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

Primary Purpose

Gout

Status

Terminated

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

ALN-XDH

Placebo

About this trial

This is an interventional treatment trial for Gout focused on measuring Serum uric acid, siRNA

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Clinical Trial Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part A: ALN-XDH

Part A: Placebo

Part B: ALN-XDH Single Dose

Part B: ALN-XDH Multiple Dose

Part B: Placebo

Part C: ALN-XDH

Part C: Placebo

Arm Description

A single dose of ALN-XDH administered by subcutaneous (SC) injection.

A single dose of placebo administered by SC injection.

A single dose of ALN-XDH administered by SC injection.

Multiple doses of ALN-XDH administered by SC injection.

Multiple doses of placebo administered by SC injection.

A single dose of ALN-XDH administered by SC injection.

A single dose of placebo administered by SC injection.

Outcomes

Primary Outcome Measures

Part A: Frequency of Adverse Events

Parts B and C: Frequency of Adverse Events

Parts B and C: Percentage of Participants with Serum Uric Acid (sUA) <6 mg/dL

Secondary Outcome Measures

Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites

Part A: Maximum Plasma Concentration (Cmax) for ALN-XDH and Potential Metabolites

Part A: Time to Maximum Plasma Concentration (tmax) for ALN-XDH and Potential Metabolites

Part A: Fractional Excreted in Urine (fe) for ALN-XDH and Potential Metabolites

Part A: Percent Change from Baseline in sUA

Parts B and C: Percentage of Participants with sUA <5 mg/dL

Parts B and C: Percentage Change from Baseline in sUA Level

Parts B and C: Plasma Concentrations of ALN-XDH and Potential Major Metabolite(s)

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.

Parts B and C: Percent Change from Baseline in 24-hour Urine Uric Acid (uUA)

Parts B and C: Percent Change from Baseline in Serum Xanthine

Parts B and C: Percent Change from Baseline in 24-hour Urine Xanthine

Parts B and C: Percent Change from Baseline in Serum Hypoxanthine

Parts B and C: Percent Change from Baseline in 24-hour Urine Hypoxanthine

Full Information

NCT ID

NCT05256810

First Posted

February 16, 2022

Last Updated

March 21, 2023

Sponsor

Alnylam Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05256810

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Terminated

Why Stopped

The Sponsor elected not to continue with the study

Study Start Date

February 25, 2022 (Actual)

Primary Completion Date

January 25, 2023 (Actual)

Study Completion Date

January 25, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alnylam Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gout

Keywords

Serum uric acid, siRNA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A: ALN-XDH

Arm Type

Experimental

Arm Description

A single dose of ALN-XDH administered by subcutaneous (SC) injection.

Arm Title

Part A: Placebo

Arm Type

Placebo Comparator

Arm Description

A single dose of placebo administered by SC injection.

Arm Title

Part B: ALN-XDH Single Dose

Arm Type

Experimental

Arm Description

A single dose of ALN-XDH administered by SC injection.

Arm Title

Part B: ALN-XDH Multiple Dose

Arm Type

Experimental

Arm Description

Multiple doses of ALN-XDH administered by SC injection.

Arm Title

Part B: Placebo

Arm Type

Placebo Comparator

Arm Description

Multiple doses of placebo administered by SC injection.

Arm Title

Part C: ALN-XDH

Arm Type

Experimental

Arm Description

A single dose of ALN-XDH administered by SC injection.

Arm Title

Part C: Placebo

Arm Type

Placebo Comparator

Arm Description

A single dose of placebo administered by SC injection.

Intervention Type

Drug

Intervention Name(s)

ALN-XDH

Intervention Description

ALN-XDH administered by SC injection

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo administered by SC injection

Primary Outcome Measure Information:

Title

Part A: Frequency of Adverse Events

Time Frame

Up to 10 months

Title

Parts B and C: Frequency of Adverse Events

Time Frame

Up to 14 months

Title

Parts B and C: Percentage of Participants with Serum Uric Acid (sUA) <6 mg/dL

Time Frame

Up to 12.25 months

Secondary Outcome Measure Information:

Title

Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-HSD and Potential Metabolites

Time Frame

Day 1 predose and up to 48 hours postdose

Title

Part A: Maximum Plasma Concentration (Cmax) for ALN-XDH and Potential Metabolites

Time Frame

Day 1 predose and up to 48 hours postdose

Title

Part A: Time to Maximum Plasma Concentration (tmax) for ALN-XDH and Potential Metabolites

Time Frame

Day 1 predose and up to 48 hours postdose

Title

Part A: Fractional Excreted in Urine (fe) for ALN-XDH and Potential Metabolites

Time Frame

Day 1 predose and up to 24 hours postdose

Title

Part A: Percent Change from Baseline in sUA

Time Frame

Baseline through Month 9

Title

Parts B and C: Percentage of Participants with sUA <5 mg/dL

Time Frame

Up to 12.25 months

Title

Parts B and C: Percentage Change from Baseline in sUA Level

Time Frame

Up to 12.25 months

Title

Parts B and C: Plasma Concentrations of ALN-XDH and Potential Major Metabolite(s)

Time Frame

Day 1 and Day 85 predose and up to 4 hours postdose

Title

Parts B and C: Frequency of Treatment-associated Gout Flares

Description

Treatment-associated gout flares are defined as gout flares that occur within 6 months of study drug initiation.

Time Frame

Up to 6 months

Title

Parts B and C: Percent Change from Baseline in 24-hour Urine Uric Acid (uUA)

Time Frame

Baseline through Month 6

Title

Parts B and C: Percent Change from Baseline in Serum Xanthine

Time Frame

Baseline through Month 6

Title

Parts B and C: Percent Change from Baseline in 24-hour Urine Xanthine

Time Frame

Baseline through Month 6

Title

Parts B and C: Percent Change from Baseline in Serum Hypoxanthine

Time Frame

Baseline through Month 6

Title

Parts B and C: Percent Change from Baseline in 24-hour Urine Hypoxanthine

Time Frame

Baseline through Month 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Alnylam Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Clinical Trial Site

City

London

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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