Clincosm LogoSign in Get a demo

Elevage: Study of Azeliragon in Patients With Mild Alzheimer's Disease and Impaired Glucose Tolerance

Sponsor
vTv Therapeutics (Industry)
Overall Status
Terminated
CT.gov ID
NCT03980730
Collaborator
(none)
43
Enrollment
33
Locations
2
Arms
19.1
Actual Duration (Months)
1.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a study to evaluate the efficacy and safety of azeliragon in patients with mild Alzheimer's disease and impaired glucose tolerance. Patients will receive either azeliragon or placebo with a patient's participation lasting approximately 9 months (in Part 1) or 21 months (in Part 2).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
43 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Randomized, Double-blind, Placebo-controlled, Multicenter Studies to Evaluate the Safety and Efficacy of Azeliragon as a Treatment for Subjects With Mild Alzheimer's Disease and Impaired Glucose Tolerance
Actual Study Start Date :
Jun 27, 2019
Actual Primary Completion Date :
Dec 1, 2020
Actual Study Completion Date :
Jan 29, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Azeliragon

Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) or 18 months (Part 2)

Drug: Azeliragon
Azeliragon 5 mg capsule administered orally, once daily
Other Names:
  • TTP488

    		•
    Placebo Comparator: Placebo

    Matching placebo capsule administered orally, once daily for 6 months (Part 1) or 18 months (Part 2)

    Drug: Placebo
    Matching placebo capsule administered orally, once daily

    Outcome Measures

    Primary Outcome Measures

    1. Part 1 : Change From Baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog14) at Month 6 [Baseline to Month 6]

      The Alzheimer's Disease Assessment Scale - Cognitive Subscale 14 Item (ADAS-cog14) scoring range is from 0 to 90, with higher scores indicating greater cognitive impairment

    Secondary Outcome Measures

    1. Part 1: Change From Baseline in the Amsterdam-Instrumental Activities of Daily Living (Amsterdam-IADL) at Month 6 [Baseline to Month 6]

      The Amsterdam-Instrumental Activities of Daily Living score is calculated from a questionnaire consisting of 70 items in seven categories using an item response theory method of scoring. Scores range from 20 to 80 where lower scores indicate greater functional impairment.

    2. Part 1: Change From Baseline in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-sb) at Month 6 [Baseline to Month 6]

      Clinical Dementia Rating - Sum of box (CDR-sb) scores range from 0 to 18 with higher scores indicating greater cognitive impairment.

    3. Part 1: Change From Baseline in the Functional Activities Questionnaire (FAQ) at Month 6 [Baseline to Month 6]

      The total FAQ score ranges from 0 to 30, with higher scores indicating greater functional loss.

    4. Mean Change From Baseline in the Mini Mental State Exam (MMSE) at Month 6. [Baseline to Month 6]

      The MMSE scale range is 0 to 30 with lower scores indicating greater cognitive impairment.

    Other Outcome Measures

    1. Count and Percentage of Subjects With Treatment-emergent Adverse Events [Baseline to Month 6]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Diagnosis of probable Alzheimer Disease (AD) with documented evidence of progression of disease

    • Mini Mental State Examination (MMSE) score of 21-26, inclusive

    • Clinical Dementia Rating global score of 0.5 or 1

    • Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog14) of 10 or more

    • Brain magnetic resonance imaging (MRI) consistent with the diagnosis of probable AD

    • Concurrent use of cholinesterase inhibitor or memantine with stable dose for at least 2 months prior to screening

    • Hemoglobin A1c (HbA1c) 6.5% - 9.5%, inclusive

    • Caregiver willing to participate and be able to attend clinic visits with patient

    • Ability to ingest oral medications

    Exclusion Criteria:

    • Significant neurological or psychiatric disease other than Alzheimer's disease

    • Previous clinical trial participation within 90 days of screening

    • Previous exposure to putative disease modifying therapy for Alzheimer's disease within 1 year of screening

    • History of cancer within the last 5 years except adequately treated cervical carcinoma in-situ, cutaneous basal cell or squamous cell cancer, or non-progressive prostate cancer not requiring current treatment

    • Women of childbearing potential

    • Uncontrolled blood pressure and/or blood pressure above 140/90

    • Participants receiving medications that may negatively impact cognitive function

