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

ALS Clinical Trial

— FOCUS-C9  

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04931862
• Other study ID #: WVE-004-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 28, 2021
• Est. completion date: June 27, 2023

Study information

• Verified date: August 2023
• Source: Wave Life Sciences Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: June 27, 2023
• Est. primary completion date: June 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• ALS
• Amyotrophic Lateral Sclerosis
• Aphasia, Primary Progressive
• Frontotemporal Dementia
• FTD
• Motor Neuron Disease
• Pick Disease of the Brain

Intervention

Drug:
• WVE-004
WVE-004 is a stereopure antisense oligonucleotide (ASO)
• Placebo
Artificial cerebrospinal fluid (aCSF)

Locations

Country	Name	City	State
Australia	The Wesley Hospital	Brisbane	Queensland
Australia	Perron Institute	Nedlands	Western Australia
Australia	Macquarie University	North Ryde	New South Wales
Belgium	UZ Leuven	Leuven
Canada	McGill University Health Center - Research Institute	Montréal	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Ireland	St James Hospital - Ireland	Dublin
Netherlands	Erasmus University MC	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
New Zealand	Auckland City Hospital	Auckland
New Zealand	New Zealand Brain Research Institute	Christchurch
Sweden	Karolinska University Hospital	Solna
United Kingdom	University of Cambridge	Cambridge
United Kingdom	King's College Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	University of Oxford - Nuffield Department of Clinical Neurosciences	Oxford
United Kingdom	University of Sheffield	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
Wave Life Sciences Ltd.

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  Ireland,  Netherlands,  New Zealand,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Proportion of patients with adverse events (AEs)		Period 1 Day 1 to Period 2 Week 24 (end of study)
Secondary	Pharmacokinetic: Concentration of WVE-004 in cerebrospinal fluid (CSF)		Period 1 Day 1 to Period 2 Week 24 (end of study)
Secondary	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)