Gout
Conditions
Keywords
Serum uric acid, siRNA
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
Interventions
DRUGALN-XDH
ALN-XDH administered by SC injection
DRUGPlacebo
Placebo administered by SC injection
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Part A: Area Under the Plasma Concentration-time Curve (AUC) for ALN-XDH and Potential Metabolites | Day 1 predose and up to 48 hours postdose | — |
| 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 | — |
| Parts B and C: Frequency of Treatment-associated Gout Flares | Up to 6 months | Treatment-associated gout flares are defined as gout flares that occur within 6 months of study drug initiation. |
| 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 | — |
| Part A: Maximum Plasma Concentration (Cmax) for ALN-XDH and Potential Metabolites | Day 1 predose and up to 48 hours postdose | — |
Countries
United Kingdom
Outcome results
None listed