DNL151 in Subjects with Parkinson’s Disease
Research type
Research Study
Full title
A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL151 in Subjects with Parkinson's Disease
IRAS ID
265193
Contact name
Aliya Asher
Contact email
Sponsor organisation
Denali Therapeutics, Inc.
Eudract number
2019-001297-28
Duration of Study in the UK
0 years, 4 months, 29 days
Research summary
Research Summary:
Parkinson’s disease is the second most common neurodegenerative (the progressive loss of structure or function of neurons) disease, affecting about 1–2% of individuals aged 65 or over. Standard medications to treat Parkinson’s disease will usually include dopamine replacement therapy (such as levodopa or Sinemet).
The purpose of this clinical research study is to investigate whether DNL151 (the study drug) is safe and tolerable in Parkinson’s disease patients and to investigate how DNL151 is absorbed, broken down, and eliminated from the body. The effect of this drug on the clinical symptoms of Parkinson’s disease is unknown.
Approximately 16 - 20 participants will receive either DNL151 or placebo in this study at study sites (hospitals, clinics and research centres) in the UK. Participants will be required to visit the study site 8 times, not including the Screening Period.
The full duration of the study, including the Follow-up Period, is approximately 10 weeks for each participant. The total duration of the study across all participants is estimated to be approximately 8 months.
The study will randomly assign participants into 3 groups: 2 groups will be given the study drug, DNL151, at two different dose levels. One treatment group will receive a low dose of DNL151 once daily and the other treatment group will receive a high dose of DNL151 once daily. The third group (“control” group) will be given placebo. A placebo is a capsule that looks like a drug, but with no DNL151 in it (also called a “dummy” drug).
The study is organised and funded by Denali Therapeutics Inc. (also known as the “Sponsor” of this study).Summary of Results:
Why Was the Research Needed?
Parkinson’s disease (PD) is a neurologic condition with symptoms that include tremor, stiffness, and slowing of movement. PD is a progressive disease, meaning that the symptoms get worse over time. Currently available drugs for PD only treat the symptoms of the disease and do not slow disease progression.
DNL151 (BIIB122) is an innovative oral treatment that is being evaluated for its potential to slow disease progression in clinical trial participants with PD. BIIB122 is thought to work by blocking activity of a protein (leucine-rich repeat kinase 2 [LRRK2]) in the brain that has been shown to be associated with PD. Overactivity of the LRRK2 protein is responsible for disrupting the normal functioning of the lysosomes, the special compartments within cells that break down excess or worn-out cell parts. Disrupted lysosome functioning may lead to the build-up of toxic compounds that are commonly found in PD.What Was the Purpose of This Study?
This study is the first time that BIIB122 has been given to participants with PD. Researchers in this study wanted to learn whether BIIIB122 was safe and tolerable for participants when given as an oral treatment. The researchers also wanted to learn whether BIIB122 could pass through the blood brain barrier (which protects the brain from foreign substances) in order to reach the brain by measuring the BIIB122 drug levels in fluid around the brain (cerebrospinal fluid). In addition, the researchers wanted to measure indicators (biomarkers) in blood that show whether BIIB122 has inhibited the LRRK2 protein.Who Took Part in the Study?
Participants with PD, aged between 30 and 75 years, were given either BIIB122 (low, medium or high dose) or placebo once daily by mouth for 28 days. The placebo looked identical to BIIB122 but contained no BIIB122. A total of 36 participants were enrolled in the study and received treatment (27 participants were male and 9 were female). Twenty-six participants received BIIB122 and 10 received placebo; participants and investigators were unaware of the treatment assignments.What Were the Study Results?
BIIB122 was generally safe and well tolerated when given to participants with PD once daily for 28 days. No participants had a serious reaction (adverse events that result in death, require either inpatient hospitalization or the prolongation of hospitalization, are life-threatening, result in a persistent or significant disability/incapacity or result in a congenital anomaly/birth defect) after taking BIIB122. The most common reaction (an unexpected medical problem that happens during treatment with a drug) in participants who received BIIB122 was headache (11 participants [42.3%] on BIIB122 compared with 2 [20.0%] participants on placebo). Four participants had low blood pressure (hypotension) while taking BIIB122, which led to discontinuation of BIIB122 in 2 participants; the remaining 2 participants had resolution of hypotension while continuing treatment with BIIB122. There was no meaningful change (increase or decrease) in PD symptoms in participants treated with BIIB122, however there was no anticipated change given the short treatment period.
BIIB122 was found in blood and was also found in abundance in cerebrospinal fluid, indicating that BIIB122 could reach the brain, the site where the drug may have an impact on the changes that occur in PD. A decrease in biomarkers in blood were seen with BIIB122 treatment compared with placebo treatment, showing that the drug had inhibited LRRK2.Conclusions
The results of this study show that BIIB122 was generally safe and well tolerated in participants with PD at doses that inhibited LRRK2, the protein it targets. This study provides support for testing BIIB122 in additional, larger and longer clinical studies as a potential treatment for patients with PD.REC name
North East - York Research Ethics Committee
REC reference
19/NE/0250
Date of REC Opinion
26 Jul 2019
REC opinion
Further Information Favourable Opinion