    • History of diabetic ketoacidosis within the past year

    • History of chronic pancreatitis

    • Stage 4 kidney disease

    • Use of insulin therapy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Tucson Neuroscience Research Tucson Arizona United States 85710
    2 Institute for Neurodegenerative Disorders New Haven Connecticut United States 06510
    3 JEM Research Institute Atlantis Florida United States 33462
    4 Brain Matters Research Delray Beach Florida United States 33445
    5 Jacksonville Center for Clinical Research Jacksonville Florida United States 32216
    6 Charter Research Lady Lake Florida United States 32159
    7 Alzheimer's Research and Treatment Center Lake Worth Florida United States 33449
    8 ClinCloud Maitland Florida United States 32751
    9 Synexus Clinical Research US Orlando Florida United States 32806
    10 Emerald Coast Center for Neurological Disorders Pensacola Florida United States 32514
    11 Progressive Medical Research Port Orange Florida United States 32127
    12 The Roskamp Institute Sarasota Florida United States 34243
    13 Brain Matters Research Stuart Florida United States 34997
    14 Emory Alzheimer's Clinical Research Unit Atlanta Georgia United States 30329
    15 NeuroStudies.net LLC Decatur Georgia United States 30033
    16 IU Health Partners, Adult Neurology Clinic Indianapolis Indiana United States 46202
    17 Memory Center / Hattiesburg Clinic Hattiesburg Mississippi United States 39401
    18 Millennium Psychiatric Associates Saint Louis Missouri United States 63132
    19 The Cognitive and Research Center of New Jersey Springfield New Jersey United States 07081
    20 Clarity Clinical Research East Syracuse New York United States 13057
    21 Neurological Associates of Long Island Lake Success New York United States 11042
    22 ANI Neurology dba Alzheimer's Memory Center Charlotte North Carolina United States 28270
    23 Raleigh Neurology Associates Raleigh North Carolina United States 27607
    24 Wake Forest School of Medicine Winston-Salem North Carolina United States 27157
    25 The Ohio State University Columbus Ohio United States 43210
    26 Summit Research Network Portland Oregon United States 97210
    27 Center for Cognitive Health Portland Oregon United States 97225
    28 Okanagan Clinical Trials Ltd. Kelowna British Columbia Canada V1Y 1Z9
    29 True North Clinical Research Inc. Halifax Nova Scotia Canada B3S 1M7
    30 True North Clinical Research Inc. Kentville Nova Scotia Canada B4N 4K9
    31 Recherches Neuro-Hippocampe Ottawa Ontario Canada K1Z IG3
    32 Recherches Neuro-Hippocampe Inc. Gatineau Quebec Canada J8T 8J1
    33 Q&T Research Sherbrooke Inc Sherbrooke Quebec Canada J1J 2G2

    Sponsors and Collaborators

    • vTv Therapeutics

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    vTv Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03980730
    Other Study ID Numbers:
    • TTP488-305
    First Posted:
    Jun 10, 2019
    Last Update Posted:
    Jan 21, 2022
    Last Verified:
    Dec 1, 2021
    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
    Keywords provided by vTv Therapeutics
    Receptor for Advanced Glycation Endproducts (RAGE)
    ADAS-cog
    CDR-sb
    Additional relevant MeSH terms:
    Alzheimer Disease
    Glucose Intolerance

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Azeliragon Placebo
    Arm/Group Description Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) Azeliragon: Azeliragon 5 mg capsule administered orally, once daily Matching placebo capsule administered orally, once daily for 6 months (Part 1) Placebo: Matching placebo capsule administered orally, once daily
    Period Title: Overall Study
    STARTED 21 22
    COMPLETED 19 18
    NOT COMPLETED 2 4

