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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04994483
Registration number
NCT04994483
Ethics application status
Date submitted
29/07/2021
Date registered
6/08/2021
Date last updated
25/05/2025
Titles & IDs
Public title
Simufilam 100 mg for Mild-to-Moderate Alzheimer's Disease
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Scientific title
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Study Evaluating the Safety and Efficacy of Simufilam 100 mg Tablets in Subjects With Mild-to-Moderate Alzheimer's Disease
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Secondary ID [1]
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PTI-125-07
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Universal Trial Number (UTN)
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Trial acronym
RETHINK-ALZ
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Alzheimer Disease
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Condition category
Condition code
Neurological
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Alzheimer's disease
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Neurological
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Dementias
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Simufilam
Treatment: Drugs - Placebo
Placebo comparator: Placebo - Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks
Experimental: Simufilam 100 mg - Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks
Treatment: Drugs: Simufilam
Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aß42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
Treatment: Drugs: Placebo
Matching placebo given b.i.d. for 52 weeks.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)
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Assessment method [1]
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The change from baseline to Week 52 in the ADAS-Cog12, a psychometrician-administered battery comprised of several cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Scores range from 0 (best) to 80 (worst).
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Timepoint [1]
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Baseline (Study Day 1) to Week 52
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Primary outcome [2]
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Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
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Assessment method [2]
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The change from baseline to Week 52 in the ADCS-ADL, a 23-item study partner questionnaire that covers both basic activities of daily living (ADL) and more complex ADL or instrumental ADL. Scores range from 0 to 78, with a lower score indicating greater severity of functional loss.
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Timepoint [2]
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Baseline (Study Day 1) to Week 52
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Secondary outcome [1]
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Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)
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Assessment method [1]
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The change from baseline to Week 52 in the iADRS, where scores range from 0 to 146 with lower scores indicating worse performance.
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Timepoint [1]
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Baseline (Study Day 1) to Week 52
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Secondary outcome [2]
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Change From Baseline in the Neuropsychiatric Inventory (NPI)
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Assessment method [2]
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The change from baseline to Week 52 in the NPI, a 12-item study partner interview, which records the frequency and severity of common neuropsychiatric symptoms in dementia, as well as the level of study partner distress due to each of the neuropsychiatric problems. Scores range from 0 to 144, with higher scores indicating more frequent and severe symptoms, and greater levels of partner distress.
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Timepoint [2]
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Baseline (Study Day 1) to Week 52
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Secondary outcome [3]
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Change From Baseline in the Mini-Mental State Exam (MMSE)
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Assessment method [3]
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The change from baseline to Week 52 in the MMSE, a set of standardized questions covering several target areas: orientation, registration, attention and calculation, short-term verbal recall, naming, repetition, 3-step command, reading, writing, and visuospatial cognitive assessment. Scores range from 0 to 30, lower scores indicate more severe impairment.
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Timepoint [3]
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Secondary outcome [4]
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Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)
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Assessment method [4]
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The change from baseline to Week 52 in the CDR-SB, which characterizes 6 domains of cognitive and functional performance applicable to AD and related dementias: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores for each domain have a minimum of 0 and a maximum of 3, and the 6 domain scores are summed to give the CDR-SB, which has a minimum score of 0 and a maximum score of 18. Higher scores indicate more severe impairment.
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Timepoint [4]
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Baseline (Study Day 1) to Week 52
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Secondary outcome [5]
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Change From Baseline in the Zarit Burden Interview (ZBI)
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Assessment method [5]
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The change from baseline to Week 52 in the ZBI, a 22-item study partner questionnaire designed to assess the stress or burden experienced by caregivers of people with dementia. Scores range from 0 to 88, with a higher score indicating greater stress or burden.
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Timepoint [5]
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Baseline (Study Day 1) to Week 52
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Eligibility
Key inclusion criteria
Key
1. Meets National Institute on Aging and Alzheimer's Association Research Framework criteria for individuals in clinical Stage 4 or 5 of the Alzheimer's continuum.
2. Evidence for AD pathophysiology, confirmed either prior to or during screening.
3. MMSE score = 16 and = 27 at screening.
4. Clinical Dementia Rating - Global Score must be 0.5, 1 or 2.
5. If receiving background AD medications, the dosing regimen must be stable for at least 12 weeks prior to randomization. Chronic medications for conditions other than AD (such as depression) must be prescribed at a stable dose for at least 4 weeks prior to screening.
