xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05986721</url>
    </required_header>
    <id_info>
      <org_study_id>AGB101 MCD P3</org_study_id>
      <nct_id>NCT05986721</nct_id>
    </id_info>
    <brief_title>Study of AGB101 in Mild Cognitive Impairment Due to Alzheimer's Disease</brief_title>
    <official_title>A Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of AGB101 (Low-dose Levetiracetam, 220 mg, Extended Release Tablet) on Slowing Progression of Mild Cognitive Impairment Due to Alzheimer's Disease.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>AgeneBio</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>AgeneBio</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The primary objective of the study is to evaluate the efficacy of AGB101 on slowing cognitive&#xD;
        and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes&#xD;
        (CDR-SB) score as compared with placebo in participants with mild cognitive impairment due to&#xD;
        Alzheimer's Disease (MCI due to AD) also known as prodromal AD. Participants will be&#xD;
        randomized to receive placebo or AGB101 (220 mg), once daily for 78 weeks. Secondary&#xD;
        objectives are to assess the effect of AGB101 compared with placebo on clinical progression&#xD;
        as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-cog14),&#xD;
        Mini-Mental State Examination (MMSE) and Functional Activities Questionnaire (FAQ).&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 2024</start_date>
    <completion_date type="Anticipated">December 2028</completion_date>
    <primary_completion_date type="Anticipated">July 2028</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>CDR-SB</measure>
      <time_frame>78 weeks</time_frame>
      <description>Change in CDR-SB score from baseline</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>ADAS-cog14</measure>
      <time_frame>78 weeks</time_frame>
      <description>Change in ADAS-cog14 score from baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>FAQ</measure>
      <time_frame>78 weeks</time_frame>
      <description>Change in FAQ score from baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>MMSE</measure>
      <time_frame>78 weeks</time_frame>
      <description>Change in MMSE score from baseline</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">1040</enrollment>
    <condition>Mild Cognitive Impairment</condition>
    <condition>Prodromal Alzheimer's Disease</condition>
    <arm_group>
      <arm_group_label>Placebo Oral Tablet</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Matching placebo to AGB101 tablet once daily, taken orally, for 78 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>AGB101 220 mg tablet</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>AGB101</intervention_name>
      <description>low-dose levetiracetam, 220 mg, extended release tablet</description>
      <arm_group_label>AGB101 220 mg tablet</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo oral tablet</description>
      <arm_group_label>Placebo Oral Tablet</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Subjects between 55 and 85 years old (inclusive) in good general health:&#xD;
  &#xD;
                 -  Willing and able to consent and participate for the duration of the study.&#xD;
  &#xD;
                 -  Have eighth-grade education or good work history sufficient to exclude mental&#xD;
                    retardation.&#xD;
  &#xD;
                 -  Have visual and auditory acuity adequate for neuropsychological testing.&#xD;
  &#xD;
                 -  Have proficient fluency of the native local language to participate in all the&#xD;
                    neuropsychological test assessments.&#xD;
  &#xD;
            2. Have a study partner who has sufficient contact with the subject to be able to provide&#xD;
               assessment of memory changes, who can accompany the subject to the screening and all&#xD;
               major clinic visits for the duration of those visits, and who is able to provide an&#xD;
               independent evaluation of the subject's functioning.&#xD;
  &#xD;
            3. Have MCI due to AD as defined by all of the following criteria and consistent with the&#xD;
               National Institute on Aging-Alzheimer's Association criteria:&#xD;
  &#xD;
                 -  MMSE scores between 24 and 30 (inclusive; exceptions may be made for subjects&#xD;
                    with &lt; 8 years of education at the discretion of the sponsor).&#xD;
  &#xD;
                 -  A memory complaint reported by the subject or his/her study partner.&#xD;
  &#xD;
                 -  Evidence of lower memory performance based on the delayed recall portion of the&#xD;
