FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)
- Registration Number
- NCT04768972
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The primary purpose of this study is to evaluate the efficacy of ION363 on clinical function and survival in carriers of fused in sarcoma mutations with amyotrophic lateral sclerosis (FUS-ALS).
- Detailed Description
This is a multi-center, three-part study of ION363 in up to 95 participants. Part 1 will consist of participants who will be randomized in a 2:1 ratio to receive a multi-dose regimen of ION363 or placebo for a period of 60 weeks, followed by Part 2, in which participants will receive open-label ION363 for a period of 84 weeks. Participants may continue to receive open-label ION363 in Part 3 for up to 3 additional years or until ION363 becomes commercially available in the patient's country or until the Sponsor discontinues the ION363 development program, whichever occurs earlier.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 95
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo will be administered by lumbar IT bolus injection every12 weeks, with an additional loading dose at 4 weeks, over a 60-week double-blind treatment period (Part 1). ION363 ION363 ION363 will be administered by lumbar intrathecal (IT) bolus injection every 12 weeks, with an additional loading dose at 4 weeks, over a 60-week double-blind treatment period in Part 1; every 12 weeks for 84 weeks in the open-label extension treatment period (Part 2), with an additional loading dose administered 4 weeks after the first dose. Patients may continue to receive open-label ION363 every 12 weeks in Part 3 for up to 3 additional years or until ION363 becomes commercially available in the patient's country or until the Sponsor discontinues the development program, whichever occurs earlier.
- Primary Outcome Measures
Name Time Method Change from Baseline (Day 1) through Study Day 505 in Part 1 in functional impairment Baseline, Day 505 in Part 1 Functional impairment to be measured by joint rank analysis of the combined assessment of: In-clinic Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score, time of rescue or discontinuation from Part 1 and entering Part 2 due to a deterioration in function, and ventilation assistance-free survival (VAFS). ALSFRS-R measures functional disease severity. The scale measures four functional domains, bulbar function, gross motor skills, fine motor skills, and respiratory function. The assessment will contain 12 questions scored from 0 (no function) to 4 (full function), with a total possible score of 48, which will indicate the highest level of function. ALSFRS-R will be a part of the combined assessment of joint rank analysis to assess efficacy in Part 1.
- Secondary Outcome Measures
Name Time Method Change from Baseline in the in-clinic Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Baseline, Day 505 in Part 1 Survival and Ventilation Assistance-Free Survival (VAFS) Up to Day 505 in Part 1 Change from Baseline in Handheld Dynamometry (HHD) to Day 505 in Part 1 Baseline, Day 505 in Part 1 Change from Baseline in Neurofilament Light (NfL) Concentration in Cerebrospinal Fluid (CSF) to Day 505 Baseline, Day 505 in Part 1 Change from Baseline in In-clinic Slow Vital Capacity (SVC) to Day 505 in Part 1 Baseline, Day 505 in Part 1 Change from Baseline in FUS Concentration in Cerebrospinal Fluid (CSF) to Day 505 Baseline, Day 505 in Part 1 Change from Baseline in Amyotrophic Lateral Sclerosis Specific Quality of Life - Revised (ALSSQOL-R) Score to Day 505 in Part 1 Baseline, Day 505 in Part 1 The ALSSQOL-R is a disease-specific 50-item assessment that measures the quality of life. Each item will be rated by the participant on a scale of 0 to 10, with 0 being the least desirable situation and 10 being the most desirable.
Trial Locations
- Locations (25)
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
University of California San Diego
🇺🇸La Jolla, California, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
UZ Leuven
🇧🇪Leuven, VL-Brabant, Belgium
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
University Hospital of Umea
🇸🇪Umeå, Sweden
Kantonsspital St. Gallen
🇨🇭Saint Gallen, Switzerland
PSEG Centro de Pesquisa Clinica S.A.
🇧🇷São Paulo, Brazil
Montreal Neurological Institute
🇨🇦Montreal, Quebec, Canada
Universitaetsmedizin Rostock
🇩🇪Rostock, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
St. James Hospital
🇮🇪Dublin, Ireland
Citta della Salute e della Scienza di Torino - Ospedale le Molinette
🇮🇹Torino, Italy
Toho University Omori Medical Center
🇯🇵Tokyo, Japan
Hanyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Linden spólka z ograniczona odpowiedzialnoscia spólka komandytow
🇵🇱Kraków, Poland
Taipei Veterans General Hospital (VGHTP)
🇨🇳Taipei City, Taiwan
King's College Hospital
🇬🇧London, United Kingdom