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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

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

Nonomura Hidenori

Takeda Pharmaceutical Company Limited

1-1, Doshomachi 4-chome, Chuo-ku, Osaka

smb.Japanclinicalstudydisclosure@takeda.com

Contact for Clinical Trial Information

Takeda Pharmaceutical Company Limited

1-1, Doshomachi 4-chome, Chuo-ku, Osaka

+81-6-6204-2111

smb.Japanclinicalstudydisclosure@takeda.com

Complete

Nov. 09, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

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.

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

Both

Multiple System Atrophy

Early PK Cohort: TAK-341
Participants will be randomized to receive TAK-341 at 4 week intervals for up to 52 weeks.

Early PK Cohort: Placebo
Participants will be randomized to receive placebo at 4-week intervals for up to 52 weeks.

Main Cohort: TAK-341
Participants will be randomized to receive TAK-341 at 4 week intervals for up to 52 weeks.

Main Cohort: Placebo
Participants will be randomized to receive placebo at 4-week intervals for up to 52 weeks.

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 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.

1. 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.

2. Change From Baseline in UMSARS Total Score (UMSARS Part I + Part II) 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).

3. 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.

4. 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.

5. 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 worse health.

6. 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).

7. 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.

8. Change from Baseline on Levels of Cerebrospinal Fluid (CSF) Free Alpha-synuclein (Alpha-SYN)
Time Frame: Up to 52 weeks

9. 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 57 applicable to only early PK cohorts)

10. 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 57 applicable to only early PK cohorts)

11. AUCtau: 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 57 applicable to only early PK cohorts)

12. 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.

13. 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).

14. Number of Participants With Antidrug Antibody
Time Frame: Up to 52 weeks

+81-11-706-7061

Nov. 15, 2022

Yes

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