AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid

Sponsor

Eisai Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04468659

Collaborator

Alzheimer's Clinical Trials Consortium (Other), Biogen (Industry), National Institute on Aging (NIA) (NIH)

1,400

Enrollment

104

Locations

Arms

87.4

Anticipated Duration (Months)

13.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary purpose of this study is to determine whether treatment with lecanemab is superior to placebo on change from baseline of the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment (A45 Trial) and to determine whether treatment with lecanemab is superior to placebo in reducing brain amyloid accumulation as measured by amyloid positron emission tomography (PET) at 216 weeks of treatment (A3 Trial).

Condition or Disease	Intervention/Treatment	Phase
Preclinical Alzheimer's Disease Early Preclinical Alzheimer's Disease	Drug: Lecanemab Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

AHEAD 3-45 Study: A Placebo-Controlled, Double-Blind, Parallel-Treatment Arm, 216 Week Study to Evaluate Efficacy and Safety of Treatment With BAN2401 in Subjects With Preclinical Alzheimer's Disease and Elevated Amyloid (A45 Trial) and in Subjects With Early Preclinical Alzheimer's Disease and Intermediate Amyloid (A3 Trial)

Actual Study Start Date :

Jul 14, 2020

Anticipated Primary Completion Date :

Oct 25, 2027

Anticipated Study Completion Date :

Oct 25, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A45 Trial: Lecanemab 5 mg/kg + 10 mg/kg Participants will receive lecanemab 5 milligram per kilogram (mg/kg), administered as intravenous (IV) infusion, every two weeks from Week 0 to 6, then 10 mg/kg, administered as IV infusion, every two weeks from Week 8 to 94, and 10 mg/kg, administered as IV infusion, every four weeks from Week 96 to 216.	Drug: Lecanemab IV infusion. Other Names: BAN2401
Placebo Comparator: A45 Trial: Placebo Participants will receive placebo (0.9 percent [%] sodium chloride solution), administered as IV infusion, every two weeks from Week 0 to 94, then every four weeks from Week 96 to 216.	Drug: Placebo IV infusion.
Experimental: A3 Trial: Lecanemab 5 mg/kg + 10 mg/kg Participants will receive lecanemab 5 mg/kg, administered as IV infusion, every four weeks from Week 0 to 4, then 10 mg/kg, administered as IV infusion, every four weeks from Week 8 to 216.	Drug: Lecanemab IV infusion. Other Names: BAN2401
Placebo Comparator: A3 Trial: Placebo Participants will receive placebo (0.9% sodium chloride solution), administered as IV infusion, every four weeks from Week 0 to 216.	Drug: Placebo IV infusion.

Outcome Measures

Primary Outcome Measures

A45 Trial: Change From Baseline in Preclinical Alzheimer Cognitive Composite 5 (PACC5) Score at Week 216 [Baseline, Week 216]
PACC5(5 components):Free/cued selective reminding test:number of words recalled without cuing/with cuing(0[worst]-96[best recall]);Delayed Paragraph Recall test: recall of 1 short story(25 bits information),immediately after reading and again after delay of 30 minutes (0[worst]-25[best recall]);Digit-symbol substitution test: Participant uses a key to fill in blank squares as fast as possible in 90 seconds(0[none]-91[best performance]);Mini Mental State Score:to evaluate orientation,memory,attention,concentration,naming,repetition,comprehension and ability to create sentence,to copy 2 overlapping pentagons, scored as number of correctly completed items(0[worse]-30[perfect performance]);Category fluency task: participants generate words in 60 second belonging to a semantic category(total score:number of appropriate words generated per task, higher values indicate better performance).
A3 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216 [Baseline, Week 216]

