Study of Pegloticase in Participants With Uncontrolled Gout Who Have Had a Kidney Transplant

• Sponsor: Horizon Therapeutics Ireland DAC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04087720
• Collaborator: (none)
• Enrollment: 20
• Locations: 8
• Arm: 1
• Actual Duration (Months): 24
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the effect of pegloticase on the response rate of sustained serum uric acid (sUA) reduction to sUA < 6 mg/dL during Month 6 of treatment.

Condition or Disease	Intervention/Treatment	Phase
Uncontrolled Gout; Kidney Transplant	Biological: Pegloticase	Phase 4

Detailed Description

The study design includes: 1) a Screening Period, lasting up to 35 days; 2) a 24-week treatment period which includes an End-of-Study (Week 24) /Early Termination Visit; 3) a safety follow-up phone/email Visit 30 days after the last infusion; and 4) a 3 month post-treatment follow up visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label, Efficacy and Safety Study of Pegloticase in Patients With Uncontrolled Gout Who Have Undergone Kidney Transplantation
• Actual Study Start Date: Sep 9, 2019
• Actual Primary Completion Date: Jul 6, 2021
• Actual Study Completion Date: Sep 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pegloticase Participants receive 8 mg pegloticase every 2 weeks from Day 1 through Week 22	Biological: Pegloticase; intravenous (IV) infusion

Outcome Measures

Primary Outcome Measures

1. Percentage of Serum Uric Acid (sUA) < 6 mg/dL Responders During Month 6 [Month 6 (Weeks 20, 21, 22, 23, 24)]

   sUA < 6 mg/dL responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 6, which includes pre-infusion and post-infusion results at Week 20, results at Week 21, pre-infusion and post-infusion results at Week 22, results at Week 23, results at Week 24, and unscheduled assessments of sUA collected between Week 20 and Week 24. Two-sided Exact Clopper-Pearson confidence interval is used for the calculation of the 95% confidence interval.

Secondary Outcome Measures

1. Percentage of sUA < 5 mg/dL Responders During Month 6 [Month 6 (Weeks 20, 21, 22, 23, and 24)]

   sUA < 5 mg/dL responders are defined as participants achieving and maintaining sUA <5 mg/dL for at least 80% of the time during Month 6, which includes pre-infusion and post-infusion results at Week 20, results at Week 21, pre-infusion and post-infusion results at Week 22, results at Week 23, results at Week 24, and unscheduled assessments of sUA collected between Week 20 and Week 24. Two-sided Exact Clopper-Pearson confidence interval is used for the calculation of the 95% confidence interval.

2. Change From Baseline in Health Assessment Questionnaire (HAQ) Pain Visual Analog Scale (VAS) Score Through Week 24 [Baseline, Weeks 6, 14, 20, 24]

   The HAQ-Pain score consists of a doubly anchored, horizontal VAS 15 cm in length, and rates a participant's pain over the past week from 0 to 100 with 0 = no pain and 100 = severe pain. Baseline is defined as the last measurement taken prior to the first infusion of pegloticase. The 95% confidence interval is a two-sided normal theory-based 95% confidence interval.

3. Change From Baseline in Heath Assessment Questionnaire - Disability Index (HAQ-DI) Score Through Week 24 [Baseline, Weeks 6, 14, 20, 24]

   The HAQ-DI is a self-reported assessment of how a participant's illness affects their ability to function in their daily life over the past week. The HAQ-DI for a participant is calculated as the mean of the following 8 category scores: Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities. The HAQ-DI ranges from 0 to 3 with higher values indicating higher disability. Baseline is defined as the last measurement taken prior to the first infusion of pegloticase. The 95% confidence interval is a two-sided normal theory-based 95% confidence interval.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Willing and able to give informed consent;

• Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study;

• Adult men or women ≥ 18 years of age;

• Is a recipient of a de novo kidney from a living or deceased donor and is >1 year post transplant prior to screening;

• Is on a stable standard of care immunosuppression therapy for at least 3 months prior to screening;

• Kidney allograft is functional at entry, based on an estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73m²;

• Women of childbearing potential have a negative screening serum pregnancy test and will be required to use a medically approved form of birth control during their participation in the study;

• Uncontrolled gout, defined as:

1. Hyperuricemia during screening as documented by sUA ≥ 7 mg/dL during Screening and prior to entry into the Treatment Period (Note: the sUA may be repeated up to 3 times during the Screening Period to confirm eligibility), and

2. Inability to maintain sUA <6 mg/dL on other urate-lowering therapy or intolerable side effects or contraindicated with conventional urate-lowering therapy, and

3. At least 1 of the following:

1. Evidence of tophaceous deposits; ii. Recurrent gout flares defined as 2 or more flares in the 12 months prior to Screening; iii. Presence of chronic gouty arthritis;

• Able to tolerate low-dose prednisone (< 10 mg/day) as part of the required standard gout flare prophylaxis regimen for ≥ 1 week before the first infusion.

