Study to Evaluate DNL201 in Subjects With Parkinson's Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03710707
• Date of registration: 15/10/2018
• Prospective Registration: Yes
• Primary sponsor: Denali Therapeutics Inc.
• Public title: Study to Evaluate DNL201 in Subjects With Parkinson's Disease
• Scientific title: A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Determine the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL201 in Subjects With Parkinson's Disease
• Date of first enrolment: December 4, 2018
• Target sample size: 29
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03710707
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

United States

Key inclusion & exclusion criteria

Key Inclusion Criteria:

- Body mass index (BMI) between 18 and 35.0 kg/m2, inclusive

- Clinical diagnosis of Parkinson's disease meeting UK Brain Bank criteria and H&Y Stage
I, II, or III.

- sPD subgroup without a LRRK2 mutation; PD LRRK2 subgroup with LRRK2 mutation

- Screening dopamine transporter (DAT) SPECT scan with a DAT deficit consistent with
Parkinson's disease

- Able to hold Parkinson's disease medications 8 hours (overnight) prior to specific
study assessments

Key Exclusion Criteria:

- Any history of clinically significant asthma, chronic obstructive pulmonary disease,
or emphysema within 5 years of screening, or other clinically significant pulmonary
disease within 6 months of screening

- Abnormal Vitals including Respiratory Rate, Body Temperature, and Blood Pressure

- Pulmonary Function Tests (PFTs) (FVC <60% predicted, FEV1 <50% predicted, FEV1:FVC
ratio <0.6, DLCO <70% predicted)

- Clinically significant neurologic disorder other than Parkinson's disease, including
history of stroke, cognitive impairment, seizure within 5 years of screening, or head
trauma with loss of consciousness within 6 months of screening

- Montreal Cognitive Assessment (MoCA) score of <24 at screening



Age minimum: 30 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Intervention(s)

Drug: DNL201

Drug: Placebo

Primary Outcome(s)

Number of Subjects with electrocardiogram (ECG) abnormalities [Time Frame: Randomization to Day 42]

Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Randomization to Day 42]

Number of Subjects with laboratory test abnormalities [Time Frame: Randomization to Day 42]

Number of Subjects with clinically significant neurological examination abnormalities [Time Frame: Randomization to Day 42]

Number of Subjects with vital sign abnormalities [Time Frame: Randomization to Day 42]

Secondary Outcome(s)

Pharmacodynamic measure of pRab10 in PBMCs [Time Frame: Randomization to Day 28]

Pharmacodynamic measure of pS935 in whole blood and/or PBMCs [Time Frame: Randomization to Day 28]

Pharmacokinetic measure of CSF concentrations of DNL201 [Time Frame: Randomization to Day 28]

Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL201 [Time Frame: Randomization to Day 28]

Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL201 [Time Frame: Randomization to Day 28]

Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL201 [Time Frame: Randomization to Day 28]

Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL201 [Time Frame: Randomization to Day 28]

Secondary ID(s)

DNLI-B-0002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors