Clinical trial NCT05256810: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Gout
Keywords: Serum uric acid
siRNA
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-02-25
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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 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

Primary outcomes:
measure: Part A: Frequency of Adverse Events
timeFrame: Up to 10 months
measure: Parts B and C: Frequency of Adverse Events
timeFrame: Up to 14 months
measure: Parts B and C: Percentage of Participants with Serum Uric Acid (sUA) <6 mg/dL
timeFrame: Up to 12.25 months
Secondary outcomes:
measure: Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-XDH and Potential Metabolites
timeFrame: Day 1 predose and up to 48 hours postdose
measure: Part A: Maximum Plasma Concentration (Cmax) for ALN-XDH and Potential Metabolites
timeFrame: Day 1 predose and up to 48 hours postdose
measure: Part A: Time to Maximum Plasma Concentration (tmax) for ALN-XDH and Potential Metabolites
timeFrame: Day 1 predose and up to 48 hours postdose
measure: Part A: Fractional Excreted in Urine (fe) for ALN-XDH and Potential Metabolites
timeFrame: Day 1 predose and up to 24 hours postdose
measure: Part A: Percent Change from Baseline in sUA
timeFrame: Baseline through Month 9
measure: Parts B and C: Percentage of Participants with sUA <5 mg/dL
timeFrame: Up to 12.25 months
measure: Parts B and C: Percentage Change from Baseline in sUA Level
timeFrame: Up to 12.25 months
measure: Parts B and C: Plasma Concentrations of ALN-XDH and Potential Major Metabolite(s)
timeFrame: Day 1 and Day 85 predose and up to 4 hours postdose
measure: Parts B and C: Frequency of Treatment-associated Gout Flares
timeFrame: Up to 6 months
measure: Parts B and C: Percent Change from Baseline in 24-hour Urine Uric Acid (uUA)
timeFrame: Baseline through Month 6
measure: Parts B and C: Percent Change from Baseline in Serum Xanthine
timeFrame: Baseline through Month 6
measure: Parts B and C: Percent Change from Baseline in 24-hour Urine Xanthine
timeFrame: Baseline through Month 6
measure: Parts B and C: Percent Change from Baseline in Serum Hypoxanthine
timeFrame: Baseline through Month 6
measure: Parts B and C: Percent Change from Baseline in 24-hour Urine Hypoxanthine
timeFrame: Baseline through Month 6
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: