AbbVie M15-566

Principal Investigator: Norman Foster
Keywords: Alzheimer's Disease Department: Alzheimer's Center
IRB Number: 00096885 Co Investigator:  
Specialty: Neurology
Sub Specialties: Cognitive Disorders
Recruitment Status: Not yet recruiting

Contact Information

Jenny Felter
jenny.felter@hsc.utah.edu
801-587-7201

Brief Summary

The primary objectives of this study are:

  • To assess the efficacy of ABBV-8E12 in slowing disease progression (cognitive and functional impairment) in subjects with Early AD as measured by the Clinical Dementia Rating, Sum of Boxes (CDR-SB).
  • To assess the long term safety of ABBV-8E12 for up to 96 weeks in subjects with Early AD.

The secondary objectives of this study are:

●  To assess the pharmacokinetics of ABBV-8E12 in subjects with Early AD.

●  To assess the efficacy of ABBV-8E12 in slowing cognitive and functional impairment in subjects with Early AD as measured by the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14), Repeatable Battery for Assessment of Neuropsychological Status (RBANS), 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients with Mild Cognitive Impairment (ADCS-MCI-ADL-24), Functional Activities Questionnaire (FAQ) and University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief).

●  To assess the global impact of ABBV-8E12 on cognition, function and behavior as measured by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC- MCI).

The exploratory objectives of this study are:

● To assess the effect of ABBV-8E12 on CSF free/total tau protein.

● To assess the effect of ABBV-8E12 on potential CSF biomarkers of disease progression.

● To assess the efficacy of ABBV-8E12 in slowing the rate of regional and/or whole brain atrophy in subjects with Early AD as measured by volumetric MRI 

Detailed Description

The primary objectives of this study are: To assess the efficacy of ABBV-8E12 in slowing disease progression (cognitive and functional impairment) in subjects with Early AD as measured by the Clinical Dementia Rating, Sum of Boxes (CDR-SB). To assess the long term safety of ABBV-8E12 for up to 96 weeks in subjects with Early AD. The secondary objectives of this study are: To assess the pharmacokinetics of ABBV-8E12 in subjects with Early AD. To assess the efficacy of ABBV-8E12 in slowing cognitive and functional impairment in subjects with Early AD as measured by the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale (14-Item) Cognition Portion (ADAS-Cog-14), Repeatable Battery for Assessment of Neuropsychological Status (RBANS), 24-Item Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for Patients with Mild Cognitive Impairment (ADCS-MCI-ADL-24), Functional Activities Questionnaire (FAQ) and University of California's Performance Based Skills Assessment, Brief Version (UPSA-Brief). To assess the global impact of ABBV-8E12 on cognition, function and behavior as measured by Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for Mild Cognitive Impairment (ADCS-CGIC- MCI). The exploratory objectives of this study are: To assess the effect of ABBV-8E12 on CSF free/total tau protein. To assess the effect of ABBV-8E12 on potential CSF biomarkers of disease progression. To assess the efficacy of ABBV-8E12 in slowing the rate of regional and/or whole brain atrophy in subjects with Early AD as measured by volumetric MRI

Inclusion Criteria

A subject will be eligible for study participation if he/she meets the following criteria:

1.  Subject must be able to understand the nature of the study and has the opportunity to have any questions answered. The subject has voluntarily signed the Independent Review Board (IRB)/Independent Ethics Committee (IEC) approved Informed Consent, prior to the conduct of any study procedures (including any changes occurring in the subject's current therapeutic regimen). If the subject is not fully competent, full informed consent must be obtained from a representative and assent must be obtained from the subject.

2.  Male or female and age is between 55 and 85 years, inclusive, at Screening Visit 1.

3.  Subject who meets the National Institute on Aging and the Alzheimer's Association (NIA-AA) clinical criteria for mild cognitive        impairment or probable AD, and have:

●   Clinical Dementia Rating (CDR)-Global Score of 0.5 at Screening Visit 1

●   A Mini-Mental State Examination (MMSE) score of 22 to 30, inclusive, at Screening Visit 1

●  Repeatable Battery for the Assessment of Neuropsychological Status-Delayed Memory Index (RBANS – DMI) score of 85     or lower

4.  Subject has a positive amyloid Positron Emission Tomography (PET) scan.

5.  Subject has a Modified Hachinski Ischemic Scale (MHIS) score of ≤ 4.

6.  Subject has an identified, reliable, study partner (e.g., family member), who has frequent contact with the subject and who will provide information as to the subject's cognitive and functional abilities. The study partner has voluntarily signed the IRB/IEC approved Study Partner Informed Consent, prior to the conduct of any study procedures.

