Dosing Begins in Early Trial of Oral Therapy to Protect Dopaminergic Neurons

Dosing has begun in a Phase 1 clinical trial testing Inhibikase Therapeutics’ investigational oral therapy IkT-148009 for Parkinson’s disease and related disorders in healthy volunteers.

This first clinical trial (NCT04350177) is expected to enroll 112 healthy adults, ages 45 to 70, at a single site in Arizona. More information can be found here.  

“The initiation of our Phase 1 study of IkT-148009 for the treatment of Parkinson’s disease represents a significant milestone for Inhibikase,” Milton Werner, PhD, CEO of Inhibikase Therapeutics, said in a press release.

“We are excited to advance into the clinic, and believe that IKT-148009 could be a transformative therapy for millions of patients worldwide,” Werner added.

lkT-148009 is a small-molecule oral medication that targets an underlying biological mechanism believed to lead to Parkinson’s disease, with the goal of restricting disease progression.

Specifically, the compound aims to block activation of Abelson tyrosine kinase (c-Abl) — a regulator that plays a central role in Parkinson’s progression — to prevent or reverse the loss of dopamine-secreting neurons in the brain and gastrointestinal tract by restoring neuroprotective mechanisms.

C-Abl kinase is thought to play a critical role in monitoring insults to neurons in and outside the brain, and regulating biological pathways responsible for protecting neurons from dying.

Studies in animal models have shown that treatment with IkT-148009, once daily, can halt and reverse functional loss in both the brain and gastrointestinal tract, the company reports.

Inhibikase’s ongoing trial is investigating the safety, tolerability, and pharmacokinetics (the movement of a compound into, through, and out of the body) of single and multiple ascending doses of IkT-148009 in adults.

Escalation to the next dose will take place only after safety, tolerability and pharmacokinetics data has been reviewed and supports an increase. The goal of the study is to determine the maximum tolerated dose of IkT-148009 for further trials in patients.

This Phase 1, placebo-controlled and double-blinded trial is divided in two parts. In its first, single-ascending dose part, healthy participants in groups of eight will be given one dose of IkT-148009 or a placebo, as oral capsules, and be at the study site for about four days. Six in each group will receive IkT-148009, and two a placebo. Participants will be followed in seven visits over a period of up to 28 days prior to dosing, and 14 days after dosing.

In the second multiple ascending dose portion of the study, participants in groups of 12 will receive either IkT-148009 or a placebo once daily for seven days, and be at the study site for about nine days. Nine people in each group will receive multiple ascending doses of IkT-148009, and three a placebo. Participants will be followed in 12 visits over 49 days, including seven days of dosing.

The trial’s main goals are the treatment’s safety, tolerability and pharmacokinetics. Additional goals include measures of possible biomarkers in the cerebral spinal fluid (CSF) — the liquid that surrounds the brain and spinal cord — for up to one year in multiple-ascending volunteer groups.

“Based on preclinical data, we believe that c-Abl plays a critical role in the Parkinson’s disease process and inhibition of c-Abl represents a promising new approach to disease modification,” Werner said.