Study to Evaluate DNL151 in Subjects With Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT04056689
• Recruitment Status: Completed
• First Posted: August 14, 2019
• Last Update Posted: January 19, 2021
• Sponsor: Denali Therapeutics Inc.
• Information provided by (Responsible Party): Denali Therapeutics Inc.

Tracking Information

• First Submitted Date: August 12, 2019
• First Posted Date: August 14, 2019
• Last Update Posted Date: January 19, 2021
• Actual Study Start Date: July 23, 2019
• Actual Primary Completion Date: December 2, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2019)

• 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 vital sign abnormalities [ Time Frame: Randomization to Day 42 ]
• Number of Subjects with electrocardiogram (ECG) abnormalities [ Time Frame: Randomization to Day 42 ]
• Number of Subjects with clinically significant neurological examination abnormalities [ Time Frame: Randomization to Day 42 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 12, 2019)

• Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL151 [ Time Frame: Randomization to Day 28 ]
• Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL151 [ Time Frame: Randomization to Day 28 ]
• Pharmacokinetic measure of trough plasma observed concentration (Ctrough) of DNL151 [ Time Frame: Randomization to Day 28 ]
• Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL151 [ Time Frame: Randomization to Day 28 ]
• Pharmacokinetic measure of CSF concentrations of DNL151 [ Time Frame: Randomization to Day 28 ]
• Pharmacodynamic measure of pS935 in whole blood [ Time Frame: Randomization to Day 28 ]
• Pharmacodynamic measure of pRab10 in PBMCs [ Time Frame: Randomization to Day 28 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate DNL151 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 DNL151 in Subjects With Parkinson's Disease
• Brief Summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL151 in subjects with Parkinson's disease.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Parkinson's Disease

Intervention

• Drug: DNL151
  Oral repeating dose
• Drug: Placebo
  Oral repeating dose

Study Arms

• Experimental: DNL151 Low Dose
  Intervention: Drug: DNL151
• Experimental: DNL151 Mid Dose
  Intervention: Drug: DNL151
• Experimental: DNL151 High Dose
  Intervention: Drug: DNL151
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 15, 2021): 36
• Original Estimated Enrollment (submitted: August 12, 2019): 24
• Actual Study Completion Date: December 2, 2020
• Actual Primary Completion Date: December 2, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

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, Blood Pressure, and Pulse Rate
• 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 within 12 months of screening, 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT04056689
• Other Study ID Numbers: DNLI-C-0003
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Denali Therapeutics Inc.
• Study Sponsor: Denali Therapeutics Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Andrés Cruz-Herranz; Denali Therapeutics Inc.

• PRS Account: Denali Therapeutics Inc.
• Verification Date: January 2021