Exclusion Criteria:

• Any other organ transplant beside kidney;

• Any severe infection, unless treated and completely resolved at least 2 weeks prior to Day 1;

• Chronic or active hepatitis B virus infection;

• Known history of hepatitis C virus ribonucleic acid (RNA) positivity unless treated and viral load is negative;

• Known history of human immunodeficiency virus (HIV) positivity;

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at the Screening Visit);

• Decompensated congestive heart failure or hospitalization for congestive heart failure within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina), or uncontrolled blood pressure (> 160/100 mm Hg) at the end of the Screening Period (Day 1 prior to infusion);

• Pregnant, planning to become pregnant, breastfeeding, planning to impregnate female partner, or not using an effective form of birth control, as determined by the Investigator;

• Prior treatment with pegloticase, another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug;

• Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product;

• Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to Day 1, or plans to take an investigational drug during the study;

• Currently receiving systemic or radiologic treatment for ongoing cancer;

• History of malignancy within 5 years other than non-melanoma skin cancer, in situ carcinoma of cervix, early stage renal cell cancer or early stage prostate cancer that has been completely resected > 2 years prior to screening;

• Uncontrolled hyperglycemia with a plasma glucose value > 240 mg/dL at Screening that is not subsequently controlled by the end of the Screening Period;

• Diagnosis of osteomyelitis;

• Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome;

• Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the study;

• Currently receiving allopurinol, febuxostat or other urate lowering medications and unable to discontinue medication 7 days prior to Day 1; or

• Currently receiving probenecid and unable to discontinue medication within 3 days, prior to Day 1.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham	Birmingham	Alabama	United States	35294
2	Nephrology Consultants	Huntsville	Alabama	United States	35805
3	Keck School of Medicine of USC	Los Angeles	California	United States	90033
4	Amicis Research Center	Northridge	California	United States	91324
5	Genesis Clinical Research	Tampa	Florida	United States	33614
6	Coastal Medical Research	Brunswick	Georgia	United States	31520
7	Duke University Medical Center	Durham	North Carolina	United States	27705
8	Clear Lake Specialties	Webster	Texas	United States	77598

Sponsors and Collaborators

• Horizon Therapeutics Ireland DAC

Investigators

• Study Director: Colleen Canavan, BS, Horizon Therapeutics Ireland DAC

Study Documents (Full-Text)

• Study Protocol - Jun 22, 2020
• Statistical Analysis Plan - Aug 26, 2020

More Information

Publications

None provided.

• Responsible Party: Horizon Therapeutics Ireland DAC
• ClinicalTrials.gov Identifier: NCT04087720
• Other Study ID Numbers: HZNP-KRY-406
• First Posted: Sep 12, 2019
• Last Update Posted: Jul 26, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Gout

Study Results

Participant Flow

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received 8 mg pegloticase by intravenous (IV) infusion every 2 weeks from Day 1 through Week 22
Period Title: Overall Study
STARTED	20
COMPLETED	15
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received 8 mg pegloticase by IV infusion every 2 weeks from Day 1 through Week 22
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.9 (10.87)
Sex: Female, Male (Count of Participants)
Female	3 15%
Male	17 85%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 15%
Not Hispanic or Latino	17 85%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 10%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 35%
White	9 45%
More than one race	2 10%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Serum Uric Acid (sUA) < 6 mg/dL Responders During Month 6
Description	sUA < 6 mg/dL responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 6, which includes pre-infusion and post-infusion results at Week 20, results at Week 21, pre-infusion and post-infusion results at Week 22, results at Week 23, results at Week 24, and unscheduled assessments of sUA collected between Week 20 and Week 24. Two-sided Exact Clopper-Pearson confidence interval is used for the calculation of the 95% confidence interval.
Time Frame	Month 6 (Weeks 20, 21, 22, 23, 24)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: participants who received at least 1 dose of pegloticase. Participants in the ITT population with no lapse or cessation in treatment due to COVID-19 prior to the analysis time-point.

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received 8 mg pegloticase by IV infusion every 2 weeks from Day 1 through Week 22
Measure Participants	18
Number (95% Confidence Interval) [percentage of participants]	88.9 444.5%

2. Secondary Outcome

Title	Percentage of sUA < 5 mg/dL Responders During Month 6
Description	sUA < 5 mg/dL responders are defined as participants achieving and maintaining sUA <5 mg/dL for at least 80% of the time during Month 6, which includes pre-infusion and post-infusion results at Week 20, results at Week 21, pre-infusion and post-infusion results at Week 22, results at Week 23, results at Week 24, and unscheduled assessments of sUA collected between Week 20 and Week 24. Two-sided Exact Clopper-Pearson confidence interval is used for the calculation of the 95% confidence interval.
Time Frame	Month 6 (Weeks 20, 21, 22, 23, and 24)

Outcome Measure Data

Analysis Population Description

ITT population: participants who received at least 1 dose of pegloticase. Participants in the ITT population with no lapse or cessation in treatment due to COVID-19 prior to the analysis time-point.