6. The subject has not been a cigarette smoker or chewed tobacco for at least 3 years.
7. Availability of a study partner.
8. Individuals who have participated in a clinical study with an investigational drug targeting the underlying AD process may be permitted to participate in this study.
9. Completed a COVID-19 vaccine primary series ("fully vaccinated") at least 2 weeks prior to randomization or had an unambiguous COVID-19 infection diagnosed more than 3 months before the start of the Screening Period.
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Minimum age
50
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Maximum age
87
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. A neurologic condition other than AD that significantly contributes to the subject's dementia.
2. Any current primary psychiatric diagnosis other than AD if it is likely to confound cognitive assessment or ability to comply with study procedures.
3. Geriatric Depression Scale (15-item) score > 8. (Note - a subject with a score > 8 may continue in screening if, in the judgment of the Investigator, the elevated score is not attributed to a major depressive episode).
4. Suicidal ideation during the past 3 months or suicidal behavior during the past 12 months.
5. Alcohol or substance use disorder within 2 years of screening.
6. MRI presence of cerebral vascular or other significant pathology.
7. History of transient ischemic attack or stroke within 12 months of screening
8. Seizure within 12 months of screening.
9. Severe head trauma or head trauma considered likely to be contributing to the subject's cognitive impairment.
10. Sleep apnea that is considered likely to be contributing to the subject's cognitive impairment.
11. Insufficiently controlled diabetes mellitus or hypertension.
12. Body mass index < 18.5 or > 37.5.
13. History or diagnosis of clinically significant cardiac disease
14. Currently or previously prescribed/administered aducanumab, lecanemab, or any anti-amyloid monoclonal antibody, more than 2 doses.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
3/11/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
2/10/2024
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Sample size
Target
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Accrual to date
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Final
804
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
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Recruitment hospital [1]
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KaRa MINDS - Macquarie Park
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Recruitment hospital [2]
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The University of Queensland - Herston
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Recruitment hospital [3]
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Impact Health Pty Ltd. - Southport
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Eastern Health - Box Hill
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Delmont Private Hospital - Glen Iris
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Austin Health - Heidelberg
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Recruitment hospital [7]
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The Alfred Hospital - Melbourne
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Recruitment hospital [8]
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Royal Melbourne Hospital - Parkville
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Recruitment hospital [9]
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Australian Alzheimer's Research Foundation - Nedlands
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Recruitment postcode(s) [1]
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2113 - Macquarie Park
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Recruitment postcode(s) [2]
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4029 - Herston
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Recruitment postcode(s) [3]
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4215 - Southport
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Recruitment postcode(s) [4]
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3128 - Box Hill
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Recruitment postcode(s) [5]
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3146 - Glen Iris
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Recruitment postcode(s) [6]
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3084 - Heidelberg
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Recruitment postcode(s) [7]
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3004 - Melbourne
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Recruitment postcode(s) [8]
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3050 - Parkville
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Recruitment postcode(s) [9]
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8009 - Nedlands
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Recruitment outside Australia
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Arizona
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California
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Colorado
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Idaho
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Illinois
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Québec
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Cassava Sciences, Inc.
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Address
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Other collaborator category [1]
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Commercial sector/industry
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Name [1]
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Premier Research Group plc
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Ethics approval
Ethics application status
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Summary
Brief summary
A 52-week safety and efficacy study of simufilam (PTI-125) given twice daily to participants with mild-to-moderate Alzheimer's disease (AD) for 52 weeks. Approximately 750 participants will be randomized (1:1) to receive either placebo or 100 mg tablets of simufilam, twice daily, for 52 weeks. Clinic visits will occur 4 weeks after the baseline visit, and then every 12 weeks until the end of the study. The safety of simufilam, and its efficacy in enhancing cognition and slowing cognitive and functional decline will be evaluated.
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Trial website
https://clinicaltrials.gov/study/NCT04994483
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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James Kupiec, MD
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Address
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Cassava Sciences
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Contact person for scientific queries
Data sharing statement
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/83/NCT04994483/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/83/NCT04994483/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT04994483
Download to PDF