Pegloticase and Methotrexate Co-administered in Participants With Uncontrolled Gout Who Previously Failed Pegloticase Monotherapy

NCT04772313 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HZNP-KRY-407
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 15

Brief Summary

This is a Phase 4, multicenter, open-label trial of pegloticase with methotrexate (MTX) in adult participants with uncontrolled gout who were previously treated with pegloticase without a concomitant immunomodulator and stopped pegloticase due to failure to maintain serum uric acid (sUA) response and/or a clinically mild infusion reaction (IR). Approximately 30 participants will be enrolled. Pegloticase + MTX will be administered for approximately 24 weeks, with an optional extension up to 48 weeks. The trial design will include 5 distinct components:

1. 1.Screening Period, lasting up to 42 days;
2. 2.6-week MTX Tolerability Assessment Period (hereafter referred to as the MTX Run-in Period);
3. 3.24-week Pegloticase + MTX Treatment Period, which will include a Week 24/End of Trial/Early Termination Visit (subjects that end MTX and pegloticase treatment prior to the Week 24 will remain on trial for follow up until the Week 24 visit)
4. 4.Optional Pegloticase + MTX Extension Period up to 24 weeks
5. 5.30-Day Post Treatment Follow -up

Conditions

Uncontrolled Gout

Keywords

Gout

Outcome Measures

Primary Outcomes (1)

• Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6

  An sUA responder is defined as a participant achieving and maintaining sUA \<6 mg/dL for at least 80% of the time during Month 6 (Weeks 20, 21, 22, 23 and 24).

  Month 6

Secondary Outcomes (6)

• Percentage of sUA Responders (sUA < 6 mg/dL) During Month 3

  Month 3

• Percentage of Participants Who Experienced Any of the Following Events From Day 1 to Week 24: Infusion Reaction (IR) Leading to Discontinuation of Treatment, Anaphylaxis or Meeting Individual Participant sUA Discontinuation Criteria

  Day1 to Week 24

• Mean Change From Baseline in Urate Deposition Volume Measured by Dual Energy Computed Tomography (DECT) to Week 24

  Baseline to Week 24

• Mean Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Weeks 14 and 24

  Baseline, Week 14, Week 24

• Mean Change From Baseline in Health Assessment Questionnaire (HAQ) Pain Score at Weeks 14 and 24

  Baseline, Week 14, Week 24

Study Arms (1)

Pegloticase plus Methotrexate (MTX)

EXPERIMENTAL

Pegloticase (8 mg) intravenous (IV) every two weeks. Methotrexate (15 or 25 mg weekly) SC.

Biological: Pegloticase; Drug: Methotrexate (MTX)

Interventions

Pegloticase BIOLOGICAL

Participants will receive pegloticase with MTX for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.

Pegloticase plus Methotrexate (MTX)

Methotrexate (MTX) DRUG

Participants will receive MTX during the run-in period then pegloticase with MTX for up to 24 weeks during the treatment period. Participants may opt to receive pegloticase with MTX for an additional 24 weeks.

Pegloticase plus Methotrexate (MTX)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give informed consent.
• Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
• Adult men or women ≥18 years of age.
• Uncontrolled gout, defined by the following criteria:
• Hyperuricemia during the Screening Period, defined as sUA ≥6 mg/dL, and;
• Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose or with a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview, and;
• Symptoms of gout, including at least 1 of the following:
• Presence of at least 1 tophus
• Recurrent flares, defined as 2 or more flares in the 12 months prior to Screening
• Presence of chronic gouty arthritis
• Subject was previously treated with pegloticase without concomitant immunomodulation and stopped pegloticase due to failure to maintain sUA reduction response (had ≥1 sUA \>6 mg/dL within 2 weeks post pegloticase infusion) and did not experience an IR (Cohort 1) and/or stopped pegloticase treatment due to pegloticase-related clinically mild IR (Cohort 2).
• Subject for whom the last pegloticase infusion occurred \>6 months prior to Screening.
• Willing to discontinue any oral urate-lowering therapy for at least 7 days prior to Day 1 and remain off other urate-lowering therapy during the Pegloticase + MTX Treatment Period.
• Women of childbearing potential (including those with an onset of menopause \<2 years prior to Screening, non-therapy-induced amenorrhea for \<12 months prior to Screening or not surgically sterile \[absence of ovaries and/or uterus\]) must have negative serum pregnancy tests during Screening:
• Subjects must agree to use 2 reliable forms of contraception during the trial, 1 of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started ≥1 full cycle prior to Week -6 (start of MTX) and continue for 30 days after the last dose of pegloticase, or at least 1 ovulatory cycle after the last dose of MTX (whichever is the longer duration after the last dose of pegloticase). Highly effective contraceptive methods (with a failure rate \<1% per year), when used consistently and correctly, include implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner.

