Catalyst Biosciences has amended the protocol of its ongoing Phase 1/2 clinical trial investigating the highly potent recombinant human factor IX variant CB 2679d in previously treated hemophilia B patients.
The amendment has shortened the study’s duration, which is a dose-escalation study to investigate the safety and drug and organism responses (pharmacokinetics and pharmacodynamics).
The trial (NCT03186677) originally was designed with five experimental groups, varying in the route of CB 2679d delivery – either subcutaneously or intravenously – and in the therapy’s concentration. Each group receives a first dose of the therapy at 75 IU/kg followed by a single administration at escalating doses: groups 2, 3 and 4 receive single subcutaneous doses administered as 75 IU/kg, 150 IU/kg and 300 IU/kg, respectively.
The recent amendment consisted of removing group 4 and moving directly into dosing of patients in group 5 with six daily subcutaneous doses of CB 2679d at 150 IU/kg.
The South Korean Ministry of Food and Drug Safety has approved the alteration to the trial’s protocol, which is still recruiting participants.
Group 1 receives an intravenous administration of 75 IU/kg BeneFix (Pfizer’s standard-of-care replacement therapy) followed by a single subcutaneous administration of 75 IU/kg of CB 2679d. Group 5 is treated with a single daily subcutaneous administration of CB2679d for six days.
An early analysis of the first group of patients with hemophilia B treated with Catalyst Biosciences’ lead candidate CB 2679d (also known as ISU304) showed its improved stability and activity compared to BeneFix; the intravenous dose of CB 2679d was 22 times more potent than an intravenous dose of BeneFix.
Catalyst is conducting the trial at three clinical sites in South Korea in collaboration with ISU Abxis.
“In approving this protocol amendment to accelerate our Phase 1/2 trial, the MFDS [Korean Ministry of Food and Drug Safety] agrees that the high single dose of CB 2679d contemplated in [group 4] is not required, as current lower subcutaneous (SQ) doses are already predicted to achieve normal Factor IX levels after multi-dose administration,” said Howard Levy, MD, chief medical officer of Catalyst in a press release.
“Data from [groups] 1 through 3 demonstrated that the half-life of CB 2679d was almost five times greater than intravenous wild-type FIX, allowing for this favorable protocol amendment. We are currently enrolling patients in the final multi-dose [group] and, with the accelerated protocol, expect to have multi-dose data in [the first quarter of] 2018,” he added.