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.
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 158 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 two treatment groups-which will remain undisclosed to the participant, care provider and investigator during the study: * TAK-341 * 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
158
Change From Baseline in Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I Total Score at Week 52
UMSARS Part I (historical review) is a 12-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 autonomic dysfunction. In this study, the UMSARS was modified to exclude the sexual function item. Thus, total 11 items were assessed. Each item was initially scored on a scale from 0 (normal) to 4 (severe); ratings of normal (0) and mild (1) were then combined and recorded as 0, making minimum score 0 and maximum score 3. The investigator rated the average functional situation for the past 2 weeks according to findings from the participant and caregiver interview and indicated the score that best fit with the participant's status. The total score is a sum of scores from all domains and range from 0 to 33. Higher scores indicate worse impairment.
Time frame: Baseline, Week 52
Change From Baseline in 11-item UMSARS at Week 52
The 11- item UMSARS includes 11 items from Part I and II to assess 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 was scored on a scale from 0 (normal) to 4 (severe); total score ranges from 0 to 44, higher scores indicated worse impairment.
Time frame: Baseline, Week 52
Change From Baseline in the UMSARS Total Score (UMSARS Part I + Part II) at Week 52
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 (for example 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. The worst affected limb was assessed, and each item was scored from 0 (normal) to 4 (severe). UMSARS Part I and Part II total score is the sum of UMSARS Part I and Part II and ranges from 0 to 104. A higher score indicates worse impairment.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Quest Research Institute - Alcanza - HyperCore
Farmington Hills, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
NYU Langone Health
New York, New York, United States
Duke University School of Medicine
Durham, North Carolina, United States
The Cleveland Clinic Foundation
Cleveland, Ohio, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Inland Northwest Research
Spokane, Washington, United States
Medizinische Universitat Graz
Graz, Styria, Austria
Bispebjerg Hospital
København NV, Capital, Denmark
Aarhus Universitetshospital
Aarhus N, Denmark
...and 31 more locations
Time frame: Baseline, Week 52
Change From Baseline in UMSARS Part I 11-Item Score at Week 52
UMSARS Part I (historical review) is a 12-item scale that was adapted from the UPDRS. In this study, the UMSARS was modified to exclude the sexual function item. The UMSARS is used to assess activities related to motor disability and autonomic dysfunction. Each item was scored on a scale from 0 (normal) to 4 (severe). UMSARS Part I 11-item total score is the total score of UMSARS Part I, excluding the sexual function item, and without collapse of ratings of scale items. The UMSARS Part I 11-item total score ranges from 0 to 44, and higher scores indicate worse impairment.
Time frame: Baseline, Week 52
Change From Baseline in UMSARS Part II at Week 52
UMSARS Part II (motor examination): 14-item scale used to measure the functional impairment (e.g., 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. the worst affected limb was assessed, and each item was scored from 0 (normal) to 4 (severe). The UMSARS Part II total score ranges from 0 to 56, and higher scores indicate worse impairment.
Time frame: Baseline, Week 52
Change From Baseline on Clinical Global Impression-Severity (CGI-S) Score
The CGI-S is used to assess the clinician's impression of the participant's clinical condition. The clinician rates the current severity of the participant's illness on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (most extremely ill). The rating was based on observed and reported symptoms, behaviour, and function and reflected the severity level at the time of the assessment. A higher score indicates worse impairment.
Time frame: Baseline, Week 24 and Week 52
Change From Baseline in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) Total Score
The SCOPA-AUT is a participant-reported outcome that assesses autonomic function. Autonomic function is a critical symptom domain for MSA. The scale was completed by participants and consisted 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 ranged from 0 (never experiencing the symptom) to 3 (often experiencing the symptom). The total composite score including all domains was reported. The score range was 0 (no symptoms) to 69 (highest burden of symptoms). A higher score indicates worse impairment.
Time frame: Baseline, Week 24 and Week 52
Overall Survival (OS) at Week 52
OS was estimated with Kaplan-Meier survival estimates, along with 95% confidence interval. A cox proportional hazards model was fitted to model the survival probability with treatment as the predictor. The participants with missing value were censored. The probabilities of survival at Week 52 for participants were estimated and reported.
Time frame: At Week 52
Change From Baseline in Cerebrospinal Fluid (CSF) Free Alpha-Synuclein (αSYN)
α-Synucleinopathies are diseases characterized by abnormal accumulation of aggregated αSYN. In participants with MSA, αSYN is seen to accumulate primarily in oligodendrocytes, forming glial cytoplasmic inclusions. A negative change from Baseline indicates an improvement.
Time frame: Baseline, Week 52
Maximum Observed Steady State Serum Concentration (Cmax) for TAK-341
Cmax is the maximum observed serum concentration for TAK-341.
Time frame: On Day 57- immediately before end of infusion (EOI) (60 minutes), 6 hours and 24 hours.
Time to Maximum Steady State Concentration (Tmax) for TAK-341
Tmax is the time of first occurrence of maximum observed concentration for TAK-341.
Time frame: On Day 57- immediately before EOI (60 minutes), 6 hours and 24 hours.
Area Under the Serum Concentration Time Curve (AUCτ) at Steady State for TAK-341
AUCτ is the area under the serum concentration-time curve during a dosing interval.
Time frame: On Day 57- immediately before EOI (60 minutes), 6 hours and 24 hours.
CSF Concentration of TAK-341
Lumbar puncture was performed for CSF on Day 1, Day 85 and Day 365, predose.
Time frame: On Day 1, Day 85 and Day 365
Number of Participants With at Least One Adverse Event (AE)
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event that occurs after administration of the first dose of study treatment and up through 90 days after the last dose of study treatment.
Time frame: Up to Week 61
Number of Participants With Anti-Drug Antibodies
Time frame: Up to Week 61