    Baseline Characteristics

    Arm/Group Title Azeliragon Placebo Total
    Arm/Group Description Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) Azeliragon: Azeliragon 5 mg capsule administered orally, once daily Matching placebo capsule administered orally, once daily for 6 months (Part 1) Placebo: Matching placebo capsule administered orally, once daily Total of all reporting groups
    Overall Participants 21 22 43
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    76.3
    (5.82)
    77.0
    (6.56)
    76.7
    (6.14)
    Sex: Female, Male (Count of Participants)
    Female
    9
    42.9%
    11
    50%
    20
    46.5%
    Male
    12
    57.1%
    11
    50%
    23
    53.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    4.8%
    1
    4.5%
    2
    4.7%
    Not Hispanic or Latino
    20
    95.2%
    21
    95.5%
    41
    95.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    9.5%
    0
    0%
    2
    4.7%
    White
    19
    90.5%
    22
    100%
    41
    95.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Years Since Diagnosis of AD (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    1.9
    (1.16)
    1.8
    (1.24)
    1.9
    (1.19)
    Education Level (Count of Participants)
    Some College
    5
    23.8%
    2
    9.1%
    7
    16.3%
    Other (Training, Certifications, etc.)
    1
    4.8%
    2
    9.1%
    3
    7%
    Master's Degree
    1
    4.8%
    4
    18.2%
    5
    11.6%
    High School
    6
    28.6%
    8
    36.4%
    14
    32.6%
    Associate's Degree
    1
    4.8%
    2
    9.1%
    3
    7%
    Bachelor's Degree
    7
    33.3%
    4
    18.2%
    11
    25.6%
    ApoE4 Carrier Status (Count of Participants)
    Non-Carrier
    9
    42.9%
    12
    54.5%
    21
    48.8%
    Carrier
    12
    57.1%
    10
    45.5%
    22
    51.2%
    ADAS-Cog 14 Total Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    30.8
    (7.53)
    29.4
    (8.87)
    30.1
    (8.17)
    CDR Global Score (Count of Participants)
    CDR Global = 1
    11
    52.4%
    9
    40.9%
    20
    46.5%
    CDR Global = 0.5
    10
    47.6%
    13
    59.1%
    23
    53.5%
    CDR Sum of Boxes (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    4.7
    (1.37)
    4.2
    (2.22)
    4.5
    (1.85)
    MMSE Total Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    23.7
    (1.48)
    23.5
    (2.24)
    23.6
    (1.89)

    Outcome Measures

    1. Primary Outcome
    Title Part 1 : Change From Baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog14) at Month 6
    Description The Alzheimer's Disease Assessment Scale - Cognitive Subscale 14 Item (ADAS-cog14) scoring range is from 0 to 90, with higher scores indicating greater cognitive impairment
    Time Frame Baseline to Month 6

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) includes all randomized subjects, whether or not they receive any study medication, and who have at least one post-Baseline assessment. The FAS was used for all hypothesis tests of efficacy.
    Arm/Group Title Azeliragon Placebo
    Arm/Group Description Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) Azeliragon: Azeliragon 5 mg capsule administered orally, once daily Matching placebo capsule administered orally, once daily for 6 months (Part 1) Placebo: Matching placebo capsule administered orally, once daily
    Measure Participants 21 22
    Least Squares Mean (Standard Error) [score on a scale]
    1.8
    (0.82)
    0.4
    (0.69)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Azeliragon, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2057
    Comments
    Method Mixed Models Analysis
    Comments
    2. Secondary Outcome
    Title Part 1: Change From Baseline in the Amsterdam-Instrumental Activities of Daily Living (Amsterdam-IADL) at Month 6
    Description The Amsterdam-Instrumental Activities of Daily Living score is calculated from a questionnaire consisting of 70 items in seven categories using an item response theory method of scoring. Scores range from 20 to 80 where lower scores indicate greater functional impairment.
    Time Frame Baseline to Month 6

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) includes all randomized subjects, whether or not they receive any study medication, and who have at least one post-Baseline assessment.
    Arm/Group Title Azeliragon Placebo
    Arm/Group Description Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) Azeliragon: Azeliragon 5 mg capsule administered orally, once daily Matching placebo capsule administered orally, once daily for 6 months (Part 1) Placebo: Matching placebo capsule administered orally, once daily
    Measure Participants 21 22
    Least Squares Mean (Standard Error) [score on a scale]
    6.2
    (1.99)
    9.3
    (2.37)
    3. Secondary Outcome
    Title Part 1: Change From Baseline in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-sb) at Month 6
    Description Clinical Dementia Rating - Sum of box (CDR-sb) scores range from 0 to 18 with higher scores indicating greater cognitive impairment.
    Time Frame Baseline to Month 6

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) includes all randomized subjects, whether or not they receive any study medication, and who have at least one post-Baseline assessment.
    Arm/Group Title Azeliragon Placebo
    Arm/Group Description Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) Azeliragon: Azeliragon 5 mg capsule administered orally, once daily Matching placebo capsule administered orally, once daily for 6 months (Part 1) Placebo: Matching placebo capsule administered orally, once daily
    Measure Participants 21 22
    Least Squares Mean (Standard Error) [score on a scale]
    0.6
    (0.29)
    1.3
    (0.36)
    4. Secondary Outcome
    Title Part 1: Change From Baseline in the Functional Activities Questionnaire (FAQ) at Month 6
    Description The total FAQ score ranges from 0 to 30, with higher scores indicating greater functional loss.
    Time Frame Baseline to Month 6

