Horizon Therapeutics has enrolled the first patient in a clinical trial of Krystexxa (pegloticase injection) plus methotrexate for treating people with chronic gout refractory to conventional therapy, also known as uncontrolled gout.
Krystexxa is a PEGylated uric acid specific enzyme and the currently recommended dosing for adult patients is 8mg administered intravenously every two weeks.
Gout refractory to conventional therapy occurs in people who could not normalise serum uric acid and have signs and symptoms that are inadequately controlled with xanthine oxidase inhibitors.
Named ‘Four-Weekly Administration for Urate Reduction (FORWARD)’, the adaptive, staggered-start trial will analyse the safety, efficacy, pharmacokinetics and pharmacodynamics of Krystexxa given monthly (Q4W).
The trial intends to enrol 30 adult subjects with uncontrolled gout.
An initial patient cohort will be given 15mg oral methotrexate every week for four weeks and then will receive oral methotrexate weekly along with Krystexxa 16mg infused every four weeks over at least two hours.
Horizon noted that testing of another dose in a second cohort will be decided depending on the preliminary analysis of the initial 16mg cohort.
The proportion of responders during the sixth month of treatment [serum uric acid (sUA) <6 mg/dl at least 80% of the time] and time to and duration of normalisation of sUA will form the primary outcome for the 48-week trial.
The safety and efficacy of this dosing regimen have not been evaluated or approved by any health authority.
Horizon rheumatology vice-president and therapeutic area head Paul Peloso said: “Our ongoing commitment to patients fuels our research to impact both the experience and outcomes for people living with uncontrolled gout.
“The FORWARD trial complements our clinical trial assessing shorter-infusion duration options, which enrolled its first patient last fall and continues our efforts to evolve the patient experience with Krystexxa.”