EyesOnGOUT: Observational Study of the Use of Pegloticase (KRYSTEXXA®) in Refractory Chronic Gout

• Sponsor: Horizon Pharma Rheumatology LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01466166
• Collaborator: (none)
• Enrollment: 188
• Locations: 67
• Actual Duration (Months): 67.5
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary purpose of this study is to observe patients being treated with pegloticase in a standard healthcare setting in order to evaluate the frequency and severity of infusion reactions, anaphylaxis and immune complex related events. Additionally, serious adverse events associated with pegloticase therapy will be identified.

Condition or Disease	Intervention/Treatment	Phase
Refractory Chronic Gout	Biological: Pegloticase

Detailed Description

This was a Phase 4, multicenter, open-label, single-arm observational study of pegloticase 8 mg administered intravenously every 2 weeks in adult hyperuricemic patients with gout refractory to conventional therapy. Study duration is approximately 63 weeks, including 51 weeks of treatment and 12 weeks of follow-up.

The design of this study follows the FDA-approved Full Prescribing Information for the use of pegloticase and allows for capturing additional data related to the safety and efficacy of pegloticase within the standard healthcare setting.

Study Design

• Study Type: Observational
• Actual Enrollment: 188 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Observational Study of the Use of KRYSTEXXA® (Pegloticase) in Adult Hyperuricemic Patients With Gout Refractory to Conventional Therapy
• Actual Study Start Date: Nov 15, 2011
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Jun 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Pegloticase Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.	Biological: Pegloticase; Pegloticase 8 mg intravenous every 2 weeks; Other Names: KRYSTEXXA®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Infusion Reactions [52 weeks]

   Infusion reactions were defined as adverse events (AEs) or clusters of events, not attributable to another cause that occurred during or within 2 hours after the infusion of pegloticase. Any other case that occurred outside of the 2-hour window was categorized per Investigator discretion.

2. Number of Participants With Anaphylaxis [52 weeks]

   Anaphylaxis was defined using the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria: Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives; pruritus or flushing; swollen lips, tongue, or uvula), and at least 1 of the following: Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia). Reduced blood pressure (i.e., systolic blood pressure < 90 mm Hg or greater than 30% decrease from that patient's baseline) or associated symptoms of end-organ failure (e.g., hypotonia [collapse], syncope, incontinence).

3. Number of Participants With Immune Complex-related Events [From first dose of study drug to the end of the 12-week follow-up period (63 weeks).]

   Immune complex-related events were defined as any presumptive immune complex-related disorders that were confirmed by an appropriate investigation of the event and of complement markers (C3 and C4 levels). Clinical manifestations could have included skin rash, arthralgia, arthritis, proteinuria, serum sickness, and cryoglobulinemia.

Secondary Outcome Measures

1. Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52 [Week 24 and week 52]

   Normalization of serum uric acid was defined as serum uric acid value less than 6 mg/dL.

2. Change From Baseline in Number of Gout Flares [Baseline, week 24 and week 48]

   The number of gout flares occurring in the 2 weeks prior to each visit. Baseline number of flares was calculated as the average number of flares that occurred in the 6-month baseline period divided by 12 weeks.

3. Number of Swollen Joints Over Time [Baseline and weeks 24 and 52]

4. Number of Tender Joints Over Time [Baseline and weeks 24 and 52]

5. Number of Palpable Tophi Over Time [Baseline and weeks 24 and 52]

   Gout tophi are nodular deposits of urate crystals and inflammatory cells in joints, soft tissues, bones, and in some organs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults (age 18 years or more) with chronic gout refractory to conventional therapy, defined as patients who have failed to normalize SUA and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose, or for whom these drugs are contraindicated.

• Patients who have made the decision, along with their treating physician, to begin treatment with KRYSTEXXA.

• Patients who are willing and able to give informed consent and adhere to visit/protocol schedules.

Exclusion Criteria:

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency

• Non-compensated congestive heart failure

• Pregnancy or breast feeding

• Prior treatment with pegloticase or another recombinant uricase

• Known allergy to urate oxidase

• Prior treatment or concomitant therapy with a polyethylene glycol (PEG)-conjugated drug

