The small molecule IRL752 may be a safe and effective treatment, which could potentially help manage symptoms known to be unresponsive to levodopa, for people with Parkinson’s disease dementia, results from a Phase 2a clinical study suggest.
Preliminary data suggests treatment with IRL752 could reduce apathy, as well as improve executive function and body postural control.
The results were discussed at the 2019 International Congress of Parkinson’s Disease and Movement Disorders, in a poster titled, “A phase IIa trial studying the safety and tolerability of IRL752 in patients with Parkinson’s disease dementia.” The conference is being held Sept. 22-26 in Nice, France.
IRL752 is a small molecule designed by IRLAB Therapeutics that has the ability to enhance communications between nerve cells in the frontal cortex — a major brain area that controls cognitive functions.
In preclinical studies, this new therapeutic candidate was found to increase the availability of two important neurotransmitters — norepinephrine and dopamine — and to modulate nerve cells’ responses and activity. Neurotransmitters are chemical messengers that allow nerve cells to communicate.
Both norepinephrine and dopamine levels are reduced in the frontal cortical brain areas of people with Parkinson’s who also have dementia, previous studies have shown. Scientists hope treatment with IRL752 may counteract these features and help manage cognitive and psychiatric symptoms in this patient population.
The safety and tolerability of IRL752 were first evaluated in 40 healthy volunteers in a placebo-controlled, double-blind Phase 1 trial. Participants were randomly selected to receive single or multiple ascending doses of IRL752 or a placebo, which covered the clinically anticipated dose.
IRL752 was well-tolerated and had a very good safety profile. No serious adverse events were reported during the study.
Supported by these positive results, IRL752’s potential was further explored in a Phase 2a trial (2017-001673-17) conducted in Sweden and Finland.
The study enrolled 32 patients with Parkinson’s disease dementia. Participants were randomly selected to receive either IRL752 or placebo for four weeks in addition to their standard antiparkinsonian medication. The IRL752 dose was adjusted for each patient during the first 14 days, after which dosing was kept stable for an additional 14 days of treatment.
A total 29 of the 32 participants completed the four-week treatment.
Similar to the previous clinical trial, no serious adverse events were reported. In general, all adverse effects were mild in severity and more frequent during the initial titration phase of the trial, when the dose is adjusted until it achieves the desired effect with as few side effects as possible.
Preliminary data on efficacy outcomes suggested that treatment with IRL752 could reduce apathy, as well as improve executive function and body postural control — symptoms known to be unresponsive to levodopa, the gold standard treatment used to manage Parkinson’s.
“These [preliminary] results will be of guidance for the design of further efficacy studies,” the researchers said.
IRLAB Therapeutics also is exploring the potential of another candidate, named IRL790, for the treatment of Parkinson’s-related dyskinesia — involuntary movements that can interfere with normal daily activities. Supported by positive results from a Phase 2 clinical study, the company is now planning a Phase 2b/3 study to be launched in the first half of 2020.