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received 8 mg pegloticase by IV infusion every 2 weeks from Day 1 through Week 22
Measure Participants	18
Number (95% Confidence Interval) [percentage of participants]	88.9 444.5%

3. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire (HAQ) Pain Visual Analog Scale (VAS) Score Through Week 24
Description	The HAQ-Pain score consists of a doubly anchored, horizontal VAS 15 cm in length, and rates a participant's pain over the past week from 0 to 100 with 0 = no pain and 100 = severe pain. Baseline is defined as the last measurement taken prior to the first infusion of pegloticase. The 95% confidence interval is a two-sided normal theory-based 95% confidence interval.
Time Frame	Baseline, Weeks 6, 14, 20, 24

Outcome Measure Data

Analysis Population Description

ITT population: participants who received at least 1 dose of pegloticase. Participants with an assessment at given time point.

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received 8 mg pegloticase by IV infusion every 2 weeks from Day 1 through Week 22
Measure Participants	20
Change at Week 6	-16.11 (29.230)
Change at Week 14	-34.81 (24.025)
Change at Week 20	-34.63 (27.543)
Change at Week 24	-33.05 (31.590)

4. Secondary Outcome

Title	Change From Baseline in Heath Assessment Questionnaire - Disability Index (HAQ-DI) Score Through Week 24
Description	The HAQ-DI is a self-reported assessment of how a participant's illness affects their ability to function in their daily life over the past week. The HAQ-DI for a participant is calculated as the mean of the following 8 category scores: Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities. The HAQ-DI ranges from 0 to 3 with higher values indicating higher disability. Baseline is defined as the last measurement taken prior to the first infusion of pegloticase. The 95% confidence interval is a two-sided normal theory-based 95% confidence interval.
Time Frame	Baseline, Weeks 6, 14, 20, 24

Outcome Measure Data

Analysis Population Description

ITT population: participants who received at least 1 dose of pegloticase. Participants with an assessment at given time point.

Arm/Group Title	Pegloticase
Arm/Group Description	Participants received 8 mg pegloticase by IV infusion every 2 weeks from Day 1 through Week 22
Measure Participants	20
Change at Week 6	-0.30 (0.522)
Change at Week 14	-0.52 (0.616)
Change at Week 20	-0.38 (0.523)
Change at Week 24	-0.25 (0.611)

Adverse Events

Time Frame	From the date of first dose of treatment through 30 days after the last dose of treatment (up to Week 22 plus 30 days).
Arm/Group Title	Pegloticase
Arm/Group Description	Participants received 8 mg pegloticase by IV infusion every 2 weeks from Day 1 through Week 22
All Cause Mortality
	Pegloticase
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Serious Adverse Events
	Pegloticase
	Affected / at Risk (%)	# Events
Total	5/20 (25%)
Cardiac disorders
Atrial fibrillation	1/20 (5%)
Gastrointestinal disorders
Duodenal ulcer	1/20 (5%)
Enterocolonic fistula	1/20 (5%)
Infections and infestations
Cellulitis	1/20 (5%)
Diverticulitis	1/20 (5%)
Localised infection	1/20 (5%)
Injury, poisoning and procedural complications
Post procedural haemorrhage	1/20 (5%)
Other (Not Including Serious) Adverse Events
	Pegloticase
	Affected / at Risk (%)	# Events
Total	16/20 (80%)
Cardiac disorders
Tachycardia	1/20 (5%)
Ear and labyrinth disorders
Inner ear disorder	1/20 (5%)
Tinnitus	1/20 (5%)
Vertigo	1/20 (5%)
Eye disorders
Conjunctival haemorrhage	2/20 (10%)
Ocular hyperaemia	1/20 (5%)
Photophobia	1/20 (5%)
Gastrointestinal disorders
Abdominal hernia	1/20 (5%)
Haemorrhoids	1/20 (5%)
Melaena	1/20 (5%)
Stomatitis	1/20 (5%)
General disorders
Asthenia	1/20 (5%)
Oedema	1/20 (5%)
Pyrexia	2/20 (10%)
Infections and infestations
Cellulitis	1/20 (5%)
Pneumonia	1/20 (5%)
Skin bacterial infection	1/20 (5%)
Subcutaneous abscess	1/20 (5%)
Injury, poisoning and procedural complications
Eye injury	1/20 (5%)
Post procedural haemorrhage	1/20 (5%)
Wound	1/20 (5%)
Investigations
Alanine aminotransferase increased	1/20 (5%)
Aspartate aminotransferase increased	1/20 (5%)
Blood calcium decreased	1/20 (5%)
Haemoglobin decreased	1/20 (5%)
Metabolism and nutrition disorders
Gout	9/20 (45%)
Hyperglycaemia	1/20 (5%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/20 (10%)
Gouty tophus	1/20 (5%)
Muscle spasms	1/20 (5%)
Osteonecrosis	1/20 (5%)
Nervous system disorders
Headache	1/20 (5%)
Hypoaesthesia	1/20 (5%)
Presyncope	1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	2/20 (10%)
Oropharyngeal pain	1/20 (5%)
Skin and subcutaneous tissue disorders
Blister	1/20 (5%)

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.