Going forward, the company must provide safety and steady-state pharmacokinetic data on the 200 mg dose of IKT-148009, as well as continued measurement of visual acuity and examination of the cornea and lens.
The FDA has lifted a full clinical hold on Inhibikase Therapeutics’ phase 2 trial 201 (NCT05424276) assessing its lead product candidate IKT-148009, an Abelson Tyrosine Kinase (Abl) inhibitor for patients with Parkinson disease (PD). Those in the 50- and 100-mg groups will resume dosing immediately, with ongoing safety observations for the 200 mg group.1
In early December 2022, the FDA placed the hold on the company’s PD and multiple system atrophy (MSA) programs for the agent, citing several points. The agency requested further evaluation of the existing safety and pharmacokinetic (PK) data of the 200 mg dose, a better understanding of how the trial will monitor the potential for detecting adverse events (AEs) that could affect vision in trial participants, and the need for material additions to the disclosures made to investigators and patients related to the clinical and safety measures completed to that point, including the potential vision risks.2
The agency decided to lift the clinical hold based on the Inhibikase’s Complete Response and Amendment issued in late December 2022, as well as further commitments made on January 20, 2023, regarding ophthalmologic monitoring in the study and various modifications to the Investigator Brochure. Going forward, the company will be required to measure the safety and steady-state PK profile of the 200 mg dose in 6 healthy individuals from a prior phase 1 study (NCT04350177) before administering the agent in patients with PD. Those in the 50 and 100 mg groups will resume dosing immediately investigators will simultaneously perform safety and PK assessments on the 200 mg group.
"We are grateful for the expeditious review by the FDA of our response to the Clinical Hold on IkT-148009 in PD," Milton H. Werner, PhD, president and chief executive office, Inhibikase, said in a statement.1 "We believe that we now have clarity on the FDA's expectations as we move forward in the 201 clinical trial for IkT-148009. We are now working to re-open clinical trial sites and initiate screening and enrollment of patients for the trial following agreed upon updates to the Protocol and Informed Consent form. We anticipate completing these restart tasks by the end of the first quarter."
Consistent with other previously approved protein kinase inhibitors, the FDA requested that the company must provide measurement of visual acuity and examination of the cornea, in addition to other analysis of retina, macula, and funder that were already a part of the ocular monitoring program in the 201 trial. The company did note that thus far, there have been no ocular pathology observed in any patient treated with the agent.
The potent, selective small-molecule medication is also being assessing in PD-related disorders of the brain and gastrointestinal tract, and orphan indications related to PD such as MSA. IKT-148009 is designed to block the activation of Abl kinase, a clinically validated drug target, to half and reverse the loss of dopamine-secreting neurons in the brain and gastrointestinal tract by restoring neuroprotective mechanisms.
The 201 trial is a double-blind, 12-week study that randomly assigned 120 patients 1:1:1:1 to either 50, 100 or 200 mg of IKT-148009 given once daily, or placebo. Patients included in the study have untreated PD, indicated by Hoehn and Yahr scores of less than 3, who have not yet progressed to the need for symptomatic therapy. Spanning across 40 sites in North America, the trial’s primary end point includes safety, tolerability, and steady-state PK of IKT-148009; although, the trial will also measure a hierarchy of PD-related disease assessments in the brain and gut as secondary or exploratory end points.3