A Long-Term Safety Extension of Studies ABE4869g and ABE4955g in Participants With Mild to Moderate Alzheimer's Disease Treated With Crenezumab
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Crenezumab
Intervention description: Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 360.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

Summary:

      This Phase II, open-label extension (OLE), multicenter study will evaluate the long-term
      safety and tolerability of crenezumab in participants with mild to moderate Alzheimer's
      disease who have participated in and completed the treatment period of the Phase II Study
      ABE4869g (NCT01343966) or ABE4955g (NCT01397578). Participants who received placebo in Study
      ABE4869g (NCT01343966) or ABE4955g (NCT01397578) will receive crenezumab. Anticipated time on
      study treatment is 144 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previous participation in Study ABE4869g or ABE4955g and completion of the Week 73
             visit

          -  Adequate visual and auditory acuity, in the investigator's judgment, to allow for
             neuropsychological testing

          -  Availability of a person ("caregiver") who can provide information on activities of
             daily living and behavior in order to complete the study-specific assessments

          -  Diagnosis of probable Alzheimer's disease according to the National Institute on
             Neurological and Communication Disease and Stroke/Alzheimer's Disease and Related
             Disorders Association (NINCDS-ADRDA) criteria (McKhann et al. 1984)

          -  Mini-Mental State Examination (MMSE) score of 10 or more at screening (Folstein et al.
             1975)

          -  For male participants with partners with reproductive potential, agreement to use a
             reliable means of contraception (e.g., condoms) during the study and for at least 8
             weeks following the last dose of study drug

          -  For female participants, a negative pregnancy test at screening

        Exclusion Criteria:

          -  Early treatment and/or study discontinuation prior to completion of the Week 73 visit
             of Genentech Study ABE4869g or ABE4955g

          -  Early discontinuation from the treatment schedule of a prior version of Study GN28525
             for safety reasons. If treatment discontinuation occurred for safety reasons,
             participants may not re-start dosing on extended treatment schedules offered in
             amendments to Study GN28525

          -  Inability to tolerate Magnetic Resonance Imaging (MRI) procedures or contraindication
             to MRI

          -  Female participants with reproductive potential: Female participants must either have
             undergone documented surgical sterilization or have not experienced menstruation for
             at least 12 consecutive months

          -  Severe or unstable medical condition that, in the opinion of the investigator or
             Sponsor, would interfere with the participant's ability to complete the study
             assessments or would require the equivalent of institutional or hospital care

          -  History or presence of clinically evident vascular disease potentially affecting the
             brain

          -  History of severe, clinically significant central nervous system trauma

          -  History or presence of clinically relevant intracranial tumor

          -  Presence of infections that affect the brain function or history of infections that
             resulted in neurologic sequelae

          -  History or presence of systemic autoimmune disorders potentially causing progressive
             neurologic disease

          -  History or presence of a neurologic disease other than Alzheimer's disease that may
             affect cognition

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric, human, or humanized antibodies or fusion proteins

          -  Evidence of malignancies (except squamous cell cancer or basal cell cancer of the
             skin), acute infections, renal failure that requires dialysis, or other unstable
             medical disease not related to Alzheimer's disease that, in the investigator's
             opinion, would preclude participant's participation. Cancer that is not being actively
             treated with anti-cancer therapy or radiotherapy as well as cancers which are
             considered to have low probability of recurrence are allowed

          -  History or presence of atrial fibrillation that, in the investigator's judgment, poses
             a risk for future stroke

          -  Chronic kidney disease of Stage greater than or equal to (>=) 4, according to the
             National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI)
             guidelines for chronic kidney disease (CKD)

          -  Impaired hepatic function

          -  Impaired coagulation (activated partial thromboplastin time [aPTT] greater than [>]
             1.2 times upper limit of normal [ULN])

          -  Platelet count less than (<) 100,000 per microliter (mcL)

          -  Presence at screening of superficial siderosis of central nervous system, more than 8
             cerebral microhemorrhages, or evidence of a prior cerebral macrohemorrhage

          -  Presence at screening of any other significant cerebral abnormalities, including
             ARIA-E

          -  Treatment with anticoagulation medications within 2 weeks prior to enrollment.
             Clopidogrel, dipyridamole, and aspirin are permitted

          -  Treatment with anticholinergic antidepressants, typical antipsychotics, or
             barbiturates within 2 weeks prior to enrollment. All other antidepressants and
             atypical antipsychotics are allowed with certain restrictions as defined in the
             protocol

          -  Chronic use of opiates, opioids, or benzodiazepines

          -  Any biologic therapy within 75 weeks prior to enrollment

          -  Any investigational agent (other than crenezumab) within 75 weeks prior to enrollment

          -  Treatment with anticholinergic antidepressants, typical antipsychotics, barbiturates,
             or narcotics within 5 half-lives or 3 months prior to screening, whichever is longer.
             All other antidepressants and atypical antipsychotics are allowed. Chronic use of
             benzodiazepines is not allowed; however, the intermittent use of benzodiazepines is
             allowed, except within 2 days prior to any neurocognitive assessment