An Inpatient Study of ALLN-346 (Engineered Urate Oxidase) in Hyperuricemic Subjects (Study 201)

Study Overview
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Brief Summary
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The purpose of this Phase IIa study is to evaluate the safety and tolerability of ALLN-346 in subjects with hyperuricemia in an inpatient, controlled setting.

Detailed Description
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This is a Phase II, 7-day, randomized, double-blind, placebo-controlled study of orally administered ALLN-346 in subjects with hyperuricemia, with subpopulations to include generally healthy hyperuricemic subjects with normal kidney function and those with mild to moderate chronic kidney disease (CKD). Study will take place at a clinical pharmacology unit (CPU). The study will have two Parts. Part 1 will include subjects with serum urate ≥ 6.8 mg/dL and eGFR ≥ 60 mL/minute/1.73 m2 (subjects with eGFR of stage 2 CKD and with normal kidney function). Part 2 will include subjects with serum urate ≥ 6.8 mg/dL and eGFR 45-100 mL/minute/1.73 m2 (eGFR of CKD Stages 2- 3a). The study will evaluate safety, tolerability, pharmacokinetics (lack of absorption) and pharmacodynamics of ALLN-346.

Official Title
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An Inpatient, Placebo-Controlled Study of ALLN-346 (Engineered Urate Oxidase) in Hyperuricemic Subjects

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 55 years sUA level ≥ 6.8 mg/dL at Screening (hyperuricemia), with or without a diagnosis of gout 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 Normal non-clinically significant abnormalities in vital signs Normal clinical laboratory test results and ECG, which are not considered to be clinically significant Exclusion Criteria: Screening eGFR of <60 mL/minute/1.73 m2 for Part 1, and for Part 2 Screening eGFR outside the range of 45-100 mL/minute/1.73 m2. History or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, urological, or psychiatric disorders. Presence or history of any other condition (including surgery) known to interfere with the absorption, distribution, metabolism, or excretion of medicines Currently taking any urate-lowering medication within 4 weeks prior to Day 1 (first dosing day) Prior uricase therapy or exposure to recombinant uricase Clinically significant abnormal findings on electrocardiogram (ECG) Positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody 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: 65 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: Study population includes generally healthy subjects with hyperuricemia without CKD, and those with eGFR of mild-moderate CKD. The maximal tolerated dose from the MAD study in normal healthy volunteers (Study 102) will be administered. The study is comprised of two Parts. Under optional Part 2, only subjects with eGFR of CKD Stages 2- 3a.
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: 5 capsules thrice daily (TID) for a total of 15 capsules per day will be evaluated for 7 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: 5 capsules thrice daily (TID) for a total of 15 capsules per day will be evaluated for 7 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) | Number of of participants with treatment emergent adverse events | 21 days per Study Part | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum ALLN-346 | Serum concentration of ALLN-346 (ng/mL) | 8 days |