A Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of DNL343 in Participants With Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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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
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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.).

Official Title
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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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: DNL343
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DNL343 (High Dose)<br> | Drug: DNL343<br>* Oral repeating dose<br>|
| Experimental: DNL343 (Low Dose)<br> | Drug: DNL343<br>* Oral repeating dose<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) throughout the double-blind period |  | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS