ALS dementia
Conditions
Interventions
The study will include two distinct periods. Period 1 will evaluate single
ascending doses (SAD), and Period 2 will evaluate multiple ascending doses
(MAD) of WVE-004.
Period 2 cohorts will be bas
Sponsors
Wave Life Sciences UK Limited
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: ALS-Specific Inclusion Criteria: 1. Diagnosis of ALS based on clinical manifestations. 2. ALS: 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. Patients receiving riluzole have been on a stable dose for a minimum of 30 days. 4. Patients on edaravone have received a minimum of 1 cycle (28 days). 5. Patients discontinuing riluzole or edaravone had the last dose administered >=1 month prior to Screening. FTD-Specific Inclusion Criteria: 6. FTD: Must have Global Clinical Dementia Rating - Frontotemporal Lobar Degeneration (CDR® plus NACC FTLD) score of 0.5 or 1. 7. FTD: Able to undergo periodic magnetic resonance imaging (MRI) of the brain. Patients with mixed phenotype (ALS and FTD) need not undergo MRI if their ALS symptoms prevent it. Mixed Phenotype (ALS and FTD) Inclusion Criteria: 8. Patients who are mixed phenotype (ALS and FTD) must meet both the ALS-specific and FTD-specific criteria. Inclusion Criteria Common to Both Diseases: 9. Patient must have the ability and be willing to provide written informed consent prior to any trial-related procedures. 10. Documented mutation (GGGGCC [G4C2] repeat expansion) in the first intronic region of the C9orf72 gene. 11. Body mass index (BMI) 50% predicted. 13. Age of >=18 and
Exclusion criteria
Exclusion 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, including, but not limited to: a. Prior or ongoing medical conditions, including acute illness, within 28 days of Screening visit; b. Clinically significant abnormality on laboratory testing at Screening, including but not limited to: i. Renal insufficiency, which is defined creatinine clearance =450 msec for males or >=470 msec for females. 8. Bone, spine, bleeding (e.g. hemophilia, Von Willenbrand diseas, liver disease), or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture. 9. Dementia due to a condition other than C9orf72-associated ALS or FTD, including, but not limited to, Alzheimer disease, Parkinson disease, dementia with Lewy bodies, Huntington's disease, or vascular dementia. Prior or Concomitant Medications 10. Positive for opioids (unprescribed), cocaine, amphetamines, methadone, barbiturates, methamphetamine, and phencyclidine at the Screening Visit. 11. Changes in nutritional or herbal supplements or concomitant medications within 1 month prior to Screening visit or plans to modify dose or regimen during the trial. 12. Received prior treatment with viral or cellular-based gene therapy. 13. Received any other investigational drug, biological agent, or device within 1 month of 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. Received prior treatment with investigational product BIIB078. 14. Anticipates using antiplatelet or anticoagulant therapy during the course of the study. Patients who received antiplatelet or anticoagulant therapy must complete one of the following washout periods before the Screening Visit: a. A 7-day washout period for antiplatelet therapy, b. A 1-day washout period for anticoagulants (except warfarin), or c. A 5-day washout period for warfarin Trial Compliance 15. Implantable central nervous system (CNS) device that may interfere with ability to administer trial drug via lumbar puncture or undergo MRI scan. 16. Deemed to be at significant risk for suicidal behavior ba
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of patients with AEs, the incidence of patients with severe AEs, incidence of patients with SAEs, and the incidence of patients who withdraw due to AEs. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoint(s) • Pharmacokinetic parameters of WVE-004 in plasma • CSF concentration of WVE-004 • Change from baseline in concentration of poly-GP levels in the CSF Exploratory Endpoint(s) Biomarker Assessments: • Change from baseline in concentration of neurodegeneration markers (including, but not limited to, neurofilament light chain in CSF and/or plasma, or the extracellular domain of the P75 neurotrophin receptor [P75NTRECD] in urine) Laboratory Assessments of Clinical Effects: • Change from baseline on electrocardiogram • Change from baseline on pulmonary function tests • Change from baseline in magnetic resonance imaging (MRI) Clinical Assessments: • Change from baseline in the following assessments of clinical signs and symptoms: Functional Assessments * CDR® plus NACC FTLD * ALS Functional Rating Scale-Revised (ALSFRS-R) * Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) * Hand-held dynamometry (HHD) * Neuropsychiatric Inventory Questionnaire (NPI-Q)© Cognitive Assessments * Trails Making A and B * Stroop Test * Verbal Fluency * Symbol Digit Modalities Test (SDMT) | — |
Countries
Netherlands
Outcome results
None listed