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A Study to Confirm Safety and Efficacy of BAN2401 in Participants With Early Alzheimer's Disease (Clarity AD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03887455
Recruitment Status : Recruiting
First Posted : March 25, 2019
Last Update Posted : March 16, 2020
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
Eisai Inc.

Tracking Information
First Submitted Date  ICMJE March 21, 2019
First Posted Date  ICMJE March 25, 2019
Last Update Posted Date March 16, 2020
Actual Study Start Date  ICMJE March 27, 2019
Estimated Primary Completion Date February 24, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2020)
  • Core Study: Change from Baseline in the CDR-SB at 18 Months [ Time Frame: Baseline, 18 months ]
  • Extension Phase: Number of Participants With Adverse Events (AEs), Clinically Significant Change From Baseline in Vital Signs Values, Abnormal MRI and ECG Values, Clinically Significant Findings in Laboratory Values, Positive ADAs, and any Suicidality [ Time Frame: Month 18 up to Month 45 ]
    Here MRI means magnetic resonance imaging, ECG means electrocardiogram, and ADAs means antidrug antibodies.
  • Extension Phase: Change from Core Study Baseline in CDR-SB [ Time Frame: Baseline up to Month 45 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
  • Core Study: Change from Baseline in the CDR-SB at 18 Months [ Time Frame: Baseline, 18 months ]
  • Extension Phase: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to Month 45 ]
  • Extension Phase: Change from Core Study Baseline in CDR-SB [ Time Frame: Baseline up to Month 45 ]
  • Extension Phase: Change from Core Study Baseline in Cerebrospinal fluid (CSF) biomarkers (neurogranin, NFL, Aβ[1-42], t-tau, and p-tau) [ Time Frame: Baseline up to Month 45 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2019)
  • Core Study: Change from Baseline in the Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) Composite at 18 Months [ Time Frame: Baseline, 18 months ]
  • Core Study: Change from Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 18 Months [ Time Frame: Baseline, 18 months ]
  • Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale 14 (ADAS-cog14) at 18 Months [ Time Frame: Baseline, 18 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
  • Core Study: Change From Baseline in the Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) Composite [ Time Frame: Baseline, 18 months ]
  • Core Study: Change from Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 18 Months [ Time Frame: Baseline, 18 months ]
  • Core Study: Change from Baseline in Alzheimer Disease Assessment Scale - Cognitive Subscale 14 (ADAS-cog14) at 18 Months [ Time Frame: Baseline, 18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Confirm Safety and Efficacy of BAN2401 in Participants With Early Alzheimer's Disease
Official Title  ICMJE A Placebo-Controlled, Double-Blind, Parallel-Group, 18-Month Study With an Open-Label Extension Phase to Confirm Safety and Efficacy of BAN2401 in Subjects With Early Alzheimer's Disease
Brief Summary This study will be conducted to evaluate the efficacy of BAN2401 in participants with early Alzheimer's disease (EAD) by determining the superiority of BAN2401 compared with placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment in the Core Study. This study will also evaluate the long-term safety and tolerability of BAN2401 in participants with EAD in the Extension Phase and whether the long-term effects of BAN2401 as measured by the CDR-SB at the end of the Core Study is maintained over time in the Extension Phase.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Early Alzheimer's Disease
Intervention  ICMJE
  • Drug: BAN2401
    10 mg/kg biweekly (once every 2 weeks) administered as i.v. infusion.
  • Drug: Placebo
    Biweekly (once every 2 weeks) administered i.v. infusion.
Study Arms  ICMJE
  • Experimental: Core Study: BAN2401 10 mg/kg biweekly
    Intervention: Drug: BAN2401
  • Placebo Comparator: Core Study: Placebo
    Intervention: Drug: Placebo
  • Experimental: Extension Phase: BAN2401 10 mg/kg biweekly
    Intervention: Drug: BAN2401
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 22, 2019)
1566
Original Estimated Enrollment  ICMJE
 (submitted: March 21, 2019)
1556
Estimated Study Completion Date  ICMJE July 3, 2024
Estimated Primary Completion Date February 24, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Core Study: Inclusion Criteria

Diagnosis: Mild Cognitive Impairment (MCI) due to Alzheimer's disease - intermediate likelihood:

  • Meet the National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria for MCI due to Alzheimer's disease - intermediate likelihood
  • Have a global Clinical Dementia Rating (CDR) score of 0.5 and CDR Memory Box score of 0.5 or greater at Screening and Baseline
  • Report a history of subjective memory decline with gradual onset and slow progression over the last 1 year before Screening; must be corroborated by an informant

