Evaluating ALLN-177 for Reducing Urinary Oxalate Excretion in Calcium Oxalate Kidney Stone Formers With Hyperoxaluria

• ClinicalTrials.gov Identifier: NCT02289755
• Recruitment Status: Completed
• First Posted: November 13, 2014
• Results First Posted: April 27, 2016
• Last Update Posted: June 5, 2019
• Sponsor: Allena Pharmaceuticals
• Information provided by (Responsible Party): Allena Pharmaceuticals

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
Hyperoxaluria; Nephrolithiasis	Drug: ALLN-177	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: September 2014
• Actual Primary Completion Date: January 2015
• Actual Study Completion Date: February 2015

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: Oxalate degrading enzyme; Oxalate decarboxylase

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline Period to Treatment Period 24-hour Urinary Oxalate Excretion [ Time Frame: 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 :

1. Percent Change From Baseline Period to Treatment Period in 24-hour Urinary Oxalate Excretion [ Time Frame: 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

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

United States, Indiana

Indiana University Physicians Urology

Indianapolis, Indiana, United States, 46202

United States, New York

North Shore Long Island Jewish Health System

Lake Success, New York, United States, 11042

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Rhode Island

Omega Clinical Research

Warwick, Rhode Island, United States, 02886

Sponsors and Collaborators

Allena Pharmaceuticals

Investigators

• Study Director: Lee Brettman, MD, FACP; Medical Director

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Allena Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02289755
• Other Study ID Numbers: 0000396
• First Posted: November 13, 2014
• Results First Posted: April 27, 2016
• Last Update Posted: June 5, 2019
• Last Verified: February 2016

Keywords provided by Allena Pharmaceuticals:

Urine Oxalate; Nephrolithiasis; Kidney Stones; Hyperoxaluria; Enteric Hyperoxaluria; Idiopathic Hyperoxaluria; Urological Diseases; Kidney Diseases

Additional relevant MeSH terms:

Kidney Calculi; Nephrolithiasis; Kidney Diseases; Urologic Diseases; Urolithiasis; Urinary Calculi; Calculi; Pathological Conditions, Anatomical