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

NCT02080364 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: TTP488-301
• Study Type: interventional
• Target: 880
• Locations: 7 countries
• Sites: 115

Brief 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.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease; RAGE; ADAS-cog; CDR-sb

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (8)

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

  Baseline and 18 months

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

  Baseline to 18 months

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

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

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

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

• Change From Baseline in Neuropsychiatric Inventory (NPI)

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

Study Arms (2)

Azeliragon 5mg

EXPERIMENTAL

Azeliragon (TTP488) 5mg orally once daily for 18 months

Drug: Azeliragon

Placebo

PLACEBO COMPARATOR

Placebo orally once daily for 18 months

Drug: Placebo

Interventions

Azeliragon DRUG

Azeliragon 5mg administered orally, once daily for 18 months

Also known as: TTP488

Azeliragon 5mg

Placebo DRUG

Placebo administered orally, once daily for 18 months

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• vTv Therapeutics: lead

Study Sites (115)

Unknown Facility

Phoenix, Arizona, 85004, United States

Location

Unknown Facility

Phoenix, Arizona, 85013, United States

Location

Unknown Facility

Phoenix, Arizona, 85018, United States

Location

Unknown Facility

Tucson, Arizona, 85724, United States

Location

Unknown Facility

Tucson, Arizona, 85741, United States

Location

Unknown Facility

Bellflower, California, 90706, United States

Location

Unknown Facility

Costa Mesa, California, 92626, United States

Location

Unknown Facility

Fullerton, California, 92835, United States

Location

Unknown Facility

Glendale, California, 91206, United States

Location

Unknown Facility

Imperial, California, 92251, United States

Location

Unknown Facility

Irvine, California, 92614, United States

Location

Unknown Facility

Laguna Hills, California, 92653, United States

Location

Unknown Facility

Long Beach, California, 90806, United States

Location

Unknown Facility

Long Beach, California, 90807, United States

Location

Unknown Facility

Orange, California, 92868, United States

Location

Unknown Facility

Riverside, California, 92506, United States

Location

Unknown Facility

San Bernardino, California, 92408, United States

Location

Unknown Facility

San Francisco, California, 94114, United States

Location

Unknown Facility

Santa Ana, California, 92705, United States

Location

Unknown Facility

Atlantis, Florida, 33462, United States

Location

Unknown Facility

Brooksville, Florida, 34601, United States

Location

Unknown Facility

Delray Beach, Florida, 33445, United States

Location

Unknown Facility

Hallandale, Florida, 33009, United States

Location

Unknown Facility

Hialeah, Florida, 33016, United States

Location

Unknown Facility

Jacksonville, Florida, 32216, United States

Location

Unknown Facility

Lake Worth, Florida, 33449, United States

Location

Unknown Facility

Leesburg, Florida, 34748, United States

Location

Unknown Facility

Miami, Florida, 33122, United States

Location

Unknown Facility

Miami, Florida, 33137, United States

Location

Unknown Facility

Miami Beach, Florida, 33140, United States

Location

Unknown Facility

Miami Lakes, Florida, 33014, United States

Location

Unknown Facility

Miami Lakes, Florida, 33016, United States

Location

Unknown Facility

Orlando, Florida, 32806, United States

Location

Unknown Facility

Pensacola, Florida, 32503, United States

Location

Unknown Facility

Sarasota, Florida, 34243, United States

Location

Unknown Facility

Sunrise, Florida, 33351, United States

Location

Unknown Facility

Atlanta, Georgia, 30331, United States

Location

Unknown Facility

Columbus, Georgia, 31909, United States

Location

Unknown Facility

Chicago, Illinois, 60640, United States

Location

Unknown Facility

Fairway, Kansas, 66205, United States

Location

Unknown Facility

Prairie Village, Kansas, 66201, United States

Location

Unknown Facility

Lexington, Kentucky, 40504, United States

Location

Unknown Facility

Baltimore, Maryland, 21208, United States

Location

Unknown Facility

Newton, Massachusetts, 02459, United States

Location

Unknown Facility

Plymouth, Massachusetts, 02360, United States

Location

Unknown Facility

Quincy, Massachusetts, 01269, United States

Location

Unknown Facility

Hattiesburg, Mississippi, 39401, United States

Location

Unknown Facility

Creve Coeur, Missouri, 63141, United States

Location

Unknown Facility

Princeton, New Jersey, 08540, United States

Location

Unknown Facility

Albuquerque, New Mexico, 87109, United States

Location

Unknown Facility

Albany, New York, 12208, United States

Location

Unknown Facility

Lake Success, New York, 11042, United States

Location

Unknown Facility

New York, New York, 10032, United States

Location

Unknown Facility

Staten Island, New York, 10312, United States

Location

Unknown Facility

Charlotte, North Carolina, 28270, United States

Location

Unknown Facility

Raleigh, North Carolina, 27607, United States

Location

Unknown Facility

Wilmington, North Carolina, 28401, United States

Location

Unknown Facility

Winston-Salem, North Carolina, 27157, United States

Location

Unknown Facility

Canton, Ohio, 44718, United States

Location

Unknown Facility

Shaker Heights, Ohio, 44122, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73103, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73118, United States

Location

Unknown Facility

Portland, Oregon, 97210, United States

Location

Unknown Facility

Portland, Oregon, 97225, United States

Location

Unknown Facility

Media, Pennsylvania, 19063, United States

Location

Unknown Facility

Norristown, Pennsylvania, 19403, United States

Location

Unknown Facility

Plains, Pennsylvania, 18705, United States

Location

Unknown Facility

East Providence, Rhode Island, 02914, United States

Location

Unknown Facility

East Providence, Rhode Island, 02916, United States

Location

Unknown Facility

Charleston, South Carolina, 24901, United States

Location

Unknown Facility

Mt. Pleasant, South Carolina, 29464, United States

Location

Unknown Facility

Cordova, Tennessee, 38018, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

Unknown Facility

Dallas, Texas, 75231, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Unknown Facility

San Antonio, Texas, 78232, United States

Location

Unknown Facility

Wichita Falls, Texas, 76309, United States

Location

Unknown Facility

Murray, Utah, 84123, United States

Location

Unknown Facility

Kirkland, Washington, 98201, United States

Location

Unknown Facility

Richland, Washington, 99352, United States

Location

Unknown Facility

Southport, Queensland, 4222, Australia

Location

Unknown Facility

Caulfield, Victoria, 3162, Australia

Location

Unknown Facility

Geelong, Victoria, 3220, Australia

Location

Unknown Facility

Heidelberg West, Victoria, 3081, Australia

Location

Unknown Facility

Nedlands, Western Australia, 6009, Australia

Location

Unknown Facility

West Perth, Western Australia, 6005, Australia

Location

Unknown Facility

Calgary, Alberta, T2N 4Z6, Canada

Location

Unknown Facility

Medicine Hat, Alberta, T1B 4E7, Canada

Location

Unknown Facility

Kentville, Nova Scotia, B4N4K9, Canada

Location

Unknown Facility

Chatham, Ontario, N7L 1C1, Canada

Location

Unknown Facility

London, Ontario, N6C 5J1, Canada

Location

Unknown Facility

Toronto, Ontario, M3B 257, Canada

Location

Unknown Facility

Gatineau, Quebec, J8T 8J1, Canada

Location

Unknown Facility

Greenfield Park, Quebec, J4V2J2, Canada

Location

Unknown Facility

Cork, Ireland

Location

Unknown Facility

Dublin, Ireland

Location

Unknown Facility

Galway, Ireland

Location

Unknown Facility

Christchurch, Canterbury, 8011, New Zealand

Location

Unknown Facility

Christchurch, Canterbury, 8022, New Zealand

Location

Unknown Facility

Cape Town, 7405, South Africa

Location

Unknown Facility

Cape Town, 7530, South Africa

Location

Unknown Facility

Johannesburg, 2196, South Africa

Location

Unknown Facility

Saint George, 6529, South Africa

Location

Unknown Facility

Glasgow, G20 OAXA, United Kingdom

Location

Unknown Facility

London, W1G 9RU, United Kingdom

Location

Unknown Facility

London, WC1X 8QD, United Kingdom

Location

Unknown Facility

Manchester, M8 5RB, United Kingdom

Location

Unknown Facility

Northampton, NN5 6UD, United Kingdom

Location

Unknown Facility

Oxford, OX3 7JX, United Kingdom

Location

Unknown Facility

Penarth, CF64 2XX, United Kingdom

Location

Unknown Facility

Preston, PR2 9HT, United Kingdom

Location

Unknown Facility

Sheffield, S5 7JT, United Kingdom

Location

Unknown Facility

Southhampton, SO30 3JB, United Kingdom

Location

Unknown Facility

Swindon, SN3 6BW, United Kingdom

Location

Unknown Facility

Warrington, WA2 8WA, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Alzheimer Disease

Interventions

azeliragon

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Ann Gooch PhD,RAC,CCRP; Vice President Clinical Development & Regulatory Operations
• Organization: vTv Therapeutics LLC

agooch@vtvtherapeutics.com

336-841-0300

Study Officials

• Aaron H Burstein, PharmD

  vTv Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2014
• First Posted: March 6, 2014
• Study Start: April 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: May 7, 2021
• Results First Posted: May 7, 2021

Record last verified: 2021-05

Locations

US (80); AU (6); CA (8); NZ (2); IE (3); ZA (4); GB (12)