Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03757351
• Other study ID #: TDR16536
• Secondary ID: DNLI-D-0003
• Status: Terminated
• Phase: Phase 1
• Start date: December 14, 2018
• Est. completion date: June 18, 2020

Study information

• Verified date: March 2021
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 in a cross-over design

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: June 18, 2020
• Est. primary completion date: June 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

Key Inclusion Criteria (Double-Blind Part):

• 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

Key Exclusion Criteria (Double-Blind Part):

• 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

Key Inclusion Criteria (Open-Label Extension):

• Successful completion of both periods of the the double-blind, crossover part of the study

• Continued 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

Key Exclusion Criteria (Open-Label Extension):

• Presence of laboratory abnormalities, physical examination findings, or AEs determined to be clinically significant by the investigator from the double-blind part of the study that have not resolved by the final follow-up visit as part of the double-blind study period

• New diagnosis of clinically significant neurological disorder (other than frontal temporal lobe dementia)

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• DNL747
Repeating oral dose
• Placebo
Repeating oral dose

Locations

Country	Name	City	State
Netherlands	CHDR	Leiden	South Holland
United States	Bioclinica	Orlando	Florida
United States	PRA Health Sciences	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Denali Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		Randomization - Day 86
Primary	Number of Subjects with clinically significant neurological examination abnormalities		Randomization - Day 86
Primary	Number of Subjects with laboratory test abnormalities		Randomization - Day 86
Secondary	Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747		Randomization - Day 86
Secondary	Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747		Randomization - Day 86
Secondary	Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747		Randomization - Day 86
Secondary	Pharmacokinetic terminal disposition rate constant (?z) with the respective t1/2 of DNL747		Randomization - Day 86
Secondary	Pharmacokinetic measure of CSF concentrations of DNL747		Randomization - Day 86
Secondary	Pharmacodynamic measure of pS166 in PBMCs		Randomization - Day 86