A PHASE II, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, EFFICACY, AND SAFETY STUDY OF MTAU9937A IN PATIENTS WITH PRODROMAL TO MILD ALZHEIMER*S DISEASE

Phase 2

Completed

• Conditions: Alzheimer's disease; Appearance of initial symptoms to a mild form of dementia; 10012272

• Registration Number: NL-OMON48730
• Lead Sponsor: Genentech

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 20

Inclusion Criteria

- Age between 50 and 80 years
- National Institute on Aging/Alzheimer*s Association core clinical criteria
for probable AD dementia or mild cognitive impairment (prodromal AD)
- Evidence of the AD pathological process, by a positive amyloid assessment
either on cerebrospinal fluid A*1*42 OR amyloid positron emission tomography
(PET) scan. Historical amyloid PET scans may be accepted in some cases
- Mild AD symptomatology, as defined by a screening Mini-Mental State
Examination score of ><= 20 points and Clinical Dementia Rating (CDR) *Global
Score of 0.5 or 1
- Abnormal memory function at screening
- Availability of a person with sufficient contact with the patient to be able
to provide accurate information on the patient*s cognitive and functional
ability

Exclusion Criteria

- Pregnant or breastfeeding
- Inability to tolerate magnetic resonance imaging (MRI) procedures or
contraindication to MRI
- Able to undergo either PET imaging or lumbar dural puncture, or both, and
patients with contraindications to both procedures are ineligible
- Residence in a skilled nursing facility
- Any serious medical condition or abnormality in clinical laboratory tests
that remains abnormal on retest and, in the investigator*s judgment, precludes
the patient*s safe participation in and completion of the study, or bias the
assessment of the clinical or mental status of the participant to a significant
degree
- Any evidence of a condition other than AD that may affect cognition
- Substance abuse meeting criteria for alcohol, cannabis, phencyclidine, other
hallucinogen, inhalant, opioid, sedative, hypnotic, anxiolytic, or stimulant
use disorder of any severity (per the Diagnostic and Statistical Manual of
Mental Disorders, Version 5) within the past 2 years
- Use of any experimental therapy within 90 days or 5 half-lives prior to
screening, whichever is greater and any passive immunotherapy (immunoglobulin)
against tau, except use of RO7105705 in Genentech Study GN39058, as long as the
last dose was at least 90 days prior to screening
- Use of any passive immunotherapy (immunoglobulin) against A*, unless the last
dose was at least 1 year prior to screening and any active immunotherapy
(vaccine) that is under evaluation to prevent or postpone cognitive decline
- Investigational biologic therapy (e.g., therapeutic proteins, monoclonal
antibodies, or other active or passive immunotherapy) within 1 year of
screening, or any expectation to require additional investigational biologic
therapy for the duration of the trial
- Any previous treatment with medications specifically intended to treat
Parkinsonian symptoms or any other neurodegenerative disorder within 1 year of
screening
- Systemic immunosuppressive therapy within 12 months of screening through the
entire study period
- Typical antipsychotic or neuroleptic medication within 6 months of screening
- Daily treatment with any of the following classes of medication, except for
intermittent short-term use, which is permitted except within 2 days or 5
half-lives (whichever is longer) prior to any COA such as atypical
antipsychotics, Opiates or opioids ,Benzodiazepines, barbiturates, or
hyponotics and any medication with centrally-acting antihistamine or
anticholinergic activity
- Stimulant medications, unless the dose has been stable within the 6 months
prior to screening and is expected to be stable throughout the study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Efficacy endpoint: Change from baseline to Week 73 on the CDR-SB.<br /><br>Safety endpoints: The nature, frequency, severity, and timing of adverse<br /><br>events and serious adverse events. Severity of adverse events will be<br /><br>determined through use of the WHO toxicity grading scale. Changes from baseline<br /><br>in vital signs, physical findings, neurologic findings, ECG, and clinical<br /><br>laboratory results during and following MTAU9937A administration. Changes from<br /><br>baseline in suicidal ideation and<br /><br>behavior during and following MTAU9937A administration as assessed by the<br /><br>C-SSRS. Nature, frequency, severity, and timing of neuroimaging abnormalities.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Efficacy endpoints: Change from baseline to Week 73 on the RBANS Total Score.<br /><br>Change from baseline to Week 73 on the ADAS-Cog 13. Change from baseline to<br /><br>Week 73 on the Amsterdam iADL questionnaire. Change from baseline to Week 73 on<br /><br>the ADCS-ADL.<br /><br>Pharmacokinetic endpoint: Serum concentrations of MTAU9937A at specified<br /><br>timepoints.<br /><br>Immunogenicity endpoint: Presence of anti-drug antibodies during the study<br /><br>relative to the presence of ADAs at baseline.</p><br>