RETHINK-ALZ: Simufilam 100 mg for Mild-to-Moderate Alzheimer's Disease
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Detailed Description
The primary objective of this study is to investigate the safety and efficacy of simufilam (PTI-125) in enhancing cognition and slowing cognitive and functional decline following 52-week, repeat-dose oral administration in participants with mild-to-moderate AD. Secondary objectives include the assessment of simufilam's effect on neuropsychiatric symptoms and caregiver burden. A third objective is to investigate the effect of simufilam treatment on plasma biomarkers. A limited number of research sites will be invited to participate in the pharmacokinetic (PK) and plasma biomarker sub-study. Collection of PK samples will enable an exposure-response analysis. Approximately 100 subjects will participate (50 per group). Plasma samples will be collected during the Screening Visit and again at Weeks 28 and 52. Change from baseline for plasma biomarkers represent additional secondary endpoints.
Safety will be evaluated by adverse event monitoring, vital signs, clinical labs, and the Columbia Suicide Severity Rating Scale at every visit. All subjects will undergo magnetic resonance imaging during screening to ensure entry criteria are met. Electrocardiograms will be conducted on Day 1 and Weeks 4, 28, and 52. A complete physical and neurological examination will be performed at screening, and brief examinations will be performed at all other visits. Weight will be measured during the Screening Period, on Study Day 1, and at all other visits.
An independent Data Safety Monitoring Board (DSMB) will meet periodically to review subject safety assessments and determine if dosing may continue. A charter will be developed with specific guidance for the DSMB.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Placebo Comparator: Placebo Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks |
Drug: Placebo
Matching placebo given b.i.d. for 52 weeks.
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Experimental: Simufilam 100 mg Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks |
Drug: 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 Aβ42. In this study, simufilam will be given b.i.d. for 52 weeks at a dose of 100 mg.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change from baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) [Baseline (Study Day 1) to Week 52]
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).
- Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) [Baseline (Study Day 1) to Week 52]
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.
Secondary Outcome Measures
- Change from baseline in the integrated Alzheimer's Disease Rating Scale (iADRS) [Baseline (Study Day 1) to Week 52]
The change from baseline to Week 52 in the iADRS, where scores range from 0 to 146 with lower scores indicating worse performance.
- Change from baseline in the Neuropsychiatric Inventory (NPI) [Baseline (Study Day 1) to Week 52]
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.
- Change from baseline in the Mini-Mental State Exam (MMSE) [Baseline (Study Day 1) to Week 52]
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. Lower sores indicate more severe impairment.
- Change from baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB) [Baseline (Study Day 1) to Week 52]
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. Higher scores indicate more severe impairment.
- Change from baseline in the Zarit Burden Interview (ZBI) [Baseline (Study Day 1) to Week 52]
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, with a higher score indicating greater stress or burden.
- Changes from baseline in plasma P-tau181, neurofilament light chain and GFAP [Baseline (Study Day 1) to Week 52]
Change from baseline in plasma biomarkers of AD pathology, neurodegeneration, and neuroinflammation.
- Changes from baseline in the plasma SavaDx biomarker [Baseline (Study Day 1) to Week 52]
Change from baseline in SavaDx, a novel plasma biomarker
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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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.
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Evidence for AD pathophysiology, confirmed either prior to or during screening.
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MMSE score ≥ 16 and ≤ 27 at screening.
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Clinical Dementia Rating - Global Score must be 0.5, 1 or 2.
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If receiving background AD medications, the dosing regimen must be stable for at least 12 weeks prior to randomization.
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The subject has been a non-smoker for at least 3 years.
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Availability of a study partner
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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.
Key Exclusion Criteria:
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A neurologic condition other than AD that significantly contributes to the subject's dementia.
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Any current primary psychiatric diagnosis other than AD if it is likely to confound cognitive assessment or ability to comply with study procedures
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Geriatric Depression Scale (15-item) score > 8
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Suicidal ideation during the past 3 months or suicidal behavior during the past 12 months
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Alcohol or substance use disorder within 2 years of screening
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MRI presence of cerebral vascular or other significant pathology
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History of transient ischemic attack or stroke within 12 months of screening
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Seizure within 12 months of screening.
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Severe head trauma or head trauma considered likely to be contributing to the subject's cognitive impairment.
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Sleep apnea that is considered likely to be contributing to the subject's cognitive impairment.
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Insufficiently controlled diabetes mellitus or hypertension
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Body mass index < 18.5 or > 35.0.
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History or diagnosis of clinically significant cardiac disease
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Prescribed aducanumab.
