The study will enroll approximately eight patients with PH1 under six years of age. The primary endpoint is the percent reduction in urinary oxalate from baseline to six months. The Company expects to report initial ILLUMINATE-B results in mid-2020.
The company also announced new positive efficacy results from the ongoing Phase 2 open-label extension (OLE) study of lumasiran. The results were presented at the International Society of Nephrology (ISN) 2019 Annual Meeting held on April 13-16 in Melbourne, Australia.
“We are pleased to start the ILLUMINATE-B pediatric trial, an important step forward in our goal to assess the safety and efficacy of lumasiran across the PH1 age and disease severity continuum, including patients in early infancy. This study adds to our overall clinical development plan for lumasiran, led by our ILLUMINATE-A pivotal study with results expected by year-end 2019,” said Pritesh J. Gandhi, PharmD, Vice President and General Manager, Lumasiran program at Alnylam.
“We are also pleased to report new results from our Phase 2 OLE study, and are encouraged by the consistently sustained reductions we observe in urinary oxalate and by the overall safety profile of lumasiran observed thus far.”
All patients (N=20) from the Phase 1/2 study of lumasiran have now transitioned to the Phase 2 OLE study designed to evaluate long-term safety and efficacy of lumasiran.
The new Phase 2 OLE results were reported with 18 patients dosed in the OLE as of the data cut-off date of February 8. Patients were on a range of lumasiran doses and regimens (1.0 mg/kg monthly, 3.0 mg/kg monthly, and 3.0 mg/kg quarterly).
There were no discontinuations from study treatment. A single patient (1/18; 5.6 percent) reported two serious adverse events (SAEs) of traumatic brain injury and bone contusion sustained in a car accident; neither was assessed as related to study drug. Adverse events (AEs) were reported in 12/18 (66.7 percent) patients.
Injection site reactions were reported in 3/18 (16.7 percent) patients; all were mild and assessed as related to study drug. There were no clinically significant laboratory changes.
Lumasiran demonstrated a 72 percent mean maximal reduction (range: 41-90 percent) in urinary oxalate excretion relative to Phase 1/2 baseline values across all dose cohorts (N=9). The mean reduction relative to baseline at Day 85 was 69 percent (N=7). Lumasiran also demonstrated a mean maximal reduction in urinary 24-hour oxalate:creatinine ratio of 77 percent (range: 57-91 percent) relative to Phase 1/2 baseline values across all dose cohorts (N=10). The mean reduction relative to baseline at Day 85 was 70 percent (N=9).
The ILLUMINATE-B Phase 3 trial is an open-label, global, multicenter study to evaluate the efficacy and safety of lumasiran in approximately eight patients less than six years of age with a documented diagnosis of PH1.
Dosing regimen will be based on patient weight. The primary endpoint is the reduction of urinary oxalate at six months relative to baseline. Key secondary and exploratory endpoints will evaluate additional measures of urinary oxalate, estimated glomerular filtration rate (eGFR), safety and tolerability, and quality of life.
Source: Company Press Release