                    ISLT.&#xD;
  &#xD;
                 -  A Clinical Dementia Rating (CDR) score of 0.5 with a memory box score of ≥ 0.5.&#xD;
  &#xD;
                 -  Essentially preserved activities of daily living.&#xD;
  &#xD;
                 -  Cognitive decline not primarily caused by vascular, traumatic, or medical&#xD;
                    problems (alternative causes of cognitive decline are ruled out).&#xD;
  &#xD;
                 -  A screening blood-based biomarker consistent with amyloid positivity&#xD;
  &#xD;
                 -  Have an apolipoprotein E genotype that does not include one or more E4 alleles&#xD;
  &#xD;
            4. Permitted medications:&#xD;
  &#xD;
                 -  With potential pro-cognitive effects, such cholinesterase inhibitors and&#xD;
                    memantine, must be at a stable dose for ≥ 3 months prior to screening and&#xD;
                    expected to remain stable throughout the study; estrogen replacement therapy,&#xD;
                    Ginkgo biloba, and vitamin E must be at a stable dose for ≥ 4 weeks prior to&#xD;
                    screening and expected to remain stable throughout the study.&#xD;
  &#xD;
                 -  Other psychotropics, such as antidepressants and antipsychotics, must be at a&#xD;
                    stable dose for ≥ 3 months prior to screening and expected to remain stable&#xD;
                    throughout the study.&#xD;
  &#xD;
            5. Willing and able to undergo an MRI scan (3 Tesla) with no contraindications to the MRI&#xD;
               or documented evidence of an MRI scan.&#xD;
  &#xD;
            6. Willing to allow collection of blood for blood-based biomarkers and genome-wide&#xD;
               association study (GWAS), apolipoprotein E (ApoE) genotyping, and DNA banking.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Carrying one or more copies of the apolipoprotein E4 (ApoE4) allele.&#xD;
  &#xD;
            2. Use of anticonvulsant medications or excluded psychotropic medications within 3 months&#xD;
               prior to the baseline visit.&#xD;
  &#xD;
            3. Participation in a therapeutic clinical study for any medical or psychiatric&#xD;
               indications within 3 months (6 months for biologics) of the screening visit, or at any&#xD;
               time during the study. Subjects must understand that they may only enroll in this&#xD;
               clinical study once; they may not enroll in any other clinical study while&#xD;
               participating in the current study, and they may not participate in a clinical study&#xD;
               of a drug, biologic, therapeutic device, or medical food, in which the last&#xD;
               dose/administration was received within 3 months (6 months for biologics) prior to&#xD;
               screening.&#xD;
  &#xD;
            4. History of hypersensitivity or lack of tolerability to AGB101 (levetiracetam).&#xD;
  &#xD;
            5. Severe renal impairment (creatinine clearance of &lt; 30 mL/minute) or undergoing&#xD;
               hemodialysis.&#xD;
  &#xD;
            6. Any significant neurological disease other than suspected incipient AD, such as&#xD;
               Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure&#xD;
               hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder (lifetime&#xD;
               history; infant febrile seizures are not exclusionary), subdural hematoma, multiple&#xD;
               sclerosis, or history of significant head trauma followed by persistent neurologic&#xD;
               deficits, or known structural brain abnormalities.&#xD;
  &#xD;
            7. If no documented MRI scan, presence of pacemakers, aneurysm clips, artificial heart&#xD;
               valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body&#xD;
               that constitute a contraindication to having an MRI scan.&#xD;
  &#xD;
            8. Diagnosis of bipolar disorder, or major depression within the past 3 years, as&#xD;
               described in the Diagnostic and Statistical Manual of Mental Disorders, 5th Ed&#xD;
               (DSM-5). Psychotic features, agitation, or behavioral problems within the last 3&#xD;
               months that could lead to difficulty complying with the protocol. Subjects must not&#xD;
               have a major depressive disorder or other types of depression that could confound&#xD;
               diagnosis of MCI due to AD, or clinical assessments, in the opinion of the&#xD;
               investigator. The Geriatric Depression Scale (long form score &gt; 9 suggests depression)&#xD;
               results should be reviewed by the investigator to assist in this determination.&#xD;
