LogicBio Therapeutics has received the green light to continue dosing participants in its Phase I/II Sunrise trial, following a clinical hold placed by the FDA due to adverse events in pediatric patients.
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LogicBio Therapeutics has been granted the green light to continue dosing participants in its Phase I/II Sunrise trial. In February, the U.S. Food and Drug Administration placed a clinical hold on the trial after a severe adverse event (SAE) was reported in four pediatric participants. Of these, two SAEs included hospitalization following a patient’s development of thrombotic microangiopathy (TMA). Both patients reportedly recovered from the event.
The open-label clinical trial (NCT04581785) is investigating the safety of LB-001 in patients with methylmalonic acidemia (MMA), characterized by methylmalonyl-CoA mutase (MMUT) gene mutations. This mutation can cause delays in normal development, including movement, eating difficulties that may require medical intervention and optic neuropathy.
LB-001 received fast track designation, rare pediatric disease designation and orphan drug designation from the FDA. The European Medicines Agency also granted orphan drug designation for the same indication. LogicBio President and Chief Executive Officer Frederic Chereau commented on the FDA’s decision.
“We are pleased that the FDA has completed its review of the information we provided and that the hold on our LB-001 IND has been lifted,” he said. “We look forward to dosing the next patient in our Sunrise trial, which we expect will occur in the third quarter of 2022.”
The early phases of clinical trials are designed to first determine the safety and tolerability, then efficacy, of all candidate products. To achieve this, early phases often include smaller enrollment numbers. The Sunrise trial is currently recruiting to reach the estimated enrollment number of 8 participants. At the time of the clinical hold placement, only four participants had been enrolled.
In order to maintain the safety of the ongoing study and avoid further clinical holds, the Sunrise study protocol has been revised to include additional monitoring. These monitoring amendments include recurrent testing of complement activation as an indicator of TMA development and the use of a complement inhibitor when TMA is indicated.
LB-001 utilizes LogicBio’s GeneRide development platform, which uses homologous recombination to edit a patient’s genome. The biologic provides the patient with a non-mutated version of the MMUT gene to increase MMUT expression in the liver. The technology is delivered through an engineered recombinant adeno-associated virus vector (rAAV-LK03).
According to the study’s design, the LB-001 biologic is intravenously administered to participants aged six months to twelve years old. The dosing will continue at a concentration of 5e13 vg/kg. Primary outcome measurements of the study include the incidence of adverse events and incidence of infusional toxicities over the course of 52 weeks. Its tentative completion date is June 2023, with interim results expected later this year.
