The 28-day, multicenter, and double-blind study (NCT04056689) is testing two doses of DNL151 against placebo in people with mild to moderate Parkinson’s disease, and with or without LRRK2 mutations, the most common genetic cause of the disease.
Twenty-four patients, ages 30 to 75, are expected to take part in the trial, and enrollment is ongoing at the Centre for Human Drug Research, in Leiden, the Netherlands. More information and contacts can be found here.
The company also announced the launch of its Engage Parkinsons website, where patients, caregivers, healthcare professionals, and advocates can find information about the disease and its link with genetics, overall advancements in Parkinson’s research, and Denali’s clinical trials. Registrants will also be informed about future studies sponsored by Denali.
“We are encouraged by the progress with our LRRK2 clinical program,” Ryan Watts, PhD, Denali’s CEO, said in a press release. “The launch of our Engage Parkinson’s website is intended to strengthen our engagement and interactions with the Parkinson’s disease patient community.”
“This is an important part of our efforts to connect with patients who may be eligible for our current and future clinical trials.”
DNL151 is a small molecule inhibitor of LRRK2, a protein that regulates the activity of cellular structures called lysosomes — tiny vesicle were a cell’s waste is broken down and recycled. High levels of LRRK2 impair lysosomal function, and may result in the formation of toxic protein clumps called Lewy bodies in brain cells. Lewy bodies are associated with neurodegeneration.
By selectively suppressing LRRK2, DNL151 aims to restore lysosomal function, which, according to Denali, may slow Parkinson’s progression in all patients.
The Phase 1b trial will primarily assess the safety, tolerability, pharmacokinetics — a compound’s absorption, distribution, metabolism, and excretion — and overall impact on the body of a high and low dose of DNL151. Biomarkers of target binding and exploratory clinical endpoints (goals) will also be evaluated.
Participants will be randomly assigned to either dose of DNL151, or a placebo. Study completion is expected by February 2020.
“Based on data generated from our prior study in healthy volunteer subjects, we are excited to evaluate DNL151 in Parkinson’s disease patients,” said Carole Ho, MD, Denali’s chief medical officer. “We believe that this study will provide additional important safety and biomarker data in patients to inform the choice between either DNL151 or DNL201 for potential registrational trials.”
These future trials are expected to form the basis of requests for regulatory approval of either therapy.
DNL201 is the company’s lead candidate for Parkinson’s disease, and is also an oral LRRK2 inhibitor able to reach the brain. A Phase 1 trial (NCT03710707) has a similar design to DNL151’s Phase 1 study, but is taking place at sites across the U.S. It is expected to conclude shortly.
Preclinical work supports the potential therapy’s ability to substantially inhibit LRKK2 activity even when administrated at lower dose.
Reported results of a prior Phase 1 study showed that DNL201 was safe and well-tolerated in healthy volunteers, and it demonstrated an ability to effectively suppress LRRK2 effects, as measured by blood biomarkers.