A Study of Lu AF82422 in Participants With Multiple System Atrophy
- Conditions
- Multiple System Atrophy
- Interventions
- Drug: Placebo
- Registration Number
- NCT05104476
- Lead Sponsor
- H. Lundbeck A/S
- Brief Summary
To find out the effect of Lu AF82422 on disease progression in participants with multiple system atrophy.
- Detailed Description
This study will consist of a double-blind period (DBP) and will include an optional open-label treatment extension (OLE) period. Participants in the DBP will be randomized to Lu AF82422 or placebo (2:1). All participants entering the OLE will receive Lu AF82422 during the OLE.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 64
- The participant is diagnosed with possible or probable MSA of the multiple system atrophy parkinsonian type (MSA-P) or multiple system atrophy cerebellar type (MSA-C) sub-type at the Screening Visit.
- The participant had onset of motor and/or autonomic (orthostatic or urinary) MSA symptoms within 5 years prior to the Screening Visit in the judgement of the investigator.
- The participant has an UMSARS Part I score ≤16 (omitting item 11 on sexual function) at the Screening Visit.
- The participant has a cognitive performance evaluated by the Montreal Cognitive Assessment (MoCA) with a score ≥22 at the Screening Visit.
Open-label Extension Entry Criteria
- The participant has completed the EoT Visit and did not withdraw in the DBP.
- The participant has consented to participate in the OLE.
- The participant has completed the DBP within the last 5 months and will be enrolled into the OLE no later than end of Q1 2024.
- The participant is, in the Investigator's opinion, likely to comply with the protocol.
- The participant has not received any other Investigational product since the EOoTDBP Visit.
Key
- The participant has been treated with an anti-α-synuclein monoclonal antibody, mesenchymal stem cells or an inhibitor of α-synuclein aggregation within the last 12 months.
- The participant has any past or current treatment with an active vaccine targeting α-synuclein.
- The participant has 2 or more blood relatives with a history of MSA.
- The participant has evidence (clinically or on MRI) and/or history of any clinically significant disease or condition other than MSA (for example, serious neurological disorder, other intracranial disease, or systemic disease).
- The participant has a current diagnosis of movement disorders that could mimic MSA (for example, Parkinson' disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, spinocerebellar ataxia, spastic paraparesis, corticobasal degeneration, or vascular, pharmacological, or post-encephalitic parkinsonism), per investigator discretion.
Other inclusion and exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants in the DBP will receive Lu AF82422 matching placebo IV infusion Q4W from Baseline for a minimum 48 weeks up to a maximum 72 weeks. Lu AF82422 Lu AF82422 Participants in the DBP will receive Lu AF82422 intravenous (IV) infusion every 4 weeks (Q4W) from Baseline for a minimum 48 weeks up to a maximum 72 weeks. In the optional OLE, all participants will receive Lu AF82422 IV infusion starting on Day 1 of the OLE up to week 92.
- Primary Outcome Measures
Name Time Method Percentage Slowing of Clinical Progression Based on Change From Baseline in the UMSARS TS at the End of Treatment (EOT) DB Period (DBP) Baseline up to Week 72 The primary endpoint assessed disease progression by a Bayesian repeated measures model on UMSARS TS. Reported here is the estimated slowing (%) of clinical progression in participants receiving Lu AF82422 relative to those receiving placebo. UMSARS is a combined clinician and patient-reported outcome assessment developed to provide a surrogate measure of disease progression in multiple system atrophy (MSA). UMSARS TS was obtained by the sum of the items from Part I and Part II. Part I assesses historical information on symptoms and activities of daily living over the past 2 weeks and Part II consists of a clinical examination of key MSA motor signs and symptoms. UMSARS TS score was the sum of all items and ranged from 0 (no impairment) to 104 (severe impairment). A higher score indicated greater impairment.
- Secondary Outcome Measures
Name Time Method Change From Baseline in the UMSARS TS at the End of Treatment (EOT) DBP Baseline, Weeks 48 and 72 UMSARS is a combined clinician and patient-reported scale to assess motor impairment in MSA participants. UMSARS TS was obtained by the sum of the items from Part I and Part II. Part I assesses historical information on symptoms and activities of daily living over the past 2 weeks (12 items) rated on a scale ranging from 0 = not affected to 4 = unable to do the activity. Part I total score ranged between 0 to 48 (higher score indicated greater impairment). Part II consists of a clinical examination of key MSA motor signs and symptoms (14 items) rated on a scale ranging from 0 = normal to 4 = marked/severe impairment. Part II total score ranged between 0 and 56 (higher score indicated greater impairment). UMSARS TS score was the sum of all 26 items and ranged from 0 (no impairment) to 104 (severe impairment). A higher score indicated greater impairment. LS mean and SE were calculated using MMRM.
