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Alzheimer's DiseasePhase 3STEADFASTNCT02080364

Evaluation of the Efficacy and Safety of Azeliragon (TTP488) in Patients With Mild Alzheimer's Disease

A Phase 3 study testing Azeliragon in people with Alzheimer's Disease, run by vTv Therapeutics at 115 sites in 7 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a study to evaluate the efficacy and safety of azeliragon in patients with mild Alzheimer's disease. Patients will receive either azeliragon or placebo with a patient's participation lasting approximately 18 months. Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Alzheimer's Disease
What is being tested?
Azeliragon
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
880 participants
Where
115 sitesin 7 countries
Study dates
Apr 2015to 1 Jun 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Rosen-Modified Hachinski Ischemia Score less than or equal to 4
  • 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 3 months prior to randomization
  • Caregiver willing to participate and be able to attend clinic visits with patient
  • Ability to ingest oral medications

Who cannot join

  • Significant neurological or psychiatric disease other than Alzheimer's disease
  • Participants with evidence or history of severe drug allergies (resulting in dyspnea or severe rash).
  • Any contraindications to MRI (e.g., clinically significant claustrophobia, non-removable ferromagnetic implants). Patients with contraindications to MRI may undergo computed tomography (CT) on approval by sponsor.
  • Any contraindications to the FDG-PET study (e.g. allergy to any component of the FDG dose) in the cohort undergoing a PET scan.
  • Previous exposure to investigational or non-investigational therapies for Alzheimer's disease within 6 months 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 treatment
Show all 11Show fewer
  • Women of childbearing potential
  • Uncontrolled blood pressure and/or blood pressure above 160/100
  • Prescription medical food intended for dietary management of the metabolic processes associated with Alzheimer's disease.
  • Diagnosis or history of cerebrovascular stroke, severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage.
  • Patients with unstable, uncontrolled diabetes (HbA1c > 7.7%) and those requiring insulin.

Trial locations and contacts

115 sites in 7 countries.

115 sites in 7 countries

United States80 sites

  • Study site

    Albany, New York, 12208

  • Study site

    Albuquerque, New Mexico, 87109

  • Study site

    Atlanta, Georgia, 30331

  • Study site

    Atlantis, Florida, 33462

  • Study site

    Baltimore, Maryland, 21208

  • Study site

    Bellflower, California, 90706

  • Study site

    Brooksville, Florida, 34601

  • Study site

    Canton, Ohio, 44718

  • Study site

    Charleston, South Carolina, 24901

  • Study site

    Charlotte, North Carolina, 28270

  • Study site

    Chicago, Illinois, 60640

  • Study site

    Columbus, Georgia, 31909

  • Study site

    Cordova, Tennessee, 38018

  • Study site

    Costa Mesa, California, 92626

  • Study site

    Creve Coeur, Missouri, 63141

  • Study site

    Dallas, Texas, 75231

  • Study site

    Delray Beach, Florida, 33445

  • Study site

    East Providence, Rhode Island, 02914

  • Study site

    East Providence, Rhode Island, 02916

  • Study site

    Fairway, Kansas, 66205

  • Study site

    Fullerton, California, 92835

  • Study site

    Glendale, California, 91206

  • Study site

    Hallandale, Florida, 33009

  • Study site

    Hattiesburg, Mississippi, 39401

  • Study site

    Hialeah, Florida, 33016

  • Study site

    Imperial, California, 92251

  • Study site

    Irvine, California, 92614

  • Study site

    Jacksonville, Florida, 32216

  • Study site

    Kirkland, Washington, 98201

  • Study site

    Laguna Hills, California, 92653

  • Study site

    Lake Success, New York, 11042

  • Study site

    Lake Worth, Florida, 33449

  • Study site

    Leesburg, Florida, 34748

  • Study site

    Lexington, Kentucky, 40504

  • Study site

    Long Beach, California, 90806

  • Study site

    Long Beach, California, 90807

  • Study site

    Media, Pennsylvania, 19063

  • Study site

    Miami, Florida, 33122

  • Study site

    Miami, Florida, 33137

  • Study site

    Miami Beach, Florida, 33140

  • Study site

    Miami Lakes, Florida, 33014

  • Study site

    Miami Lakes, Florida, 33016

  • Study site

    Mt. Pleasant, South Carolina, 29464

  • Study site

    Murray, Utah, 84123

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    New York, New York, 10032

  • Study site

    Newton, Massachusetts, 02459

  • Study site

    Norristown, Pennsylvania, 19403

  • Study site

    Oklahoma City, Oklahoma, 73103

  • Study site

    Oklahoma City, Oklahoma, 73118

  • Study site

    Orange, California, 92868

  • Study site

    Orlando, Florida, 32806

  • Study site

    Pensacola, Florida, 32503

  • Study site

    Phoenix, Arizona, 85004

  • Study site

    Phoenix, Arizona, 85013

  • Study site

    Phoenix, Arizona, 85018

  • Study site

    Plains, Pennsylvania, 18705

  • Study site

    Plymouth, Massachusetts, 02360

  • Study site

    Portland, Oregon, 97210

  • Study site

    Portland, Oregon, 97225

  • Study site

    Prairie Village, Kansas, 66201

  • Study site

    Princeton, New Jersey, 08540

  • Study site

    Quincy, Massachusetts, 01269

  • Study site

    Raleigh, North Carolina, 27607

  • Study site

    Richland, Washington, 99352

  • Study site

    Riverside, California, 92506

  • Study site

    San Antonio, Texas, 78229

  • Study site

    San Antonio, Texas, 78232

  • Study site

    San Bernardino, California, 92408

  • Study site

    San Francisco, California, 94114

  • Study site

    Santa Ana, California, 92705

  • Study site

    Sarasota, Florida, 34243

  • Study site

    Shaker Heights, Ohio, 44122

  • Study site

    Staten Island, New York, 10312

  • Study site

    Sunrise, Florida, 33351

  • Study site

    Tucson, Arizona, 85724

  • Study site

    Tucson, Arizona, 85741

  • Study site

    Wichita Falls, Texas, 76309

  • Study site

    Wilmington, North Carolina, 28401

  • Study site

    Winston-Salem, North Carolina, 27157

Other trials in United States

United Kingdom12 sites

  • Study site

    Glasgow, G20 OAXA

  • Study site

    London, W1G 9RU

  • Study site

    London, WC1X 8QD

  • Study site

    Manchester, M8 5RB

  • Study site

    Northampton, NN5 6UD

  • Study site

    Oxford, OX3 7JX

  • Study site

    Penarth, CF64 2XX

  • Study site

    Preston, PR2 9HT

  • Study site

    Sheffield, S5 7JT

  • Study site

    Southhampton, SO30 3JB

  • Study site

    Swindon, SN3 6BW

  • Study site

    Warrington, WA2 8WA

Other trials in United Kingdom

Canada8 sites

  • Study site

    Calgary, Alberta, T2N 4Z6

  • Study site

    Chatham, Ontario, N7L 1C1

  • Study site

    Gatineau, Quebec, J8T 8J1

  • Study site

    Greenfield Park, Quebec, J4V2J2

  • Study site

    Kentville, Nova Scotia, B4N4K9

  • Study site

    London, Ontario, N6C 5J1

  • Study site

    Medicine Hat, Alberta, T1B 4E7

  • Study site

    Toronto, Ontario, M3B 257

Other trials in Canada

Australia6 sites

  • Study site

    Caulfield, Victoria, 3162

  • Study site

    Geelong, Victoria, 3220

  • Study site

    Heidelberg West, Victoria, 3081

  • Study site

    Nedlands, Western Australia, 6009

  • Study site

    Southport, Queensland, 4222

  • Study site

    West Perth, Western Australia, 6005

Other trials in Australia

South Africa4 sites

  • Study site

    Cape Town, 7405

  • Study site

    Cape Town, 7530

  • Study site

    Johannesburg, 2196

  • Study site

    Saint George, 6529

Other trials in South Africa

Ireland3 sites

  • Study site

    Cork

  • Study site

    Dublin

  • Study site

    Galway

Other trials in Ireland

New Zealand2 sites

  • Study site

    Christchurch, Canterbury, 8011

  • Study site

    Christchurch, Canterbury, 8022

Other trials in New Zealand

About this study

Official title: Randomized, Double-blind, Placebo Controlled, Multi-center Registration Trial to Evaluate the Efficacy and Safety of Azeliragon (TTP488) in Patients With Mild Alzheimer's Disease Receiving Acetylcholinesterase Inhibitors and/or Memantine

This is a study to evaluate the efficacy and safety of azeliragon in patients with mild Alzheimer's disease. Patients will receive either azeliragon or placebo with a patient's participation lasting approximately 18 months.

Being tested
Azeliragon, Placebo
Keywords
Alzheimer's disease, RAGE, ADAS-cog, CDR-sb
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzeliragonDrug

    Also called TTP488

    Azeliragon 5mg administered orally, once daily for 18 months

  • PlaceboDrug

    Placebo administered orally, once daily for 18 months

Study groups in NCT02080364
Study groupRoleWhat they receive
Azeliragon 5mgExperimentalAzeliragon (TTP488) 5mg orally once daily for 18 months
Receives: Drug: Azeliragon
PlaceboPlacebo comparatorPlacebo orally once daily for 18 months
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Total Score

    The ADAS-cog is a structured scale (approximately 40 minutes to complete) that evaluates memory, orientation, attention, reasoning, language and constructional praxis (Rosen, 1984). The ADAS-cog scoring range for the version used in this study is from 0 to 70, with higher scores indicating greater cognitive impairment.

    Measured: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

  2. Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-sb)

    The CDR scale is used as a global measure of dementia and is completed by a clinician in the setting of detailed knowledge of the individual patient collected from interviews with the patient and caregiver (Berg, 1988). The CDR describes 5 degrees of impairment in performance on each of 6 categories including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. CDR ratings are 0 for healthy individuals, 0.5 for questionable dementia and 1, 2 and 3 for mild, moderate and severe dementia as defined in the CDR scale. The scores for each category can also be summed and this is known as the sum of box score (CSR-SB). Sum of box scores range from 0 to 18 with higher scores indicating greater cognitive impairment.

