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:




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

Clinical Operations / email hidden; JavaScript is required / 855-215-4687

Study Sponsor:

Wave Life Sciences Ltd.

Estimated Enrollment:


Estimated Study Start Date:

06 / 28 / 2021

Estimated Study Completion Date:

02 / 01 / 2023

Posting Last Modified Date:

09 / 01 / 2022

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 | Recruiting

Principal Investigator : Dominic Rowe, AM BSc, MBBS, PhD

North Ryde, New South Wales 2109

The Wesley Hospital | Recruiting

Principal Investigator : Robert Henderson, MD, PhD

Brisbane, Queensland QLD 4066

Perron Institute | Recruiting

Principal Investigator : Merrilee Needham, MBBS, PhD, FRACP

Nedlands, Western Australia 6009

UZ Leuven | Recruiting

Rik Vandenberghe, MD, PhD / 016344280 / email hidden; JavaScript is required

Principal Investigator : Rick Vandenberghe, MD, PhD

Leuven 3000

Sunnybrook Health Sciences Centre | Recruiting

Principal Investigator : Mario Masellis, MD, PhD, M.Sc., Hon B.Sc,

Toronto, Ontario M4N 3M5

McGill University Health Center - Research Institute | Recruiting

/ email hidden; JavaScript is required

/ email hidden; JavaScript is required

Principal Investigator : Simon Ducharme, MD, MSc, FRCPC

Montréal, Quebec

St James Hospital - Ireland | Recruiting

Principal Investigator : Orla Hardiman, BSc MB BCh BAO MD FRCPI FAAN

Dublin D08 NHY1

Universitair Medisch Centrum Utrecht | Recruiting

Principal Investigator : Leonard van den Berg, MD, PhD


Erasmus University MC | Recruiting

Principal Investigator : Harro Seelar, MD, PhD, MSc

Rotterdam 3015

Auckland City Hospital | Recruiting

Principal Investigator : Julian Bauer, MD

Auckland 1023
New Zealand

New Zealand Brain Research Institute | Recruiting

Principal Investigator : John Anderson, BSc(Hons), MBChB, MD, FRACP

Christchurch 8011
New Zealand

Karolinska University Hospital | Recruiting

Principal Investigator : Anne B Hanson, MD, PhD


University of Cambridge | Recruiting

Principal Investigator : James Rowe, MD, PhD

United Kingdom

University College London Hospital | Recruiting

Principal Investigator : Jonathan Rohrer, MD, PhD

London WC1N 3BG
United Kingdom

King's College Hospital | Recruiting

Principal Investigator : Christopher Shaw, MD, FRACP

London WC2R 2LS
United Kingdom

University of Oxford - Nuffield Department of Clinical Neurosciences | Recruiting

Principal Investigator : Kevin Talbot, MB BS, DPhil, FRCP

Oxford OX3 7LF
United Kingdom

University of Sheffield | Recruiting

Jonathan Cooper-Knock, MD, PhD / email hidden; JavaScript is required

Principal Investigator : Jonathan Cooper-Knock, MD, PhD

Sheffield S10 2TN
United Kingdom