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

Phase 3

Active, not recruiting

• Conditions: Early Preclinical Alzheimer's Disease; Preclinical Alzheimer's Disease
• Interventions: Drug: Placebo; Drug: Lecanemab

• Registration Number: NCT04468659
• Lead Sponsor: Eisai Inc.

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). This study will also evaluate the long-term safety and tolerability of lecanemab in participants enrolled in the Extension Phase.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-09
• Study First Submitted QC: 2020-07-09
• Study First Posted: 2020-07-13
• Study Start: 2020-07-14
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-31
• Last Update Posted: 2025-01-01
• Primary Completion: 2028-12-21
• Study Completion: 2031-01-16

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1400

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A45 Trial: Placebo (Core Study)	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.
A3 Trial: Lecanemab 5 mg/kg + 10 mg/kg (Core Study)	Lecanemab	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 in core study.
A3 Trial: Placebo (Core Study)	Placebo	Participants will receive placebo (0.9% sodium chloride solution), administered as IV infusion, every four weeks from Week 0 to 216.
A45 Trial: Lecanemab 5 mg/kg + 10 mg/kg (Core Study)	Lecanemab	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 in core study.
A45 Trial: Lecanemab 10 mg/kg (Extension Phase)	Lecanemab	Participants progressing to early Alzheimer's disease (EAD) during the core study (progressors) will receive lecanemab 10 mg/kg, administered as IV infusion, every two weeks after transition to the extension phase through to at least Week 216 from randomization in the core study. Participants completing the core study (completers) will enter extension phase and will receive lecanemab 10 mg/kg, administered as IV infusion, every two weeks for up to Week 312. Eligible participants receiving placebo in core study will continue to extension phase.
A3 Trial: Lecanemab 10 mg/kg (Extension Phase)	Lecanemab	Participants progressing to EAD during the core study (progressors) will receive lecanemab 10 mg/kg, administered as IV infusion, every two weeks after transition to the extension phase through to at least Week 216 from randomization in the core study. Participants completing the core study (completers) will enter extension phase and will receive lecanemab 10 mg/kg, administered as IV infusion, every two weeks for up to Week 312. Eligible participants receiving placebo in core study will continue to extension phase.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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

Trial Locations

Locations (105)

University of Alabama, Birmingham; 🇺🇸 Birmingham, Alabama, United States

Banner Alzheimer's Institute; 🇺🇸 Phoenix, Arizona, United States

Banner Sun Health Research Institute; 🇺🇸 Sun City, Arizona, United States

UCI MIND; 🇺🇸 Irvine, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

Hoag Memorial Hospital Presbyterian; 🇺🇸 Newport Beach, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Sharp Mesa Vista Hospital; 🇺🇸 San Diego, California, United States

Univeristy of California, San Francisco; 🇺🇸 San Francisco, California, United States

University of California, Davis; 🇺🇸 Walnut Creek, California, United States

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