Provention Bio has completed patient enrollment for a Phase 2a clinical trial evaluating the efficacy and safety of its investigational oral therapy — PRV-6527 — for moderate to severe Crohn’s disease, and plans to report its first top-line results in the fourth quarter of this year.
The company believes the small molecule inhibitor will prevent disease flares (relapses) or disease progression, with longer-term effects, by blocking the first steps of the inflammatory process from happening in the gut, according to a press release.
The Phase 2a PRINCE (PRovention Investigation in Crohn’s DiseasE) clinical trial (NCT03854305) is a proof-of-concept study to evaluate PRV-6527’s anti-inflammatory benefit, both in terms of clinical manifestations and gut tissue inflammation, after 12 weeks of treatment.
Enrollment took place in several European countries and Russia, recruiting 93 patients with moderate-to-severe active Crohn’s disease who never received a biologic medication or who failed at least one biologic treatment.
Patients will be randomly assigned to either oral PRV-6527 or a placebo, given twice daily over 12 weeks, followed by a four-week safety follow-up period.
The treatment’s effects will be primarily assessed by comparing the Crohn’s Disease Activity Index (CDAI) score at the study start, and at treatment’s end — at week 12 — in both groups.
Other secondary assessments of effectiveness will include endoscopy, intestinal biopsies, histological examination, and analysis of other biomarkers, including genetic markers.
PRV-6527, previously known as JNJ-40346527, is an oral, small-molecule inhibitor of colony stimulating factor-1 (CSF-1) receptor.
CSF-1 is a signaling protein, or cytokine — small secreted proteins released by cells that have a specific effect on the interactions and communications between cells — that binds to its receptor on myeloid cells and drives their differentiation into inflammatory dendritic cells and macrophages. Myeloid cells are precursor immune cells formed in the bone marrow, and are thought to play a central role in the disease.
Normally, dendritic cells and macrophages work as “sentinels” in the body, constantly surveilling, recognizing, and destroying bacteria and other harmful organisms.
But in people with Crohn’s they are thought to mistakenly attack the bacteria colonizing the gut, promoting an inflammatory response that also damages the body’s own cells.
By blocking the CSF-1 receptor, PRV-6527 is anticipated to “intercept” the formation of dendritic cells and macrophages, and block the first steps of gut inflammation. By doing that, the treatment is expected to bring significant clinical benefits, including preventing relapses or delaying disease progression.
The compound was initially developed by Janssen, which has sponsored clinical testing in more than 200 subjects to date.
“In prior studies, PRV-6527 demonstrated proof of mechanism with evidence of tolerability and favorable pharmacology,” said Ashleigh Palmer, Provention Bio’s CEO.
“The results from the PRINCE study may establish the potential of this oral candidate in Crohn’s disease, an indication which is currently dominated by biologics that offer limited benefit over the long-term,” Palmer said. “We look forward to reporting top-line data in the fourth quarter of 2019.”