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

Multiple System Atrophy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05526391
• Other study ID #: TAK-341-2001
• Secondary ID: 2022-000336-28jR
• Status: Recruiting
• Phase: Phase 2
• Start date: November 9, 2022
• Est. completion date: August 1, 2025

Study information

• Verified date: April 2024
• Source: Takeda
• Contact: Takeda Contact
• Phone: +1-877-825-3327
• Email: medinfoUS[@]takeda.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 138
• Est. completion date: August 1, 2025
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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 a-synuclein (aSYN) for progressive disease (PD) or MSA, or has had immunoglobulin G therapy, within 6 months before screening.

Related Conditions & MeSH terms

• Atrophy
• Multiple System Atrophy
• Shy-Drager Syndrome

Intervention

Drug:
• TAK-341
TAK-341 IV infusion
• Placebo
TAK-341 placebo-matching IV infusion

Locations

Country	Name	City	State
Austria	Medizinische Universitat Graz	Graz	Steiermark
Austria	Medizinische Universitat Innsbruck	Innsbruck	Tirol
Denmark	Aarhus Universitetshospital	Aarhus N
Denmark	Bispebjerg Hospital	Kobenhavn NV	Capital
France	Hopitaux de La Timone	Marseille	Bouches-du-Rhone
France	Hopitaux Universitaires de Strasbourg	Strasbourg
France	Hopital Purpan	Toulouse	Haute-Garonne
Germany	Charite - Universitatsmedizin Berlin	Berlin
Germany	Universitaetsklinikum der Ruhr-Universitaet Bochum (UKRUB) - St. Josef-Hospital	Bochum	Nordrhein-Westfalen
Germany	Deutsches Zentrum fur Neurodegenerative Erkrankung	Bonn	Nordrhein-Westfalen
Germany	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden	Sachsen
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Paracelsus-Elena-Klinik Kassel	Kassel	Hessen
Germany	Universitatsklinikum Leipzig	Leipzig	Sachsen
Germany	Universitatsklinikum Giesen und Marburg GmbH	Marburg	Hessen
Germany	Klinikum Groshadern, LMU	Munchen	Bayern
Germany	Universitatsklinikum Munster	Munster	Nordrhein-Westfalen
Germany	Universitatsklinikum Tubingen	Tubingen	Baden-Wurttemberg
Germany	Universitatsklinikum Ulm	Ulm	Baden-Wurttemberg
Italy	Ospedale Bellaria	Bologna	Emilia-Romagna
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano	Lombardia
Italy	Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta	Milano	Lombardia
Italy	Azienda Ospedale Universita Padova	Padova	Veneto
Italy	Fondazione Istituto Neurologico Mondino IRCCS	Pavia
Italy	IRCCS San Raffaele Roma	Roma	Lazio
Italy	Istituto Clinico Humanitas	Rozzano	Lombardia
Italy	Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio Ruggi dAragona	Salerno
Japan	Medical Hospital of Tokyo Medical and Dental University	Bunkyo-Ku	Tokyo
Japan	The University of Tokyo Hospital	Bunkyo-Ku	Tokyo
Japan	Chiba University Hospital	Chuo-ku	Tiba
Japan	National Center of Neurology and Psychiatry	Kodaira-Shi	Tokyo
Japan	Kyoto University Hospital	Kyoto-Shi	Kyoto
Japan	Hokkaido University Hospital	Sapporo-Shi	Hokkaido
Portugal	Hospital de Santa Maria-Avenida Prof. Egas Moniz	Lisboa
Portugal	Campus Neurologico Senior	Loures	Lisboa
Portugal	Hospital Pedro Hispano	Senhora Da Hora	Porto
Spain	Hospital Universitario Cruces	Barakaldo	Vizcaya
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
United Kingdom	The National Hospital for Neurology and Neurosurgery	London
United Kingdom	Newcastle University	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United States	Beth Israel Deaconess Medical Center - 330 Brookline Ave	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	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	Quest Research Institute - Alcanza - HyperCore	Farmington Hills	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	UAMS Health - Movement Disorders Clinic	Little Rock	Arkansas
United States	UCLA Neurological Services	Los Angeles	California
United States	NYU Langone Health	New York	New York
United States	AdventHealth Innovation Tower	Orlando	Florida
United States	Mayo Clinic	Rochester	Minnesota
United States	Inland Northwest Research	Spokane	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	AstraZeneca

Countries where clinical trial is conducted

United States,  Austria,  Denmark,  France,  Germany,  Italy,  Japan,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in a Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I at Week 52	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.	Up to 52 weeks
Secondary	Change From Baseline in 11-item UMSARS at Week 52	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.	Up to 52 weeks
Secondary	Change From Baseline in 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 (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).	Up to 52 weeks
Secondary	Change From Baseline in UMSARS Part I at Week 52	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.	Up to 52 weeks
Secondary	Change From Baseline in UMSARS Part II at Week 52	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.	Up to 52 weeks
Secondary	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 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.	Up to 52 weeks
Secondary	Change From Baseline in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) Total Score	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).	Up to 52 weeks
Secondary	Overall Survival (OS)	OS is defined as time from the first day of study drug administration to death due to any cause.	Up to 52 weeks
Secondary	Change from Baseline on Levels of Cerebrospinal Fluid (CSF) Free Alpha-synuclein (aSYN)		Up to 52 weeks
Secondary	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)
Secondary	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)
Secondary	AUCt: 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)
Secondary	CSF Concentration of TAK-341	Lumbar puncture for CSF sampling will be performed.	Pre-dose on Days 1, 85 (applicable to only early PK cohorts), and 365
Secondary	Number of Participants With at Least one Adverse Event (AE)	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).	Up to 52 weeks
Secondary	Number of Participants With Antidrug Antibody		Up to 52 weeks

External Links

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