Clinical Trials/NCT04931862

NCT04931862

Terminated

Phase 1

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-004 Administered Intrathecally to Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD)

Wave Life Sciences Ltd.17 sites in 8 countries35 target enrollmentJune 28, 2021

ConditionsALS FTD

InterventionsWVE-004 Placebo

DrugsWVE-004 Placebo

Overview

Phase: Phase 1
Intervention: WVE-004
Conditions: ALS
Sponsor: Wave Life Sciences Ltd.
Enrollment: 35
Locations: 17
Primary Endpoint: Safety: Proportion of patients with adverse events (AEs)
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

This is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of intrathecal (IT) WVE-004 in adult patients with C9orf72-associated ALS or FTD. To participate in the study, patients must have a documented mutation (GGGGCC [G4C2] repeat expansion) in the first intronic region of the C9orf72 gene and be diagnosed with ALS or FTD.

Registry

clinicaltrials.gov

Start Date

June 28, 2021

End Date

June 27, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Wave Life Sciences Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•ALS-specific: Diagnosis of ALS based on clinical manifestations.
•ALS-specific: Clinically diagnosed possible, laboratory supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology revised El Escorial criteria.
•ALS-specific: Patients receiving riluzole have been on a stable dose for a minimum of 30 days.
•ALS-specific: Patients on edaravone have received a minimum of 1 cycle (28 days).
•ALS-specific: Patients discontinuing riluzole or edaravone had the last dose administered ≥1 month prior to Screening.
•FTD-specific: Must have Global Clinical Dementia Rating - Frontotemporal Lobar Degeneration (CDR® plus NACC FTLD) score of 0.5 or
•FTD-specific: Able to undergo periodic magnetic resonance imaging (MRI) of the brain. Participants with mixed phenotype (ALS and FTD) need not undergo MRI if their ALS symptoms prevent it.
•Mixed-phenotype: Patients who are mixed phenotype (ALS and FTD) must meet both the ALS-specific and FTD-specific criteria.

Exclusion Criteria

•Clinically significant medical finding on the physical examination other than C9orf72-associated ALS or FTD that, in the judgment of the Investigator, will make the patient unsuitable for participation in, and/or completion of the trial procedures
•Received any other investigational drug, biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Received an investigational oligonucleotide, within the past 6 months or 5 half-lives of the drug, whichever is longer.

Arms & Interventions

WVE-004 (Dose C) or placebo

Intervention: WVE-004

WVE-004 (Dose C) or placebo

Intervention: Placebo

WVE-004 (Dose A) or placebo

Intervention: WVE-004

WVE-004 (Dose A) or placebo

Intervention: Placebo

WVE-004 (Dose B) or placebo

Intervention: WVE-004

WVE-004 (Dose B) or placebo

Intervention: Placebo

WVE-004 (Dose D) or placebo

Intervention: WVE-004

WVE-004 (Dose D) or placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Safety: Proportion of patients with adverse events (AEs)

Time Frame: Period 1 Day 1 to Period 2 Week 24 (end of study)

Secondary Outcomes

Pharmacodynamic: Change from baseline in concentration of poly-GP levels in the CSF(Period 1 Day 1 to Period 2 Week 24 (end of study))
Pharmacokinetic: Concentration of WVE-004 in cerebrospinal fluid (CSF)(Period 1 Day 1 to Period 2 Week 24 (end of study))