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

March 28, 2024 updated by: Alnylam Pharmaceuticals

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

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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 allopurinol 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Maximum Plasma Concentration (Cmax) for ALN-XDH and Potential Metabolites
Time Frame: Day 1 predose and up to 48 hours postdose
Day 1 predose and up to 48 hours postdose
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
Day 1 predose and up to 48 hours postdose
Part A: Fractional Excreted in Urine (fe) for ALN-XDH and Potential Metabolites
Time Frame: Day 1 predose and up to 24 hours postdose
Day 1 predose and up to 24 hours postdose
Part A: Percent Change from Baseline in sUA
Time Frame: Baseline through Month 9
Baseline through Month 9
Parts B and C: Percentage of Participants with sUA <5 mg/dL
Time Frame: Up to 12.25 months
Up to 12.25 months
Parts B and C: Percentage Change from Baseline in sUA Level
Time Frame: Up to 12.25 months
Up to 12.25 months
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
Day 1 and Day 85 predose and up to 4 hours postdose
Parts B and C: Frequency of Treatment-associated Gout Flares
Time Frame: Up to 6 months
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)
Time Frame: Baseline through Month 6
Baseline through Month 6
Parts B and C: Percent Change from Baseline in Serum Xanthine
Time Frame: Baseline through Month 6
Baseline through Month 6
Parts B and C: Percent Change from Baseline in 24-hour Urine Xanthine
Time Frame: Baseline through Month 6
Baseline through Month 6
Parts B and C: Percent Change from Baseline in Serum Hypoxanthine
Time Frame: Baseline through Month 6
Baseline through Month 6
Parts B and C: Percent Change from Baseline in 24-hour Urine Hypoxanthine
Time Frame: Baseline through Month 6
Baseline through Month 6
Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-XDH and Potential Metabolites
Time Frame: Day 1 predose and up to 48 hours postdose
Day 1 predose and up to 48 hours postdose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alnylam Pharmaceuticals

Investigators

  • Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 25, 2022

Primary Completion (Actual)

January 25, 2023

Study Completion (Actual)

January 25, 2023

Study Registration Dates

First Submitted

February 16, 2022

First Submitted That Met QC Criteria

February 16, 2022

First Posted (Actual)

February 25, 2022

Study Record Updates

Last Update Posted (Actual)

March 29, 2024

Last Update Submitted That Met QC Criteria

March 28, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALN-XDH-001
  • 2021-005773-68 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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