A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Participants With Early Alzheimer's Disease (MissionAD1)

Eisai

Status and phase: Terminated; Phase 3

Conditions: Alzheimer's Disease

Treatments: Drug: Elenbecestat; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02956486

E2609-G000-301

2016-003928-23 (EudraCT Number)

2016-004128-42 (EudraCT Number)

Details and patient eligibility

About

The name of this trial is MissionAD1. This phase 3 study consists of a Core and Open Label Extension (OLE) Phase in participants with Early Alzheimer's Disease (EAD), and will be conducted to evaluate the efficacy and safety of E2609. The Core is a 24-month treatment, multicenter, double blind, placebo controlled parallel group study. The OLE is a 24-month treatment, one group study. The data for the studies E2609-G000-301 (NCT02956486, MissionAD1) and E2609-G000-302 (NCT03036280, MissionAD2) will be pooled.

Enrollment: 2,212 patients

Sex: All

Ages: 50 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Core Study

• Mild cognitive impairment due to Alzheimer's disease (AD) or mild AD dementia including

  1. Mini Mental State Examination score equal to or greater than 24
  2. Clinical Dementia Rating (CDR) global score of 0.5
  3. CDR Memory Box score of 0.5 or greater

• Impaired episodic memory confirmed by a list learning task

• Positive biomarker for brain amyloid pathology as indicated by either amyloid positron emission tomography or cerebrospinal fluid AD assessment or both

Extension Phase

• Participants who complete the Core Study

Exclusion criteria

Core Study

• Females who are breastfeeding or pregnant at Screening or Baseline. Females of child-bearing potential must use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation

• Any condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD

• Participants with a history of seizures within 5 years of Screening

• History of transient ischemic attacks or stroke within 12 months of Screening

• Psychiatric diagnosis or symptoms (example, hallucinations, major depression, delusions etc.)

• Suicidal ideation or any suicidal behavior within 6 months before Screening or has been hospitalized or treated for suicidal behavior in the past 5 years

• Have any contraindications to magnetic resonance imaging (MRI) scanning or

  1. Have lesions that could indicate a dementia diagnosis other than AD on brain MRI
  2. Exhibit other significant pathological findings on brain MRI.

• Participants who have a history of moderate to severe hepatic impairment (example, Child-Pugh Class B or C)

• Results of laboratory tests conducted during Screening that are outside the following limits:

  1. Absolute lymphocyte count below the lower limit of normal (LLN)
  2. Thyroid stimulating hormone above normal range
  3. Abnormally low Vitamin B12 levels

• Participants at increased risk of infection

• Have received any live vaccine/live attenuated vaccine in the 3 months before randomization

• Any chronic inflammatory disease that is not adequately controlled or that requires systemic immunosuppressive or immunomodulatory therapy

• Any other clinically significant abnormalities

• Severe visual or hearing impairment

• A prolonged corrected QT (QTc) interval (QT interval with Fridericia's correction [QTcF] greater than 450 milliseconds [ms])

• Malignant neoplasms within 5 years of Screening

• Known or suspected history of drug or alcohol abuse

• Taking prohibited medications, which must be reviewed with the Investigator

• Have participated in a recent clinical study

Note: Other protocol-defined Inclusion/Exclusion Criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,212 participants in 3 patient groups, including a placebo group

Core Study: Elenbecestat 50 mg

Experimental group

Description:

Participants will receive one 50 milligram (mg) elenbecestat tablet, orally, once a day in the morning. The core study will be double blinded.

Treatment:

Drug: Elenbecestat

Core Study: Placebo

Placebo Comparator group

Description:

Participants will receive one matching placebo tablet, orally, once a day in the morning. The core study will be double blinded.

Treatment:

Drug: Placebo

Open-label Extension Phase: Elenbecestat 50 mg

Experimental group

Description:

Participants completing the core study will receive one 50 mg elenbecestat tablet, orally, once a day in the morning.

Treatment:

Drug: Elenbecestat