  &#xD;
            9. Modified Hachinski Ischemic Scale (HIS) score &gt; 4.&#xD;
  &#xD;
           10. History of schizophrenia (DSM-5 criteria).&#xD;
  &#xD;
           11. History of alcohol or substance abuse or dependence within the past 3 years (DSM-5&#xD;
               criteria).&#xD;
  &#xD;
           12. Any significant systemic illness or unstable medical condition that could lead to&#xD;
               difficulty in complying with the protocol requirements. Patients with a history of&#xD;
               cancer with a high risk of recurrence and preventing completion of the trial.&#xD;
  &#xD;
           13. Any unstable medical condition that is likely to require new medical or surgical&#xD;
               treatment during the course of the study and where such treatments might affect the&#xD;
               collection of efficacy data.&#xD;
  &#xD;
           14. Clinically significant abnormalities in B12 or thyroid function test that might&#xD;
               interfere with the study. A low B12 (below normative range for elderly) is&#xD;
               exclusionary, unless follow-up labs (homocysteine and methylmalonic acid) indicate&#xD;
               that it is not physiologically significant. If the B12 deficiency is treated, subjects&#xD;
               may become eligible to participate in the study.&#xD;
  &#xD;
           15. Residence in a skilled nursing facility. Individuals in independent living&#xD;
               communities, assisted living facilities, residential care facilities, or continuing&#xD;
               care communities are eligible provided they engage in a sufficient spectrum of&#xD;
               activity to permit assessment of all 6 domains contributing to the Clinical Dementia&#xD;
               Rating-Sum of Boxes (CDR-SB). Individuals in these facilities must also have a study&#xD;
               partner who has the ability to observe the subject during the study and can&#xD;
               participate in clinical evaluations.&#xD;
  &#xD;
           16. Any use of excluded medications (eg, antiepileptics, certain antidepressants or&#xD;
               antipsychotics, antihistamines with anticholinergic properties, opiates).&#xD;
  &#xD;
           17. Participation in clinical studies using the ISLT, BPS-O task, or the trail making test&#xD;
               (A, B) within 1 month of screening.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>55 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 3, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Alzheimer Disease</mesh_term>
      <mesh_term>Cognitive Dysfunction</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05986721
  org study id: AGB101 MCD P3
  nct id: NCT05986721
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The primary objective of the study is to evaluate the efficacy of AGB101 on slowing cognitive
        and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes
        (CDR-SB) score as compared with placebo in participants with mild cognitive impairment due to
        Alzheimer's Disease (MCI due to AD) also known as prodromal AD. Participants will be
        randomized to receive placebo or AGB101 (220 mg), once daily for 78 weeks. Secondary
        objectives are to assess the effect of AGB101 compared with placebo on clinical progression
        as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-cog14),
        Mini-Mental State Examination (MMSE) and Functional Activities Questionnaire (FAQ).
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: CDR-SB
  time frame: 78 weeks
  description: Change in CDR-SB score from baseline
  measure: ADAS-cog14
  time frame: 78 weeks
  description: Change in ADAS-cog14 score from baseline
  measure: FAQ
  time frame: 78 weeks
  description: Change in FAQ score from baseline
  measure: MMSE
  time frame: 78 weeks
  description: Change in MMSE score from baseline
  arm group label: Placebo Oral Tablet
  arm group type: Placebo Comparator
  description: Matching placebo to AGB101 tablet once daily, taken orally, for 78 weeks
  arm group label: AGB101 220 mg tablet
  arm group type: Experimental
  description: Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks.
  intervention type: Drug
  intervention name: AGB101
  description: low-dose levetiracetam, 220 mg, extended release tablet
  arm group label: AGB101 220 mg tablet
  intervention type: Drug
  intervention name: Placebo
  description: Placebo oral tablet
  arm group label: Placebo Oral Tablet
  criteria: 
  gender: All
  minimum age: 55 Years
  maximum age: 85 Years
  healthy volunteers: No
  responsible party type: Sponsor
  mesh term: Alzheimer Disease
  mesh term: Cognitive Dysfunction
  sharing ipd: No