Efficacy and Safety Trial of Verubecestat (MK-8931) in Participants With Prodromal Alzheimer's Disease (MK-8931-019)


About this study

This study consists of two parts, Part I and Part II. The purpose of Part I of the study is to assess the efficacy and safety of verubecestat (MK-8931) compared with placebo administered for 104 weeks in the treatment of amnestic mild cognitive impairment (aMCI) due to Alzheimer's Disease (AD), also known as prodromal AD. Participants will be randomized to receive placebo, or 12 mg or 40 mg verubecestat, once daily. The primary study hypothesis for Part I is that at least one verubecestat dose is superior to placebo with respect to the change from baseline in the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB) score at 104 weeks. Participants who complete Part I of the study may choose to participate in Part II, which is a long term double-blind extension to assess efficacy and safety of verubecestat administered for up to an additional 260 weeks. In Part II, all participants will receive either 12 mg or 40 mg verubecestat, once daily.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  1. Diagnosis of prodromal AD, including the following:
    1. History of subjective memory decline with gradual onset and slow progression for at least one year corroborated by an informant,
    2. Objective impairment in episodic memory by memory test performed at Screening,
    3. Does not meet criteria for dementia, AND
    4. Positive Screening amyloid imaging PET scan using [18F]flutametamol tracer or positive Screening CSF tau:amyloid-β42 (Aβ42) ratio
  2. Able to read at a 6th grade level or equivalent
  3. If participant is receiving an acetylcholinesterase inhibitor or memantine, the dose must have been stable for at least three months before Screening
  4. Must have a reliable and competent trial partner/informant who has a close relationship with the participant and is willing to accompany the participant to all required trial visits, and to monitor compliance of the administration of the trial medication
  5. Agree to inform their general practitioner of their participation in this study

Inclusion Criteria for Extension Period (Part II):

  1. Tolerated study drug and completed the initial 104-week period of the trial (Part I)
  2. Participant must have a reliable and competent trial partner who must have a close relationship with the subject

Exclusion Criteria:

  1. History of stroke
  2. Evidence of a clinically relevant neurological disorder other than the disease being studied (i.e., prodromal AD)
  3. History of seizures or epilepsy within the last 5 years
  4. Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
  5. Participant is at imminent risk of self-harm or of harm to others
  6. History of alcoholism or drug dependency/abuse within the last 5 years before Screening
  7. Participant does not have a magnetic resonance imaging (MRI) scan obtained within 12 months of Screening and is unwilling or not eligible to undergo an MRI scan at the Screening Visit. With Sponsor approval, a head computed tomography (CT) scan may be substituted for MRI scan to evaluate eligibility
  8. History of hepatitis or liver disease that has been active within the 6 months prior to Screening
  9. Recent or ongoing, uncontrolled, clinically significant medical condition within 3 months of Screening
  10. History of malignancy occurring within the 5 years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma
  11. Clinically significant vitamin B12 or folate deficiency in the 6 months before Screening
  12. Use of any investigational drugs or participation in clinical trials within the 30 days before Screening
  13. History of a hypersensitivity reaction to more than three drugs
  14. Has human immunodeficiency virus (HIV) by medical history
  15. Participant is unwilling or has a contraindication to undergo PET scanning including but not limited to claustrophobia, excessive weight or girth
  16. History or current evidence of long QT syndrome, corrected QT (QTc) interval ≥470 milliseconds (for male participants) or ≥480 milliseconds (for female participants), or torsades de pointes
  17. Close family member (including the trial partner, spouse or children) who is among the personnel of the investigational or sponsor staff directly involved with this trial

Exclusion Criteria for Extension Period (Part II):

  1. Participant is at imminent risk of self-harm or of harm to others
  2. Has developed a recent or ongoing, uncontrolled, clinically significant medical or psychiatric condition
  3. Results of safety assessments (e.g., laboratory tests) performed in participant at end of Part I that are clinically unacceptable to the Investigator
  4. Has developed a form of dementia that is not AD

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Richard Caselli, M.D.

Closed for enrollment

More information


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Additional contact information

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