    Measured: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

Secondary outcomes (8)

  1. Change From Baseline in Magnetic Resonance Imaging (MRI) Brain Volumetric Measures

    Percent of Total Hippocampus Atrophy to Intracranial Volume

    Measured: Baseline and 18 months

  2. Change From Baseline in the Normalized Mean Composite SUVR of the 5 Regions

    Extent and severity of brain hypometabolism was assessed centrally at Baseline and Month 18. SUVR PET was designed to make use of FreeSurfer-based segmentations of the brain obtained using the 3DT1 MRI. Following the methods published by Landau and Jagust (Landau SM, Annals of Neurology 2012) and described on the ADNI website (http://adni.loni.usc.edu/methods/pet-analysis-method/), regions were defined in native patient space on the 3DT1 MRI acquired at the Baseline visit and at Month 18 visit. An SUVR measure was computed regionally over five sub-regions (anterior/posterior cingulate, temporal, parietal, frontal and hippocampal areas), normalized to activity in the cerebral white matter. These sub-regions were selected to optimize sensitivity in longitudinal studies. This outcome measure presents the change from baseline in the normalized mean composite SUVR of the 5 regions. A negative change from baseline indicates a decrease (worsening) in brain glucose metabolism/utilization.

    Measured: Baseline to 18 months

  3. Change From Baseline in Alzheimer's Disease Cooperative Study- Activities of Daily Living Inventory (ADCS-ADL)

    The ADCS-ADL is an activity of daily living inventory developed by the ADCS to assess functional performance in participants with AD (Galasko et al., 1997). Informants are queried via a structured interview format as to whether participants attempted each item in the inventory during the preceding 4 weeks, as well as their level of performance. Scores range from 0-78 with lower scores indicating greater functional impairment.

    Measured: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

  4. Change From Baseline in Mini-Mental State Examination (MMSE)

    The MMSE is a brief 30-point test that is used to assess cognition (Folstein, 1975). It is commonly used to screen for dementia. In the time span of about 10 minutes, it samples various functions, including arithmetic, memory and orientation. Scores range from 0-30 with lower scores indicating greater cognitive impairment.

    Measured: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

  5. Change From Baseline in Neuropsychiatric Inventory (NPI)

    The NPI is a well-validated, reliable, multi-item instrument to assess psychopathology in AD based on an interview with the caregiver (Cummings et al, 1994). It evaluates both the frequency and severity of 12 behavioral areas including delusions, hallucinations, dysphoria (depression) anxiety, agitation/aggression, euphoria, disinhibition, irritability, lability, apathy, aberrant motor behavior, appetite and eating changes and night-time behaviors.

    Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1= mild, 2 = moderate, 3 = severe). Distress is rated by the study partner or caregiver and ranges from 0 (no distress) to 5 (very severe or extreme). The overall score and the score for each subscale are the product of severity and frequency. Scores range from 0-144 with higher scores indicating a greater presence of neuropsychiatric symptoms.

    Measured: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

  6. Change From Baseline in Dementia Quality of Life (DEMQOL)

    The DEMQOL-Proxy questionnaire is a validated and reliable questionnaire that is interview administered and completed by the caregiver about the patient's health related quality of life (Smith et al, 2005). It consists of 31 items representing 5 domains (daily activities and looking after yourself, health and well-being, cognitive functioning, social relationships, and self-concept) and takes approximately 20 minutes to complete. Scores range 31-124 with higher scores indicate better health related quality of life.

    Measured: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

  7. Change From Baseline in Continuous Oral Word Association Task (COWAT)

    The COWAT is a measure of verbal fluency in which the participant is asked to generate orally as many words as possible that begin with the letters "F", "A", and "S", excluding proper names and different forms of the same word. (Borkowski, 1967, Loonstra 2001) For each letter, the participant is allowed one minute to generate the words. Performance is measured by the total number of correct words produced summed across the three letters. Perseverations (i.e., repetitions of a correct word) and intrusions (i.e., words not beginning with the designated letter) are noted.

    Measured: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

  8. Change From Baseline in Category Fluency Test (CFT)

    Study participants are given one minute to provide exemplars of the category 'animals'.

    Measured: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2014 (estimated)
  2. Study startApr 2015
  3. Primary completion1 Jun 2018
  4. Study completion1 Jun 2018

Why it stopped: Not due to safety but due to a lack of efficacy at the 5 mg azeliragon dose.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
880 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02080364
Sponsor's protocol ID
TTP488-301
Acronym
STEADFAST
Status last verified
May 2021
First submitted
25 Feb 2014
Last updated
7 May 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Azeliragon in people with Alzheimer's Disease, run by vTv Therapeutics at 115 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 115 sites in United States, United Kingdom, Canada, Australia, South Africa and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Total Score (time frame: Baseline and 18 months (A-Study); baseline and 12 months (B-Study)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02080364.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2021.

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