Secondary Outcome Measures

A45 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Weeks 96 and 216 [Baseline, Week 96, Week 216]
A45 Trial: Change From Baseline in tau Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Weeks 96 and 216 [Baseline, Week 96, Week 216]
A45 Trial: Change From Baseline in Cognitive Function Index (CFI) at Week 216 [Baseline, Week 216]
CFI assessment to assess the participant's perceived ability to perform high-level functional tasks in daily life and sense of overall cognitive functional ability. Study participants (18 questions) and their study partners (15 questions) independently rate the participant's abilities. Total score combines participant and study partner scores, with higher scores indicating greater impairment.
A3 Trial: Change From Baseline in tau Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216 [Baseline, Week 216]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Participants must meet all of the following criteria to be included in this study:

Male or female, age 55 to 80 years inclusive at the time of informed consent, with a plasma biomarker result that is predictive of intermediate or elevated brain amyloid at Screening or known before Screening to have elevated or intermediate amyloid according to previous PET, cerebrospinal fluid (CSF), or plasma testing

• Those 55 to 64 must have 1 of the following additional risk factors, given the relatively low rates of amyloid positivity less than (<) 65 years, before screening:

First degree relative diagnosed with dementia onset before age 75, or
Known to possess at least 1 apolipoprotein E4 variant (APOE4) allele, or
Known before screening to have elevated brain amyloid according to previous PET or CSF testing

Global Clinical Dementia Rating (CDR) score of 0 at screening
Mini Mental State Examination score greater than or equal to (>=) 27 (with educational adjustments) at screening.
Wechsler Memory Scale-Revised Logical Memory subscale II (WMS-R LM II) score at screening of >=6
A45 Trial: Elevated brain amyloid pathology by amyloid PET: defined as approximately greater than (>) 40 Centiloids on screening scan A3 Trial: Intermediate levels of brain amyloid pathology by amyloid PET: defined as approximately 20 to 40 Centiloids on screening scan
Has a study partner that is willing to participate as a source of information and has approximately weekly contact with the participant (contact can be in-person, via telephone or electronic communication). The study partner must have sufficient contact such that the investigator feels the study partner can provide meaningful information about the participant's daily function
Provide written (or electronic, if allowed per country-specific regulations) informed consent
Willing and able to comply with all aspects of the protocol

Exclusion criteria:

Participants who meet any of the following criteria will be excluded from this study:

Females who are breastfeeding or pregnant at screening or baseline
Females of childbearing potential who:

• Within 28 days before study entry, did not use a highly effective method of contraception For sites outside of Europe, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception

History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of screening
Current or history within the past 2 years of psychiatric diagnosis or symptoms that, in the opinion of the investigator, could interfere with study procedures
Contraindications to 3 Tesla magnetic resonance imaging (MRI) scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in-skull and cardiac devices other than those approved as safe for use in MRI scanners), or exhibit other significant pathological findings on brain MRI at Screening
Hypersensitivity to any monoclonal antibody treatment
Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
Bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5) at screening
Results of laboratory tests conducted during screening that are outside the following limits:

Thyroid stimulating hormone (TSH) above normal range
Abnormally low (below lower limit of normal [LLN]) serum vitamin B12 levels for the testing laboratory (if participant is taking vitamin B12 injections, level should be at or above the LLN for the testing laboratory). A low vitamin B12 is exclusionary, unless the required follow-up labs (homocysteine and methylmalonic acid [MMA]) indicate that it is not physiologically significant

Known to be human immunodeficiency virus (HIV) positive
Any other clinically significant abnormalities that in the opinion of the investigator require further investigation or treatment or may interfere with study procedures or safety
Malignant neoplasms within 3 years of screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants with treatment cycles completed at least 6 months before screening). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before screening need not be excluded
Answer "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before screening, at screening, or at baseline, or has been hospitalized or treated for suicidal behavior in the past 5 years before screening
Known or suspected history of drug or alcohol abuse or dependence within 2 years before screening or a positive urine drug test at screening. Participants who test positive for benzodiazepines, opioids, or tetrahydrocannabinol (THC) in urine drug testing need not be excluded unless in the clinical opinion of the investigator this is due to potential drug abuse
Taking prohibited medications
Participation in a clinical study involving:

