Organoid-Based Personalized Medicine Trial Enrollment Complete

Enrollment is complete for a European initiative to test an organoid-based, personalized-medicine approach to treating cystic fibrosis, with the first trial starting later this year, said Proteostasis Therapeutics (PTI) and CF Europe.

The Human Individualized Therapy of CF (HIT-CF) initiative will test PTI drug combinations through the company’s CHOICES clinical trial, which will be the first to gauge the potential of personalized therapies for CF.

The study will use tissue samples from 502 adults with CF to evaluate three of PTI’s cystic fibrosis transmembrane conductance regulator (CFTR) modulators. These modulators act directly on the CFTR protein, which is faulty in CF, to restore its normal function. Tested compounds will include the CFTR potentiator dirocaftor (PTI-808), the CFTR corrector posenacaftor (PTI-801), and the CFTR amplifier nesolicaftor (PTI-428).

CHOICES builds on early findings from the HIT-CF initiative showing the feasibility of testing these CFTR modulators in organoids. Organoids — in effect, mini organs — are made up of cells grown in a dish. Unlike conventional cells, organoids are grown in specific three-dimensional structures that more closely resemble how cells are arranged within organs in the body.

In the first phase of the study, researchers will use biopsies to develop organoids for each patient. All three CFTR modulators will be tested in these organoids to assess efficacy. The results of the tests will be used to define which treatment each participant will receive in the trial itself.

During the trial, participants will be given either an active treatment or a placebo, and then switch. The crossover study design allows for greater statistical power, because each participant serves as his or her own control.

“With the successful translation of activity from organoids to patients, this study has the potential to usher in a personalized medicine approach to CF,” Geoffrey Gilmartin, MD, chief medical officer at PTI, said in a press release.

“This approach would begin with patients who have less common mutations, but could ultimately serve the broader CF community by delivering personalized treatment choices that maximize benefit based on each patient’s responsiveness to therapy,” Gilmartin said.

The CHOICES results may serve as the foundation for a future submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) next year, PTI said.

“We are excited that Proteostasis is participating in the HIT-CF project and supporting our efforts to bring CF treatment to more people across Europe,” said Jacquelien Noordhoek, president of CF Europe.

“Enrolled individuals are a portion of the approximately 2,300 adults in the European patient registry who are not eligible for any currently approved modulator due to their genotype, and the HIT-CF project represents the only option to explore potential benefit of disease modifying drugs for this group,” Noordhoek said. “Putting patients with CF first is our highest priority. We are looking forward to continuing our partnerships and providing Europeans with CF the best possible care.”

PTI is conducting another Phase 3 trial, MORE, to confirm the safety and efficacy of its CFTR modulators in patients carrying the F508del mutation, the most common mutation found in people with CF.