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)

Study Purpose:

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.

Study Status:

Not recruiting



Study Type:


Type of Intervention:


Intervention Name:

WVE-004, Placebo




Phase 1/Phase 2

Study Chair(s)/Principal Investigator(s):

Medical Director, MD, Wave Life Sciences

Clinicaltrials.gov ID:


Neals Affiliated?


Coordinating Center Contact Information

Study Sponsor:

Wave Life Sciences Ltd.

Estimated Enrollment:


Estimated Study Start Date:

06 / 28 / 2021

Estimated Study Completion Date:

12 / 01 / 2023

Posting Last Modified Date:

02 / 03 / 2023

Date Study Added to neals.org:

06 / 18 / 2021

Minimum Age:

18 Years

Maximum Age:

80 Years

Inclusion Criteria:

1. ALS-specific: Diagnosis of ALS based on clinical manifestations.

2. 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.

3. ALS-specific: Patients receiving riluzole have been on a stable dose for a minimum of 30 days.

4. ALS-specific: Patients on edaravone have received a minimum of 1 cycle (28 days).

5. ALS-specific: Patients discontinuing riluzole or edaravone had the last dose administered ≥1 month prior to Screening.

6. FTD-specific: Must have Global Clinical Dementia Rating - Frontotemporal Lobar Degeneration (CDR® plus NACC FTLD) score of 0.5 or 1.

7. 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.

8. Mixed-phenotype: Patients who are mixed phenotype (ALS and FTD) must meet both the ALS-specific and FTD-specific criteria.

Exclusion Criteria:

1. 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

2. 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.

Macquarie University

North Ryde, New South Wales 2109

The Wesley Hospital

Brisbane, Queensland QLD 4066

Perron Institute

Nedlands, Western Australia 6009

UZ Leuven

Leuven 3000

Sunnybrook Health Sciences Centre

Toronto, Ontario M4N 3M5

McGill University Health Center - Research Institute

Montréal, Quebec

St James Hospital - Ireland

Dublin D08 NHY1

Universitair Medisch Centrum Utrecht


Erasmus University MC

Rotterdam 3015

Auckland City Hospital

Auckland 1023
New Zealand

New Zealand Brain Research Institute

Christchurch 8011
New Zealand

Karolinska University Hospital


University of Cambridge

United Kingdom

University College London Hospital

London WC1N 3BG
United Kingdom

King's College Hospital

London WC2R 2LS
United Kingdom

University of Oxford - Nuffield Department of Clinical Neurosciences

Oxford OX3 7LF
United Kingdom

University of Sheffield

Sheffield S10 2TN
United Kingdom