Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer*s Disease
- Conditions
- Early Symptomatic Alzheimer's DiseaseAlzheimersenile psychosis
- Registration Number
- NL-OMON52785
- Lead Sponsor
- Eli Lilly
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 27
1. 60 to 85 years of age inclusive, at the time of signing the informed consent.
2. Gradual and progressive change in memory function reported by the
participant or informant for >=6 months.
3. An MMSE score of 20 to 28 (inclusive) at LEAD-IN SCREENING or COMPLETE
SCREENING,
4. Meet flortaucipir F18 scan (central read) criteria
5. Meet florbetapir F18 scan (central read) criteria
6. Have a study partner who will provide written informed consent to
participate, is in frequent contact with the participant (defined as at least
10 hours per week), and will accompany the participant to study visits or be
available by telephone at designated times.
7. Have adequate literacy, vision, and hearing for neuropsychological testing
in the opinion of the investigator at the time of screening.
8. Are reliable and willing to make themselves available for the duration of
the study and are willing to follow study procedures.
9. Males and females will be eligible for this study.
10.Capable of giving signed informed consent as described in Section 10.1.3
which includes compliance with the requirements and restrictions listed in the
informed consent form (ICF) and in this protocol.
12. Significant neurological disease affecting the central nervous system
(CNS), other than AD, that may affect cognition or ability to complete the
study, including but not limited to, other dementias, serious infection of the
brain, Parkinson*s disease, multiple concussions, or epilepsy or recurrent
seizures (except febrile childhood seizures).
13. Current serious or unstable illnesses including cardiovascular, hepatic,
renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than
AD), psychiatric, immunologic, or hematologic disease and other conditions
that, in the investigator*s opinion, could interfere with the analyses in this
study; or has a life expectancy of <24 months.
14. History of cancer within the last 5 years, with the exception of
non-metastatic basal and/or squamous cell carcinoma of the skin, in situ
cervical cancer, nonprogressive prostate cancer, or other cancers with low risk
of recurrence or spread.
15. Participants with any current primary psychiatric diagnosis other than AD
if, in the judgment of the investigator, the psychiatric disorder or symptom is
likely to confound interpretation of drug effect, affect cognitive assessment,
or affect the participant*s ability to complete the study. Participants with
history of schizophrenia or other chronic psychosis are excluded.
16. Are, in the judgment of the investigator, actively suicidal and therefore
deemed to be at significant risk for suicide.
17. History of alcohol or drug use disorder (except tobacco use disorder)
within 2 years before the screening visit.
18. Have a history of clinically significant multiple or severe drug allergies,
significant atopy, or severe posttreatment hypersensitivity reactions
(including but not limited to erythema multiforme major, linear immunoglobulin
A dermatosis, toxic epidermal necrolysis, and/or exfoliative dermatitis).
19. Have any clinically important abnormality at screening, as determined by
investigator, in physical or neurological examination, vital signs, ECG, or
clinical laboratory test results that could be detrimental to the patient,
could compromise the study, or show evidence of other etiologies for dementia.
20. Screening MRI which shows evidence of significant abnormality that would
suggest another potential etiology for progressive dementia or a clinically
significant finding that may impact the patient*s ability to safely participate
in the study.
21. Have any contraindications for MRI, including claustrophobia or the
presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker.
22. Have a centrally read MRI demonstrating presence of ARIA-E, >4 cerebral
microhemorrhages, more than 1 area of superficial siderosis, any
macrohemorrhage or severe white matter disease at screening.
23. Sensitivity to florbetapir F18 or flortaucipir F18.
24. Poor venous access.
25. Contraindication to PET.
26. Present or planned exposure to ionizing radiation that, in combination with
the planned administration of study PET ligands, would result in a cumulative
exposure that exceeds local recommended exposure limits.
27. A corrected QT (QTcF) interval measurement >450 msec (men) or >470 msec
(women) at screening (as determined at the investigational site). The site may
request a central read prior to making determination of thi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>iADRS change from baseline through Week 76 </p><br>
- Secondary Outcome Measures
Name Time Method <p>Change from baseline through Week 76 as measured by:<br /><br>• iADRS<br /><br>• CDR-SB<br /><br>• ADAS-Cog13 score<br /><br>• ADCS-iADL score<br /><br>• MMSE score<br /><br><br /><br>Change in brain amyloid plaque deposition from baseline through Week 76 as<br /><br>measured by florbetapir F18 PET scan<br /><br>Change in brain tau deposition from baseline through Week 76 as measured by<br /><br>flortaucipir F18 PET scan<br /><br>Change in volumetric MRI measures from baseline through Week 76<br /><br>Standard safety assessments: Spontaneously reported AEs, Clinical laboratory<br /><br>tests, Vital sign and body weight measurements, 12-lead ECGs, Physical and<br /><br>neurological examinations<br /><br>- MRI (ARIA and emergent radiological findings)<br /><br>- Infusion related reactions<br /><br>- C-SSRS<br /><br><br /><br>Plasma PK of donanemab<br /><br>ADAs against donanemab including<br /><br>• treatment emergent ADAs<br /><br>• neutralizing antibodies</p><br>