Any anti-amyloid immunotherapy (example, therapeutic monoclonal antibody or active anti-amyloid vaccine) at any time, unless it can be documented that the participant was randomized to placebo or never received study drug
Any immunoglobulin therapy, or vaccine within 6 months before Screening, unless it can be documented that the participant was randomized to placebo or never received study drug
Lecanemab
Any new chemical entities or investigational drug for AD within 6 months before screening unless it can be documented that the participant received only placebo
Any other investigational medication or device study in the 8 weeks or 5 half-lives (whichever is longer) of the medication before randomization unless it can be documented that the participant was in a placebo treatment arm

Planned surgery during the pre-randomization phase or within 3 months of randomization, which requires general anesthesia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama, Birmingham	Birmingham	Alabama	United States	35233
2	Banner Alzheimer's Institute	Phoenix	Arizona	United States	85006
3	Banner Sun Health Research Institute	Sun City	Arizona	United States	85351
4	UCI MIND	Irvine	California	United States	92697-4285
5	University of Southern California	Los Angeles	California	United States	90033
6	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
7	Stanford University	Palo Alto	California	United States	94304
8	Sharp Mesa Vista Hospital	San Diego	California	United States	92123
9	Univeristy of California, San Francisco	San Francisco	California	United States	94158
10	UCD-SAC	Walnut Creek	California	United States	94598
11	Yale University School of Medicine	New Haven	Connecticut	United States	06510
12	Georgetown University	Washington	District of Columbia	United States	20057
13	Howard University	Washington	District of Columbia	United States	20060
14	Advanced Clinical Research Network, Corp	Coral Gables	Florida	United States	33134-1613
15	Brain Matters Research	Delray Beach	Florida	United States	33445
16	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
17	Wien Center for Clinical Research	Miami Beach	Florida	United States	33140
18	Gonzalez MD & Aswad MD Health Sciences	Miami	Florida	United States	33125
19	Renstar Medical Research	Ocala	Florida	United States	34470
20	Synexus Clinical Research	Orlando	Florida	United States	32806
21	Progressive Medical Research	Port Orange	Florida	United States	32127
22	University of South Florida - Health Byrd Alzheimer Institute	Tampa	Florida	United States	33613
23	Synexus Clinical Research	The Villages	Florida	United States	32162
24	Alzheimer's Research and Treatment Center	Wellington	Florida	United States	33414
25	Charter Research	Winter Park	Florida	United States	31792
26	Emory University	Atlanta	Georgia	United States	30329
27	Columbus Memory Center, PC	Columbus	Georgia	United States	31909
28	Northwestern University	Chicago	Illinois	United States	60611
29	Rush University Medical Center	Chicago	Illinois	United States	60612
30	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
31	University of Kansas	Fairway	Kansas	United States	66205
32	University of Kentucky	Lexington	Kentucky	United States	40504
33	Johns Hopkins University	Baltimore	Maryland	United States	21224
34	Boston University	Boston	Massachusetts	United States	02118
35	Brigham and Woman's Hospital Center for Alzheimer Research and Treatment	Boston	Massachusetts	United States	21155
36	Donald S.Marks, M.D.,P.C.	Plymouth	Massachusetts	United States	02360
37	University of Michigan (UMICH)	Ann Arbor	Michigan	United States	48105
38	Mayo Clinic, Rochester	Rochester	Minnesota	United States	55905
39	Washington University	Saint Louis	Missouri	United States	63108
40	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada	United States	89106
41	Advanced Memory Research Institute of New Jersey	Toms River	New Jersey	United States	08755
42	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
