Phase 2 Study of TAK-341 for Multiple System Atrophy
Research type
Research Study
Full 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
IRAS ID
1005598
Contact name
Nirav Desai
Contact email
Sponsor organisation
Takeda Development Center Americas, Inc.
Eudract number
2022-000336-28
Clinicaltrials.gov Identifier
Research summary
"Multiple system atrophy (MSA) is a rare brain condition where certain brain cells stop working or die. This affects movement and automatic body functions like breathing, digestion, and blood pressure. TAK-341 is a medicine that was being developed to treat adults with MSA. The purpose of this study was to see whether TAK-341 may help slow the worsening of MSA.
The main aim of the study was to check how well TAK-341 worked compared to placebo. A placebo looks the same as TAK-341 but has no medicine in it. Researchers wanted to check how well TAK-341 worked compared to placebo in participants with MSA. To do this, they asked the following question: What was the change observed after 52 weeks in the modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part 1 with TAK-341 compared to placebo?
The UMSARS is a 4-part scale that is used to measure how severe MSA symptoms are and to check how they affect their daily life. In this study, researchers used the modified UMSARS Part 1 to check the severity of MSA.
Any medical problems that happened during the study were also recorded. Medical problems are any new or worsening problems that the participants had after they took the study medications. They may or may not be related to the study medicine or placebo.
This was a Phase 2 study, where a small number of people with MSA received the medicine. This was to learn if the medicine could help people with this condition.
This was a double-blind study. This meant that none of the participants, doctors, or other study clinic staff knew which treatment each participant received. This is done because knowing what treatment the participants are receiving could affect the results of the study. Participants were assigned to their treatment group by chance (randomly). This helped to make the treatment groups as similar as possible.
The participants received 1 of the following treatments:
• TAK-341, 2000 or 2400 milligrams (mg) given as a slow injection into the vein, called intravenous (IV) infusion, every 4 weeks.
• Placebo, given as IV infusion, every 4 weeks.
The study doctors checked that each participant met the study rules before they joined the study.
The study was done in the following parts:
Screening Period (6 weeks)
Treatment Period (52 weeks)
Early treatment group:
• Initially, a few participants were randomly assigned to receive either TAK-341 or placebo. Participants started on a dose of 2400 mg every 4 weeks. Based on the results of this group, the dose was then lowered to 2000 mg for a short period of time.
• After receiving the third infusion at Visit 4, participants had continuous blood tests to check how TAK-341 was processed by the body.
• Based on the results of these blood tests, researchers decided on a final dose of 2400 mg for the rest of the study.
Main treatment group:
After the early treatment group started, more participants joined the study in the main treatment group.
• At Visit 2 on Day 1, participants in the main group were randomly assigned to receive either TAK-341 2000 mg or placebo.
• Once the final dose was decided from the results of participants in the early treatment group, all participants were randomly assigned to receive TAK-341 2400 mg or placebo.
During the treatment period, researchers continued to perform blood tests, monitored vital signs, and assessed medical problems. Blood samples were also collected to check for any antibodies against TAK-341.
Follow-up Period
Participants visited the clinic about 3 months after their last infusion. Along with blood tests, researchers also took brain-related exams, physical exams, monitored vital signs, and medical problems.
Results:
Out of 158 participants who joined the study, 157 were treated. They were from 41 to 81 years old when they joined the study. This study took place in 41 study clinics in 10 countries worldwide (Japan, Austria, Denmark, France, Germany, Italy, Portugal, Spain, United Kingdom, United States).
The study started in November 2022 and ended in July 2025. Participants were in the study for up to 1 year and 5 months. The study duration was 2 years and 8 months.
• Average UMSARS score change: 5.1 (TAK-341) vs. 5.2 (placebo) after 52 weeks.
• No meaningful difference between TAK-341 and placebo groups.
• 1 participant withdrew before treatment.
• 28 of 157 treated participants (18%) had side effects, mostly mild or moderate; headache was most common.
• No participant stopped treatment early due to side effects; no serious side effects reported.
• 10 participants (6%) died during the study; the deaths were not thought to be caused by the study treatment.
• TAK-341 was generally well-tolerated by participants.
Conclusion:
Overall, researchers did not observe a meaningful difference between the TAK-341 and placebo groups after 52 weeks of treatment. There are no ongoing studies and plans for further studies with TAK-341."Multiple System Atrophy (MSA ) is a rare disease of the brain that affects multiple functions of the body, including blood pressure, breathing, urinary function, and various body movements. The study drug in this study, TAK-341, is being developed in the hope that it may help to slow disease progression in MSA. It is a monoclonal antibody (a protein made in the laboratory to fight against foreign substances) that specifically targets a substance called α-synuclein which is found in people with MSA and Parkinson’s disease.
There are currently no available therapies on the market that can slow or prevent the progression of MSA, therefore, there is a need for effective treatment options for this disease.
The purpose of this clinical research study is to investigate whether TAK-341 is safe and tolerable, and effective in MSA patients and to investigate how TAK-341 is absorbed, broken down, and eliminated from the body.
The study drug will be given as intravenous (IV) infusions and there are 2 groups in this study:
• Early Pharmacokinetic (PK) Group (check how the body handles the study drug): 15 participants will be assigned by chance (like flipping a coin, which is known as randomisation) to receive either TAK-341 or placebo (placebo is a substance that looks like drug but does not contain any active drug in it) in the ratio 2:1 by a computer.
• Main Group: 123 participants will be randomised in the ratio 1:1; which means you have equal chances of receiving TAK-341 or placebo.
Study procedures include physical examination, blood pressure, heart rate, respiratory rate, temperature, blood and urine sampling, electrocardiogram (ECG), neurological examination (to check how the brain, spinal cord, and nerves are working), eye test, brain MRI scan, lumbar puncture to collect cerebrospinal fluid samples and various questionnaires.
The total study participation time including the follow-up period is approximately 67 weeks for each participant.REC name
London - Westminster Research Ethics Committee
REC reference
22/LO/0563
Date of REC Opinion
31 Oct 2022
REC opinion
Further Information Favourable Opinion