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Study to Evaluate DNL201 in Subjects With Parkinson's Disease

Primary Purpose

Parkinson Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
DNL201
Placebo
Sponsored by
Denali Therapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring LRRK2, Parkinson's Disease, Movement Disorders

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Clinical Site(s)
  • Clinical Site(s)
  • Clinical Site(s)
  • Clinical Site(s)
  • Clinical Site(s)
  • Clinical Site(s)
  • Clinical Site(s)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

DNL201 low dose

DNL201 high dose

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of Subjects with laboratory test abnormalities
Number of Subjects with vital sign abnormalities
Number of Subjects with electrocardiogram (ECG) abnormalities
Number of Subjects with clinically significant neurological examination abnormalities

Secondary Outcome Measures

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

Full Information

First Posted
October 15, 2018
Last Updated
January 8, 2020
Sponsor
Denali Therapeutics Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03710707
Brief Title
Study to Evaluate DNL201 in Subjects With Parkinson's Disease
Official 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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
December 4, 2018 (Actual)
Primary Completion Date
December 6, 2019 (Actual)
Study Completion Date
December 6, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Denali Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
Keywords
LRRK2, Parkinson's Disease, Movement Disorders

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DNL201 low dose
Arm Type
Experimental
Arm Title
DNL201 high dose
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
DNL201
Intervention Description
Oral repeating dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral repeating dose
Primary Outcome Measure Information:
Title
Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Randomization to Day 42
Title
Number of Subjects with laboratory test abnormalities
Time Frame
Randomization to Day 42
Title
Number of Subjects with vital sign abnormalities
Time Frame
Randomization to Day 42
Title
Number of Subjects with electrocardiogram (ECG) abnormalities
Time Frame
Randomization to Day 42
Title
Number of Subjects with clinically significant neurological examination abnormalities
Time Frame
Randomization to Day 42
Secondary Outcome Measure Information:
Title
Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL201
Time Frame
Randomization to Day 28
Title
Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL201
Time Frame
Randomization to Day 28
Title
Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL201
Time Frame
Randomization to Day 28
Title
Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL201
Time Frame
Randomization to Day 28
Title
Pharmacokinetic measure of CSF concentrations of DNL201
Time Frame
Randomization to Day 28
Title
Pharmacodynamic measure of pS935 in whole blood and/or PBMCs
Time Frame
Randomization to Day 28
Title
Pharmacodynamic measure of pRab10 in PBMCs
Time Frame
Randomization to Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Clinical Site(s)
City
Long Beach
State/Province
California
ZIP/Postal Code
90808
Country
United States
Facility Name
Clinical Site(s)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Clinical Site(s)
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Clinical Site(s)
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Clinical Site(s)
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
Clinical Site(s)
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Clinical Site(s)
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States

12. IPD Sharing Statement

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Study to Evaluate DNL201 in Subjects With Parkinson's Disease

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