Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS
Brief summary
This is a Phase 1b, multicenter, randomized, placebo-controlled, double-blind study of 28 days, followed by an 18-month open-label extension, designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL343 in participants with amyotrophic lateral sclerosis (ALS)
Detailed description
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
Interventions
DRUGDNL343
Oral repeating dose
DRUGPlacebo
Oral repeating dose
Sponsors
Denali Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of sporadic or familial ALS * ≤ 4 years since ALS symptom onset * Stable doses of approved ALS treatments (riluzole and/or edaravone) for at least 2 months prior to screening * Participants must be able to swallow the study intervention * Vital capacity \>50% predicted at screening * Women must have been surgically sterilized, be postmenopausal, or for participants of childbearing potential, must not be pregnant, and both the participant and the male partner must use highly effective contraception * Men, and sex partner if a woman of childbearing potential, must use highly effective contraception Key
Exclusion criteria
* Any history of unstable or poorly controlled psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders * Positive serum pregnancy test or currently lactating or breastfeeding * History of malignancy within 5 years * History of clinically significant neurologic disorders other than ALS
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period | 28 Days |
Secondary
| Measure | Time frame |
|---|---|
| PK parameter: Maximum concentration (Cmax) of DNL343 in plasma | 19 months |
| PK parameter: Time to reach maximum concentration (tmax) of DNL343 in plasma | 19 months |
| PK parameter: Trough concentration (Ctrough) of DNL343 in plasma | 19 months |
| PK parameter: Area under the concentration-time curve from time zero to 24 hours (AUC24) of DNL343 in plasma | 19 months |
| Cerebrospinal fluid-to-plasma concentration ratio of DNL343 following multiple oral doses | 19 months |
Countries
Netherlands, United States
Outcome results
None listed