Change From Baseline in the Modified UMSARS Part I (mUMSARS) Score at the EOT DBP Baseline, Weeks 48 and 72 UMSARS Part 1 assesses historical information on symptoms and activities of daily living over the past 2 weeks as reported by participants and caregivers (12 items) rated on a scale ranging from 0 to 4; with 0 = not affected/normal 1= mildly affected/impaired, 2= moderately affected/impaired, 3= severely affected/impaired, and 4 = helpless or entirely affected/impaired. The modified UMSARS part I (mUMSARS) score was derived by collapsing the response option 0 and 1 within each item (0 \& 1 =1). Hence, the mUMSARS score ranged from 12 to 48 (higher score indicated greater impairment). LS mean and SE were calculated using MMRM.
Change From Baseline in the UMSARS Part I Scores at the EOT DBP Baseline, Weeks 48 and 72 UMSARS Part 1 assesses historical information on symptoms and activities of daily living over the past 2 weeks as reported by participants and caregivers (12 items: speech, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, walking, falling, orthostatic symptoms, urinary function, sexual function, and bowel function) each rated on a scale ranging from 0 to 4; with 0 = not affected/normal 1= mildly affected/impaired, 2= moderately affected/impaired, 3= severely affected/impaired, and 4 = helpless or entirely affected/impaired. Part I total score ranged between 0 to 48 (higher score indicated greater impairment). LS mean and SE were calculated using MMRM.
Change From Baseline in the UMSARS Part II Scores at the EOT DBP Baseline, Weeks 48 and 72 UMSARS Part II consists of a clinical examination of key MSA motor signs and symptoms (14 items: facial expression, speech, ocular motor dysfunction, tremor at rest, action tremor, increased tone, rapid alternating movements of hands, finger taps, leg agility, heel-knee-shin test, arising from chair, posture, body sway, gait) each rated on a scale ranging from 0 to 4; with 0 = not affected/normal 1= mildly affected/impaired, 2= moderately affected/impaired, 3= severely affected/impaired, and 4 = helpless or entirely affected/impaired. Part II total score ranged between 0 and 56 (higher score indicated greater impairment). LS mean and SE were calculated using MMRM.
Change From Baseline in Schwab and England Activities of Daily Living (SE-ADL) Score at Week 48 in the DBP Baseline, Week 48 The SE-ADL is a combined participant- and clinician-reported scale to assess participants physical functioning in activities in daily living to grade functional status. For this study, only the clinician-rated part was administered. The SE-ADL scale uses percentages to represent how much effort and dependence on others, participants need to complete daily chores. The SE-ADL scale ranged from 0% indicating worst possible function (fully dependent) to 100% indicating no impairment (completely independent). LS mean and SE were calculated using MMRM.
Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 48 in the DBP Baseline, Week 48 The CGI-S was administered by an experienced neurologist familiar with MSA participants to make an expert clinical global judgement about the severity of the disease across various time points. The rating was based upon observed and reported symptoms, behaviour, and function in the past seven days. The CGI-S was rated on a scale ranging from 0 to 4 (whereas the 0 = normal, not impaired; 1 = mildly impaired; 2 = moderately impaired; 3 = severely impaired; 4 = extremely impaired). LS mean and SE were calculated using MMRM.
Change From Baseline in Patient Global Impression - Severity of Illness (PGI-S) Score at Week 48 in the DBP Baseline, Week 48 The PGI-S is a self-reported single item to evaluate all aspects of participants' MSA symptoms. Participants were asked to choose the response that best described the severity of their MSA symptoms over the past week. The question was rated on a 5-point scale ranging from 0 to 4 (0 = none; 1 = minor; 2 = moderate; 3 = severe; 4 = very severe). LS mean and SE were calculated using MMRM.
Change From Baseline in Observer-Reported Global Impression - Severity of Illness (OGI-S) Score at Week 48 in the DBP Baseline, Week 48 The OGI-S is a single-question carer/observer-reported outcome to evaluate all aspects of participants' MSA symptoms. Carer/observers were asked to choose the response that best described the observed severity of MSA symptoms in the person they care for over the past week. The question was rated on a 5-point scale ranging from 0 to 4 (0 = none; 1 = minor; 2 = moderate; 3 = severe; 4 = very severe). LS mean and SE were calculated using MMRM.
