2-Year Extension Study of Azeliragon in Subjects With Alzheimer's Disease (STEADFAST Extension)

• Sponsor: vTv Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02916056
• Collaborator: (none)
• Enrollment: 297
• Locations: 71
• Arm: 1
• Actual Duration (Months): 18
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is an open-label extension study in patients with mild Alzheimer's disease who have completed participation in the azeliragon Phase 3 (STEADFAST) trial. Patients will receive azeliragon 5 mg/day for up to 2 years.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Azeliragon 5mg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 297 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label Extension Study for Continued Safety and Efficacy Evaluation of Azeliragon in Patients With Mild Alzheimer's Disease
• Actual Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Jun 1, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azeliragon 5 mg Azeliragon (TTP488) 5mg orally once daily for 2 years	Drug: Azeliragon 5mg; Other Names: TTP488

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With at Least One Treatment-Emergent Adverse Event [up to 18 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Successful completion of Study TTP488-301 through the Month 18 Visit without ongoing serious adverse events or history of serious adverse drug reactions during study TTP488-301.

• Patients must enroll in the present study within 7 days of completion of study TTP488-301.

• 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.

• Participants and caregiver/informants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

• 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.

• 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.

• Subject must be able to ingest oral medications.

Exclusion Criteria:

• The subject is felt by the investigator to be unsuitable (on the basis of health, compliance, caregiver availability, or for any other reason) for inclusion in the study.

• Subjects with serious suicide risk. If there are "yes" answers on items 4, 5 or on any behavioral question of the C-SSRS, a suicide risk assessment must be done by a qualified mental health professional with expertise in the evaluation of suicidality in the elderly (e.g., psychiatrist, geriatrician or neurologist specializing in treatment of patients with AD) to determine whether it is safe for the subject to participate in the study.

• Subjects demonstrating a QTcF > 480 msec or a >45 msec change from the TTP488-301 Baseline value based on the locally read ECG performed at the TTP488-301 Month 18 Visit (TTP488-303 Baseline). Participants with known history of bundle branch block (either right or left) are allowed if absolute QTcF value does not exceed 500 msec. Participants with a functioning pacemaker, indicated by an ECG displaying paced rhythm, are allowed with no QTc upper limit.

• Other acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may prevent the subject from completing the 2-year study or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States	85004
2		Phoenix	Arizona	United States	85013
3		Tucson	Arizona	United States	85724
4		Bellflower	California	United States	90706
5		Costa Mesa	California	United States	92626
6		Fullerton	California	United States	92835
7		Glendale	California	United States	91206
8		Imperial	California	United States	92251
9		Irvine	California	United States	92614
10		Laguna Hills	California	United States	92653
11		Long Beach	California	United States	90806
12		Riverside	California	United States	92506
13		San Bernardino	California	United States	92408
14		Santa Ana	California	United States	92705
15		Atlantis	Florida	United States	33462
16		Delray Beach	Florida	United States	33445
17		Hallandale Beach	Florida	United States	33009
18		Hialeah	Florida	United States	33016
19		Jacksonville	Florida	United States	32216
20		Lake Worth	Florida	United States	33449
21		Miami Beach	Florida	United States	33140
22		Miami Lakes	Florida	United States	33014
23		Miami	Florida	United States	33122
24		Miami	Florida	United States	33137
25		Orlando	Florida	United States	32806
26		Sarasota	Florida	United States	34243
27		Sunrise	Florida	United States	33351
28		The Villages	Florida	United States	32162
29		Columbus	Georgia	United States	31909
30		Chicago	Illinois	United States	60640
31		Fairway	Kansas	United States	66205
32		Lexington	Kentucky	United States	40504
33		Baltimore	Maryland	United States	21208
34		Newton	Massachusetts	United States	02459
35		Plymouth	Massachusetts	United States	02360
36		Quincy	Massachusetts	United States	02169
37		Hattiesburg	Mississippi	United States	39401
38		Creve Coeur	Missouri	United States	63141
39		Saint Louis	Missouri	United States	63141
40		Princeton	New Jersey	United States	08540
41		Albuquerque	New Mexico	United States	87109
42		Albany	New York	United States	12208
43		Lake Success	New York	United States	11042
44		New York	New York	United States	10032
45		Staten Island	New York	United States	10312
46		Charlotte	North Carolina	United States	28270
47		Raleigh	North Carolina	United States	27607
48		Wilmington	North Carolina	United States	28401
49		Winston-Salem	North Carolina	United States	27157
50		Canton	Ohio	United States	44718
51		Shaker Heights	Ohio	United States	44122
52		Oklahoma City	Oklahoma	United States	73103
53		Oklahoma City	Oklahoma	United States	73118
54		Portland	Oregon	United States	97210
55		Portland	Oregon	United States	97225
56		Plains	Pennsylvania	United States	18705
57		East Providence	Rhode Island	United States	02914
58		East Providence	Rhode Island	United States	02916
59		Cordova	Tennessee	United States	38018
60		Dallas	Texas	United States	75231
61		San Antonio	Texas	United States	78229
62		San Antonio	Texas	United States	78232
63		Wichita Falls	Texas	United States	76309
64		Murray	Utah	United States	84123
65		Kirkland	Washington	United States	98033
66		Calgary	Alberta	Canada	T2N 4Z6
67		Medicine Hat	Alberta	Canada	T1B 4E7
68		Chatham	Ontario	Canada	N7L 1C1
69		Toronto	Ontario	Canada	M3B 2S7
70		Gatineau	Quebec	Canada	J8T 8J1
71		Greenfield Park	Quebec	Canada	J4V 2J2