• Recipient of an investigational drug within 4 weeks prior to study drug administration or plans to take an investigational agent during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rheumatology Associates, PC	Birmingham	Alabama	United States	35205
2	UAB Rheumatology	Birmingham	Alabama	United States	35294
3	Saadat Ansari, MD, LLC	Huntsville	Alabama	United States	35801
4	Medvin Clinical Research	Covina	California	United States	91723
5	Alliance Clinical Research, LLC	Laguna Hills	California	United States	92653
6	Advanced Medical Research, LLC	Lakewood	California	United States	90712
7	Pacific Arthritis Care Center	Los Angeles	California	United States	90045
8	R Srinivasan, MD, Inc	Monterey Park	California	United States	91754
9	Brigid Freyne, MD, Inc	Murrieta	California	United States	92563
10	Alliance Clinical Research	Poway	California	United States	92064
11	Denver Nephrologists, PC	Denver	Colorado	United States	80218
12	New England Research Associates, LLC	Trumbull	Connecticut	United States	06611
13	Howard University Hospital	Washington	District of Columbia	United States	20060
14	Washington DC Veteran's Affairs Medical Center	Washington	District of Columbia	United States	20422
15	Bay Area Arthritis and Osteoporosis	Brandon	Florida	United States	33511
16	Countryside Arthritis Center	Clearwater	Florida	United States	33761
17	Science and Research Institute, Inc	Jupiter	Florida	United States	33458
18	A & O Research Center	Miami	Florida	United States	33174
19	Arthritis Research of Florida, Inc.	Palm Harbor	Florida	United States	34684
20	Family Clinical Trials, LLC	Pembroke Pines	Florida	United States	33026
21	Jedidiah Clinical Research	Tampa	Florida	United States	33604
22	Midtown Medical Center	Tampa	Florida	United States	33614
23	Global Research Partners & Consultants, Inc.	Calhoun	Georgia	United States	30701
24	Arthritis Research & Treatment Center	Stockbridge	Georgia	United States	30281
25	University of Chicago Medical Center	Chicago	Illinois	United States	60637
26	Diagnostic Rheumatology and Research PC	Indianapolis	Indiana	United States	46227
27	Physicians' Clinic of Iowa, P.C.	Cedar Rapids	Iowa	United States	52401
28	Central Kentucky Research Associates of Kentucky	Mount Sterling	Kentucky	United States	40353
29	Research Integrity, LLC	Owensboro	Kentucky	United States	42303
30	Horizon Research Group of Opelousas, LLC	Eunice	Louisiana	United States	70535
31	Arthritis and Diabetes Clinic, Inc.	Monroe	Louisiana	United States	71203
32	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5630
33	Klein & Associates MD, PA.	Hagerstown	Maryland	United States	21740
34	The Center for Rheumatology and Bone Research	Wheaton	Maryland	United States	20902
35	Clinical Pharmacology Study Groups	Worcester	Massachusetts	United States	01605
36	Reliant Medical Group, Inc.	Worcester	Massachusetts	United States	01605
37	University of Michigan Health System	Ann Arbor	Michigan	United States	48109-5422
38	Caro Health Plaza	Caro	Michigan	United States	48723
39	Infusion Associates	Grand Rapids	Michigan	United States	49525
40	Justus J. Fiechtner, MD, PC	Lansing	Michigan	United States	48910
41	Shores Rheumatology, PC	Saint Clair Shores	Michigan	United States	48081
42	Saint Paul Rheumatology, PA	Eagan	Minnesota	United States	55121
43	Kansas City Internal Medicine	Kansas City	Missouri	United States	64114
44	Arthritis Medical Clinic	Las Vegas	Nevada	United States	89118
45	Rheumatology Associates of North Jersey	Teaneck	New Jersey	United States	07666
46	Rheumatology Associates of Long Island	Smithtown	New York	United States	11787
47	NorthEast Rheumatology	Concord	North Carolina	United States	28025
48	Duke University Medical Center	Durham	North Carolina	United States	27710
49	Physicians East, PA	Greenville	North Carolina	United States	27832
50	Shanahan Rheumatology and Immunotherapy, PLLC	Raleigh	North Carolina	United States	27617
51	Specialty Medical Clinic and Research Center	Sanford	North Carolina	United States	27330
52	Southern Ohio Rheumatology	Portsmouth	Ohio	United States	45662
53	Keystone Pain Institute, Ilumina Clinical Associates	Altoona	Pennsylvania	United States	16602
54	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
55	Low Country Rheumatology	Charleston	South Carolina	United States	29406
56	Acme Research L.L.C.	Orangeburg	South Carolina	United States	29118
57	Ramesh C. Gupta, M.D.	Memphis	Tennessee	United States	38119
58	Austin Regional Clinic	Austin	Texas	United States	78731
59	Dr. Raj Marwah	El Paso	Texas	United States	79902
60	Diagnostic Clinic of Houston	Houston	Texas	United States	77004
61	Rheumatic Disease Clinical Research Center	Houston	Texas	United States	77004
62	Arthritis Clinic of Northern Virginia, P.C.	Arlington	Virginia	United States	22205
63	Arthritis & Osteoporosis Center of North Virginia	Manassas	Virginia	United States	20109
64	Sentara Rheumatology Specialists	Norfolk	Virginia	United States	23502
65	Apex Clinical Research	Kennewick	Washington	United States	99336
66	Mountain State Clinical Research	Clarksburg	West Virginia	United States	26301
67	Rheumatic Disease Center, LLP	Glendale	Wisconsin	United States	53217

