
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02289755
Brief Title
Evaluating ALLN-177 for Reducing Urinary Oxalate Excretion in Calcium Oxalate Kidney Stone Formers With Hyperoxaluria
Official Title
A Phase 2 Multicenter, Open Label, Single Arm Study Evaluating the Effect of ALLN-177 to Reduce Urinary Oxalate Excretion in Recurrent Calcium Oxalate Kidney Stone Formers With Hyperoxaluria
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
February 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allena Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperoxaluria, Nephrolithiasis
Keywords
Urine Oxalate, Nephrolithiasis, Kidney Stones, Hyperoxaluria, Enteric Hyperoxaluria, Idiopathic Hyperoxaluria, Urological Diseases, Kidney Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ALLN-177
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ALLN-177
Other Intervention Name(s)
Oxalate degrading enzyme, Oxalate decarboxylase
Intervention Description
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.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lee Brettman, MD, FACP
Organizational Affiliation
Medical Director
Official's Role
Study Director
Facility Information:
Facility Name
Indiana University Physicians Urology
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
North Shore Long Island Jewish Health System
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Omega Clinical Research
City
Warwick
State/Province
Rhode Island
ZIP/Postal Code
02886
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30783888
Citation
Lingeman JE, Pareek G, Easter L, Pease R, Grujic D, Brettman L, Langman CB. ALLN-177, oral enzyme therapy for hyperoxaluria. Int Urol Nephrol. 2019 Apr;51(4):601-608. doi: 10.1007/s11255-019-02098-1. Epub 2019 Feb 19.
Results Reference
derived
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Evaluating ALLN-177 for Reducing Urinary Oxalate Excretion in Calcium Oxalate Kidney Stone Formers With Hyperoxaluria
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