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COVID-19 infection within 3 months of screening. If no history of a prior COVID-19 infection, subject must be fully vaccinated for COVID-19 at least 2 weeks prior to randomization.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | MDFirst Research | Chandler | Arizona | United States | 85286 |
2 | CCT Research - Gilbert Neurology Partners | Gilbert | Arizona | United States | 85297 |
3 | Xenoscience, Inc. | Phoenix | Arizona | United States | 85004 |
4 | Advanced Research Center, Inc | Anaheim | California | United States | 92805 |
5 | Axiom Research, LLC | Colton | California | United States | 92324 |
6 | ATP Clinical Research, Inc. | Costa Mesa | California | United States | 92626 |
7 | Sun Valley Research Center, Inc. | Imperial | California | United States | 92251 |
8 | Senior Clinical Trials | Laguna Hills | California | United States | 92653 |
9 | Artemis Institute for Clinical Research | Riverside | California | United States | 92503 |
10 | Syrentis Clinical Research | Santa Ana | California | United States | 92705 |
11 | Mountain Neurological Research Center | Basalt | Colorado | United States | 81621 |
12 | Colorado Neurological Research Center, PC | Denver | Colorado | United States | 80210 |
13 | Topaz Clinical Research | Apopka | Florida | United States | 32703 |
14 | Neurology Offices of South Florida | Boca Raton | Florida | United States | 33428 |
15 | Boynton Beach Medical Research Institute (GMI) | Boynton Beach | Florida | United States | 33437 |
16 | Neuropsychiatric Research Center of Southwest Florida | Fort Myers | Florida | United States | 33912 |
17 | Velocity Clinical Research, Hallandale Beach | Hallandale Beach | Florida | United States | 33009 |
18 | Galiz Research | Hialeah | Florida | United States | 33016 |
19 | CNS Healthcare - Jacksonville | Jacksonville | Florida | United States | 32256 |
20 | Charter Research | Lady Lake | Florida | United States | 32792 |
21 | Parker Jewish Institute | Lauderhill | Florida | United States | 33319 |
22 | Segal Trials - West Broward Outpatient Site | Lauderhill | Florida | United States | 33319 |
23 | ClinCloud | Maitland | Florida | United States | 32751 |
24 | Quantam Clinical Trials | Miami Beach | Florida | United States | 33140 |
25 | South Florida Research Phase I-IV INC | Miami Springs | Florida | United States | 33166 |
26 | Central Miami Medical Institute (GMI) | Miami | Florida | United States | 33125 |
27 | New Horizon Research Center | Miami | Florida | United States | 33165 |
28 | Suncoast Clinical Research, Inc. | New Port Richey | Florida | United States | 34652 |
29 | Renstar Medical Research | Ocala | Florida | United States | 34470 |
30 | Combined Research Orlando Phase I-IV | Orlando | Florida | United States | 32807 |
31 | Progressive Medical Research | Port Orange | Florida | United States | 32127 |
32 | Infinity Clinical Research - Sunrise | Sunrise | Florida | United States | 33351 |
33 | Clinical Research of Brandon, LLC (Tampa) | Tampa | Florida | United States | 33603 |
34 | Stedman Clinical Trials | Tampa | Florida | United States | 33613 |
35 | Premier Research Institute at Palm Beach Neurology | West Palm Beach | Florida | United States | 33407 |
36 | Charter Research | Winter Park | Florida | United States | 32792 |
37 | Velocity Clinical Research, Boise | Meridian | Idaho | United States | 83642 |
38 | Ascension Via Christi Research | Wichita | Kansas | United States | 67214 |
39 | Neuro Medical Clinic of Central Louisiana, LLC | Alexandria | Louisiana | United States | 71301 |
40 | Boston Neuro Research Center | North Dartmouth | Massachusetts | United States | 02747 |
41 | Clinical Research Professionals | Chesterfield | Missouri | United States | 63005 |
42 | CCT Research - Papillion Research Center | Papillion | Nebraska | United States | 68046 |
43 | Advanced Clinical Institute, Inc | Neptune | New Jersey | United States | 07753 |
44 | Albuquerque Neuroscience, Inc | Albuquerque | New Mexico | United States | 87109 |
45 | Dent Neurologic Institute | Amherst | New York | United States | 14226 |
46 | Mid Hudson Medical Research | New Windsor | New York | United States | 12553 |
47 | NY Neurology Associates | New York | New York | United States | 10003 |
48 | University of Rochester Medical Center - Alzheimer's Disease Care, Research and Education Program | Rochester | New York | United States | 14620 |
49 | Five Town Neuroscience Research | Woodmere | New York | United States | 11598 |
50 | Triad Clinical Trials, LLC | Greensboro | North Carolina | United States | 27410 |
51 | Alzheimer's Memory Center | Matthew | North Carolina | United States | 28105 |
52 | Insight Clinical Trials LLC | Beachwood | Ohio | United States | 44122 |
53 | NeuroScience Research Center, LLC | Canton | Ohio | United States | 44718 |
54 | Dayton Center for Neurological Disorders | Centerville | Ohio | United States | 45459 |
55 | Summit Research Network, LLC | Portland | Oregon | United States | 97210 |
56 | Lehigh Center for Clinical Research | Allentown | Pennsylvania | United States | 18104 |
57 | Rhode Island Mood & Memory Research Institute | East Providence | Rhode Island | United States | 02914 |
58 | Ralph H. Johnson VA Health Care System | Charleston | South Carolina | United States | 29401 |
59 | Palmetto Clinical Research | Summerville | South Carolina | United States | 29485 |
60 | Senior Adults Specialty Research, Inc | Austin | Texas | United States | 78757 |
61 | Texas Neurology, PA | Dallas | Texas | United States | 75206 |
62 | Mt. Olympus Medical Research, LLC | Katy | Texas | United States | 77450 |
63 | Grayline Research Center | Wichita Falls | Texas | United States | 76309 |
64 | Green Mountain Research Institute, Inc. | Rutland | Vermont | United States | 05701 |
65 | Re:Cognition Health | Fairfax | Virginia | United States | 22031 |
66 | Memory and Brain Wellness Center at Harborview | Seattle | Washington | United States | 98104 |
67 | KaRa MINDS | Macquarie Park | New South Wales | Australia | 2113 |
68 | LMC Clinical Research - London | London | Ontario | Canada | N6A 5R9 |
69 | Bluewater Clinical Research Group Inc | Sarnia | Ontario | Canada | N7T 4X3 |
70 | Q & T Research | Sherbrooke | Quebec | Canada | J1J 2G2 |
71 | Diex Research Sherbrooke Inc. | Sherbrooke | Quebec | Canada | J1L0H8 |
72 | Alpha Recherche Clinique | Québec | Canada | G3K 2P8 |
Sponsors and Collaborators
- Cassava Sciences, Inc.
- Premier Research Group plc
Investigators
- Study Chair: Jim Kupiec, MD, Cassava Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PTI-125-07