Yesterday Ionis Pharmaceuticals announced that it has resumed enrollment of new participants in PrProfile, its Phase 1/2a trial of ION717, a PrP-lowering ASO for prion disease (NCT06153966).

This concludes a 132-day pause in patient enrollment into the trial. On April 5, Ionis issued a letter to the community stating that “Due to exceptionally fast enrollment, we have reached capacity at the current stage of the trial”. As unpacked in this blog post, this was not due to safety concerns, and did not impact continued dosing of people already in the trial. Rather, I speculated it might have been due to needing to observe people at a certain dose for a certain amount of time, before escalating to a higher dose in the next stage of the trial.

As of yesterday, recruitment is back online. The new community statement explains that:

Earlier this year a global recruitment pause was instituted per the study design to allow for the collection and review of data from the first group of individuals enrolled in PrProfile before allowing additional individuals into the clinical trial. The required data collection and review has been completed and global recruitment has resumed.

Here’s what probably happened. They finished analyzing the data from the first X months of follow-up on people treated with Y milligrams of drug. They concluded that Y was safe enough and therefore it was OK to escalate to a higher dose. This is good news both because people can enroll again, and, because it probably rules out the worst outcomes from the initial dose(s) tested in this trial. If the data had looked awful, as though patients were getting worse on drug than on placebo, then they would have stopped the trial completely. That didn’t happen.

The other good news in here is that they have added even more trial sites. The community statement says that this is now all of the sites they planned for this trial:

U.S.

  • Boston
  • Cleveland
  • Denver
  • Los Angeles
  • New York

Canada

  • Edmonton
  • Montreal

Australia

  • Melbourne (Parkville)

Europe

  • Barcelona
  • Goettingen
  • Milan
  • Paris

Israel

  • Tel Aviv

Japan

  • Gunma
  • Tokyo
  • Yamaguchi

16 sites — it’s an impressively long list, and in a way, it’s a boon to our disease community that Ionis has now gotten so many different clinical sites worldwide oriented on how to participate in a multi-site global trial with intrathecal dosing and CSF collection. The infrastructure and know-how built through this trial will be an asset for future trials, both of ASOs and other drugs.

Now people can enroll again, but we’ve still got a long wait ahead of us before we hear any results from the trial. The ClinicalTrials.gov entry lists a study completion date of October 2025, but that really doesn’t mean that much. Technically, that’s just the date when the last timepoint generating primary or secondary endpoints or adverse events is projected to occur for the last participant in the trial. To a close approximation, that means the final person’s final study visit. On one hand, that final visit could move sooner if the trial enrolls quickly (which it seems to be doing). On the other hand, after all those visits are complete, Ionis will still have months of work to do: running analyses on all the blood and spinal fluid collected in the trial, crunching all the patient data, and finally writing a press release or paper or conference presentation. So: don’t hold your breath for results. For now, let’s just be glad the trial is back online.