Phase
Condition
Amyloidosis
Down's Syndrome
Treatment
Placebo
Donanemab
Clinical Study ID
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Documentation of the participant's informed consent to study procedures
Ages 35-50 years (inclusive).
Plasma Phosphorylated tau (pTau) 217 levels at screening consistent with amyloid PETeligibility.
Diagnosis of Down syndrome (including trisomy 21, mosaic trisomy 21, Robertsoniantranslocation trisomy 21, or partial trisomy 21) as confirmed by medical recordreview or Karyotype genetic testing.
Intelligence quotient (IQ) equal to or greater than 40 based on Kaufman BriefIntelligence Test, Second Edition.
Participants must be in good general health as evidenced by medical history with nodiagnosis of dementia.
Elevated brain amyloid (>18 centiloids) at screening.
Stable dose of permitted medications as described protocol for 4 weeks prior toscreening.
In the opinion of the site PI, has a study partner able and willing to provideaccurate information (including clinical symptoms and medical history) about theparticipant and participate in study visits and informant-based assessments (usuallyrequires at least 5 hours of contact per week) for the duration of the study.
As assessed by the site PI, participant is likely to be able to comply with theprotocol for the duration of the study, and has adequate vision, hearing (hearingaid permitted), and literacy sufficient for compliance with required testingprocedures.
Must complete all screening evaluations as outlined in protocol
Exclusion
Exclusion Criteria:
Females who are lactating or pregnant (as confirmed by a urine pregnancy test)during screening, or plan to become pregnant during the study.
Females of childbearing potential or males with a female partner of childbearingpotential who did not use a highly effective method of contraception within 28 daysof screening alongside with a suitable barrier method (e.g., male condom) and/or arenot willing to use both methods for the duration of their participation in the studyand for 3 months after the last dose of study drug.
Weight less than 40kg at screening.
Lack of good venous access such that intravenous (IV) drug delivery or multipleblood draws would be precluded.
Suspected or known allergic reactions, adverse reactions, or hypersensitivity tohumanized monoclonal antibodies or any components of the study treatments (donanemabor placebo).
Previous treatment with donanemab unless there is firm evidence that the participantreceived placebo only.
Prior or current treatment with a prohibited medication as described in protocol.
Enrollment in another investigational study, or intake of investigational drug,within 30 days prior to screening or five half-lives of the investigational drug,whichever is longer.
MRI scan at screening showing a single area of cerebral vasogenic edema, superficialsiderosis, or evidence of a prior macro-hemorrhage, or showing more than one (1)cerebral microhemorrhage (regardless of their anatomical location with a diagnosticcharacterization as "definite"), evidence of space occupying lesions, more than two (2) lacunar infarcts, or one (1) infarct larger than 1cm in diameter, severe whitematter disease, and structural evidence of alternative pathology not consistent withAD and considered to be at the origin of participant's symptoms. NOTE: Small incidental meningiomas and arachnoid cysts (<1cm in diameter) may bepermitted with Medical Monitor review and approval.
Contraindication(s) to MRI studies, including metal (ferromagnetic) implants, acardiac pacemaker or other devices that are not compatible with MRI, and/or severeclaustrophobia.
Contraindications to amyloid positron emission tomography (PET) imaging and/or useof florbetapir.
Any unstable and/or clinically significant medical condition likely to hamper theevaluation of safety and/or efficacy of study drug (e.g., moderate and/or severeuntreated obstructive sleep apnea, clinically significant reduction in serum B12 orfolate levels, clinically significant abnormalities of thyroid function, stroke, orother cerebrovascular conditions), as per the site PI's judgement.
History of severe allergic reaction (e.g., anaphylaxis) including, but not limitedto: severe allergic reaction to previous vaccines, foods, and/or medications.
Hospitalization within 30 days prior to screening or baseline.
Clinically significant infections or major surgical operation within 3 months priorto screening.
History of chronic or recurrent infections judged to be clinically significant bythe site PI and which would potentially hamper the evaluation of efficacy and safetyassessments.
Myocardial infarction within one (1) year prior to baseline, unstable anginapectoris, or significant coronary artery disease.
History of cancer within the past five (5) years other than treated squamous cellcarcinoma, basal cell carcinoma and melanoma in-situ, in-situ prostate cancer, orin-situ breast cancer, which have been fully removed and are considered cured.
History or presence of immunological or inflammatory conditions, includingneurological disorders, judged to be clinically significant by the site PI.
History of meningitis or meningoencephalitis.
History of moderate or severe traumatic brain injury.
History or presence of uncontrolled seizures. If history of seizures, they must bewell controlled with no occurrence of seizures in the 2 years prior to studyscreening. The use of antiepileptic medications is permitted.
Concomitant or past history of psychiatric or neurologic disorder (e.g., head injurywith loss of consciousness, symptomatic stroke, Parkinson's disease, severe carotidocclusive disease, transient ischemic attacks, hemorrhagic and/or non-hemorrhagicstroke) other than those considered to be related to AD.
Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteriafor drug or alcohol abuse or dependence currently met within the past 5 years.
Significant risk of suicide defined, using the Columbia-Suicide Severity RatingScale (C-SSRS) (Child Version), as the participant answering "yes" to suicidalideation questions 4 or 5 or answering "yes" to suicidal behavior within the past 12months.
Clinically significant abnormal vital signs including sustained sitting bloodpressure >160/90 millimeters of mercury (mmHg).
Participants with diabetes mellitus with hemoglobin A1c (HbA1c) levels of ≥8.0%.
In the opinion of the site PI, clinically significant deviations from normal valuesfor hematologic parameters, liver function tests, and other biochemical measures.
Participants with a known history of human immunodeficiency virus (HIV-1 and 2).
Participants with known history of acute/chronic hepatitis B or C.
Clinically significant arrhythmias or other clinically significant abnormalities onelectrocardiogram (ECG) at screening (minor abnormalities documented as clinicallyinsignificant by the site PI are allowed).
Residing in a continuous care nursing facility.
For participants undergoing Lumbar Puncture (LP) as part of the optionallongitudinal cerebrospinal fluid (CSF) biomarker sub-study, any contraindication toLP including, but not limited to: inability to tolerate an appropriately flexedposition for the time necessary to perform an LP; international normalized ratio (INR) >1.4 or other metrics indicating coagulopathy; platelet count of <120,000/microliter(μL); infection at the desired lumbar puncture site; takinganti-coagulant medication within 90 days of LP (Note: low dose (up to 81 milligram (mg)) aspirin is permitted); degenerative arthritis of the lumbar spine; suspectedor known non-communicating hydrocephalus or intracranial mass, or elevatedintracranial pressure from any cause; prior history of spinal mass or trauma.
Participants unwilling to learn their APOE genotype and/or amyloid PET scan results
Participants who are apolipoprotein E ε4 (APOE ε4) homozygotes.
Participants who receive anti-coagulants or thrombolytics within 30 days prior tobaseline. Any use of anticoagulants or thrombolytics during the study will lead todiscontinuation of the study drug.
Participants with clotting disorders.
Any condition, which in the opinion of the site PI, Coordinating Center, regulatorysponsor, or Project Lead/Protocol PI, makes the participant unsuitable forinclusion.