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

Phase 1

Terminated

• Conditions: ALS; FTD
• Interventions: Drug: WVE-004; Drug: Placebo

• Registration Number: NCT04931862
• Lead Sponsor: Wave Life Sciences Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-11
• Study First Submitted QC: 2021-06-11
• Study First Posted: 2021-06-18
• Study Start: 2021-06-28
• Primary Completion: 2023-06-27
• Study Completion: 2023-06-27
• Status Verified: 2023-08
• Last Update Submitted: 2023-10-18
• Last Update Posted: 2023-10-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 35

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
WVE-004 (Dose D) or placebo	WVE-004	-
WVE-004 (Dose A) or placebo	WVE-004	-
WVE-004 (Dose A) or placebo	Placebo	-
WVE-004 (Dose B) or placebo	WVE-004	-
WVE-004 (Dose B) or placebo	Placebo	-
WVE-004 (Dose C) or placebo	Placebo	-
WVE-004 (Dose C) or placebo	WVE-004	-
WVE-004 (Dose D) or placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Safety: Proportion of patients with adverse events (AEs)	Period 1 Day 1 to Period 2 Week 24 (end of study)

Secondary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (17)

Perron Institute; 🇦🇺 Nedlands, Western Australia, Australia

Erasmus University MC; 🇳🇱 Rotterdam, Netherlands

McGill University Health Center - Research Institute; 🇨🇦 Montréal, Quebec, Canada

St James Hospital - Ireland; 🇮🇪 Dublin, Ireland

Macquarie University; 🇦🇺 North Ryde, New South Wales, Australia

UZ Leuven; 🇧🇪 Leuven, Belgium

Karolinska University Hospital; 🇸🇪 Solna, Sweden

Auckland City Hospital; 🇳🇿 Auckland, New Zealand

Universitair Medisch Centrum Utrecht; 🇳🇱 Utrecht, Netherlands

University of Cambridge; 🇬🇧 Cambridge, United Kingdom

University College London Hospital; 🇬🇧 London, United Kingdom

King's College Hospital; 🇬🇧 London, United Kingdom

University of Sheffield; 🇬🇧 Sheffield, United Kingdom

University of Oxford - Nuffield Department of Clinical Neurosciences; 🇬🇧 Oxford, United Kingdom

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

New Zealand Brain Research Institute; 🇳🇿 Christchurch, New Zealand

The Wesley Hospital; 🇦🇺 Brisbane, Queensland, Australia