First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS)

Official title

First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ALN-SOD in Participants With Amyotrophic Lateral Sclerosis and SOD1 Mutations

Overview

This study is researching an experimental drug called ALN-SOD (called "study drug"). This study is focused on people with Amyotrophic Lateral Sclerosis (ALS) caused by a change in a gene called the Superoxide Dismutase-1 (SOD1) gene. This type of ALS is known as "SOD1-ALS". This is the first time that ALN-SOD will be given to people. The aim of the study is to see how safe and tolerable the study drug is. The study is looking at several other research questions, including: * The effect the study drug has on specific biomarkers, which are substances in the blood or in the fluid that surrounds the brain and spinal cord, known as Cerebrospinal Fluid (CSF) * How much study drug is in the blood and in the CSF, at different times * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects) * What effects the study drug has on ALS symptoms

Interventions

• Drug ALN-SOD
  Administered per the protocol
• Other Diluent
  Administered per the protocol
• Drug Placebo (PB)
  Administered per the protocol

Primary outcome measures

• Incidence of Treatment-Emergent Adverse Event (TEAEs) in participants treated with ALN-SOD [Time frame: At week 4 and through week 228]
• Severity of TEAEs in participants treated with ALN-SOD [Time frame: At week 4 and through week 228]

Secondary outcome measures (11)

• Concentration of Neurofilament Light chain (NfL) in plasma over time [Time frame: Up to approximately week 228]
• Change in concentration of NfL in plasma over time [Time frame: Up to approximately week 228]
• Concentration of SOD1 protein in Cerebrospinal Fluid (CSF) over time [Time frame: Up to approximately week 228]
• Change in concentration of SOD1 protein in CSF over time [Time frame: Up to approximately week 228]
• Concentration of NfL in CSF over time [Time frame: Up to approximately week 228]
• Change in concentration of NfL in CSF over time [Time frame: Up to approximately week 228]
• Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) over time [Time frame: Up to approximately week 228]
• Concentration of ALN-SOD in plasma over time [Time frame: Up to approximately week 228]
• Concentration of ALN-SOD in CSF over time [Time frame: Up to approximately week 228]
• Incidence of Anti-Drug Antibodies (ADAs) to ALN-SOD in serum over time [Time frame: Up to approximately week 228]
• Titer of ADAs to ALN-SOD in serum over time [Time frame: Up to approximately week 228]

Eligibility criteria

Inclusion criteria

• Weakness attributable to ALS and a SOD1 variant that has been previously described as associated with ALS or is considered likely to cause ALS, as defined in the protocol
• Slow Vital Capacity (SVC) ≥50% predicted value based on age, gender and height, measured in upright position
• Body Mass Index (BMI) ≤35 kg/m2 at time of screening
• If participants are taking riluzole or edaravone, they must be on a stable dose for at least 4 weeks prior to initial dosing visit and are expected to remain at that dose until the end of the study
• Platelet count >50,000/microliter
• Has normal blood pressure readings, as defined in the protocol

Exclusion criteria

• Concurrent participation in another interventional clinical trial
• Has had a tracheostomy
• Has dementia, as assessed by the investigator
• Has uncontrolled psychiatric disease, including psychosis, active or recent suicidal ideation, untreated major depression, in the past 30 days
• Has a medical history of brain or spinal disease/injury that would interfere with the Lumbar Puncture (LP) process, CSF circulation or safety assessment, as defined in the protocol
• Presence of an implanted shunt for the drainage of CSF or an implanted Central Nervous System (CNS) catheter
• Presents any concern to the study investigator that might confound the results of the study or poses an additional risk to the participant by their participation in the study
• Was hospitalized (ie, >24 hours) for any reason other than ALS within 30 days of screening
• Has received treatment with tofersen within 6 months prior to screening

NOTE: Other protocol defined inclusion / exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 4 centers

• University of Alberta Hospital, Edmonton, Division of Neurology — Edmonton
• University Hospital - London Health Sciences Centre — London
• Sunnybrook Research Institute — Toronto
• Montreal Neurological Institute and Hospital — Montreal

Japan · 4 centers

• Hokkaido University Hospital — Sapporo
• Tokushima University Hospital — Tokushima
• Toho University Omori Medical Center — Ōta-ku
• Kyoto University Hospital — Kyoto

Australia · 3 centers

• Concord Repatriation General Hospital — Concord
• Macquarie University — Sydney
• Sunshine Coast University Hospital — Birtinya

Poland · 2 centers

• Medical University of Silesia — Zabrze
• MTZ Clinical Research powered by Pratia — Warsaw

South Korea · 2 centers

• Hanyang University Seoul Hospital — Seoul
• Seoul National University Hospital — Seoul

Taiwan · 2 centers

• Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City
• Taipei Veterans General Hospital — Taipei

Belgium · 1 center

• KU Leuven — Leuven

Germany · 1 center

• Universitaetsklinikum Ulm AoR — Ulm

Sweden · 1 center

• Noorlands University Hospital-Department of Neurology — Umeå

Identifiers

NCT: NCT06351592 · ALN-SOD-ALS-2351 · 2023-510344-20-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