Mild Alzheimer's disease dementia:

  • Meet the NIA-AA core clinical criteria for probable Alzheimer's disease dementia
  • Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of 0.5 or greater at Screening and Baseline

Key Inclusion Criteria that must be met by all participants:

  • Objective impairment in episodic memory as indicated by at least 1 standard deviation below age-adjusted mean in the Wechsler Memory Scale IV-Logical Memory (subscale) II (WMS-IV LMII)
  • Positive biomarker for brain amyloid pathology
  • Male or female participants aged greater than or equal to (>=) 50 and less than or equal to (<=) 90 years, at the time of informed consent
  • Mini mental state examination (MMSE) score >=22 at Screening and Baseline and <=30 at Screening and Baseline
  • Body mass index (BMI) greater than (>)17 and less than (<) 35 at Screening
  • If receiving an approved Alzheimer's disease treatment such as acetylcholinesterase inhibitor (AChEIs) or memantine or both for Alzheimer's disease, must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naive participants for Alzheimer's disease can be entered into the study. Unless otherwise stated, participants must have been on stable doses of all other (that is, non-Alzheimer's disease-related) permitted concomitant medications for at least 4 weeks prior to Baseline. Use of memantine will not be allowed for Japanese participants
  • Have an identified study partner (defined as a person able to support the participant for the duration of the study and who spends at least 8 hours per week with the participant)
  • Provide written informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled

Extension Phase: Inclusion Criteria:

  • Participants who have completed the Core Study
  • Have a BMI >17 and <35
  • Must continue to have a study partner who is willing and able to provide follow-up information on the participant throughout the course of the Extension Phase
  • Provide written informed consent for the Extension Phase. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required and in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Germany and Spain), they will not be enrolled

Exclusion Criteria

  • Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's Alzheimer's disease
  • History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of Screening
  • Any psychiatric diagnosis or symptoms (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant
  • Geriatric Depression Scale (GDS) score >=8 at Screening
  • Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example in skull and cardiac devices other than those approved as safe for use in MRI scanners)
  • Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than Alzheimer's disease
  • Other significant pathological findings on brain MRI at screening, including but not limited to: more than 4 microhemorrhages (defined as 10 millimeter [mm] or less at the greatest diameter); a single macrohemorrhage >10 mm at greatest diameter; an area of superficial siderosis; evidence of vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors (however, lesions diagnosed as meningiomas or arachnoid cysts and <1 centimeter [cm] at their greatest diameter need not be exclusionary)
  • Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
  • Participants with a bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5 for participants who are not on anticoagulant treatment, example, warfarin). Participants who are on anticoagulant therapy should have their anticoagulant status optimized and be on a stable dose for 4 weeks before Screening
  • Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
  • Participation in a clinical study involving any therapeutic monoclonal antibody, protein derived from a monoclonal antibody, immunoglobulin therapy, or vaccine within 6 months before screening unless it can be documented that the participant was randomized to placebo
  • Participation in a clinical study involving any anti-amyloid therapies (including any monoclonal antibody therapies and any β-site amyloid precursor protein cleaving enzyme [BACE] inhibitor therapies) unless it can be documented that the participant only received placebo
  • Participants who have any known prior exposure to BAN2401
  • Participants who were dosed in a clinical study involving any new chemical entities for Alzheimer's disease (AD) within 6 months prior to screening unless it can be documented that the participant was in a placebo treatment arm

Extension Phase: Exclusion Criteria

  • Participants who discontinued early from the Core Study
  • Participants who develop the following conditions from the time of Screening for the Core Study to the start of the Extension Phase

    • TIA, stroke, or seizures
    • Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD
    • Any psychiatric diagnosis or symptoms, (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant
    • Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in skull and cardiac devices other than those approved as safe for use in MRI scanners)
    • Other significant pathological findings on brain MRI during the Core Study including but not limited to: cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors (however, lesions diagnosed as meningiomas or arachnoid cysts and <1 cm at their greatest diameter need not be exclusionary
    • Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
    • Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eisai Medical Information 1-888-274-2378 esi_medinfo@eisai.com
Listed Location Countries  ICMJE Australia,   Canada,   China,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Russian Federation,   Singapore,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03887455
Other Study ID Numbers  ICMJE BAN2401-G000-301
2018-004739-58 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
Responsible Party Eisai Inc.
Study Sponsor  ICMJE Eisai Inc.
Collaborators  ICMJE Biogen
Investigators  ICMJE Not Provided
PRS Account Eisai Inc.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP