Mar 25, 2023

Inhibikase takes steps ahead of study of IkT

No serious side effects found with 200 mg dose in healthy people

by Margarida Maia, PhD | May 3, 2023

A once-daily 200 mg dose of IkT-148009, Inhibikase Therapeutics‘ investigational therapy for Parkinson's disease, reached steady levels in the body after four days without causing any serious side effects in healthy volunteers.

The company plans to include this dose in its ongoing Phase 2 study (NCT05424276) in people with Parkinson's — a trial that's part of its so-called 201 program — and has shared the new data with the U.S. Food and Drug Administration (FDA).

The agency had issued a full clinical hold on IkT-148009 late last year, just a few months after Inhibikase had begun dosing the first patients, due to safety concerns over the use of the 200 mg dose.

After the clinical hold was lifted in January this year, the company resumed testing of IkT-148009 at two lower doses of 50 and 100 mg per day, with closer monitoring for any side effects.

"We continue to make progress in our ‘201’ program in Parkinson's disease following the clinical hold lift by the FDA earlier this year," Milton Werner, PhD, president and CEO of Inhibikase, said in a press release, adding, "These data … support the inclusion of the 200mg dose in the ‘201’ trial."

The 201 study is testing how safe and well tolerated IkT-148009 is versus a placebo in up to 120 people with Parkinson's who have received no prior treatment. The therapy will be given by mouth as a gelatin capsule at a dose of 50, 100, or 200 mg per day for 12 weeks, or about three months.

The trial also is testing the drug's pharmacokinetics, which refers to how the therapy moves into, through, and out of the body, as well as its preliminary efficacy.

Additionally, the 201 study is looking at levels of phosphorylated alpha-synuclein — the abnormal form of alpha-synuclein protein that forms aggregates, or clumps, and leads to the death of dopamine-producing neurons.

The levels of this protein will be assessed in the skin and cerebrospinal fluid (CSF), which is the liquid surrounding the brain and spinal cord. A recent study showed this type of analysis can detect Parkinson's disease with high accuracy.

"We have implemented newly described biomarker analyses in the skin and spinal fluid into the trial to analyze the response to treatment for enrolled patients," Werner said.

As many as 30 of a total 35 sites are expected to be screening patients, ages 30 to 75, by the end of the year, according to Inhibikase.

"We have worked diligently to implement protocol changes arising from our agreements with the FDA and now have multiple sites screening patients," Werner said.

Multiple patients are expected to join the study by the end of June, Werner said, adding that the company "will provide additional updates as enrollment progresses."

These [new] data … support the inclusion of the 200mg dose in the ‘201’ trial.

IkT-148009 is a small molecule designed to get into the brain and block the activity of Abelson tyrosine kinase (c-Abl), a protein known to play a role in regulating how neurons (nerve cells) respond to damage. Blocking c-Abl is expected to halt disease progression and reverse the loss of dopamine-secreting neurons — those gradually lost in Parkinson's disease.

An earlier Phase 1 study (NCT04350177) looked at the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of IkT-148009 versus a placebo. That trial involved healthy volunteers and Parkinson's patients, ages 55 to 70 years. Both IkT-148009 and placebo were given once daily for up to seven days.

Six patients were assigned to the 50 mg dose, five patients to the 100 mg dose, and three patients to a placebo. Final data from all 14 patients, including an additional two weeks that followed treatment, have now been analyzed by researchers.

The team used the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) to check for changes in non-motor symptoms (part 1) and motor symptoms affecting daily living (part 2).

On average, MDS-UPDRS part 1 scores dropped by 4.33 points in the 50 mg group and by 1.8 points in the 100 mg group, indicating an improvement over the duration of the study.

In MDS-UPDRS part 2, scores decreased by an average 2 points in the 50 mg group and by 1.4 points in the 100 mg group. In the placebo group, the scores either remained unchanged or increased.

Improvements also were observed in the Non-Motor Symptom Score (NMSS) for those who received either dose. Small improvements were observed in upper and lower gastrointestinal tract (gut) function.

While these data are based on a small number of patients, the company noted in the release that they are "encouraging observations as the 201 trial gets underway."

Full data from the study are expected to be shared soon.