Amyotrophic Lateral Sclerosis and Frontotemporal Dementia MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10068968 Term: Frontotemporal dementia System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Wave Life Sciences UK Limited
Eligibility
Sex/Gender
All
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) =32 kg/m2. 12. Forced vital capacity (FVC) of >50% predicted. 13. Age of =18 and =80 years at Screening visit. 14. Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, trial restrictions, and all trial procedures. 15. Willingness to practice highly effective contraception for the duration of the trial if patients or their partners are of childbearing potential. Non-childbearing potential and highly effective methods of contraception will be defined in the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 31 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 11
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: - Renal insufficiency, which is defined as creatinine clearance <40 mL/min. 2. Positive hepatitis B surface antigen or hepatitis C antibody test. 3. Known to be positive for human immunodeficiency virus (HIV). 4. History of substance use disorder (except nicotine) within 6 months prior to the Screening Visit. 5. Significant cognitive impairment; or unstable psychiatric illness, including active psychosis, active suicidal ideation, recent suicide attempt, or untreated major depression, within the last 90 days, as determined by the Investigator. Mental status, psychiatric medical history, and eligibility for the study must be documented in the screening questionnaire. 6. Pregnant (as determined by a serum pregnancy test) or breast feeding at the Screening Visit, or plans to become pregnant during the trial. 7. Clinically significant abnormality on Screening electrocardiogram (ECG), including, but not limited to, a confirmed QT interval using Fridericia’s correction method (QTcF) of =450 msec for males or =470 msec for females. 8. Bone, spine, bleeding (e.g. hemophilia, Von Willenbrand disease, 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. Trial Compliance 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. 15. Deemed to be at significant risk for suicidal behavior based on Investigator assessment and/or active suicidal ideation. 16. Known hypersensitivity to any oligonucleotide, as demonstrated by a systemic allergic reaction, such as changes in pulse, blood pressure, breathing function, etc. 17. Patient is directly or indirectly involved in the conduct and administration of this trial as an Investigator, sub investigator, trial coordina
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the safety and tolerability of WVE-004 in patients with ALS or FTD with a documented mutation in the C9orf72 gene.;Secondary Objective: •Characterize the pharmacokinetics (PK) of WVE-004 in plasma. •Characterize cerebrospinal fluid (CSF) concentration of WVE-004. •Evaluate the pharmacodynamic (PD) effect of WVE-004 via measurement of poly-glycine-proline (poly-GP) in CSF. ;Primary end point(s): 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. ;Timepoint(s) of evaluation of this end point: Period 1: week 1 - 24 Period 2: week 1 - 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Period 1: week 1 - 24 Period 2: week 1 - 24 ;Secondary end point(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 | — |
Countries
Australia, Belgium, Canada, Germany, Ireland, Netherlands, New Zealand, Sweden, United Kingdom, United States
Contacts
Public ContactRegulatory Submissions
Medpace, Inc.
Outcome results
None listed