Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 23 May 2022
• Main ID: NCT03757351
• Date of registration: 27/11/2018
• Prospective Registration: Yes
• Primary sponsor: Sanofi
• Public title: Study to Evaluate DNL747 in Subjects With Amyotrophic Lateral Sclerosis
• Scientific 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
• Date of first enrolment: December 14, 2018
• Target sample size: 15
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03757351
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Netherlands, United States

Contacts

• Name: Clinical Sciences & Operations
• Affiliation: Sanofi

Key inclusion & exclusion criteria

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)



Age minimum: 21 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis

Intervention(s)

Drug: Placebo

Drug: DNL747

Primary Outcome(s)

Number of Subjects with laboratory test abnormalities [Time Frame: Randomization - Day 86]

Number of Subjects with clinically significant neurological examination abnormalities [Time Frame: Randomization - Day 86]

Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Randomization - Day 86]

Secondary Outcome(s)

Pharmacokinetic measure of CSF concentrations of DNL747 [Time Frame: Randomization - Day 86]

Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747 [Time Frame: Randomization - Day 86]

Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747 [Time Frame: Randomization - Day 86]

Pharmacodynamic measure of pS166 in PBMCs [Time Frame: Randomization - Day 86]

Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747 [Time Frame: Randomization - Day 86]

Pharmacokinetic terminal disposition rate constant (?z) with the respective t1/2 of DNL747 [Time Frame: Randomization - Day 86]

Secondary ID(s)

TDR16536

DNLI-D-0003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Denali Therapeutics Inc.