Open-Label Extension Study for Patients Who Completed a Phase 3 Double-blind Study of PEG-uricase for Symptomatic Gout - Study Results

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Gout
Intervention:	Biological: pegloticase

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects completing one of the randomized, controlled Phase 3 clinical trials (RCTs) of pegloticase [C0405 and C0406 (NCT00325195)] were invited to participate in this open-label extension study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants made the decision, along with the treating investigator, of which dose to receive in this study while remaining blinded to treatment received and results during the RCT. Cohort designations are based on participants' initial RCT treatment and whether uric acid remained <6 mg/dL for 80% of the time during months 3 and 6 in the RCT.

Reporting Groups

	Description
q2 RCT, Responder	Responder in Pegloticase every 2 wk arm of Randomized Controlled Trial (RCT), continued to receive pegloticase every 2 weeks (q2 wk) or every 4 weeks (q4 wk) in Open Label Extension (OLE) study
q4 RCT, Responder	Responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q2 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 2 weeks (q2 wk)in Open Label Extension (OLE) study
q2 RCT, Non-responder	Non-responder in Pegloticase every 2 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
q4 RCT Non-responder	Non-responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q4 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 4 weeks (q4 wk)in Open Label Extension (OLE) study

Participant Flow: Overall Study

	q2 RCT, Responder	q4 RCT, Responder	Placebo in RCT, q2 in OLE	q2 RCT, Non-responder	q4 RCT Non-responder	Placebo in RCT, q4 in OLE
STARTED	35	25 ^[1]	23	22	28	16
COMPLETED	24	17	11	8	8	2
NOT COMPLETED	11	8	12	14	20	14

[1]	2 other patients received no investigational drug in C0407 but elected to be followed in Observation

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
q2 RCT, Responder	Responder in Pegloticase every 2 wk arm of Randomized Controlled Trial (RCT), continued to receive pegloticase every 2 weeks (q2 wk) or every 4 weeks (q4 wk) in Open Label Extension (OLE) study
q4 RCT, Responder	Responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q2 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 2 weeks (q2 wk)in Open Label Extension (OLE) study
q2 RCT, Non-responder	Non-responder in Pegloticase every 2 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
q4 RCT Non-responder	Non-responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q4 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Total	Total of all reporting groups

Baseline Measures

	q2 RCT, Responder	q4 RCT, Responder	Placebo in RCT, q2 in OLE	q2 RCT, Non-responder	q4 RCT Non-responder	Placebo in RCT, q4 in OLE	Total
Number of Participants [units: participants]	35	25	23	22	28	16	149
Age [units: participants]
<=18 years	0	0	0	0	0	0	0
Between 18 and 65 years	20	17	18	16	23	11	105
>=65 years	15	8	5	6	5	5	44
Age [units: years] Mean ± Standard Deviation	62.4 ± 13.66	58.6 ± 13.59	56.6 ± 10.53	52.0 ± 13.12	53.5 ± 12.25	54.6 ± 13.62	56.8 ± 13.19
Gender [units: participants]
Female	10	7	4	4	4	3	32
Male	25	18	19	18	24	13	117
Region of Enrollment [units: participants]
United States	32	22	22	17	27	13	133
Canada	0	1	1	0	0	0	2
Mexico	3	2	0	5	1	3	14

Outcome Measures

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1. Primary:

Uric Acid (mg/dL) [ Time Frame: Week 13, Week 25, Week 53, Week 101 ]

Measure Type	Primary
Measure Title	Uric Acid (mg/dL)
Measure Description	Uric acid measured at 3 month-intervals
Time Frame	Week 13, Week 25, Week 53, Week 101
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT

Reporting Groups

	Description
q2 RCT, Responder	Responder in Pegloticase every 2 wk arm of Randomized Controlled Trial (RCT), continued to receive pegloticase every 2 weeks (q2 wk) or every 4 weeks (q4 wk) in Open Label Extension (OLE) study
q4 RCT, Responder	Responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q2 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 2 weeks (q2 wk)in Open Label Extension (OLE) study
q2 RCT, Non-responder	Non-responder in Pegloticase every 2 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
q4 RCT Non-responder	Non-responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q4 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 4 weeks (q4 wk)in Open Label Extension (OLE) study

Measured Values

	q2 RCT, Responder	q4 RCT, Responder	Placebo in RCT, q2 in OLE	q2 RCT, Non-responder	q4 RCT Non-responder	Placebo in RCT, q4 in OLE
Number of Participants Analyzed [units: participants]	31	24	18	17	22	10
Uric Acid (mg/dL) [units: mg/dL] Mean ± Standard Deviation
OLE Week 13	1.33 ± 3.103	1.91 ± 4.082	5.06 ± 4.538	9.76 ± 1.346	9.66 ± 2.529	8.08 ± 3.561
OLE Week 25	1.4 ± 3.196	1.95 ± 3.761	4.69 ± 4.454	8.89 ± 3.984	9.94 ± 2.646	8.09 ± 3.536
OLE Week 53	0.87 ± 2.327	1.55 ± 3.690	2.7 ± 4.255	9.18 ± 2.946	9.59 ± 2.782	6.45 ± 3.248
OLE Week 101	0.84 ± 2.619	1.47 ± 3.317	4.29 ± 3.985	7.7 ± 4.244	9.42 ± 1.961	8.5 ± NA ^[1]