43	Columbia University	New York	New York	United States	10032
44	University of Rochester	Rochester	New York	United States	14620
45	Duke Health Center	Durham	North Carolina	United States	27705
46	AMC Research	Matthews	North Carolina	United States	28105
47	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
48	Case Western Reserve University/University Hospitals	Beachwood	Ohio	United States	44122
49	Cleveland Clinic Lou Ruvo Center for Brain Health	Cleveland	Ohio	United States	44195
50	Ohio State University	Columbus	Ohio	United States	43210
51	Central States Research, LLC	Tulsa	Oklahoma	United States	74136
52	Summit Research Network, Oregon	Portland	Oregon	United States	97210
53	Oregon Health & Science University	Portland	Oregon	United States	97239
54	Abington Neurological Associates	Abington	Pennsylvania	United States	19001
55	Keystone Clinical Studies, LLC	Norristown	Pennsylvania	United States	19403
56	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
57	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
58	Rhode Island Hospital	Providence	Rhode Island	United States	02903
59	Butler Hospital Memory and Aging Program	Providence	Rhode Island	United States	02906
60	Ralph H. Johnson VA Medical Center	Charleston	South Carolina	United States	29403
61	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
62	University of Texas, Southwestern MC at Dallas	Dallas	Texas	United States	75390
63	University of North Texas Health Sciences Center	Fort Worth	Texas	United States	76107
64	Baylor College of Medicine	Houston	Texas	United States	77030
65	Houston Methodist Neurological Institute	Houston	Texas	United States	77030
66	The University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900
67	Eastern Virginia Medical School	Norfolk	Virginia	United States	23507
68	National Clinical Research, Inc	Richmond	Virginia	United States	23294
69	University of Washington Memory and Brain Wellness Center	Seattle	Washington	United States	98104
70	SIBCR	Seattle	Washington	United States	98108
71	University of Wisconsin	Madison	Wisconsin	United States	53792
72	St Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia
73	Westmead Hospital	Westmead	New South Wales	Australia
74	CALHN Memory Trials	Adelaide	South Australia	Australia
75	Austin Hospital - Medical and Cognitive Research Unit	Ivanhoe	Victoria	Australia
76	Australian Alzheimer's Research Foundation	Nedlands	Western Australia	Australia	6009
77	True North Clinical Research Inc.	New Minas	Nova Scotia	Canada	B4N 3R7
78	Parkwood Institute Main Building	London	Ontario	Canada	N6C0A7
79	Toronto Memory Program	Toronto	Ontario	Canada	M3B 2S7
80	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
81	McGill University / Jewish General Hospital Memory Clinic	Montreal	Quebec	Canada	H3T 1E2
82	Eisai Trial Site #2	Obu-shi	Aichi	Japan
83	Eisai Trial Site #9	Fukuoka-shi	Fukuoka	Japan
84	Eisai Trial Site #10	Kamakura-shi	Kanagawa	Japan
85	Eisai Trial Site #11	Kyoto-shi	Kyoto	Japan
86	Eisai Trial Site #5	Sendai-shi	Miyagi	Japan
87	Eisai Trial Site #6	Osaka-shi	Osaka	Japan
88	Eisai Trial Site #12	Suita-shi	Osaka	Japan
89	Eisai Trial Site #4	Bunkyo-ku	Tokyo	Japan
90	Eisai Trial Site #1	Hachioji -shi	Tokyo	Japan
91	Eisai Trial Site #7	Itabashi-ku	Tokyo	Japan
92	Eisai Trial Site #8	Kodaira-shi	Tokyo	Japan
93	Eisai Trial Site #3	Shinjuku-Ku	Tokyo	Japan
94	Eisai Trial Site #13	Hyogo		Japan
95	Brain Research Center	Amsterdam		Netherlands	01000
96	National University Hospital	Singapore		Singapore
97	Fundació ACE	Barcelona		Spain	08028
98	Hospital Universitario Quirón Salud Madrid	Madrid		Spain	28223
99	Fundacion CITA ALZHEIMER	San Sebastian		Spain	20009
100	Hospital Universitario Marqués de Valdeciila	Santander		Spain	39008
101	Bristol Brain Centre	Bristol		United Kingdom	BS10 5NB
102	Glasgow Memory Clinic	Glasgow		United Kingdom	ML1 4UF
103	St Pancras Clinical Research	London		United Kingdom	EC2Y 8EA
104	Imperial Memory Unit	London		United Kingdom	W6 8RF