Study to Evaluate DNL201 in Subjects With Parkinson's Disease

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

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL201 in subjects with Parkinson's disease.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Placebo; Drug: DNL201

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90808
      • Clinical Site(s)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Clinical Site(s)
  • Florida
    • Miami, Florida, United States, 33143
      • Clinical Site(s)
    • Orlando, Florida, United States, 32806
      • Clinical Site(s)
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Clinical Site(s)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Clinical Site(s)
  • Washington
    • Spokane, Washington, United States, 99202
      • Clinical Site(s)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Oral repeating dose
EXPERIMENTAL: DNL201 low dose	Drug: DNL201; Oral repeating dose
EXPERIMENTAL: DNL201 high dose	Drug: DNL201; Oral repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Randomization to Day 42
Number of Subjects with laboratory test abnormalities	Randomization to Day 42
Number of Subjects with vital sign abnormalities	Randomization to Day 42
Number of Subjects with electrocardiogram (ECG) abnormalities	Randomization to Day 42
Number of Subjects with clinically significant neurological examination abnormalities	Randomization to Day 42

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamic measure of pRab10 in PBMCs	Randomization to Day 28
Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL201	Randomization to Day 28
Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL201	Randomization to Day 28
Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL201	Randomization to Day 28
Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL201	Randomization to Day 28
Pharmacokinetic measure of CSF concentrations of DNL201	Randomization to Day 28
Pharmacodynamic measure of pS935 in whole blood and/or PBMCs	Randomization to Day 28

Collaborators and Investigators

• Sponsor: Denali Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 4, 2018
• Primary Completion (ACTUAL): December 6, 2019
• Study Completion (ACTUAL): December 6, 2019

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 16, 2018
• First Posted (ACTUAL): October 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 8, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Movement Disorders; LRRK2
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: DNLI-B-0002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No