[1]	One subject only

No statistical analysis provided for Uric Acid (mg/dL)

2. Secondary:

Tophus Response [ Time Frame: Up to 2 years ]

Measure Type	Secondary
Measure Title	Tophus Response
Measure Description	Target tophi evaluated during the randomized, controlled study were followed for response at 3, 6, 12, 18 and 24 months in this open-label extention study. Results from each participant's final assessment on drug are reported (as last observation carried forward). Complete response=complete disappearance of at least one tophus with no new or worsening tophus. Partial Response=a 50% or more decrease in at least one tophus with no new or worsening tophus.
Time Frame	Up to 2 years
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT, Last observation(on drug) carried forward showing patients with an Overall Tophus Response of Complete or Partial Response.

Reporting Groups

	Description
q2 RCT, Responder	Responder in Pegloticase every 2 wk arm of Randomized Controlled Trial (RCT), continued to receive pegloticase every 2 weeks (q2 wk) or every 4 weeks (q4 wk) in Open Label Extension (OLE) study
q4 RCT, Responder	Responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q2 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 2 weeks (q2 wk)in Open Label Extension (OLE) study
q2 RCT, Non-responder	Non-responder in Pegloticase every 2 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
q4 RCT Non-responder	Non-responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q4 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 4 weeks (q4 wk)in Open Label Extension (OLE) study

Measured Values

	q2 RCT, Responder	q4 RCT, Responder	Placebo in RCT, q2 in OLE	q2 RCT, Non-responder	q4 RCT Non-responder	Placebo in RCT, q4 in OLE
Number of Participants Analyzed [units: participants]	23	14	16	16	20	5
Tophus Response [units: participants]
Complete Response	19	13	10	4	7	3
Partial Response	4	0	3	4	2	1

No statistical analysis provided for Tophus Response

3. Secondary:

Patient Reported Outcome: SF-36 Physical Component Summary Score [ Time Frame: RCT Week 25; OLE Week 25; OLE Week 53, OLE Week 77, OLE Week 101 ]

Measure Type	Secondary
Measure Title	Patient Reported Outcome: SF-36 Physical Component Summary Score
Measure Description	SF-36 is the Medical Outcomes Survey Short Form-36, a 36-item self-reported questionnaire which assesses health-related limitations in 8 dimensions. The Physical Component Summary Score (PCS) is a composite summary score derived from the dimensions related to physical functioning outcomes: Physical Function, Role Physical, General Health and Bodily Pain (each with a 0 to 100 scale where 0=worst, 100=best). The Summary Score is constructed as a T-score with a mean of 50 and standard deviation of 10, where higher scores indicate a better health status.
Time Frame	RCT Week 25; OLE Week 25; OLE Week 53, OLE Week 77, OLE Week 101
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Number of participants was the subset of the ITT population with SF-36 baseline data

Reporting Groups

	Description
q2 RCT, Responder	Responder in Pegloticase every 2 wk arm of RCT, continued to received pegloticase (q2 wk or q4 wk) in OLE
q4 RCT Responder	REsponder in Pegloticase every 4 wk arm of RCT, contuned to received pegloticase (q2 wk or q4 wk) in OLE
Placebo in RCT, q2 in OLE	Placebo arm in RCT, initiated pegloticase treatment q2 wk in OLE
q2 RCT, Non-responder	Non-responder in pegloticase every 2 wk arm of RCT, continued to received pegloticase (q2 wk or q4 wk) in OLE
q4 RCT, Non-responder	Non-responder in Pegloticase every 4 wk arm of RCT, continued to received pegloticase (q2 wk or q4 wk) in OLE
Placebo in RCT, q4 in OLE	Placebo arm in RCT, initiated pegloticase treatment q4 wk in OLE

Measured Values

	q2 RCT, Responder	q4 RCT Responder	Placebo in RCT, q2 in OLE	q2 RCT, Non-responder	q4 RCT, Non-responder	Placebo in RCT, q4 in OLE
Number of Participants Analyzed [units: participants]	34	25	23	19	26	15
Patient Reported Outcome: SF-36 Physical Component Summary Score [units: units on a scale] Mean ± Standard Deviation
Baseline value (pre-pegloticase)	34.92 ± 10.988	34.11 ± 10.022	27.55 ± 11.405	33.71 ± 11.581	32.8 ± 10.129	36.2 ± 11.926
Final Visit value (LOCF)	40.40 ± 13.393	40.82 ± 7.482	30.34 ± 11.132	37.68 ± 10.298	34.76 ± 11.413	38.8 ± 13.155

No statistical analysis provided for Patient Reported Outcome: SF-36 Physical Component Summary Score

4. Secondary:

Gout Flare Frequency [ Time Frame: Up to 2 years ]

Measure Type	Secondary
Measure Title	Gout Flare Frequency
Measure Description	The the mean number of flares per subject (flare frequency)was assessed over 3-month periods for up to 2 years of treatment
Time Frame	Up to 2 years
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis is based on ITT population, and is presented by intervals of time on pegloticase

Reporting Groups

	Description
q2 RCT, Responder	Responder in Pegloticase every 2 wk arm of Randomized Controlled Trial (RCT), continued to receive pegloticase every 2 weeks (q2 wk) or every 4 weeks (q4 wk) in Open Label Extension (OLE) study
q4 RCT, Responder	Responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q2 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 2 weeks (q2 wk)in Open Label Extension (OLE) study
q2 RCT, Non-responder	Non-responder in Pegloticase every 2 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
q4 RCT Non-responder	Non-responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q4 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 4 weeks (q4 wk)in Open Label Extension (OLE) study

Measured Values

	q2 RCT, Responder	q4 RCT, Responder	Placebo in RCT, q2 in OLE	q2 RCT, Non-responder	q4 RCT Non-responder	Placebo in RCT, q4 in OLE
Number of Participants Analyzed [units: participants]	35	25	23	22	28	16
Gout Flare Frequency [units: Flares] Mean ± Standard Deviation
Months 1-3	0.4 ± 0.69	0.8 ± 0.90	2.3 ± 2.91	0.6 ± 0.90	1.3 ± 1.49	1.5 ± 1.41
Months 4-6	0.4 ± 0.96	0.7 ± 0.95	1.3 ± 2.17	1.0 ± 1.73	0.8 ± 0.94	0.8 ± 1.18
Months 7-9	0.0 ± 0.17	0.3 ± 0.54	1.2 ± 1.80	0.6 ± 1.20	0.6 ± 0.97	0.4 ± 1.01
Months 10-12	0.1 ± 0.30	0.2 ± 0.51	0.6 ± 1.18	0.9 ± 1.34	0.9 ± 1.46	0.4 ± 0.63
Months 16-18	0.1 ± 0.25	.3 ± 0.44	0.2 ± 0.40	0.7 ± 1.18	0.6 ± 0.85	0.4 ± 0.89
Months 22-24	0.1 ± 0.37	0.1 ± 0.23	0.4 ± 0.67	0.3 ± 0.65	0.6 ± 0.53	0.7 ± 1.15

No statistical analysis provided for Gout Flare Frequency

5. Secondary:

Gout Flare Incidence [ Time Frame: Assessed in 3-month intervals up to 2 years ]

Measure Type	Secondary
Measure Title	Gout Flare Incidence
Measure Description	Percentage of participants remaining in the study during the specified interval who experienced a gout flare during this interval.
Time Frame	Assessed in 3-month intervals up to 2 years
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The flare incidence is reported as the percentage of participants reporting flares during each 3-month interval.

Reporting Groups

	Description
q2 RCT, Responder	Responder in Pegloticase every 2 wk arm of Randomized Controlled Trial (RCT), continued to receive pegloticase every 2 weeks (q2 wk) or every 4 weeks (q4 wk) in Open Label Extension (OLE) study
q4 RCT, Responder	Responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q2 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 2 weeks (q2 wk)in Open Label Extension (OLE) study
q2 RCT, Non-responder	Non-responder in Pegloticase every 2 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
q4 RCT Non-responder	Non-responder in Pegloticase every 4 wk arm of Randomized Controlled Trial, continued to receive pegloticase every 2 weeks (q2 wk)or every 4 weeks (q4 wk)in Open Label Extension (OLE) study
Placebo in RCT, q4 in OLE	Placebo arm in Randomized Controlled Trial (RCT), initiated pegloticase treatment every 4 weeks (q4 wk)in Open Label Extension (OLE) study

Measured Values

	q2 RCT, Responder	q4 RCT, Responder	Placebo in RCT, q2 in OLE	q2 RCT, Non-responder	q4 RCT Non-responder	Placebo in RCT, q4 in OLE
Number of Participants Analyzed [units: participants]	35	25	23	22	28	16
Gout Flare Incidence [units: Percentage of participants]
Months 1-3	25.7	56.0	65.2	45.5	67.9	68.8
Months 4-6	23.5	40.0	45.0	35.0	50.0	38.5
Months 7-9	3.0	24.0	43.8	27.8	42.9	22.2
Months 10-12	9.4	16.7	28.6	47.1	45.0	28.6
Months 16-18	6.5	25.0	18.2	33.3	38.9	20.0
Months 22-24	3.4	5.3	27.3	25.0	55.6	33.3

No statistical analysis provided for Gout Flare Incidence

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Savient Pharmaceuticals, Inc.
phone: 732-418-9300

No publications provided

Responsible Party:	Savient Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01356498 History of Changes
Other Study ID Numbers:	C0407
Study First Received:	October 27, 2008
Results First Received:	August 5, 2011
Last Updated:	October 28, 2011
Health Authority:	United States: Food and Drug Administration