7. If female, subject must be postmenopausal defined as: 

·      Age ≥ 55 years with no menses for 12 or more months without an alternative medical cause.

OR

·      Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

          8.  If the male subject is sexually active with female partner(s) of childbearing potential, he must agree, from Study Day 1 through 20 weeks after the last dose of study drug to practice the protocol specified contraception (Section 5.2.4) and must refrain from sperm donation.

          9.  If using medications to treat symptoms related to AD, doses must be stable for at least 12 weeks prior to randomization.

Exclusion Criteria

1.Subject has visual, auditory or other impairment that in the opinion would preclude collection of outcome measures.

2. Subject has any contraindication to or inability to tolerate brain MRIs (e.g., a pacemaker or any other implanted device or condition that would preclude proximity to a strong magnetic field).

3.      Subject has any contraindication to or inability to tolerate a PET scan (includes current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the subject in any given year would exceed the local country limits of annual and total dose).

  1. Subject has any contraindications to or inability to tolerate lumbar punctures (e.g., use of anticoagulant medications such as warfarin and inability to temporarily cease use of such therapy for a limited duration surrounding lumbar punctures).
  2. Subject has evidence of any other clinically significant neurological disorder other than Early AD, including but not limited to:

·       Parkinson's disease

·       vascular dementia

·       significant cerebrovascular abnormalities

·       frontal-temporal dementia

·       Huntington's disease

·       normal pressure hydrocephalus

·       brain tumor

·       progressive supranuclear palsy

·       seizure disorder

·       subdural hematoma

·       multiple sclerosis

·       history of significant head trauma followed by persistent neurologic deficits

·       known structural brain abnormalities

6.Subject has a screening MRI scan,interpreted by a radiologist with evidence of  infection, infarction (including multiple lacunas in a critical memory structure),or other focal lesions.

  1. Subject has a history of or currently has schizophrenia, schizoaffective disorder or bipolar disorder according to DMV-V or ICD-10 criteria.

8. In the opinion of the investigator, the subject has any clinically significant or uncontrolled medical or psychiatric illness, or has had an infection requiring medical intervention in the past 30 days.

  1. Subject has significant current suicidal ideation within one year prior to Screening as evidenced by answering "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at Screening or a history of suicidal attempts within the last 2 years.
  1. Subject has a positive screen for drugs of abuse or marijuana at Screening Visit.

11.   Subject has a current diagnosis or history of drug or alcohol abuse (by DSM -V criteria) within 24 months prior to screening visit.

12.   Subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions (e.g., coronary artery bypass graft, percutaneous coronary intervention via cardiac catheterization, thrombolytic therapy), within 6 months of Screening Visit 1.

13. Subject has a history or evidence of a malignancy within the 2 years prior to Screening Visit 1. Subjects with some indolent malignancies (e.g., basal cell carcinoma or squamous cell carcinoma of the skin) may be permitted to enroll with the permission of the AbbVie Therapeutic Area Medical Director. 

14. Subject has a positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) or known history of HIV infection.

15. Subject has had surgery under general anesthesia within 3 months prior to Screening or has a planned major surgical procedure scheduled during the period when the subject would be participating in this study. The subject may subsequently be considered for the study following full recuperation from the surgical procedure.

16. Receipt of an investigational product within a time period equal to 5 half-lives, if known, or within 6 weeks (for small molecules) or 6 months (for monoclonal antibodies or other biologics) prior to study drug administration

17. Subject has any history of prior receipt of active immunotherapy directed against tau or amyloid

18. Subject is taking specific exclusionary psychoactive medications or any other exclusionary medications

19. Subject has an abnormally low vitamin B12 (cobalamin), abnormal thyroxine (T4)or an abnormally high thyroid stimulating hormone (TSH) at Screening that is considered clinically significant by the investigator.

20. The investigator considers subject, for any reason, as an unsuitable candidate to receive ABBV-8E12 or unable or unlikely to comply with the dosing schedule or study evaluations.