Sponsors and Collaborators

• Horizon Pharma Rheumatology LLC

Investigators

• Study Director: Jeffery Nieves, PharmD, Horizon Pharma Rheumatology LLC

Study Documents (Full-Text)

• Study Protocol - Jul 11, 2011
• Statistical Analysis Plan - Mar 25, 2018

More Information

Additional Information:

• Related Info

Publications

• Sundy JS, Baraf HS, Yood RA, Edwards NL, Gutierrez-Urena SR, Treadwell EL, Vázquez-Mellado J, White WB, Lipsky PE, Horowitz Z, Huang W, Maroli AN, Waltrip RW 2nd, Hamburger SA, Becker MA. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA. 2011 Aug 17;306(7):711-20. doi: 10.1001/jama.2011.1169.

• Responsible Party: Horizon Pharma Rheumatology LLC
• ClinicalTrials.gov Identifier: NCT01466166
• Other Study ID Numbers: M0401
• First Posted: Nov 6, 2011
• Last Update Posted: Jan 11, 2019
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Gout

Study Results

Participant Flow

Recruitment Details	A total of 249 patients were screened at 66 of 112 activated clinical sites in the United States; 61 (24.5%) of the 249 patients were screen failures and 188 were enrolled.

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Period Title: Overall Study
STARTED	188
Received Treatment	188
Completed 24 Weeks of Treatment	55
COMPLETED	25
NOT COMPLETED	163

Baseline Characteristics

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Overall Participants	188
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.32 (13.15)
Sex: Female, Male (Count of Participants)
Female	19 10.1%
Male	169 89.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 10.6%
Not Hispanic or Latino	168 89.4%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	131 69.7%
Asian	16 8.5%
Black or African American	30 16%
Native Hawaiian or Pacific Islander	1 0.5%
American Indian or Alaskan Native	2 1.1%
Other	8 4.3%
Baseline Serum Uric Acid (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	9.03 (2.29)
Duration Since Initial Gout Diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.54 (10.36)
Number of Gout Flares in Last 6 Months (flares) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [flares]	7.60 (12.17)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Infusion Reactions
Description	Infusion reactions were defined as adverse events (AEs) or clusters of events, not attributable to another cause that occurred during or within 2 hours after the infusion of pegloticase. Any other case that occurred outside of the 2-hour window was categorized per Investigator discretion.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

The intent-to-treat population included all enrolled participants

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Measure Participants	188
Count of Participants [Participants]	42 22.3%

2. Primary Outcome

Title	Number of Participants With Anaphylaxis
Description	Anaphylaxis was defined using the National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria: Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives; pruritus or flushing; swollen lips, tongue, or uvula), and at least 1 of the following: Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia). Reduced blood pressure (i.e., systolic blood pressure < 90 mm Hg or greater than 30% decrease from that patient's baseline) or associated symptoms of end-organ failure (e.g., hypotonia [collapse], syncope, incontinence).
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Measure Participants	188
Count of Participants [Participants]	5 2.7%

3. Primary Outcome

Title	Number of Participants With Immune Complex-related Events
Description	Immune complex-related events were defined as any presumptive immune complex-related disorders that were confirmed by an appropriate investigation of the event and of complement markers (C3 and C4 levels). Clinical manifestations could have included skin rash, arthralgia, arthritis, proteinuria, serum sickness, and cryoglobulinemia.
Time Frame	From first dose of study drug to the end of the 12-week follow-up period (63 weeks).

