A Phase 4, Open-Label, Multicenter, Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Trial of Intravenous KRYSTEXXA® (Pegloticase) Administered Every 4 Weeks With Co-Administration of Weekly Doses of Methotrexate in Patients With Uncontrolled Refractory Gout (FORWARD Open-Label [OL] Trial)
Overview
- Phase
- Phase 4
- Intervention
- Pegloticase
- Conditions
- Uncontrolled Gout
- Sponsor
- Amgen
- Enrollment
- 50
- Locations
- 12
- Primary Endpoint
- Proportion of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
This trial is to assess efficacy, safety, blood levels and bodily effects of up to 2 dose levels of intravenous (IV) pegloticase (KRYSTEXXA) infusions at every 4 week intervals (Q4 Weeks) for up to 6 months (Day 1 to 24 weeks with an optional 24 - 48 weeks treatment duration) when given in combination with weekly oral doses of methotrexate (MTX). The goal is to identify an appropriate dose to be administered every 4 weeks to be used for future clinical trials for patients with chronic gout that does not adequately respond to conventional therapy.
Detailed Description
The primary objective is to choose a dose for further investigation by assessing the effect of up to 2 dose levels of pegloticase administered IV Q4 weeks, co-administered with weekly doses of oral MTX, as measured by the sustained normalization of serum uric acid (sUA) to \< 6 mg/dL for at least 80% of the time during Month 6 and the duration of sUA to \< 6 mg/dL over 24 week treatment period in adult participants with chronic gout refractory to conventional therapy. Acquired from Horizon in 2024.
Investigators
Eligibility Criteria
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 trial.
- •Adult men or women ≥18 and \<80 years of age.
- •Uncontrolled gout, defined as meeting 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 one tophus
- •Recurrent flares defined as 2 or more flares in the past 12 months prior to screening
- •Presence of chronic gouty arthritis as evidenced by either clinical signs consistent with chronic synovitis on clinical examination or the presence of typical gouty erosion(s) on hand and/or foot X-rays
Exclusion Criteria
- •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 Day 1 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, or mycophenolate mofetil; prednisone ≥10 mg/day or equivalent dose of other corticosteroid on a chronic basis (3 months or longer) would also meet exclusion criteria.
- •History of any transplant surgery requiring maintenance immunosuppressive therapy.
- •Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity.
- •Known history of hepatitis C virus RNA positivity, unless treated and viral load is negative.
- •Known history of Human Immunodeficiency Virus (HIV) positivity.
- •Glucose-6-phosphate dehydrogenase deficiency (tested at the Screening Visit centrally or locally).
- •Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) \<40 mL/min/1.73 m\^2 or currently on dialysis.
Arms & Interventions
Pegloticase 16mg cohort
16 mg IV dose of pegloticase q4 weeks with 15 mg methotrexate (MTX) weekly
Intervention: Pegloticase
Pegloticase 16mg cohort
16 mg IV dose of pegloticase q4 weeks with 15 mg methotrexate (MTX) weekly
Intervention: Methotrexate (MTX)
Pegloticase 24/32mg cohort
24 to 32 mg IV dose of pegloticase q4 weeks with 15 mg MTX weekly
Intervention: Pegloticase
Pegloticase 24/32mg cohort
24 to 32 mg IV dose of pegloticase q4 weeks with 15 mg MTX weekly
Intervention: Methotrexate (MTX)
Outcomes
Primary Outcomes
Proportion of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6
Time Frame: Month 6 (Weeks 20, 21, 22, 23, and 24)
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 1 Visit) were counted as non-responders.
Time to first sUA ≥6 mg/dL after first achieving sUA <6 mg/dL, from the first pegloticase infusion until Week 24
Time Frame: Day 1 to Week 24
Secondary Outcomes
- Proportion of the subjects sustained sUA< 6 mg/dL from Day 1 to Week 24 and Day 1 to Week 48(Day 1 to Week 24 and Day 1 to Week 48)
- Proportion of subjects with pre-infusion sUA <6 mg/dL at each scheduled visit(Baseline to Week 48)
- Area under the sUA concentration vs time curve from Day 1 to Week 24 and Day 1 to Week 48(Day 1 to Week 24 and Day 1 to Week 48)
- Proportion of subjects with anti-uricase antibodies and the proportion of subjects with anti-poly (ethylene glycol) antibodies and their titers at each scheduled visit(Baseline to Week 48)
- Pharmacokinetic parameters (e.g., AUC and, Cmax)(Baseline to Week 48)