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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
15/11/2024

Titles & IDs
Public title
Simufilam 100 Mg for Mild-to-Moderate Alzheimer's Disease
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
Secondary ID [1] 0 0
PTI-125-07
Universal Trial Number (UTN)
Trial acronym
RETHINK-ALZ
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)
Timepoint [1] 0 0
Baseline (Study Day 1) to Week 52
Primary outcome [2] 0 0
Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Timepoint [2] 0 0
Baseline (Study Day 1) to Week 52
Secondary outcome [1] 0 0
Change from baseline in the integrated Alzheimer's Disease Rating Scale (iADRS)
Timepoint [1] 0 0
Baseline (Study Day 1) to Week 52
Secondary outcome [2] 0 0
Change from baseline in the Neuropsychiatric Inventory (NPI)
Timepoint [2] 0 0
Baseline (Study Day 1) to Week 52
Secondary outcome [3] 0 0
Change from baseline in the Mini-Mental State Exam (MMSE)
Timepoint [3] 0 0
Baseline (Study Day 1) to Week 52
Secondary outcome [4] 0 0
Change from baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)
Timepoint [4] 0 0
Baseline (Study Day 1) to Week 52
Secondary outcome [5] 0 0
Change from baseline in the Zarit Burden Interview (ZBI)
Timepoint [5] 0 0
Baseline (Study Day 1) to Week 52
Secondary outcome [6] 0 0
Changes from baseline in plasma phospho-tau181 (P-tau181) and/or phospho-tau217 (P-tau217), and neurofilament light chain.
Timepoint [6] 0 0
Baseline (Study Day 1) to Week 52
Secondary outcome [7] 0 0
Changes from baseline in the plasma SavaDx biomarker
Timepoint [7] 0 0
Baseline (Study Day 1) to Week 52

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.

Key
Minimum age
50 Years
Maximum age
87 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/10/2024
Sample size
Target
Accrual to date
Final
804
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
KaRa MINDS - Macquarie Park
Recruitment hospital [2] 0 0
The University of Queensland - Herston
Recruitment hospital [3] 0 0
Impact Health Pty Ltd. - Southport
Recruitment hospital [4] 0 0
Eastern Health - Box Hill
Recruitment hospital [5] 0 0
Delmont Private Hospital - Glen Iris
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [8] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [9] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment postcode(s) [1] 0 0
2113 - Macquarie Park
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
4215 - Southport
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3146 - Glen Iris
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 0 0
3050 - Parkville
Recruitment postcode(s) [9] 0 0
8009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Nebraska
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New Mexico
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oregon
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
Rhode Island
Country [21] 0 0
United States of America
State/province [21] 0 0
South Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Vermont
Country [24] 0 0
United States of America
State/province [24] 0 0
Virginia
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cassava Sciences, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Premier Research Group plc
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/study/NCT04994483
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jim Kupiec, MD
Address 0 0
Cassava Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04994483