Micrograph showing MDS
The US Food and Drug Administration (FDA) has lifted the clinical hold on a phase 1b trial of APTO-253.
APTO-253 is a small molecule that inhibits expression of the c-Myc oncogene without causing general myelosuppression of the bone marrow, according to Aptose Biosciences Inc., the company developing the drug.
Aptose was testing APTO-253 in a phase 1b trial of patients with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) before the FDA put the trial on hold in November 2015.
The hold was placed after an event that occurred during dosing at a clinical site. The event was stoppage of an intravenous infusion pump that was caused by back pressure resulting from clogging of the in-line filter.
Aptose said no drug-related serious adverse events were reported, and the observed pharmacokinetic levels in patients treated with APTO-253 were within the expected range.
However, a review revealed concerns about the documentation records of the manufacturing procedures associated with APTO-253. So Aptose voluntarily stopped dosing in the phase 1b trial, and the FDA placed the trial on hold.
A root cause investigation revealed that the event with the infusion pump resulted from chemistry and manufacturing-based issues.
Therefore, Aptose developed a new formulation of APTO-253 that did not cause filter clogging or pump stoppage during simulated infusion studies.
Now that the FDA has lifted the hold on the phase 1b trial, Aptose said screening and dosing will resume “as soon as practicable.”
“We are eager to return APTO-253 back into the clinic,” said William G. Rice, PhD, chairman, president and chief executive officer of Aptose.
“Our understanding of this molecule has evolved dramatically, and we are excited to deliver a MYC gene expression inhibitor to patients with debilitating hematologic malignancies.”
The phase 1b trial is designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of APTO-253 as a single agent and determine the recommended phase 2 dose of the drug.
APTO-253 will be administered once weekly, over a 28-day cycle. The dose-escalation cohort of the study could potentially enroll up to 20 patients with relapsed or refractory AML or high-risk MDS. The study is designed to then transition, as appropriate, to single-agent expansion cohorts in AML and MDS.