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

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ClinicalTrials.gov Identifier: NCT05526391
Recruitment Status : Recruiting
First Posted : September 2, 2022
Last Update Posted : March 21, 2023
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Takeda

Study Description
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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.


Condition or disease Intervention/treatment Phase
Multiple System Atrophy Drug: TAK-341 Drug: Placebo Phase 2

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 Dose 1
  • Early PK Cohort: Placebo
  • Main Cohort: TAK-341 Dose 2
  • 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. Early-termination participants will not make a follow-up safety visit.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 9, 2022
Estimated Primary Completion Date : August 1, 2025
Estimated Study Completion Date : August 1, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Early PK Cohort: TAK-341 Dose 1
Participants will be randomized to receive TAK-341 at a starting Dose 1 at 4 week intervals for up to 52 weeks.
 Drug: TAK-341
TAK-341 IV infusion
Other Name: MEDI1341
Placebo Comparator: Early PK Cohort: Placebo
Participants will be randomized to receive TAK-341 placebo, up to 52 weeks.
 Drug: Placebo
TAK-341 placebo-matching IV infusion
Experimental: Main Cohort: TAK-341 Dose 2
Participants will be randomized to receive TAK-341 at a starting Dose 2 at 4 week intervals for up to 52 weeks.
 Drug: TAK-341
TAK-341 IV infusion
Other Name: MEDI1341
Placebo Comparator: Main Cohort: Placebo
Participants will be randomized to receive TAK-341 placebo, up to 52 weeks.
 Drug: Placebo
TAK-341 placebo-matching IV infusion


Outcome Measures
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Primary Outcome Measures :
  1. Change from Baseline in a Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I at Week 52 [ Time Frame: 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 1 (normal) to 4 (severe). The total score is a sum of scores from all domains and can range from 11 to 44. Higher scores mean poorer health.


Secondary Outcome Measures :
  1. Cmax: Maximum Observed Serum Concentration for TAK-341 [ Time Frame: 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 85 applicable to only early PK cohorts) ]
  2. Tmax: Time of First Occurrence of Cmax in Serum for TAK-341 [ Time Frame: 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 85 applicable to only early PK cohorts) ]
  3. AUCτ: Area Under the Concentration-time Curve During a Dosing Interval in Serum for TAK-341 [ Time Frame: 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 85 applicable to only early PK cohorts) ]
  4. Cerebrospinal Fluid (CSF) Concentration of TAK-341 [ Time Frame: Pre-dose on Days 1, 85 (applicable to only early PK cohorts), and 365 ]
    Lumbar puncture for CSF sampling will be performed.

  5. Change From Baseline in 11-item UMSARS at Week 52 [ Time Frame: 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.

  6. Change From Baseline in UMSARS Total Score at Week 52 [ Time Frame: 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).

  7. Change From Baseline in UMSARS Part I at Week 52 [ Time Frame: 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.

  8. Change From Baseline in UMSARS Part II at Week 52 [ Time Frame: 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.

  9. Change from Baseline in Clinical Global Impression-Severity (CGI-S) Score [ Time Frame: 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.

  10. Change From Baseline in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) Total Score [ Time Frame: 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).

  11. Overall Survival (OS) [ Time Frame: Up to 52 weeks ]
    OS is defined as time from the first day of study drug administration to death due to any cause.

  12. Number of Participants With at Least one Adverse Event (AE) [ Time Frame: 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).

  13. Number of Participants With Antidrug Antibody [ Time Frame: Up to 52 weeks ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05526391


Contacts
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Contact: Takeda Contact +1-877-825-3327 medinfoUS@takeda.com

Locations
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Sponsors and Collaborators
Takeda
AstraZeneca
Investigators
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Study Director: Study Director Takeda
More Information
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Additional Information:

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT05526391    
Other Study ID Numbers: TAK-341-2001
2022-000336-28 ( EudraCT Number )
First Posted: September 2, 2022    Key Record Dates
Last Update Posted: March 21, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
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.
URL: https://vivli.org/ourmember/takeda/

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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
Keywords provided by Takeda:
Drug Therapy
Additional relevant MeSH terms:
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Multiple System Atrophy
Shy-Drager Syndrome
Atrophy
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
 Brain Diseases
Central Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases