Ignite Creation Date:
2024-05-05 @ 11:42 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00111657
Status:
COMPLETED
Last Update Posted:
2014-10-03
First Post:
2005-05-24
Brief Title:
Pegylated Recombinant Mammalian Uricase PEG-uricase as Treatment for Refractory Gout
Sponsor:
John Sundy
Organization:
Duke University
Study Overview
Official Title:
A Phase II Multidose Study of Intravenous PEG-uricase in Patients With Refractory Gout
Status:
COMPLETED
Status Verified Date:
2014-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to determine whether PEG-uricase a chemically modified recombinant mammalian enzyme that degrades uric acid is effective in controlling hyperuricemia in patients with chronic gout who cannot tolerate or have not responded adequately to conventional therapy for gout
Funding Source - FDA OOPD
Funding Source - FDA OOPD
Detailed Description:
Inflammatory arthritis in patients with gout is caused by crystals of monosodium urate MSU that form as a result of chronically elevated levels of uric acid in plasma and extracellular fluids Recurrent attacks can usually be prevented by treatment with drugs that block urate synthesis by inhibiting xanthine oxidase or that promote uric acid excretion If for various reasons noncompliance drug intolerance inadequate dosage or inefficacy therapy fails to maintain serum urate concentration below about 6 mgdL gout can progress to a chronic stage characterized by destructive arthropathy deposition of urate crystals in soft tissues tophi and nephropathy The management of chronic gout in such patients is often complicated by co-morbidities such as hypertension heart disease diabetes and renal insufficiency which may limit the use of anti-inflammatory agents to treat arthritis
Urate levels are low and gout does not occur in species that express the enzyme urate oxidase uricase which converts urate to the more soluble and easily excreted compound allantoin Humans do not express this enzyme owing to a mutation of the uricase gene during evolution Parenteral uricase is thus a potential means of controlling hyperuricemia and depleting urate stores in patients with chronic refractory gout Infusion of recombinant fungal uricase is effective in preventing acute uric acid nephropathy due to tumor lysis in patients with malignancies However the short circulating life and potential immunogenicity of fungal uricase prevents its chronic use for treating gout
PEG-uricase is a recombinant porcine urate oxidase to which multiple strands of polyethylene glycol PEG of average molecular weight 10000 have been attached PEGylation is intended to reduce the immunogenicity of uricase and greatly prolong its circulating life This mammalian PEG-uricase was non-immunogenic and effective in preventing uric acid nephropathy in a uricase-deficient strain of mice Kelly et al J Am Soc Nephrol 121001-09 2001 It has been licensed to Savient Pharmaceuticals for clinical development and has received Orphan Drug designation for the treatment of refractory gout by the FDA Office of Orphan Product Development
In a Phase I trial sponsored by Savient Pharmaceuticals in 24 subjects with symptomatic gout single intravenous IV infusions of 05 to 12 mg of PEG-uricase were well tolerated and at doses of 4 mg to 12 mg were effective in normalizing plasma and urinary uric acid levels over a 21-day period post-infusion Some subjects in this trial developed antibodies to PEG-uricase but the only serious adverse events observed were attacks of gout The present Phase II clinical trial in subjects with refractory gout will evaluate the efficacy safety and immunogenicity of PEG-uricase when administered at a dose of 8 mg by IV infusion once every 3 weeks for a total of 5 infusions The primary measure of efficacy will be a reduction in plasma uric acid to less than 6 mgdL and reduction in the ratio of uric acid to creatinine in urine to 02 In addition the ability of PEG-uricase to lower the total uric acid pool size will be evaluated in a subset of treatment subjects Uric acid pool size will be measured by a method that involves an infusion of uric acid labeled with N15 a stable non-radioactive isotope of nitrogen
Urate levels are low and gout does not occur in species that express the enzyme urate oxidase uricase which converts urate to the more soluble and easily excreted compound allantoin Humans do not express this enzyme owing to a mutation of the uricase gene during evolution Parenteral uricase is thus a potential means of controlling hyperuricemia and depleting urate stores in patients with chronic refractory gout Infusion of recombinant fungal uricase is effective in preventing acute uric acid nephropathy due to tumor lysis in patients with malignancies However the short circulating life and potential immunogenicity of fungal uricase prevents its chronic use for treating gout
PEG-uricase is a recombinant porcine urate oxidase to which multiple strands of polyethylene glycol PEG of average molecular weight 10000 have been attached PEGylation is intended to reduce the immunogenicity of uricase and greatly prolong its circulating life This mammalian PEG-uricase was non-immunogenic and effective in preventing uric acid nephropathy in a uricase-deficient strain of mice Kelly et al J Am Soc Nephrol 121001-09 2001 It has been licensed to Savient Pharmaceuticals for clinical development and has received Orphan Drug designation for the treatment of refractory gout by the FDA Office of Orphan Product Development
In a Phase I trial sponsored by Savient Pharmaceuticals in 24 subjects with symptomatic gout single intravenous IV infusions of 05 to 12 mg of PEG-uricase were well tolerated and at doses of 4 mg to 12 mg were effective in normalizing plasma and urinary uric acid levels over a 21-day period post-infusion Some subjects in this trial developed antibodies to PEG-uricase but the only serious adverse events observed were attacks of gout The present Phase II clinical trial in subjects with refractory gout will evaluate the efficacy safety and immunogenicity of PEG-uricase when administered at a dose of 8 mg by IV infusion once every 3 weeks for a total of 5 infusions The primary measure of efficacy will be a reduction in plasma uric acid to less than 6 mgdL and reduction in the ratio of uric acid to creatinine in urine to 02 In addition the ability of PEG-uricase to lower the total uric acid pool size will be evaluated in a subset of treatment subjects Uric acid pool size will be measured by a method that involves an infusion of uric acid labeled with N15 a stable non-radioactive isotope of nitrogen
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| FD-R-0002537 | OTHER | FDA OOPD | None |