Composite Autonomic Symptom Score Select Change (COMPASS Select Change) Total Score at Week 48 in the DBP Week 48 The COMPASS Select, a participant-reported scale, consists of a subset of 36 items derived from the original COMPASS, to assess severity of autonomic symptoms in MSA during the last year. The COMPASS Select includes 3 domains related to blood pressure control: syncope, orthostatic intolerance, and vasomotor symptoms; and 3 domains focused on symptoms of disturbed secretomotor, bladder, and sleep function. The COMPASS Select Change is a derivate of COMPASS Select, consisting of 16 items in which participants were asked to score their change in autonomic symptoms since their last visit. The scoring algorithm of COMPASS was highly complicated and required computer analysis for score generation. COMPASS Change Select score ranged from -150 to 150. A higher score indicated greater autonomic symptom severity.
Change From Baseline in UMSARS Part IV Score at Week 48 in the DBP Baseline, Week 48 The UMSARS part IV comprised a global disability scale ranging from 1-5, with 1 = 'Completely independent. Able to do all chores with minimal difficulty or impairment. Essentially normal. Unaware of any difficulty'; 2 = 'Not completely independent. Needs help with some chores'; 3 = 'More dependent. Help with half of chores. Spends a large part of the day with chores'; 4 = 'Very dependent. Now and then does a few chores alone or begins alone. Much help needed'; and 5 = 'Totally dependent and helpless. Bedridden'. LS mean and SE were calculated using MMRM.
Change From Baseline in Speech, Swallowing, Falls, and Walking, as Assessed by the UMSARS Part I Item Scores at Week 48 in the DBP Baseline, Week 48 UMSARS Part I assesses historical information on symptoms and activities of daily living over the past 2 weeks as reported by participants and caregivers (12 items: speech, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, walking, falling, orthostatic symptoms, urinary function, sexual function, and bowel function) each rated on a scale ranging from 0 to 4; with 0 = not affected/normal 1= mildly affected/impaired, 2= moderately affected/impaired, 3= severely affected/impaired, and 4 = helpless or entirely affected/impaired. LS mean and SE were calculated using MMRM.
Change From Baseline in Number of Falls, as Assessed by the Fall Diary Periods (Weeks 44 to 48) in the DBP Baseline, Weeks 44 to 48 Fall Diary period was defined as the period between the two visits where the diary was filled out according to the protocol. LS mean and SE were calculated using MMRM.
Change From Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Score at Week 48 in the DBP Baseline, Week 48 The EQ-5D-5L is a participant-reported assessment designed to measure the participant's wellbeing. It consisted of 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a visual analogue scale (VAS) of the overall health state. Each descriptive item was rated on a 5-point index ranging from 1 (no problems) to 5 (extreme problems). The VAS ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). LS mean and SE were calculated using MMRM.
Percent Change From Baseline in Brain Volume With Ventricles, as Measured by Volumetric MRI (vMRI) at Week 48 in the DBP Baseline, Week 48 LS mean and SE were calculated using MMRM.
Percent Change From Baseline in P-Neurofilament Light Chain (NfL) Protein Concentration at Week 48 in the DBP Baseline, Week 48 LS mean and SE were calculated using MMRM.
Lu AF82422 Plasma Concentration in the DBP Weeks 0, 4, 6, 8, 12, 24, 36, 48, 60, 72, 88 Lu AF82422 Cerebrospinal Fluid (CSF) Concentrations in the DBP Weeks 0 and 48 Lu AF82422 CSF/Plasma Concentration Ratio in the DBP Weeks 0 and 48
Trial Locations
- Locations (19)
The Parkinson's and Movement Disorder Institute
🇺🇸Fountain Valley, California, United States
University of California - San Diego
🇺🇸La Jolla, California, United States
UCSF Memory and Aging Center
🇺🇸San Francisco, California, United States
Movement Disorders Center - Colorado Neurological Institute (CNI)
🇺🇸Englewood, Colorado, United States
Parkinson's Disease And Movement Disorder Center Of Boca Raton
🇺🇸Boca Raton, Florida, United States
University of Florida Norman Fixel Institute for Neurological Diseases
🇺🇸Gainesville, Florida, United States
Rush University Medical Center, Rush University Cancer Center
🇺🇸Chicago, Illinois, United States
Endeavor Health - Glenbrook Hospital
🇺🇸Glenview, Illinois, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
NYU Medical Center - Dysautonomia center
🇺🇸New York, New York, United States
Columbia University Medical Center - The Neurological Institute of New York
🇺🇸New York, New York, United States
Penn State Milton S. Hershey Medical Center - Penn State Hershey Neuroscience Institute (PSHNI)
🇺🇸Hershey, Pennsylvania, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University Of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Fujita Health University Hospital
🇯🇵Toyoake, Aichi, Japan
Gifu University Hospital
🇯🇵Gifu City, Gifu Prefecture, Japan
National Hospital Organization Sendai Nishitaga Hospital
🇯🇵Sendai-shi, Miyagi, Japan