Ensayos clínicos

Inclusion Criteria:

• Ability of the participant and/or his/her legally authorized representative (e.g., parent, spouse, or legal guardian), as appropriate and applicable, to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information in accordance with national and local privacy and ethics regulations.
• Participant was participating in an aducanumab clinical study at the time of the announcement of early termination (feeder studies).
  • Note #1: Participants who formerly participated in feeder studies and had to permanently discontinue the investigational product and/or exited a feeder study due to protocol mandatory requirements for discontinuation that are no longer applicable at the time of screening will be evaluated by the Sponsor on a case-by-case basis.
  • Note #2: Participants who completed screening in Study 221AD205 and were confirmed eligible prior to 21 March 2019 but were not randomized due to the discontinuation of the trial may have the opportunity to screen on this study upon review/approval from the Sponsor.
• Must have the ability to comply with protocol-related tests and procedures and have an MMSE score above 10 at Screening.
• Has one care partner who, in the Investigator’s opinion, has adequate contact with the participant as to be able to provide accurate information about the participant’s cognitive and functional abilities. The care partner must be available to provide information to the Investigator and site staff about the participant and attend in-person clinic visits that require care partner input for clinic assessments. The care partner should be available for the duration of the study.
• Female participants of childbearing potential must practice effective contraception during the study and for 5 times the half-life or 24 weeks (whichever is longer) after their last dose of study treatment.
• Apart from a clinical diagnosis of Alzheimer’s disease, the participant must be in good health as determined by the Investigator, based on medical history and screening assessments.

Exclusion Criteria:

• Any uncontrolled medical or neurological/neurodegenerative condition (other than Alzheimer’s disease) that, in the opinion of the Investigator, might be a contributing cause of the participant’s cognitive impairment (e.g., substance abuse, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, Lewy body dementia, fronto-temporal dementia, head trauma).
• Clinically significant unstable psychiatric illness (e.g., uncontrolled major depression, uncontrolled schizophrenia, uncontrolled bipolar affective disorder) within 6 months prior to Screening.
• Stroke or any unexplained loss of consciousness within 1 year prior to Screening.
• Brain MRI (performed at Screening, centrally read) evidence of any of the following:
  • Acute or subacute hemorrhage;
  • Prior macro-hemorrhage (defined as > 1 cm in diameter on T2* sequence) or prior subarachnoid hemorrhage unless it can be documented that the finding is not due to an underlying structural or vascular abnormality (i.e., finding does not suggest participant is at risk of recurrent hemorrhage);
  • Greater than 4 (for treatment-naïve participants) or ≥ 10 (for aducanumab previously treated participants) micro-hemorrhages (defined as ≤ 1 cm in diameter on T2* sequence);
  • Cortical infarct (defined as > 1.5 cm in diameter; irrespective of anatomic location);
  • Any focal area of superficial siderosis (for treatment-naïve participants) or 3 or more focal areas of superficial siderosis (for aducanumab previously treated participants).
  • History of bleeding disorder or predisposing conditions, blood clotting, or clinically significant abnormal results on coagulation profile at Screening, as determined by the Investigator.
• Presence of diabetes mellitus that, in the judgment of the Investigator, cannot be controlled or adequately managed.
• History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening.
• Clinically significant 12-lead ECG abnormalities, as determined by the Investigator.
• Uncontrolled hypertension defined as: average of 3 SBP/DBP readings > 165 mmHg and/or > 100 mmHg at Screening (blood pressure measurements exceeding these limits may be repeated as warranted by the Investigator, but values must be within the specified limits for the participant to be eligible for the study), or persistent SBP and/or DBP readings > 180 mmHg and/or >100 mmHg, respectively, 3 months prior to treatment (Day 1) that, in the opinion of the Investigator, are indicative of chronic uncontrolled hypertension.
• History of malignancy or carcinoma. The following exceptions may be made after discussion with the Sponsor:
  • Participants whose cancer is in remission according to the cancer specialist prior to Screening;
  • Participants with a history of excised or treated basal cell or squamous carcinoma of the skin.
• A seizure event that occurred after the last visit of the feeder study and before Screening for this study.
• Evidence of impaired liver function as shown by an abnormal liver function profile at Screening (e.g., repeated values of AST and ALT ≥ 2 × the upper limit of normal).
• History or evidence of an autoimmune disorder considered clinically significant by the Investigator or requiring chronic use of systemic corticosteroids or other immunosuppressants.
• Recent history (within 1 year of Screening) of alcohol or substance abuse as determined by the Investigator, a positive urine drug (due to nonprescription drug) or alcohol test at Screening or use of cannabinoids (prescription or recreational).
• Clinically significant systemic illness or serious infection (e.g., pneumonia, septicemia) within 30 days prior to or during Screening.
• History of or known seropositivity for HIV.
• Current hepatitis C infection (defined as positive HCV antibody and detectable HCV RNA. Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study (Reference: United States Centers for Disease Control and Prevention).
• Current hepatitis B infection (defined as positive for HBsAg and/or total anti-HBc). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.
• History of severe allergic or anaphylactic reactions, or history of hypersensitivity to any of the inactive ingredients in the drug product (refer to the IB for information on the clinical formulation).
• Any other medical conditions (e.g., renal disease) that are not stable or controlled, or, which in the opinion of the Investigator, could affect the participant’s safety or interfere with the study assessments.
• Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participant at higher risk for AEs, or impair the participant’s ability to perform cognitive testing or complete study procedures.
• Use of allowed medications for chronic conditions at doses that have not been stable for at least 4 weeks prior to Screening up to Day 1, or use of Alzheimer’s disease medications (including but not limited to donepezil, rivastigmine, galantamine, tacrine, and memantine) at doses that have not been stable for at least 8 weeks prior to Screening up to Day 1.
• Chronic use of systemic immunosuppressive drugs (including systemic corticosteroids). Local and/or topical immunosuppressants will be allowed.
• Use of chemotherapeutic agents and checkpoint inhibitors.
• Use of parenteral immunoglobulin, blood products, plasma derivatives, plasma exchange, or plasmapheresis.
• Use of vaccinations within 10 days prior to Day 1.
• Use of medications with platelet anti-aggregant or anticoagulant properties (the use of aspirin at a dose ≤ 325 mg daily is allowed).
• Use of illicit narcotic medication.
• Participation in any study in which the participant is taking an investigational product for Alzheimer’s disease (with purported disease-modifying treatment or not) unless the participant has fulfilled a wash-out period of at least 5 half-lives for that particular investigational product or is able to provide documentation of having received placebo in that investigational product study.
• Contraindications to having a brain MRI (e.g., pacemaker; MRI-incompatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed).
• Only for participation in the PET substudies:
  • Contraindication to having a PET scan (e.g., inability to lie flat or still for the duration of the scan) or intolerance to previous PET scans (i.e., previous hypersensitivity reactions to PET ligand or imaging agent, failure to participate in and comply with previous PET scans);
  • Have had or plan exposure to experimental radiation within 12 months prior to Screening such that radiodosimetry limits would be exceeded by participating in this study.
• Only for participants who consent to LP: any contraindications to having an LP (e.g., platelet count < 100,000/µL, lumbar spine deformity). Any symptoms caused by or related to the optional LP during Screening must be resolved prior to Day 1. Participants may still participate in the overall study even if participation in the optional LP portion is contraindicated. Others
• Female participants who are pregnant or currently breastfeeding.
• Participant currently living in an organized care facility with extensive intervention and/or support of daily living activities.
• Blood donation (≥ 1 unit) within 1 month prior to Screening
• Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the participant unsuitable for enrollment.