You may not qualify if:

• Known history of medically confirmed prior anaphylactic reaction.
• Known history of moderate or severe IR (including but not limited to difficulty in breathing, hypotension, generalized urticaria, generalized erythema, angioedema and/or required treatment with IV steroids or epinephrine; or other serious adverse events (SAEs) related to pegloticase or any other pegylated product treatment.
• Weight \>160 kg (352 pounds) at Screening.
• Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week 6 Visit.
• Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
• Current or chronic treatment with systemic immunosuppressive agents, such as MTX, azathioprine, cyclosporine, leflunomide, cyclophosphamide or mycophenolate mofetil.
• Current treatment with prednisone \>10 mg/day or equivalent dose of another corticosteroid on a chronic basis (defined as 3 months or longer).
• Known history of any solid organ transplant surgery requiring maintenance immunosuppressive therapy.
• Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity, unless treated, viral load is negative and no chronic or active infection confirmed by hepatitis B virus serology.
• Known history of hepatitis C virus RNA positivity, unless treated and viral load is negative.
• Known history of human immunodeficiency virus positivity.
• glucose-6-phosphate dehydrogenase (G6PD) deficiency (tested at the Screening Visit).
• Severe chronic renal impairment (eGFR \<30 mL/min/1.73 m\^2) at the Screening Visit based on 4 variable Modification of Diet in Renal Disease \[MDRD\] formula or currently on dialysis.
• Non-compensated congestive heart failure, hospitalization for congestive heart failure or treatment for acute coronary syndrome (myocardial infarction or unstable angina) within 3 months of the Screening Visit, current uncontrolled arrhythmia or current uncontrolled blood pressure (\>160/100 mm Hg) prior to Week -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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (15)

University of Alabama at Birmingham (UAB) - Center for Education & Research on Therapeutics of Musculoskeletal Disorders

Birmingham, Alabama, 35294-0002, United States

Location

Arizona Arthritis and Rheumatology Associates

Flagstaff, Arizona, 86001, United States

Location

Arizona Arthritis and Rheumatology Associates

Glendale, Arizona, 85306, United States

Location

Arizona Arthritis and Rheumatology Associates

Mesa, Arizona, 85210, United States

Location

East Bay Rheumatology Medical Group

San Leandro, California, 94578, United States

Location

Providence St. John's Health Clinic

Santa Monica, California, 90404, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045-2536, United States

Location

Life Clinical Trials

Margate, Florida, 33063, United States

Location

IRIS Research and Development, LLC

Plantation, Florida, 33324, United States

Location

Napa Research

Pompano Beach, Florida, 33046, United States

Location

GCP Clinical Research, LLC

Tampa, Florida, 33609, United States

Location

The Center for Rheumatology and Bone Research

Wheaton, Maryland, 20902, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Biopharma Informatic, LLC

Houston, Texas, 77043, United States

Location

Western Washington Arthritis Clinic

Bothell, Washington, 98021, United States

Location

MeSH Terms

Conditions

Gout

Interventions

Pegloticase; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Supra Verma, MD
• Organization: Horizon Therapeutics USA, Inc.

clinicaltrials@horizontherapeutics.com

866-479-6742

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: February 26, 2021
• Study Start: March 8, 2021
• Primary Completion: August 23, 2022
• Study Completion: April 24, 2023
• Last Updated: June 27, 2024
• Results First Posted: October 10, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (15)