Sponsors and Collaborators

• vTv Therapeutics

Investigators

• Study Director: Ann Gooch, Ph.D., vTv Therapeutics LLC

Study Documents (Full-Text)

• Study Protocol - Aug 9, 2017
• Statistical Analysis Plan - Sep 21, 2018

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: vTv Therapeutics
• ClinicalTrials.gov Identifier: NCT02916056
• Other Study ID Numbers: TTP488-303
• First Posted: Sep 27, 2016
• Last Update Posted: Jun 1, 2021
• Last Verified: May 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by vTv Therapeutics: Alzheimer's disease; RAGE; ADAS-cog; CDR-sb
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Recruitment Details	Eligible participants who completed TTP488-301 were enrolled into the TTP488-303 Open label extension from December 2016 through April 2018 in the United States and Canada.

Arm/Group Title	Azeliragon 5 mg
Arm/Group Description	Azeliragon (TTP488) 5mg orally once daily
Period Title: Overall Study
STARTED	297
COMPLETED	0
NOT COMPLETED	297

Baseline Characteristics

Arm/Group Title	Azeliragon 5 mg
Arm/Group Description	Azeliragon (TTP488) 5mg orally once daily
Overall Participants	297
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.9 (8.43)
Sex: Female, Male (Count of Participants)
Female	144 48.5%
Male	153 51.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	31 10.4%
Not Hispanic or Latino	266 89.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	6 2%
Native Hawaiian or Other Pacific Islander	1 0.3%
Black or African American	9 3%
White	280 94.3%
More than one race	1 0.3%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With at Least One Treatment-Emergent Adverse Event
Time Frame	up to 18 months

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Azeliragon 5 mg
Arm/Group Description	Azeliragon (TTP488) 5mg orally once daily
Measure Participants	297
Count of Participants [Participants]	193 65%

Adverse Events

Time Frame	Adverse events were collected from consent through end of study participation. Duration of study participation was up to 456 days.
Arm/Group Title	Azeliragon 5 mg
Arm/Group Description	Azeliragon (TTP488) 5mg orally once daily
All Cause Mortality
	Azeliragon 5 mg
	Affected / at Risk (%)	# Events
Total	0/297 (0%)
Serious Adverse Events
	Azeliragon 5 mg
	Affected / at Risk (%)	# Events
Total	25/297 (8.4%)
Cardiac disorders
Aortic valve stenosis	1/297 (0.3%)
Atrial fibrillation	1/297 (0.3%)
Bradycardia	1/297 (0.3%)
Ear and labyrinth disorders
Vertigo	1/297 (0.3%)
Infections and infestations
Bacterial prostatitis	1/297 (0.3%)
Cellulitis	1/297 (0.3%)
Enterocolitis infectious	1/297 (0.3%)
Pneumonia	1/297 (0.3%)
Pyelonephritis	1/297 (0.3%)
Injury, poisoning and procedural complications
Fall	2/297 (0.7%)
Pelvic fracture	2/297 (0.7%)
Femoral neck fracture	1/297 (0.3%)
Hip fracture	1/297 (0.3%)
Lumbar vertebral fracture	1/297 (0.3%)
Subdural haematoma	1/297 (0.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/297 (0.3%)
Nervous system disorders
Transient ischaemic attack	3/297 (1%)
Ataxia	1/297 (0.3%)
Cerebral infarction	1/297 (0.3%)
Complex partial seizures	1/297 (0.3%)
Convulsion	1/297 (0.3%)
Dysarthria	1/297 (0.3%)
Haemorrhagic stroke	1/297 (0.3%)
Ischaemic cerebral infarction	1/297 (0.3%)
Syncope	1/297 (0.3%)
Renal and urinary disorders
Renal failure acute	1/297 (0.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/297 (0.3%)
Vascular disorders
Orthostatic hypotension	2/297 (0.7%)
Aortic stenosis	1/297 (0.3%)
Other (Not Including Serious) Adverse Events
	Azeliragon 5 mg
	Affected / at Risk (%)	# Events
Total	137/297 (46.1%)
General disorders
Fatigue	7/297 (2.4%)
Gait disturbance	7/297 (2.4%)
Infections and infestations
Upper respiratory tract infection	9/297 (3%)
Urinary tract infection	9/297 (3%)
Injury, poisoning and procedural complications
Fall	29/297 (9.8%)
Laceration	6/297 (2%)
Investigations
Weight decreased	9/297 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/297 (2.7%)
Nervous system disorders
Dizziness	12/297 (4%)
Headache	7/297 (2.4%)
Psychiatric disorders
Depression	13/297 (4.4%)
Insomnia	8/297 (2.7%)
Respiratory, thoracic and mediastinal disorders
Cough	7/297 (2.4%)
Vascular disorders
Hypertension	6/297 (2%)

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.