ALLN-346 Single Ascending Dose (SAD) Study in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of ALLN-346 in healthy volunteers, in this first in human, single ascending dose study. ALLN-346 is an enzyme that degrades urate in the gastrointestinal tract.

Detailed Description
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This is a Phase I, randomized, double-blind, placebo-controlled single ascending dose study of orally administered ALLN-346. The study will evaluate the safety and tolerability, inflammation and immunogenicity, pharmacokinetics and pharmacodynamics of ALLN-346 in healthy volunteers. The study consists of a Screening Period, a Treatment Period of 3 days, which includes 1 single day of dosing and 3 days of in-house observation, and a safety Follow-up Period through Day 28 following dosing.

Official Title
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A Phase I Randomized, Double-Blind, Placebo-Controlled Single Ascending Dose Study of ALLN-346 (Engineered Urate Oxidase)

Conditions
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Hyperuricemia

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: Signed informed consent form Incapable of pregnancy, not nursing, and agrees to use an effective method of contraception; males subjects must agree to abstain from sperm donation Good general health as determined by medical history and physical examination Normal clinical laboratory test results and ECG Exclusion Criteria: Presence or history of any significant cardiovascular, gastrointestinal, hepatic, renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurological, psychiatric disease or history of hyperuricemia Any other condition (including surgery) known to interfere with the absorption, distribution, metabolism, or excretion of medicines Positive screen results for drugs of abuse, alcohol, or cotinine or recent history of drug or alcohol abuse Clinically significant abnormal findings on physical examination, vital signs or 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 Per Investigator judgment, is not an ideal clinical study candidate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALLN-346<br>ALLN-346 | Drug: ALLN-346<br>* ALLN-346 is novel urate oxidase provided as capsules for oral administration. Single ascending doses within 3 sequential cohorts: Cohort A - 3 capsules administered once, Cohort B - 6 capsules administered once and Cohort C - 12 capsules administered as 6 capsules twice on 1 day.<br>* Other names: Engineered urate oxidase;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Matching placebo capsules for oral administration. Single ascending doses within 3 sequential cohorts: Cohort A - 3 capsules administered once, Cohort B - 6 capsules administered once and Cohort C - 12 capsules administered as 6 capsules twice on 1 day.<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 participants with treatment emergent adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-drug antibody assessment of immune response | Development of anti-drug antibodies (total Immunoglobin levels, mg/dL) | 28 days | 
| Serum level of ALLN-346 | Change of serum ALLN-346 level (ng/mL) | 48 hours | 
| Serum ALLN-346 uricase activity level | Change of serum ALLN-346 activity (ng/mL) | 48 hours | 
| Serum uric acid assessment of pharmacodynamic response | Change in serum uric acid concentration (mg/dL) | 48 hours | 
| C-reactive protein (CRP) assessment of inflammation response | Change in CRP blood levels (mg/L) | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperuricemia, gout, urate oxidase, uric acid