A Study to Evaluate ALN-XDH in Healthy Subjects and Patients With Gout

Study Overview
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Brief Summary
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The purpose of this study is to: Part A: Evaluate the safety and tolerability of single ascending doses of ALN-XDH in healthy adult participants Part B: Evaluate the safety, tolerability and efficacy of ALN-XDH as monotherapy in adult patients with gout Part C: Evaluate the safety, tolerability and efficacy of ALN-XDH as add-on therapy in adult patients with gout

Official Title
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A Phase 1/2, Randomized, Double-blind, Placebo-controlled, Single Ascending and Multiple Dose Study of the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of ALN-XDH in Healthy Adult Subjects and Adult Patients With Gout

Conditions
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Gout

Intervention / Treatment
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* Drug: ALN-XDH
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A: has serum uric acid (sUA) level ≥4 mg/dL and ≤7 mg/dL Parts B and C: meets the American College of Rheumatology criteria for acute arthritis of primary gout Part B: has an sUA level ≥8 mg/dL while not receiving urate-lowering therapy (ULT) or following a 1-week washout period of prior ULT Part C: has been on a stable dose of al lopurinol for gout for ≥6 weeks prior to screening Part C: has an sUA level ≥6 mg/dL Exclusion Criteria: Parts A, B and C: Has received an investigational agent within the last 30 days Parts A, B and C: Has experienced or is being treated for acute gout flare(s) within 14 days prior to randomization

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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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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: ALN-XDH<br>A single dose of ALN-XDH administered by subcutaneous (SC) injection. | Drug: ALN-XDH<br>* ALN-XDH administered by SC injection<br>|
| Placebo Comparator: Part A: Placebo<br>A single dose of placebo administered by SC injection. | Drug: Placebo<br>* Placebo administered by SC injection<br>|
| Experimental: Part B: ALN-XDH Single Dose<br>A single dose of ALN-XDH administered by SC injection. | Drug: ALN-XDH<br>* ALN-XDH administered by SC injection<br>|
| Experimental: Part B: ALN-XDH Multiple Dose<br>Multiple doses of ALN-XDH administered by SC injection. | Drug: ALN-XDH<br>* ALN-XDH administered by SC injection<br>|
| Placebo Comparator: Part B: Placebo<br>Multiple doses of placebo administered by SC injection. | Drug: Placebo<br>* Placebo administered by SC injection<br>|
| Experimental: Part C: ALN-XDH<br>A single dose of ALN-XDH administered by SC injection. | Drug: ALN-XDH<br>* ALN-XDH administered by SC injection<br>|
| Placebo Comparator: Part C: Placebo<br>A single dose of placebo administered by SC injection. | Drug: Placebo<br>* Placebo administered by SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Frequency of Adverse Events |  | Up to 10 months | 
| Parts B and C: Frequency of Adverse Events |  | Up to 14 months | 
| Parts B and C: Percentage of Participants with Serum Uric Acid (sUA) <6 mg/dL |  | Up to 12.25 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites |  | Day 1 predose and up to 48 hours postdose | 
| Part A: Maximum Plasma Concentration (Cmax) for ALN-XDH and Potential Metabolites |  | Day 1 predose and up to 48 hours postdose | 
| Part A: Time to Maximum Plasma Concentration (tmax) for ALN-XDH and Potential Metabolites |  | Day 1 predose and up to 48 hours postdose | 
| Part A: Fractional Excreted in Urine (fe) for ALN-XDH and Potential Metabolites |  | Day 1 predose and up to 24 hours postdose | 
| Part A: Percent Change from Baseline in sUA |  | Baseline through Month 9 | 
| Parts B and C: Percentage of Participants with sUA <5 mg/dL |  | Up to 12.25 months | 
| Parts B and C: Percentage Change from Baseline in sUA Level |  | Up to 12.25 months | 
| Parts B and C: Plasma Concentrations of ALN-XDH and Potential Major Metabolite(s) |  | Day 1 and Day 85 predose and up to 4 hours postdose | 
| Parts B and C: Frequency of Treatment-associated Gout Flares | Treatment-associated gout flares are defined as gout flares that occur within 6 months of study drug initiation. | Up to 6 months | 
| Parts B and C: Percent Change from Baseline in 24-hour Urine Uric Acid (uUA) |  | Baseline through Month 6 | 
| Parts B and C: Percent Change from Baseline in Serum Xanthine |  | Baseline through Month 6 | 
| Parts B and C: Percent Change from Baseline in 24-hour Urine Xanthine |  | Baseline through Month 6 | 
| Parts B and C: Percent Change from Baseline in Serum Hypoxanthine |  | Baseline through Month 6 | 
| Parts B and C: Percent Change from Baseline in 24-hour Urine Hypoxanthine |  | Baseline through Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Serum uric acid, siRNA