ProQR Therapeutics has finished a dose-escalating Phase 1b clinical trial evaluating the safety, stability and distribution throughout the body of its investigational therapy QR-010 in cystic fibrosis (CF) patients with a confirmed F508del CFTR gene mutation. Interim top-line results should be released by late September.
A missing amino acid in the 508 position of the CFTR gene is the leading cause of CF, affecting 85 percent of all patients and producing a misfolded CFTR protein that cannot function properly. ProQR, a Dutch biotech company, has developed QR-010 to specifically target and reverse the effects of this genetic alteration. The RNA-based therapy, which patients inhale directly into their lungs, binds to the defective CFTR RNA sequence and restores its function.
The PQ-010-01 Phase 1b clinical trial (NCT02532764) tested QR-010 in 64 patients with CF due to F508del mutation in both copies of the CFTR gene. Researchers randomly divided participants into eight groups of eight patients each. All were adults with mild CF, stable lung function and a baseline predicted forced expiratory volume in one second (FEV1; a measure of lung function) above 70 percent.
In each study group, six patients received QR-010 and the other two got placebo. Four different concentrations of the drug — 6.25, 12.5, 25 and 50 mg in solution to be administrated via inhalation – were tested in single-dose regimen or three times weekly up to a total study period of four weeks.
In October 2016, ProQR announced preliminary data of the study’s single-dose portion. Overall, QR-010 was found to be safe, with no major adverse effects reported, and seemed to restore CFTR function (study PQ-010-002, or NCT02564354).
“QR-010 has the potential to be an innovative RNA therapy for patients with CF due to the F508del mutation,” Dr. Noreen R. Henig, ProQR’s chief medical officer, said in a press release. “Completion of the Phase 1b study is an important step in development, and builds upon the pre-clinical data and positive PQ-010-002 study where QR-010 demonstrated a direct effect on restoring CFTR function.”
She added: “We are grateful to the patients and the medical community who participated in this early trial. ProQR is committed to creating meaningful RNA therapies for patients with CF.”
Full data from the PQ-010-001 study will be presented at the North American CF Conference to be held Nov. 2-4 in Indianapolis.
The U.S. Food and Drug Administration (FDA) and the European Medicines Agency have granted orphan drug designation to QR-010. The FDA has also granted the drug fast-track status. Development of QR-010 is funded by Horizon 2020, the European Union’s research and innovation program.