This follows an assessment by a protocol review safety committee, which reviewed the study’s protocol and interim safety data. The committee approved the continuation of the trial as planned, allowing researchers to advance MRT5005 for MAD analysis.
“The initiation of the multiple-dose portion of the Phase 1/2 clinical trial of MRT5005 is an important milestone as it represents the first time that multiple doses of an mRNA therapeutic have been given to patients for the treatment of a genetic disease,” Ronald Renaud, CEO of Translate Bio, said in a press release.
“We look forward to expanding our knowledge of the safety profile of MRT5005 with multiple doses and believe that this progress underscores its potential to make an impact in the treatment of patients with cystic fibrosis,” Renaud added.
The ongoing Phase 1/2 trial (NCT03375047), called RESTORE-CF, which is testing the safety and efficacy of MRT5005, is being conducted in collaboration with the Cystic Fibrosis Foundation Therapeutics Development Network.
It was designed to explore the impact of a single-ascending dose (SAD) and MAD of the investigational therapy in 32 adults with CF who have class I or II genetic mutations.
According to a corporate presentation, the SAD portion of the trial included 12 CF patients who were randomized to receive a single administration of increasing doses of MRT5005 — 8, 16, or 24 mg — or a placebo. Another 12 patients will be included in the MAD portion, in which they will receive weekly administrations of the treatment or a placebo for five weeks.
In a final analysis, the study will include eight patients who will receive one of the two highest, well-tolerated MRT5005 doses for five weeks.
During these studies, researchers will evaluate the safety and tolerability of MRT5005, as well as its impact on lung tissue and CFTR protein production through biopsy analysis. They will also explore its beneficial effects on patient’s lung function, as determined by changes in forced expiratory volume in one second (FEV1).
MRT5005 is a messenger RNA product specifically designed to address the underlying cause of CF. It delivers the correct coding sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene (which is defective in CF patients) to lung cells, allowing the production of fully functional CFTR protein regardless of the disease-causing genetic mutation carried by the CF patient.
MRT5005 is also the first potential mRNA approach to specifically target the lungs.
Previous studies showed that nebulized MRT5005 can effectively reach lung cells and cross the mucus barrier in mice and rats with CF. This strategy was able to support the production of fully functional CFTR protein in these animals without damaging lung tissue.
The U.S. Food and Drug Administration granted orphan drug status to MRT5005 for the treatment of CF in 2015, a designation that supports and expedites the clinical development, regulatory review, and approval of therapeutic candidates.
Translate Bio expects to announce preliminary results of the RESTORE-CF trial during the second half of 2019.
For additional information about the trial, its locations, and contacts, visit the study webpage here.