Study of WVE-004 in Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD)

NCT04931862 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: WVE-004-001
• Study Type: interventional
• Target: 35
• Locations: 8 countries
• Sites: 17

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.

Conditions

ALS; FTD

Outcome Measures

Primary Outcomes (1)

• Safety: Proportion of patients with adverse events (AEs)

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

Secondary Outcomes (2)

• Pharmacokinetic: Concentration of WVE-004 in cerebrospinal fluid (CSF)

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

• 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)

Study Arms (4)

WVE-004 (Dose A) or placebo

EXPERIMENTAL

Drug: WVE-004; Drug: Placebo

WVE-004 (Dose B) or placebo

EXPERIMENTAL

Drug: WVE-004; Drug: Placebo

WVE-004 (Dose C) or placebo

EXPERIMENTAL

Drug: WVE-004; Drug: Placebo

WVE-004 (Dose D) or placebo

EXPERIMENTAL

Drug: WVE-004; Drug: Placebo

Interventions

WVE-004 DRUG

WVE-004 is a stereopure antisense oligonucleotide (ASO)

WVE-004 (Dose A) or placebo; WVE-004 (Dose B) or placebo; WVE-004 (Dose C) or placebo; WVE-004 (Dose D) or placebo

Placebo DRUG

Artificial cerebrospinal fluid (aCSF)

WVE-004 (Dose A) or placebo; WVE-004 (Dose B) or placebo; WVE-004 (Dose C) or placebo; WVE-004 (Dose D) or placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wave Life Sciences Ltd.: lead

Study Sites (17)

Macquarie University

North Ryde, New South Wales, 2109, Australia

Location

The Wesley Hospital

Brisbane, Queensland, QLD 4066, Australia

Location

Perron Institute

Nedlands, Western Australia, 6009, Australia

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

McGill University Health Center - Research Institute

Montreal, Quebec, Canada

Location

St James Hospital - Ireland

Dublin, D08 NHY1, Ireland

Location

Erasmus University MC

Rotterdam, 3015, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

New Zealand Brain Research Institute

Christchurch, 8011, New Zealand

Location

Karolinska University Hospital

Solna, Sweden

Location

University of Cambridge

Cambridge, United Kingdom

Location

University College London Hospital

London, WC1N 3BG, United Kingdom

Location

King's College Hospital

London, WC2R 2LS, United Kingdom

Location

University of Oxford - Nuffield Department of Clinical Neurosciences

Oxford, OX3 7LF, United Kingdom

Location

University of Sheffield

Sheffield, S10 2TN, United Kingdom

Location

Study Officials

• Medical Director, MD

  Wave Life Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2021
• First Posted: June 18, 2021
• Study Start: June 28, 2021
• Primary Completion: June 27, 2023
• Study Completion: June 27, 2023
• Last Updated: October 23, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); NZ (2); GB (5); SE (1); AU (3); CA (2); IE (1); NL (2)