Infusion Duration Study To Assess Tolerability of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate

Gout Clinical Trial

Official title:

A Phase 4, Multicenter, Open-Label, Infusion Duration Study To Assess Safety, Tolerability and Efficacy of Pegloticase Administered With a Shorter Infusion Duration in Subjects With Uncontrolled Gout Receiving Methotrexate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04511702
• Other study ID #: HZNP-KRY-403
• Status: Completed
• Phase: Phase 4
• Start date: October 2, 2020
• Est. completion date: March 25, 2024

Study information

• Verified date: May 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety, tolerability and efficiency of pegloticase administered with a shorter infusion duration in participants with uncontrolled gout receiving methotrexate.

Description:

Approximately 180 participants will be enrolled. After a 4-week methotrexate run-in period, participants will be treated for up to 24 weeks with weekly oral methotrexate and biweekly 8mg pegloticase infusions. Up to three pegloticase infusion durations will be assessed in the study: 60-minute infusion, 45-minute infusion and 30-minute infusion. Safety evaluations will be performed regularly throughout the course of the study. Acquired from Horizon in 2024.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 191
• Est. completion date: March 25, 2024
• Est. primary completion date: January 18, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult men or women =18 years of age.

2. Uncontrolled gout, defined as meeting the following criteria:

• Hyperuricemia during the screening period defined as sUA =6 mg/dL
• Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with intolerable side effects or a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview.
• Symptoms of gout including at least 1 of the following:
• Presence of at least one tophus
• Recurrent flares defined as 2 or more flares in the past 12 months prior to screening
• Presence of chronic gouty arthritis

3. Willing to discontinue all oral urate-lowering therapy at least 7 days prior to MTX dosing at Week -4 and remain off of urate lowering therapy when receiving pegloticase infusions during the study.

Exclusion Criteria:

1. Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.

2. Current or chronic treatment with systemic immunosuppressive agents such as MTX, azathioprine, or mycophenolate mofetil; prednisone =10 mg/day or equivalent dose of other corticosteroid on a chronic basis (defined as 3 months or longer) would also meet exclusion criteria.

3. Glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at Screening Visit).

4. Severe chronic renal impairment (estimated glomerular filtration rate <40 mL/min/1.73 m2) at the Screening Visit based on 4 variable-Modification of Diet in Renal Disease [MDRD] formula or currently on dialysis.

5. Non-compensated congestive heart failure or hospitalization for congestive heart failure or treatment for acute coronary syndrome (myocardial infarction or unstable angina) within 3 months of the Screening Visit, or current uncontrolled arrhythmia, or current uncontrolled blood pressure (BP) (>160/100 mmHg) prior to Week -4.

6. Pregnant, planning to become pregnant, breastfeeding, planning to impregnate female partner, or not on an effective form of birth control, as determined by the Investigator.

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

8. Currently receiving systemic or radiologic treatment for ongoing cancer.

9. History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.

Related Conditions & MeSH terms

• Chronic Uncontrolled Gout
• Gout
• Uncontrolled Gout

Intervention

Biological:
• Pegloticase with MTX
Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period

Locations

Country	Name	City	State
United States	Orthopedic Physicians Alaska	Anchorage	Alaska
United States	University of Colorado Division of Rheumatology	Aurora	Colorado
United States	Long Island Arthritis & Osteoporosis Care	Babylon	New York
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Western Washington Medical Group	Bothell	Washington
United States	Bradenton Research Center	Bradenton	Florida
United States	Chattanooga Research & Medicine PLLC (CHARM)	Chattanooga	Tennessee
United States	Velocity Clinical Research Cincinnati	Cincinnati	Ohio
United States	Medvin Clinical Research	Covina	California
United States	Denver Arthritis Clinic	Denver	Colorado
United States	Research Carolina Elite	Denver	North Carolina
United States	Prohealth Research Center	Doral	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Arizona Arthritis & Rheumatology Research	Gilbert	Arizona
United States	PMG Research of Hickory, LLC	Hickory	North Carolina
United States	Abigail Rebecca Neiman, MD, PA	Houston	Texas
United States	Pioneer Research Solutions Inc - Houston	Houston	Texas
United States	Cape Fear Arthritis Care	Leland	North Carolina
United States	LIFE Clinical Trials	Margate	Florida
United States	Arthritis & Rheumatology Research	Mesa	Arizona
United States	MedPharmics, LLC	Metairie	Louisiana
United States	D&H National Research Centers	Miami	Florida
United States	Amicis Research Center	Northridge	California
United States	MD Medical Research	Oxon Hill	Maryland
United States	Arizona Arthritis & Rheumatology Research	Phoenix	Arizona
United States	IRIS Research and Development, LLC	Plantation	Florida
United States	Napa Research Center	Pompano Beach	Florida
United States	PMG Research of Salisbury, LLC	Salisbury	North Carolina
United States	Santa Fe Rheumatology	Santa Fe	New Mexico
United States	Providence Saint John's Health Center	Santa Monica	California
United States	Shelby Clinical Research, LLC	Shelby	North Carolina
United States	Arthritis Northwest	Spokane	Washington
United States	D&H Tamarac Research Centers	Tamarac	Florida
United States	ClinPro Research Solutions	Tampa	Florida
United States	ForCare Clinical Research	Tampa	Florida
United States	GCP Clinical Research	Tampa	Florida
United States	Medvin Clinical Research	Thousand Oaks	California
United States	Medvin Clinical Research	Tujunga	California
United States	Velocity Clinical Research, Salt Lake City	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of participants experiencing Infusion Reactions (IRs), including anaphylaxis related to pegloticase		Day 1 through Week 24.
Secondary	Proportion of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6	Responders are defined as participants achieving and maintaining sUA < 6 mg/dL for at least 80% of the time during Month 6. Participants meeting the sUA discontinuation criteria (pre-infusion sUA >6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit) were counted as non-responders.	Month 6 (Weeks 20, 22, 24)
Secondary	The proportion of participants who experienced any of the following events: IR leading to discontinuation of treatment, anaphylaxis, or meeting Individual participant sUA Discontinuation Criteria.	A participant meets the Individual participant sUA Discontinuation Criteria if he or she has a pre-infusion sUA level >6 mg/dL at 2 consecutive study visits beginning with the Week 2 Visit. When this occurs, the participants must discontinue treatment, and continues on the study.	Day 1 to Week 24
Secondary	Time to any of the following events: IR leading to discontinuation of treatment, anaphylaxis, or meeting individual participant sUA Discontinuation Criteria (two consecutive pre-infusion sUAs > 6mg/dL).	A participant meets the Individual participant sUA Discontinuation Criteria if he or she has a pre-infusion sUA level >6 mg/dL at 2 consecutive study visits beginning with the Week 2 Visit. When this occurs, the participants must discontinue treatment, and continues on the study.	Day 1 to Week 24