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Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis

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ClinicalTrials.gov Identifier: NCT03757351
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : February 8, 2019
Sponsor:
Information provided by (Responsible Party):
Denali Therapeutics Inc.

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL747 in subjects with Amyotrophic Lateral Sclerosis when administered for 29 days in a cross-over design

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: DNL747 Drug: Placebo Phase 1

Detailed Description:
This is a Phase 1b randomized, placebo-controlled, double-blind, crossover study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL747 in subjects with Amyotrophic Lateral Sclerosis (ALS)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL747 in Subjects With Amyotrophic Lateral Sclerosis
Actual Study Start Date : December 28, 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019


Arm Intervention/treatment
Experimental: DNL747 First, Placebo Second
Subjects will receive DNL747 for 29 days for the first period and then will switch to placebo for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods.
Drug: DNL747
DNL747

Drug: Placebo
Placebo

Experimental: Placebo First, DNL747 Second
Subjects will receive placebo for 29 days for the first period and then will switch to DNL747 for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods.
Drug: DNL747
DNL747

Drug: Placebo
Placebo




Primary Outcome Measures :
  1. Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Randomization - Day 86 ]
  2. Number of Subjects with clinically significant neurological examination abnormalities [ Time Frame: Randomization - Day 86 ]
  3. Number of Subjects with laboratory test abnormalities [ Time Frame: Randomization - Day 86 ]

Secondary Outcome Measures :
  1. Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747 [ Time Frame: Randomization - Day 86 ]
  2. Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747 [ Time Frame: Randomization - Day 86 ]
  3. Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747 [ Time Frame: Randomization - Day 86 ]
  4. Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747 [ Time Frame: Randomization - Day 86 ]
  5. Pharmacokinetic measure of CSF concentrations of DNL747 [ Time Frame: Randomization - Day 86 ]
  6. Pharmacodynamic measure of pS166 in PBMCs [ Time Frame: Randomization - Day 86 ]


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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women of non-childbearing potential and men, aged 21−80 years
  • Willingness and ability to complete all aspects of the study; participant should be capable of completing assessments either alone or with help of a caregiver
  • Diagnosis of laboratory-supported probable, probable, or definite (sporadic or familial) ALS according to the El Escorial World Federation of Neurology revised research diagnostic criteria
  • Less than 3 years since symptom onset
  • Forced vital capacity (FVC) >50% predicted measured within 30 days of screening
  • If subject is taking approved ALS treatments (riluzole and/or edaravone), doses must be stable for ≥2 months prior to screening and subject is expected to stay on a stable regimen throughout the study

Exclusion Criteria:

  • History of a clinically significant non-ALS neurologic disorder (other than frontal temporal lobe dementia), including, but not limited to, muscular dystrophy, spinal stenosis, peripheral neuropathy, inherited neuropathies, AD, Parkinson's disease, Lewy body dementia, vascular dementia, Huntington's disease, epilepsy, stroke, multiple sclerosis, brain tumor, or brain infection or abscess
  • Unstable or poorly controlled comorbid disease process of any organ system currently requiring active treatment or likely to require treatment adjustment during the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03757351


Contacts
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Contact: Melissa Leedom 1 913 624 4970 Melissa.Leedom@iqvia.com

Locations
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Netherlands
CHDR Recruiting
Leiden, South Holland, Netherlands, 2333
Sponsors and Collaborators
Denali Therapeutics Inc.

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Responsible Party: Denali Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03757351     History of Changes
Other Study ID Numbers: DNLI-D-0003
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019

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

Additional relevant MeSH terms:
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Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases