Evaluation of the Efficacy and Safety of Azeliragon (TTP488) in Patients with mild Alzheimer's Disease (STEADFAST)

Phase 1

Conditions: MedDRA version: 19.0Level: PTClassification code 10012294Term: Dementia of the Alzheimer's type, with deliriumSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0Level: LLTClassification code 10012292Term: Dementia of the Alzheimer's type NOSSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0Level: HLTClassification code 10001897Term: Alzheimer's disease (incl subtypes)System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0Level: LLTClassification code 10066571Term: Progression of Alzheimer's diseaseSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0Level: PTClassification code 10012271Term: Dementia Alzheimer's typeSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0Level: HLTClassification code 10012268Term: Dementia (excl Alzheimer's type)System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0Level: PTClassification code 10012296Term: Dementia of the Alzheimer's type, with depressed moodSystem Organ Class: 10029205 - Nervous system disorders
MILD ALZHEIMER'S DISEASE RECEIVING ACETYLCHOLINESTERASE INHIBITORS AND/OR MEMANTINE
MedDRA version: 19.0Level: PTClassification code 10012295Term: Dementia of the Alzheimer's type, with delusionsSystem Organ Class: 10029205 - Nervous system disorders

Registration Number: EUCTR2016-002005-19-IE

Lead Sponsor: vTv THERAPEUTICS LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 800

Inclusion Criteria

1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally authorized representative) and caregiver/informant has been informed of all pertinent aspects of the study. Participants must be able to provide assent (where this is in accordance with local laws, regulations and ethics committee policy) and assent may be re-evaluated during the study at regular intervals.
2. Participants and caregiver/informants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. The subject must have a reliable caregiver/informant with regular contact (i.e., 10 hours a week as combination of face-to-face visits and telephone contact acceptable) who will facilitate the subject’s full participation in the study. Caregivers/informant must have sufficient subject interaction to be able to provide meaningful input into the rating scales administered in this study where caregiver/informant input is required, in particular the CDR and evidence of this should be documented in source documentation. Participants who reside in assisted living facilities are permitted provided that they meet caregiver/informant criteria.
4. Participants and caregiver/informants must be able to read, write, and speak the language in which psychometric tests are provided with visual and auditory acuity (corrected) sufficient to allow for accurate psychometric testing.
5. Males and females (of non-childbearing potential) ages =50 years of age at screening.
6. Diagnosis of probable AD, consistent with the criteria from the 2011 National Institute on Aging and the Alzheimer’s Association workgroup (McKhann et al., 2011). Evidence of progression needs to be documented in source documentation at the time of screening based on review of prior medical records and/or information gathered from the subject or caregiver/informant(s). Biomarker evidence of the pathophysiological process or neuronal injury associated with AD should be documented if data is available in participant’s medical records (not specifically measured for inclusion in this study).
7. MRI consistent with a diagnosis of probable Alzheimer’s disease. A head CT scan may be used for evaluation if there is a documented contraindication to an MRI (e.g. pacemaker).
8. Mini-Mental State Exam (MMSE) score of 21-26 inclusive at screening.
9. CDR global score of 0.5 or 1 at screening.
10. Rosen-Modified Hachinski Ischemia Score =4 at screening.
11. Participants must be on a stable dose of a background cholinesterase inhibitor and/or memantine (approved by the relevant health authority where the trial is being conducted) at least 3 months prior to randomization and must agree not to change the dose during the study period unless the investigator judges that the dose needs to be reduced or stopped due to a safety and/or tolerability reason.
12. No clinically significant, (in the opinion of the investigator) laboratory abnormalities at screening. If the results of clinical laboratory testing are outside normal reference ranges, the subject may be enrolled but only if these findings are determined to be not clinically significant by the investigator. This determination must be recorded in the subject’s source documents. A summary of values of potential clinical concern is provided in protocol appendix 1.
13. Subject must be able to ingest oral medications.
Are the trial subjects under 18? no
Number of subject

Exclusion Criteria

1. Current evidence or history of neurological, psychiatric, and any other illness that could contribute to dementia including, but not limited to other neurodegenerative disorders (e.g., Lewy body disease, fronto-temporal dementia, vascular dementia), head injury with loss of consciousness proximate to the onset of dementia, participation in contact sports characterized by repeated head injuries, DSM-IV-TR criteria for any major psychiatric disorder including psychosis, current major depression, bipolar disorder, alcohol or substance abuse or dependence, neurosyphilis, vitamin B12 deficiency (see Exclusion 3, below), thyroid disease (unless adequately treated for at least 3 months with normalization of laboratory values) or any form of dementia other than AD.
2. Participants from a family with known autosomal dominant AD associated with mutations in APP, PS1 or PS2 genes or strongly suspected, but not yet identified mutations in APP, PS1 or PS2 genes, or Down’s syndrome. Individuals from families with any number of late onset AD affected family members may participate in this study.
3. Vitamin B12 levels lower than laboratory reported normal limits (and remains below on repeat testing). Participants may be enrolled following the initiation of B12 therapy for 4 weeks prior to dosing and confirmed within normal limits upon repeat.
4. Diagnosis or history of cerebrovascular stroke, severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage that, as determined by the investigator, could either contribute to the patient’s current cognitive or functional status, impair his/her ability to fully participate in the trial or that may impact his/her status during an 18-month trial.
5. Specific exclusionary brain MRI findings (as identified on the central MRI read) as determined by the investigator that could either significantly contribute to the patient’s current cognitive or functional decline, impair his/her ability to fully participate in the trial or that may impact his/her status during 18-month course of the trial. In any case, 10 or more microhemorrhages as identified by the central reading, is exclusionary. Grade three deep white matter changes (diffuse involvement of entire region) on the central reading report is exclusionary. If a head CT is used for assessment of eligibility, structural abnormalities as determined by the investigator that could either significantly contribute to the patient’s current cognitive or functional decline, impair his/her ability to fully participate in the trial or that may impact his/her status during 18-month course of the trial would be exclusionary.
6. A current primary diagnosis of major psychiatric disorder, e.g., schizophrenia, bipolar disorder, major depressive disorder, or other severe psychiatric illness per the DSM-IV-TR criteria per the investigator’s judgment.
7. Serious suicide risk
8. 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.
9. Current (e.g., within the last 3 months) body mass index (BMI) of greater than or equal to 35 kg/m2 or a current (e.g., within the last 3 months) weight less than 45 kg.
10. Any clinically significant hepatic or renal disease, elevated transaminase levels of greater than 1.5 times the upper limit of normal (ULN), creatinine greater than 1.5 x ULN.
Patients with unstabl

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of azeliragon on cognitive [Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)] and global function [Clinical Dementia Rating Scale Sum of Boxes (CDR-sb)] measures in patients with mild AD.;Secondary Objective: Key Secondary<br>To examine the effect of azeliragon on MRI volumetrics (e.g., whole brain volume, ventricular volume, hippocampal volume).<br>* note: the decision as to the specific key secondary to support disease modification claim will be made prior to database lock.<br><br>Secondary:<br>Please refer to protocol for the full list;Primary end point(s): Co-primary Endpoints:<br>- Change from Baseline in the ADAS-cog at Month 18.<br>- Change from Baseline in the CDR-sb at Month 18.<br><br>;Timepoint(s) of evaluation of this end point: 18 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key Secondary Endpoints:<br>- Change from Baseline in brain volumetrics (e.g., whole brain volume, ventricular volume, hippocampal volume) at Month 18.<br><br>Other Secondary Endpoints:<br>- Please refer to the study protocol;Timepoint(s) of evaluation of this end point: 18 months

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