A Study of TAK-341 in Treatment of Multiple System Atrophy
- Conditions
- Multiple System Atrophy
- Interventions
- Drug: TAK-341Drug: Placebo
- Registration Number
- NCT05526391
- Lead Sponsor
- Takeda
- Brief Summary
The main aim is to see how TAK-341 works after 52 weeks in participants with multiple system atrophy as measured by the Unified Multiple System Atrophy Rating Scale Part I (UMSARS).
The study will enroll approximately 138 patients. Participants will receive a total of 13 intravenous infusions every 4 weeks approximately, these may be either of TAK-341 or placebo, after each infusion some blood samplings will be taken and other assessments completed.
This trial will be conducted in North America, Europe and Asia.
- Detailed Description
The drug being tested in this study is called TAK-341. The study will evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of intravenous (IV) TAK-341 in participants with multiple system atrophy (MSA).
The study will enroll approximately 138 participants. The study comprises a screening period of up to 42 days (6 weeks), a 52-week double-blind treatment period, and a follow-up safety visit. Participants will be randomly assigned (by chance, like flipping a coin) to one of the treatment schedules-which will remain undisclosed to the participant, care provider and investigator during the study:
* Early PK Cohort: TAK-341
* Early PK Cohort: Placebo
* Main Cohort: TAK-341
* Main Cohort: Placebo
The change from baseline in UMSARS will be measured at Week 52 post-dose.
This multi-center trial will be conducted worldwide. The duration of treatment in this study will be 52 weeks. Participants will make a follow-up visit to the site after approximately 90 days after the last dose of study treatment.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 159
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Early PK Cohort: TAK-341 TAK-341 Participants will be randomized to receive TAK-341 at 4-week intervals for up to 52 weeks. Early PK Cohort: Placebo Placebo Participants will be randomized to receive placebo at 4-week intervals for up to 52 weeks. Main Cohort: TAK-341 TAK-341 Participants will be randomized to receive TAK-341 at 4-week intervals for up to 52 weeks. Main Cohort: Placebo Placebo Participants will be randomized to receive placebo at 4-week intervals for up to 52 weeks.
- Primary Outcome Measures
Name Time Method Change from Baseline in a Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I at Week 52 Up to 52 weeks UMSARS Part I (historical review) is a 11-item scale that was adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) and is used to assess activities related to motor disability and related to autonomic dysfunction. Each item is scored from 0 (normal) to 3 (severe). The total score is a sum of scores from all domains and can range from 0 to 33. Higher scores mean poorer health.
- Secondary Outcome Measures
Name Time Method Clinical Global Impression-Severity (CGI-S) Score Up to 52 weeks The CGI-S is used to assess the clinician's impression of the participant's clinical condition. The clinician should use his or her total clinical experience with this participant population and rate the current severity of the participant's illness on a 7-point scale ranging from 1 for normal, not at all ill to 7 for among the most extremely ill participants. Higher scores mean better health.
Overall Survival (OS) Up to 52 weeks OS is defined as time from the first day of study drug administration to death due to any cause.
Change From Baseline in UMSARS Total Score (UMSARS Part I + Part II) at Week 52 Up to 52 weeks UMSARS total scale consists of all items from UMSARS Parts I and II. UMSARS Part I (historical review): 12-item scale used to assess activities related to motor disability and autonomic dysfunction. Each item is scored from 0 (normal) to 4 (severe). UMSARS Part II (motor examination): 14-item scale used to measure the functional impairment (eg, speech, rapid alternating movements of the hands, finger taps, leg agility) of selected complex movements, and specific parkinsonian (tremor at rest) or cerebellar (ocular motor dysfunction, heel-shin test) features. Each item is scored from 0 (normal) to 4 (severe).
Change From Baseline in 11-item UMSARS at Week 52 Up to 52 weeks The 11- item UMSARS includes 11 items from Part I and II to assesses both motor and autonomic disability. UMSARS Part I (historical review) is used to assess activities related to motor disability and autonomic dysfunction. UMSARS Part II (motor examination) is used to measure the functional impairment and specific parkinsonian or cerebellar features. Each item is scored from 0 (normal) to 4 (severe). The total score is a sum of scores from all domains and can range from 0 to 44. Higher scores mean poorer health.
Change from Baseline on Levels of Cerebrospinal Fluid (CSF) Free Alpha-synuclein (αSYN) Up to 52 weeks Change From Baseline in UMSARS Part I at Week 52 Up to 52 weeks UMSARS Part I (historical review) is a modified 11-item scale that was adapted from the UPDRS and is used to assess activities related to motor disability (first 8 items) and 4 novel items related to autonomic dysfunction. Each item is scored from 0 (normal) to 4 (severe). The total score is a sum of scores from all items and can range from 0 to 44. Higher scores mean poorer health.
Change From Baseline in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) Total Score Up to 52 weeks The SCOPA-AUT is a patient-reported outcome that assesses autonomic function. Autonomic function is a critical symptom domain for MSA. The scale is self-completed by participants and consists of 25 items assessing the following domains: gastrointestinal (7 items), urinary (6 items), cardiovascular (3 items), thermoregulatory (4 items), pupillomotor (1 item), and sexual (2 items for men and 2 items for women). The score for each item ranges from 0 (never experiencing the symptom) to 3 (often experiencing the symptom). The total composite score including all domains will be reported. The score range is 0 (no symptoms) to 69 (highest burden of symptoms).
Change From Baseline in UMSARS Part II at Week 52 Up to 52 weeks UMSARS Part II (motor examination) is a 14-item scale. Most of the items (e.g., speech, rapid alternating movements of the hands, finger taps, leg agility) measure the functional impairment of selected complex movements, and only a few items directly refer to specific parkinsonian (tremor at rest) or cerebellar (ocular motor dysfunction, heel-shin test) features. The motor examination section of UMSARS was based on modified UPDRS-III items in addition to novel items such as heel-knee-shin ataxia. Each item is scored from 0 (normal) to 4 (severe). The total score is a sum of scores from all items and can range from 0 to 56. Higher scores mean poorer health.
Cmax: Maximum Observed Serum Concentration for TAK-341 Pre-dose on Days 1, 29, 57, 85, 169, 253, 337; at multiple timepoints (up to 24 hours) post-dose on Days 1, 57, 85, 169, 337; anytime once on Days 365, 427 or at early termination (Day 57 applicable to only early PK cohorts) AUCÏ„: Area Under the Concentration-time Curve During a Dosing Interval in Serum for TAK-341 Pre-dose on Days 1, 29, 57, 85, 169, 253, 337; at multiple timepoints (up to 24 hours) post-dose on Days 1, 57, 85, 169, 337; anytime once on Days 365, 427 or at early termination (Day 57 applicable to only early PK cohorts) CSF Concentration of TAK-341 Pre-dose on Days 1, 85 (applicable to only early PK cohorts), and 365 Lumbar puncture for CSF sampling will be performed.
Number of Participants With at Least one Adverse Event (AE) Up to 52 weeks An adverse event (AE) is defined as any untoward medical occurrence in a participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. Data will be reported for number of participants to be analyzed for safety parameters that will include clinically significant abnormal values for clinical laboratory evaluations, vital signs, ECG parameters, physical examination, neurological examination and Columbia-Suicide Severity Rating Scale (C-SSRS).
Number of Participants With Antidrug Antibody Up to 52 weeks Tmax: Time of First Occurrence of Cmax in Serum for TAK-341 Pre-dose on Days 1, 29, 57, 85, 169, 253, 337; at multiple timepoints (up to 24 hours) post-dose on Days 1, 57, 85, 169, 337; anytime once on Days 365, 427 or at early termination (Day 57 applicable to only early PK cohorts)
Trial Locations
- Locations (41)
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Duke University School of Medicine
🇺🇸Durham, North Carolina, United States
Universitatsklinikum Leipzig
🇩🇪Leipzig, Sachsen, Germany
Hokkaido University Hospital
🇯🇵Sapporo-Shi, Hokkaido, Japan
Campus Neurologico Senior
🇵🇹Loures, Lisboa, Portugal
Medizinische Universitat Graz
🇦🇹Graz, Steiermark, Austria
Chiba University Hospital
🇯🇵Chuo-ku, Tiba, Japan
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
Azienda Ospedale Universita Padova
🇮🇹Padova, Veneto, Italy
National Center of Neurology and Psychiatry
🇯🇵Kodaira-Shi, Tokyo, Japan
Medical Hospital of Tokyo Medical and Dental University
🇯🇵Bunkyo-Ku, Tokyo, Japan
NYU Langone Health
🇺🇸New York, New York, United States
Kyoto University Hospital
🇯🇵Kyoto-Shi, Kyoto, Japan
Bispebjerg Hospital
🇩🇰Kobenhavn NV, Capital, Denmark
Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi dAragona
🇮🇹Salerno, Italy
Universitatsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Dresden, Sachsen, Germany
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Quest Research Institute - Alcanza - HyperCore
🇺🇸Farmington Hills, Michigan, United States
Inland Northwest Research
🇺🇸Spokane, Washington, United States
Aarhus Universitetshospital
🇩🇰Aarhus N, Denmark
Hopitaux de La Timone
🇫🇷Marseille, Bouches-du-Rhone, France
Klinikum Groshadern, LMU
🇩🇪Munchen, Bayern, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Niedersachsen, Germany
Deutsches Zentrum fur Neurodegenerative Erkrankung
🇩🇪Bonn, Nordrhein-Westfalen, Germany
Paracelsus-Elena-Klinik Kassel
🇩🇪Kassel, Hessen, Germany
Universitaetsklinikum der Ruhr-Universitaet Bochum (UKRUB) - St. Josef-Hospital
🇩🇪Bochum, Nordrhein-Westfalen, Germany
Universitatsklinikum Munster
🇩🇪Munster, Nordrhein-Westfalen, Germany
IRCCS San Raffaele Roma
🇮🇹Roma, Lazio, Italy
Charite - Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
🇮🇹Milano, Lombardia, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Lombardia, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Lombardia, Italy
The University of Tokyo Hospital
🇯🇵Bunkyo-Ku, Tokyo, Japan
Hospital Pedro Hispano
🇵🇹Senhora Da Hora, Porto, Portugal
Hospital de La Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Cruces
🇪🇸Barakaldo, Vizcaya, Spain
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain