Study of AROSOD-1 in Adult Participants With Amyotrophic Lateral Sclerosis (ALS)

April 16, 2024 updated by: Arrowhead Pharmaceuticals

A Phase 1 Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ARO-SOD1 in Adult Patients With Amyotrophic Lateral Sclerosis Harboring a Superoxide Dismutase-1 Mutation Considered to be Causative of Amyotrophic Lateral Sclerosis

In this Phase 1 adult symptomatic patients with amyotrophic lateral sclerosis (ALS) carrying a superoxide dismutase 1 (SOD1) gene mutation thought to be causative of ALS, will receive single ascending doses of ARO-SOD1 administered by intrathecal (IT) infusion. The study is primarily intended to evaluate safety, but will also evaluate the effect of ARO-SOD1 on SOD1 cerebrospinal fluid (CSF) levels as a biomarker of pharmacodynamic (PD) effect, therefore lumbar punctures will be required at timepoints throughout the study. After each participant has completed their individual final visit, participants whose SOD1 CSF levels have recovered to a satisfactory level may rescreen and enroll into higher dose cohorts; or if unable or unwilling to rescreen may enroll into an open-label study to be added by amendment when supported by nonclinical data for multidose administration.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of ALS based on source-verifiable medical record and meets the Gold Coast Criteria
  • Pathogenic or likely pathogenic SOD1 mutation based on source-verifiable medical records or genetic testing during Screening
  • Slow Vital Capacity (SVC) ≥ 50% of predicted value adjusted for sex, age, and height (from a sitting position) at Screening
  • Body Mass Index (BMI) ≥ 18.0 kg/m2 at Screening
  • Able to complete at least 6 months of follow-up
  • If taking any medication or supplement to treat ALS or ALS symptoms, must be on stable dose for ≥ 4 weeks prior to Day 1 and expected to remain at that dose until final study visit and not expected to start these medications after the first dose of ARO-SOD1
  • Able and willing to provide written informed consent and to comply with all study assessments
  • Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of study or last dose of study drug, whichever is later. Males must not donate sperm and females must not donate eggs during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later.

Exclusion Criteria:

  • Current or anticipated need of a diaphragm pacing system (DPS) during the study
  • Participants using tofersen can be enrolled only after a washout period of approximately 20 weeks from the last tofersen dose to the first planned dose of ARO-SOD1
  • History of having received stem cell therapy for ALS treatment
  • Any current or anticipated contraindications to lumbar puncture (LP)
  • The presence of an implanted shunt for drainage of CSF or an implanted central nervous system (CNS) catheter
  • Human immunodeficiency virus (HIV), seropositive for hepatitis B virus (HBV), seropositive for hepatitis C virus (HCV)
  • Uncontrolled hypertension
  • Severe cardiovascular disease
  • History of drug abuse or alcoholism within 6 months of study enrollment
  • Inability to comply with study requirements

Note: additional inclusion/exclusion criteria may apply per protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ARO-SOD1
ARO-SOD1 Injection
Drug: ARO-SOD1 Injection
single doses of ARO-SOD1 Injection by IT infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From first dose of study drug through the end of study (EOS; up to 168 days)
From first dose of study drug through the end of study (EOS; up to 168 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Change Over Time from Baseline in CSF SOD1 Protein Levels
Time Frame: Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)
Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)
Change Over Time from Baseline in Plasma Levels of Neurofilament Light Chain (NfL)
Time Frame: Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)
Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)
Pharmacokinetics (PK) of ARO-SOD1: Maximum Observed Plasma Concentration (Cmax)
Time Frame: Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
PK of ARO-SOD1: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
PK of ARO-SOD1: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
Time Frame: Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
PK of ARO-SOD1: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)
Time Frame: Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
PK of ARO-SOD1: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf)
Time Frame: Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
PK of ARO-SOD1: Terminal Elimination Half-Life (t1/2)
Time Frame: Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
PK of ARO-SOD1: Apparent Systemic Clearance (CL/F)
Time Frame: Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
Days 1, 2, 15, 29, 57, 85 and EOS (Day 168): Pre-dose, post-dose at 1, 3, 5, 7, 12 and 24 hours
PK of ARO-SOD1: Recovery of Unchanged Drug in Urine Over 0-24 Hours (Amount Excreted: Ae)
Time Frame: Pre-dose through 24 hours post-dose
Pre-dose through 24 hours post-dose
PK of ARO-SOD1: Percentage of Administered Drug Recovered in Urine Over 0-24 Hours
Time Frame: Pre-dose through 24 hours post-dose
Pre-dose through 24 hours post-dose
PK of ARO-SOD1: Renal Clearance (CLr)
Time Frame: Pre-dose through 24 hours post-dose
Pre-dose through 24 hours post-dose
Change From Baseline in Total Protein in CSF
Time Frame: Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)
Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)
Change From Baseline in Glucose in CSF
Time Frame: Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)
Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)
Change From Baseline in Cell Count in CSF
Time Frame: Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)
Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Arrowhead Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 8, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 8, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 18, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 17, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 16, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AROSOD1-1001
  • 2023-509032-26 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings