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

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Primary Purpose

Status

Not yet recruiting

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

ARO-SOD1 Injection

Placebo: ARO-aCSF1 Injection

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of ALS based on source-verifiable medical record 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 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 during the study and for at least 12 weeks 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 12 weeks 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 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ARO-SOD-1

ARO-aCSF1

Arm Description

ARO-SOD-1 Injection

ARO-aCSF1 Injection (artificial CSF)

Outcomes

Primary Outcome Measures

Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

Secondary Outcome Measures

Change Over Time from Baseline in CSF SOD1 Protein Levels

Change Over Time from Baseline in Plasma Levels of Neurofilament Light Chain (NfL)

Pharmacokinetics (PK) of ARO-SOD1: Maximum Observed Plasma Concentration (Cmax)

PK of ARO-SOD1: Time to Reach Maximum Observed Plasma Concentration (Tmax)

PK of ARO-SOD1: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)

PK of ARO-SOD1: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)

PK of ARO-SOD1: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf)

PK of ARO-SOD1: Terminal Elimination Half-Life (t1/2)

PK of ARO-SOD1: Apparent Systemic Clearance (CL/F)

PK of ARO-SOD1: Recovery of Unchanged Drug in Urine Over 0-24 Hours (Amount Excreted: Ae)

PK of ARO-SOD1: Percentage of Administered Drug Recovered in Urine Over 0-24 Hours

PK of ARO-SOD1: Renal Clearance (CLr)

Change From Baseline in Total Protein in CSF

Change From Baseline in Glucose in CSF

Change From Baseline in Cell Count in CSF

Full Information

NCT ID

NCT05949294

First Posted

July 8, 2023

Last Updated

July 8, 2023

Sponsor

Arrowhead Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05949294

Brief Title

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

Official Title

A Phase 1 Randomized Placebo-Controlled 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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

October 2023 (Anticipated)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Arrowhead Pharmaceuticals

4. Oversight

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

Data Monitoring Committee

No

5. Study Description

Brief Summary

In this Phase 1 double-blind, placebo-controlled study, adult symptomatic patients with amyotrophic lateral sclerosis (ALS) carrying a superoxide dismutase 1 (SOD1) gene mutation thought to be causative of ALS, will be randomized to 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. Participants whose SOD1 CSF levels have recovered to a satisfactory level may rescreen and rerandomize 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ARO-SOD-1

Arm Type

Experimental

Arm Description

ARO-SOD-1 Injection

Arm Title

ARO-aCSF1

Arm Type

Placebo Comparator

Arm Description

ARO-aCSF1 Injection (artificial CSF)

Intervention Type

Drug

Intervention Name(s)

ARO-SOD1 Injection

Intervention Description

single doses of ARO-SOD1 Injection by IT infusion

Intervention Type

Drug

Intervention Name(s)

Placebo: ARO-aCSF1 Injection

Other Intervention Name(s)

artificial CSF

Intervention Description

single doses of ARO-aCSF1 Injection by IT infusion, calculated volume to match active treatment

Primary Outcome Measure Information:

Title

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)

Secondary Outcome Measure Information:

Title

Change Over Time from Baseline in CSF SOD1 Protein Levels

Time Frame

Pre-dose on Day 1 (Baseline) through EOS (up to 168 days)

Title

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)

Title

Pharmacokinetics (PK) of ARO-SOD1: Maximum Observed Plasma Concentration (Cmax)

Time Frame