A Study of TAK-341 in Treatment of Multiple System Atrophy

A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous TAK-341 in Subjects With Multiple System Atrophy

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.

Study Overview

• Status: Completed
• Conditions: Multiple System Atrophy
• Intervention / Treatment: Drug: TAK-341; Drug: Placebo

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 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
• Enrollment (Actual): 158
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8036
      • Medizinische Universität Graz
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital
  • Capital
    • København NV, Capital, Denmark, 2400
      • Bispebjerg Hospital
• France
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13385
      • Hopitaux de La Timone
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Bavaria
    • München, Bavaria, Germany, 81377
      • Klinikum Groshadern, LMU
  • Hesse
    • Kassel, Hesse, Germany, 34128
      • Paracelsus-Elena-Klinik Kassel
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Medizinische Hochschule Hannover
  • North Rhine-Westphalia
    • Bochum, North Rhine-Westphalia, Germany, 44791
      • Universitaetsklinikum der Ruhr-Universitaet Bochum (UKRUB) - St. Josef-Hospital
    • Bonn, North Rhine-Westphalia, Germany, 53127
      • Deutsches Zentrum fur Neurodegenerative Erkrankung
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitätsklinikum Münster
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitatsklinikum Carl Gustav Carus an der TU Dresden
    • Leipzig, Saxony, Germany, 04103
      • Universitatsklinikum Leipzig
• Italy
  • Salerno, Italy, 84131
    • Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi dAragona
  • Lazio
    • Rome, Lazio, Italy, 00163
      • IRCCS San Raffaele Roma
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
    • Rozzano, Lombardy, Italy, 20089
      • Istituto Clinico Humanitas
  • Veneto
    • Padova, Veneto, Italy, 35126
      • Azienda Ospedale Universita Padova
• Japan
  • Chiba
    • Chuo-ku, Chiba, Japan, 260-8677
      • Chiba University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8638
      • Hokkaido University Hospital
  • Kyoto
    • Kyoto, Kyoto, Japan, 606-8507
      • Kyoto University Hospital
  • Tokyo
    • Bunkyo-Ku, Tokyo, Japan, 113-0033
      • The University of Tokyo Hospital
    • Bunkyo-Ku, Tokyo, Japan, 113-8519
      • Medical Hospital of Tokyo Medical and Dental University
    • Kodaira-Shi, Tokyo, Japan, 187-8551
      • National Center of Neurology and Psychiatry
• Portugal
  • Lisbon District
    • Loures, Lisbon District, Portugal, 2674-514
      • Campus Neurológico Sénior
  • Porto District
    • Senhora da Hora, Porto District, Portugal, 4464-513
      • Hospital Pedro Hispano
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08041
    • Hospital de La Santa Creu i Sant Pau
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Hospital Universitario Cruces
• United Kingdom
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton General Hospital
• United States
  • Michigan
    • Farmington Hills, Michigan, United States, 48025
      • Quest Research Institute - Alcanza - HyperCore
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10016-6402
      • NYU Langone Health
  • North Carolina
    • Durham, North Carolina, United States, 27705-4410
      • Duke University School of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Texas
    • Dallas, Texas, United States, 75390-7208
      • University of Texas Southwestern Medical Center
  • Washington
    • Spokane, Washington, United States, 99202-1342
      • Inland Northwest Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

Diagnostic:

1. The participant has a diagnosis of possible or probable MSA using the modified Gilman et al, 2008 diagnostic criteria.
2. The participant's onset of first MSA symptoms occurred ≤4 years before screening, as assessed by the investigator.
3. Evidence of MSA specific symptoms and deficits as measured by the UMSARS scale.

Exclusion criteria:

Medical History:

1. The participant has any contraindication to study procedures.

Diagnostic Assessments:

1. Presence of confounding diagnosis and/or conditions that could affect participant's safety during the study per investigator judgement.
2. The participant's participation in a previous study of a disease-modifying therapy (with proven receipt of active treatment) will compromise the interpretability of the data from the present study, per consultation with medical monitor or designee.

Other:

1. The participant has participated in another study investigating active or passive immunization against α-synuclein (αSYN) for progressive disease (PD) or MSA, or has had immunoglobulin G therapy, within 6 months before screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received TAK-341 matching placebo intravenous (IV) infusions, once every 4 weeks (Q4W) for 52 weeks.	Drug: Placebo; TAK-341-matching placebo IV infusion
Experimental: TAK-341; Participants received TAK-341, IV Q4W for 52 weeks. An early set of participants initially received 2400 milligrams (mg) to determine pharmacokinetic (PK) parameters. Following the early participants, a dose of 2000 mg was given until the data from the PK participants became available. All participants then received 2400 mg until the end of treatment at 52 weeks.	Drug: TAK-341; TAK-341 IV infusion; Other Names: MEDI1341

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	Baseline, Week 52
Maximum Observed Steady State Serum Concentration (Cmax) for TAK-341	Cmax is the maximum observed serum concentration for TAK-341.	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.	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.	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.	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.	Up to Week 61
Number of Participants With Anti-Drug Antibodies		Up to Week 61

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: AstraZeneca
• Investigators: Study Director: Medical Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information about this study, click this link.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2022
• Primary Completion (Actual): July 28, 2025
• Study Completion (Actual): July 28, 2025

Study Registration Dates

• First Submitted: September 1, 2022
• First Submitted That Met QC Criteria: September 1, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Multiple System Atrophy
• Other Study ID Numbers: TAK-341-2001; 2022-000336-28 (EudraCT Number); jRCT2011220029 (Registry Identifier: jRCT); 2023-509876-40-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes