ALSPhase 1/2FOCUS-C9NCT04931862
Study of WVE-004 in Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD)
A Phase 1/2 study testing WVE-004 in people with ALS and FTD, run by Wave Life Sciences USA, Inc. at 17 sites in 8 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- What is being tested?
- WVE-004
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 17 sitesin 8 countries
- Study dates
- 28 Jun 2021to 27 Jun 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
17 sites in 8 countries.
17 sites in 8 countries
United Kingdom5 sites
University of Cambridge
Cambridge
University College London Hospital
London, WC1N 3BG
King's College Hospital
London, WC2R 2LS
University of Oxford - Nuffield Department of Clinical Neurosciences
Oxford, OX3 7LF
University of Sheffield
Sheffield, S10 2TN
Australia3 sites
The Wesley Hospital
Brisbane, Queensland, QLD 4066
Perron Institute
Nedlands, Western Australia, 6009
Macquarie University
North Ryde, New South Wales, 2109
Canada2 sites
McGill University Health Center - Research Institute
Montreal, Quebec
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Netherlands2 sites
Erasmus University MC
Rotterdam, 3015
Universitair Medisch Centrum Utrecht
Utrecht
New Zealand2 sites
Auckland City Hospital
Auckland, 1023
New Zealand Brain Research Institute
Christchurch, 8011
About this study
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)
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.
- Being tested
- WVE-004, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WVE-004Drug
WVE-004 is a stereopure antisense oligonucleotide (ASO)
PlaceboDrug
Artificial cerebrospinal fluid (aCSF)
| Study group | Role | What they receive |
|---|---|---|
| WVE-004 (Dose A) or placebo | Experimental | Not described Receives: Drug: WVE-004; Drug: Placebo |
| WVE-004 (Dose B) or placebo | Experimental | Not described Receives: Drug: WVE-004; Drug: Placebo |
| WVE-004 (Dose C) or placebo | Experimental | Not described Receives: Drug: WVE-004; Drug: Placebo |
| WVE-004 (Dose D) or placebo | Experimental | Not described Receives: Drug: WVE-004; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Proportion of patients with adverse events (AEs)
Measured: Period 1 Day 1 to Period 2 Week 24 (end of study)
Secondary outcomes (2)
Pharmacokinetic: Concentration of WVE-004 in cerebrospinal fluid (CSF)
Measured: 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
Measured: Period 1 Day 1 to Period 2 Week 24 (end of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2021
- Study start28 Jun 2021
- Primary completion27 Jun 2023
- Study completion27 Jun 2023
Why it stopped: Despite robust, sustained reductions in poly(GP), no clinical benefit was seen at 24 weeks, and reductions in poly(GP) were not associated with stabilization in functional outcomes. Based on these data, Wave decided to stop development of WVE-004.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wave Life Sciences USA, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, MD, Study director, Wave Life Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04931862
- Sponsor's protocol ID
- WVE-004-001
- Acronym
- FOCUS-C9
- Status last verified
- Aug 2023
- First submitted
- 11 Jun 2021
- Last updated
- 23 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04931862
- Acronym / sponsor ID
- FOCUS-C9 / WVE-004-001
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Despite robust, sustained reductions in poly(GP), no clinical benefit was seen at 24 weeks, and reductions in poly(GP) were not associated with stabilization in functional outcomes. Based on these data, Wave decided to stop development of WVE-004.
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Wave Life Sciences USA, Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Jun 2021 (actual)
- Primary completion
- 27 Jun 2023 (actual)
- Study completion
- 27 Jun 2023 (actual)
- First posted
- 18 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WVE-004WVE-004 is a stereopure antisense oligonucleotide (ASO) | Drug | WVE-004 (Dose A) or placebo, WVE-004 (Dose B) or placebo, WVE-004 (Dose C) or placebo, WVE-004 (Dose D) or placebo |
| PlaceboArtificial cerebrospinal fluid (aCSF) | Drug | WVE-004 (Dose A) or placebo, WVE-004 (Dose B) or placebo, WVE-004 (Dose C) or placebo, WVE-004 (Dose D) or placebo |
Primary outcome
Safety: Proportion of patients with adverse events (AEs)
Time frame: Period 1 Day 1 to Period 2 Week 24 (end of study)
2 secondary outcomes
Pharmacokinetic: Concentration of WVE-004 in cerebrospinal fluid (CSF)
Time frame: 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
Time frame: Period 1 Day 1 to Period 2 Week 24 (end of study)
Results and safety
The study was stopped early (reason given: Despite robust, sustained reductions in poly(GP), no clinical benefit was seen at 24 weeks, and reductions in poly(GP) were not associated with stabilization in functional outcomes. Based on these data, Wave decided to stop development of WVE-004.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director, MD study director
Wave Life Sciences
17 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing WVE-004 in people with ALS and FTD, run by Wave Life Sciences USA, Inc. at 17 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United Kingdom, Australia, Canada, Netherlands, New Zealand and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Despite robust, sustained reductions in poly(GP), no clinical benefit was seen at 24 weeks, and reductions in poly(GP) were not associated with stabilization in functional outcomes. Based on these data, Wave decided to stop development of WVE-004.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Proportion of patients with adverse events (AEs) (time frame: Period 1 Day 1 to Period 2 Week 24 (end of study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2023.