RETHINK-ALZ: Simufilam 100 mg for Mild-to-Moderate Alzheimer's Disease

Sponsor
Cassava Sciences, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04994483
Collaborator
Premier Research Group plc (Industry)
750
72
2
22.9
10.4
0.5

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
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

Study Type:
Interventional
Anticipated Enrollment :
750 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Approximately 750 patients will be enrolled into the study. All patients will be randomized (1:1) to receive either placebo or 100 mg tablets of simufilam, twice daily, for 52 weeks.Approximately 750 patients will be enrolled into the study. All patients will be randomized (1:1) to receive either placebo or 100 mg tablets of simufilam, twice daily, for 52 weeks.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Randomized treatments will be assigned by subject numbers in a randomly generated numeric sequence. Randomization (1:1) will be stratified by low or high Mini-Mental State Exam (MMSE; 16-20 and 21-27). The randomization code will not be revealed to study subjects, Investigators, clinical staff, study monitors or the Sponsor until all subjects have completed therapy and the database has been finalized and locked.
Primary Purpose:
Treatment
Official 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
Actual Study Start Date :
Nov 3, 2021
Anticipated Primary Completion Date :
Oct 1, 2023
Anticipated Study Completion Date :
Oct 1, 2023

Arms and Interventions

Arm Intervention/Treatment
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.

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:
  • PTI-125
  • Outcome Measures

    Primary Outcome Measures

    1. 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).

    2. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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

    Ages Eligible for Study:
    50 Years to 87 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    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.

    6. The subject has been a non-smoker 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.

    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

    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 > 35.0.

    13. History or diagnosis of clinically significant cardiac disease

    14. Prescribed aducanumab.

    15. 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
    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.
    Responsible Party:
    Cassava Sciences, Inc.
    ClinicalTrials.gov Identifier:
    NCT04994483
    Other Study ID Numbers:
    • PTI-125-07
    First Posted:
    Aug 6, 2021
    Last Update Posted:
    Aug 10, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 10, 2022