    Outcome Measure Data

    Analysis Population Description
    The full analysis set (FAS) includes all randomized subjects, whether or not they receive any study medication, and who have at least one post-Baseline assessment.
    Arm/Group Title Azeliragon Placebo
    Arm/Group Description Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) Azeliragon: Azeliragon 5 mg capsule administered orally, once daily Matching placebo capsule administered orally, once daily for 6 months (Part 1) Placebo: Matching placebo capsule administered orally, once daily
    Measure Participants 21 22
    Least Squares Mean (Standard Error) [score on a scale]
    -0.5
    (0.84)
    2.8
    (0.84)
    5. Secondary Outcome
    Title Mean Change From Baseline in the Mini Mental State Exam (MMSE) at Month 6.
    Description The MMSE scale range is 0 to 30 with lower scores indicating greater cognitive impairment.
    Time Frame Baseline to Month 6

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set
    Arm/Group Title Azeliragon Placebo
    Arm/Group Description Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) Azeliragon: Azeliragon 5 mg capsule administered orally, once daily Matching placebo capsule administered orally, once daily for 6 months (Part 1) Placebo: Matching placebo capsule administered orally, once daily
    Measure Participants 21 22
    Least Squares Mean (Standard Error) [score on a scale]
    -1.8
    (0.41)
    -1.7
    (0.43)
    6. Other Pre-specified Outcome
    Title Count and Percentage of Subjects With Treatment-emergent Adverse Events
    Description
    Time Frame Baseline to Month 6

    Outcome Measure Data

    Analysis Population Description
    The safety set (SAF) includes all subjects who receive any study medication.
    Arm/Group Title Azeliragon Placebo
    Arm/Group Description Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) Azeliragon: Azeliragon 5 mg capsule administered orally, once daily Matching placebo capsule administered orally, once daily for 6 months (Part 1) Placebo: Matching placebo capsule administered orally, once daily
    Measure Participants 21 22
    Subjects with at least 1 adverse event
    16
    76.2%
    16
    72.7%
    Subjects with at least 1 serious adverse event
    1
    4.8%
    0
    0%
    Subjects who had drug withdrawn due to AE
    2
    9.5%
    0
    0%

    Adverse Events

    Time Frame 6 months
    Adverse Event Reporting Description
    Arm/Group Title Azeliragon Placebo
    Arm/Group Description Azeliragon 5mg capsule administered orally, once daily for 6 months (Part 1) Azeliragon: Azeliragon 5 mg capsule administered orally, once daily Matching placebo capsule administered orally, once daily for 6 months (Part 1) Placebo: Matching placebo capsule administered orally, once daily
    All Cause Mortality
    Azeliragon Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/21 (0%) 0/22 (0%)
    Serious Adverse Events
    Azeliragon Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/21 (4.8%) 0/22 (0%)
    General disorders
    Gait disturbance 1/21 (4.8%) 1 0/22 (0%) 0
    Other (Not Including Serious) Adverse Events
    Azeliragon Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/21 (42.9%) 13/22 (59.1%)
    Gastrointestinal disorders
    Diarrhoea 2/21 (9.5%) 1/22 (4.5%)
    Infections and infestations
    Urinary tract infection 2/21 (9.5%) 2/22 (9.1%)
    Injury, poisoning and procedural complications
    Fall 3/21 (14.3%) 3/22 (13.6%)
    Metabolism and nutrition disorders
    Diabetes mellitus 1/21 (4.8%) 4/22 (18.2%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 0/21 (0%) 2/22 (9.1%)
    Nervous system disorders
    Cognitive disorder 0/21 (0%) 2/22 (9.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/21 (9.5%) 1/22 (4.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Where PI requires the use of the Study Results for publication, the PI shall seek the Sponsor's written approval which shall not be unreasonably withheld; provided, however, that (i) Sponsor may require removal of any Confidential Information of Sponsor or may delay publication for a reasonable period of time in order to secure protection any IP Rights; and, (ii) as the Study is designed as a multi-center Study, no publication shall be made until after the first multi-center publication.

    Results Point of Contact

    Name/Title VP Clinical Operations
    Organization vTv Therapeutics LLC
    Phone 3368410300
    Email jfreeman@vtvtherapeutics.com
    Responsible Party:
    vTv Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03980730
    Other Study ID Numbers:
    • TTP488-305
    First Posted:
    Jun 10, 2019
    Last Update Posted:
    Jan 21, 2022
    Last Verified:
    Dec 1, 2021