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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04931862




Registration number
NCT04931862
Ethics application status
Date submitted
11/06/2021
Date registered
18/06/2021
Date last updated
23/10/2023

Titles & IDs
Public title
Study of WVE-004 in Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD)
Scientific 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)
Secondary ID [1] 0 0
WVE-004-001
Universal Trial Number (UTN)
Trial acronym
FOCUS-C9
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ALS 0 0
FTD 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Dementias
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - WVE-004
Treatment: Drugs - Placebo

Experimental: WVE-004 (Dose A) or placebo -

Experimental: WVE-004 (Dose B) or placebo -

Experimental: WVE-004 (Dose C) or placebo -

Experimental: WVE-004 (Dose D) or placebo -


Treatment: Drugs: WVE-004
WVE-004 is a stereopure antisense oligonucleotide (ASO)

Treatment: Drugs: Placebo
Artificial cerebrospinal fluid (aCSF)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety: Proportion of patients with adverse events (AEs)
Timepoint [1] 0 0
Period 1 Day 1 to Period 2 Week 24 (end of study)
Secondary outcome [1] 0 0
Pharmacokinetic: Concentration of WVE-004 in cerebrospinal fluid (CSF)
Timepoint [1] 0 0
Period 1 Day 1 to Period 2 Week 24 (end of study)
Secondary outcome [2] 0 0
Pharmacodynamic: Change from baseline in concentration of poly-GP levels in the CSF
Timepoint [2] 0 0
Period 1 Day 1 to Period 2 Week 24 (end of study)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/06/2023
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Macquarie University - North Ryde
Recruitment hospital [2] 0 0
The Wesley Hospital - Brisbane
Recruitment hospital [3] 0 0
Perron Institute - Nedlands
Recruitment postcode(s) [1] 0 0
2109 - North Ryde
Recruitment postcode(s) [2] 0 0
QLD 4066 - Brisbane
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Leuven
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
Ireland
State/province [4] 0 0
Dublin
Country [5] 0 0
Netherlands
State/province [5] 0 0
Rotterdam
Country [6] 0 0
Netherlands
State/province [6] 0 0
Utrecht
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland
Country [8] 0 0
New Zealand
State/province [8] 0 0
Christchurch
Country [9] 0 0
Sweden
State/province [9] 0 0
Solna
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Cambridge
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Oxford
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Wave Life Sciences Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04931862
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director, MD
Address 0 0
Wave Life Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04931862