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Measure Participants	188
Count of Participants [Participants]	3 1.6%

4. Secondary Outcome

Title	Percentage of Participants With Normalization of Serum Uric Acid at Week 24 and Week 52
Description	Normalization of serum uric acid was defined as serum uric acid value less than 6 mg/dL.
Time Frame	Week 24 and week 52

Outcome Measure Data

Analysis Population Description

Participants with missing values at week 24 or 52 are counted as not achieving normalization

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Measure Participants	188
Week 24	27.7 14.7%
Week 52	12.2 6.5%

5. Secondary Outcome

Title	Change From Baseline in Number of Gout Flares
Description	The number of gout flares occurring in the 2 weeks prior to each visit. Baseline number of flares was calculated as the average number of flares that occurred in the 6-month baseline period divided by 12 weeks.
Time Frame	Baseline, week 24 and week 48

Outcome Measure Data

Analysis Population Description

Enrolled participants with a value at baseline and each time point

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Measure Participants	188
Week 24	-0.83 (0.88)
Week 48	-1.00 (0.89)

6. Secondary Outcome

Title	Number of Swollen Joints Over Time
Time Frame	Baseline and weeks 24 and 52

Outcome Measure Data

Analysis Population Description

Enrolled participants with available data at baseline and each time point.

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Measure Participants	188
Baseline	8.60 (10.847)
Week 24	4.05 (7.241)
Week 52	1.46 (3.336)

7. Secondary Outcome

Title	Number of Tender Joints Over Time
Time Frame	Baseline and weeks 24 and 52

Outcome Measure Data

Analysis Population Description

Enrolled participants with available data at baseline and each time point.

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Measure Participants	188
Baseline	9.33 (11.715)
Week 24	2.38 (5.539)
Week 52	0.79 (1.318)

8. Secondary Outcome

Title	Number of Palpable Tophi Over Time
Description	Gout tophi are nodular deposits of urate crystals and inflammatory cells in joints, soft tissues, bones, and in some organs.
Time Frame	Baseline and weeks 24 and 52

Outcome Measure Data

Analysis Population Description

Enrolled participants with available data at baseline and each time point.

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
Measure Participants	188
Baseline	13.58 (18.999)
Week 24	5.70 (5.643)
Week 52	3.68 (3.038)

Adverse Events

Time Frame	From first dose of study drug to the end of the 12-week follow-up period (63 weeks).
Arm/Group Title	Pegloticase
Arm/Group Description	Participants received pegloticase 8 mg by intravenous (IV) infusion every 2 weeks for up to 1 year, as prescribed by their treating physician.
All Cause Mortality
	Pegloticase
	Affected / at Risk (%)	# Events
Total	3/188 (1.6%)
Serious Adverse Events
	Pegloticase
	Affected / at Risk (%)	# Events
Total	31/188 (16.5%)
Blood and lymphatic system disorders
Haemolytic anaemia	1/188 (0.5%)
Cardiac disorders
Atrial fibrillation	1/188 (0.5%)
Cardiac failure	1/188 (0.5%)
Cardiac failure congestive	2/188 (1.1%)
Coronary artery disease	1/188 (0.5%)
Congenital, familial and genetic disorders
Gastrointestinal arteriovenous malformation	1/188 (0.5%)
Gastrointestinal disorders
Large intestinal haemorrhage	1/188 (0.5%)
Pancreatitis	1/188 (0.5%)
Upper gastrointestinal haemorrhage	1/188 (0.5%)
Immune system disorders
Anaphylaxis	5/188 (2.7%)
Drug hypersensitivity	3/188 (1.6%)
Infections and infestations
Cellulitis	2/188 (1.1%)
Pneumonia	1/188 (0.5%)
Septic shock	1/188 (0.5%)
Urinary tract infection	1/188 (0.5%)
Metabolism and nutrition disorders
Gout	2/188 (1.1%)
Hyperglycaemia	1/188 (0.5%)
Hypoglycaemia	1/188 (0.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/188 (0.5%)
Osteoarthritis	1/188 (0.5%)
Pain in extremity	1/188 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer	1/188 (0.5%)
Nervous system disorders
Cerebral haemorrhage	1/188 (0.5%)
Transient ischaemic attack	1/188 (0.5%)
Psychiatric disorders
Mental status changes	2/188 (1.1%)
Renal and urinary disorders
Renal failure	1/188 (0.5%)
Renal failure acute	4/188 (2.1%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/188 (1.1%)
Pneumothorax spontaneous	1/188 (0.5%)
Skin and subcutaneous tissue disorders
Subcutaneous emphysema	1/188 (0.5%)
Vascular disorders
Hypertension	1/188 (0.5%)
Hypotension	1/188 (0.5%)
Other (Not Including Serious) Adverse Events
	Pegloticase
	Affected / at Risk (%)	# Events
Total	130/188 (69.1%)
Immune system disorders
Drug hypersensitivity	11/188 (5.9%)
Metabolism and nutrition disorders
Gout	126/188 (67%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Horizon requests that any investigator/institution that plans on presenting/publishing results provide written notification of their request 60 days prior to their presentation/publication. Horizon requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Horizon needs to secure patent or proprietary protection.