Phase IIa Study of ALLN-346 (Engineered Urate Oxidase) in Subjects With Hyperuricemia, Gout and Chronic Kidney Disease

Study Overview
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Brief Summary
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The purpose of this Phase IIa study is to evaluate the safety, tolerability and pharmacodynamics of ALLN-346 in subjects with hyperuricemia and gout, and with mild to moderate chronic kidney disease.

Detailed Description
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This is a randomized, double-blind, placebo-controlled parallel group, multi-center phase II clinical study or orally administered ALLN-346 in subjects with hyperuricemia, gout and mild to moderate chronic kidney disease over a two-week period. Subjects will be enrolled in two cohorts based on estimated glomerular filtration rate (eGFR).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study of ALLN-346 (Engineered Urate Oxidase) in Hyperuricemic Subjects With Gout and Mild to Moderate Chronic Kidney Disease

Conditions
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Hyperuricemia, Gout, Chronic Kidney Diseases

Intervention / Treatment
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* Drug: ALLN-346
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age 18 to 70 years Serum UA level ≥ 8.0 mg/dL at Screening (hyperuricemia) Meets 2015 American College of Rheumatology (ACR)/EULAR criteria for gout Screening eGFR of ≥60 - <90 mL/minute/1.73 m2 for Cohort A and ≥30 - <60 mL/minute/1.73 m2 for Cohort B. Concomitant medications stable for a minimum of 4 weeks prior to and during Screening Body Mass Index (BMI) ≥ 18 and ≤ 40 kg/m2, inclusive, at screening Not pregnant, not capable of pregnancy, not nursing, and agrees to use an effective method of contraception; males subjects must agree to abstain from sperm donation Exclusion Criteria: Currently taking any oral urate-lowering medication within 2 weeks prior to Screening Prior uricase therapy or exposure to recombinant uricase, such as Rasburicase or Pegloticase Gout flare requiring treatment within 14 days prior to or during Screening Clinically significant finding during Screening, any ongoing clinically significant illness requiring a clinically significant intervention or change in management within 4 weeks prior to or during Screening History of GI surgery, including gastric sleeve, Roux-en-Y or gastric banding (unless gastric band removed for a minimum of 12 months prior to Screening Received treatment with or exposure to an Investigational drug or device within 30 days - prior to or during Screening Prior dosing in ALLN-346 clinical study Per Investigator judgment, is not an ideal clinical study candidate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized 2:1 to receive ALLN-346 or placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALLN-346 (Engineered Urate Oxidase)<br>ALLN-346 is novel urate oxidase provided as capsules for oral administration. ALLN-346 will be administered as 5 capsules thrice daily (15 capsules per day total) to each of two subject cohorts based on estimated glomerular filtration rate (eGFR). Treatment Period is 14 Days. | Drug: ALLN-346<br>* ALLN-346 (Engineered Urate Oxidase) is an orally administered, novel urate oxidase; provided as capsules for oral administration<br>* Other names: Engineered urate oxidase;|
| Placebo Comparator: Placebo<br>Matching placebo capsules for oral administration. Placebo capsules will be administered as 5 capsules thrice daily (15 capsules per day total) to each of two subject cohorts based on estimated glomerular filtration rate (eGFR). Treatment Period is 14 Days. | Drug: Placebo<br>* Matched placebo capsules are similar in weight and appearance to the ALLN-346 capsules<br>* Other names: Matching placebo capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | Treatment emergent adverse events | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Urate | Serum urate [mg/dL] | 14 Days |