Clinical trial NCT05526391: A Study of TAK-341 in Treatment of Multiple System Atrophy
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple System Atrophy
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2022-09-02
Enrollment: 159
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in a Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I at Week 52
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Change From Baseline in 11-item UMSARS at Week 52
timeFrame: Up to 52 weeks
measure: Change From Baseline in UMSARS Total Score (UMSARS Part I + Part II) at Week 52
timeFrame: Up to 52 weeks
measure: Change From Baseline in UMSARS Part I at Week 52
timeFrame: Up to 52 weeks
measure: Change From Baseline in UMSARS Part II at Week 52
timeFrame: Up to 52 weeks
measure: Clinical Global Impression-Severity (CGI-S) Score
timeFrame: Up to 52 weeks
measure: Change From Baseline in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) Total Score
timeFrame: Up to 52 weeks
measure: Overall Survival (OS)
timeFrame: Up to 52 weeks
measure: Change from Baseline on Levels of Cerebrospinal Fluid (CSF) Free Alpha-synuclein (αSYN)
timeFrame: Up to 52 weeks
measure: Cmax: Maximum Observed Serum Concentration for TAK-341
timeFrame: 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)
measure: Tmax: Time of First Occurrence of Cmax in Serum for TAK-341
timeFrame: 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)
measure: AUCτ: Area Under the Concentration-time Curve During a Dosing Interval in Serum for TAK-341
timeFrame: 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)
measure: CSF Concentration of TAK-341
timeFrame: Pre-dose on Days 1, 85 (applicable to only early PK cohorts), and 365
measure: Number of Participants With at Least one Adverse Event (AE)
timeFrame: Up to 52 weeks
measure: Number of Participants With Antidrug Antibody
timeFrame: Up to 52 weeks
Other outcomes:
Locations:
city: Farmington Hills
country: United States
facility: Quest Research Institute - Alcanza - HyperCore
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: Graz
country: Austria
facility: Medizinische Universitat Graz
state: Steiermark
city: Kobenhavn NV
country: Denmark
facility: Bispebjerg Hospital
state: Capital
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
city: Marseille
country: France
facility: Hopitaux de La Timone
state: Bouches-du-Rhone
city: Munchen
country: Germany
facility: Klinikum Groshadern, LMU
state: Bayern
city: Kassel
country: Germany
facility: Paracelsus-Elena-Klinik Kassel
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Bochum
country: Germany
facility: Universitaetsklinikum der Ruhr-Universitaet Bochum (UKRUB) - St. Josef-Hospital
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Deutsches Zentrum fur Neurodegenerative Erkrankung
state: Nordrhein-Westfalen
city: Munster
country: Germany
facility: Universitatsklinikum Munster
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus an der TU Dresden
state: Sachsen
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
state: Sachsen
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin
city: Roma
country: Italy
facility: IRCCS San Raffaele Roma
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
state: Lombardia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardia
city: Padova
country: Italy
facility: Azienda Ospedale Universita Padova
state: Veneto
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi dAragona
city: Sapporo-Shi
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kyoto-Shi
country: Japan
facility: Kyoto University Hospital
state: Kyoto
city: Chuo-ku
country: Japan
facility: Chiba University Hospital
state: Tiba
city: Bunkyo-Ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Bunkyo-Ku
country: Japan
facility: Medical Hospital of Tokyo Medical and Dental University
state: Tokyo
city: Kodaira-Shi
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
city: Loures
country: Portugal
facility: Campus Neurologico Senior
state: Lisboa
city: Senhora Da Hora
country: Portugal
facility: Hospital Pedro Hispano
state: Porto
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: