Clinical trial NCT05006352: A Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis
Official title: A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study, Followed by an Open-Label Extension, to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Lead sponsor: Denali Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-16
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.).

Eligibility 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period
timeFrame: 28 Days
Secondary outcomes:
measure: PK parameter: Maximum concentration (Cmax) of DNL343 in plasma
timeFrame: 19 months
measure: PK parameter: Time to reach maximum concentration (tmax) of DNL343 in plasma
timeFrame: 19 months
measure: PK parameter: Trough concentration (Ctrough) of DNL343 in plasma
timeFrame: 19 months
measure: PK parameter: Area under the concentration-time curve from time zero to 24 hours (AUC24) of DNL343 in plasma
timeFrame: 19 months
measure: Cerebrospinal fluid-to-plasma concentration ratio of DNL343 following multiple oral doses
timeFrame: 19 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Orlando
country: United States
facility: PPD Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Charlotte
country: United States
facility: Atrium Health Neurosciences Institute
state: North Carolina
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research (CHDR)
state: South Holland
Study officials:
affiliation: Denali Therapeutics Inc.
name: Linus Sun, MD, PhD
role: STUDY_DIRECTOR
References: