Dose-confirmation Study Launched for Hem B Gene Therapy FLT180a
“We are very excited about this progress in our hemophilia B program as our enhanced focus on execution is starting to pay dividends to unlock the value of our clinical programs,” Michael Parini, CEO of the U.K.-based Freeline, said in a press release.
“This is the first patient Freeline has dosed in the U.S., which affirms our commitment to diversify our clinical trial footprint and build resiliency into our programs,” Parini added.
The trial, called B-LIEVE (NCT05164471), is currently recruiting participants at the Children’s Hospital of Los Angeles, in California. The study is open to males, ages 18–65, who have a severe or moderately severe deficiency of factor IX (2% of normal activity levels or lower), the clotting protein that is missing in people with hemophilia B.
Most participants are being recruited through a Freeline-funded gene therapy screening study called ECLIPSE (NCT04272554).
“We believe we have already identified enough patients to fully enroll the B-LIEVE trial via the ECLIPSE run-in study, and expect to complete the dosing of the first cohort [patient group] and share initial results by the end of the first half of this year,” Parini said.
“We continue to progress against these key milestones as we chart the path toward a pivotal Phase 3 study of FLT180a, and currently plan to initiate start-up activities for that study in the first half of 2023,” he added.
Hemophilia B is caused by genetic mutations that render the body unable to produce factor IX, an important clotting protein. FLT180a is a gene therapy that uses a specifically engineered viral vector, called AAVS3, to deliver a healthy version of the gene that codes for factor IX to the body’s cells — with the end goal of restoring the production of a functional version of the clotting protein.
Participants in the B-LIEVE trial will receive a single infusion of FLT180a, given in combination with immune-suppressing medicines to help stop the immune system from attacking the viral vector.
The first three participants will receive a dose of 7.7e11 vector genomes per kilogram (vg/kg), with subsequent doses determined based on a safety review. Results from the first dosing group are expected by June. Should additional patients be included in the first dosing group, or a second dosing group be necessary, the company anticipates that to be completed by the third quarter of the year.
“We are optimistic that the combination of a low dose (7.7e11 vg/kg) of our high-expression AAVS3 capsid with a short prophylactic [preventive] immune management regimen can get and keep hemophilia B patients in the normal range of Factor IX expression,” said Pamela Foulds, MD, Freeline’s chief medical officer. “This is a meaningful step towards realizing the potential of FLT180a to provide a functional cure through sustained, normalized FIX activity.”
Data from a previous Phase 1/2 trial called B-AMAZE (NCT03369444) and its long-term follow-up study (NCT03641703) indicated that treatment with FLT180a could increase and maintain factor IX levels within a normal range and, consequently, reduce bleeding, for at least three years.