A Study to Evaluate the Efficacy and Safety of Semorinemab in Patients With Prodromal to Mild Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Semorinemab; Placebo; [18F]GTP1
Intervention description: Participants will receive Semorinemab intravenously (IV).; Matching placebo doses of Semorinemab given intravenously (IV).; [18F]GTP1 will be administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: Additional blinded personnel will include study site personnel who will evaluate participant status, contract research organization (CRO) personnel who will review case report forms (CRFs), and other sponsor agents (with the exception of the interactive voice or web-based response system [IxRS] vendor).
Enrollment: 457.0
Sex: All
Minimum age: 50 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Alzheimer Disease; Brain Diseases; Dementia; Neurodegenerative Diseases; Neurocognitive Disorders

Summary:

      This was a phase II, randomized, placebo-controlled, double-blind study to evaluate the
      efficacy and safety of Semorinemab in participants with prodromal to mild Alzheimer's
      disease. An optional 96-week open-label extension period was available to participants who
      completed the double-blind treatment period and who, in the judgment of the investigator,
      would potentially benefit from open-label Semorinemab treatment.
    

Eligibility criteria:

        Inclusion criteria

          -  Age between 50 and 80 years

          -  National Institute on Aging/Alzheimer's Association core clinical criteria for
             probable Alzheimer's disease (AD) dementia or mild cognitive impairment (prodromal AD)

          -  Evidence of the AD pathological process, by a positive amyloid assessment either on
             cerebrospinal fluid Aβ1-42 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 participant to be able to
             provide accurate information on the participant's cognitive and functional ability

        Exclusion criteria

          -  Pregnant or breastfeeding

          -  Inability to tolerate magnetic resonance imaging (MRI) procedures or contraindication
             to MRI

          -  Contraindications to both PET imaging and lumbar dural puncture (must be able to
             undergo at least one of these procedures to be eligible)

          -  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

          -  Alcohol or substance abuse 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 Aβ, 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

          -  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: atypical antipsychotics, opiates or opioids,
             benzodiazepines, barbiturates, hypnotics, or any medication with clinically
             significant 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