A Study of Semorinemab in Patients With Moderate Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Semorinemab; Placebo; [18F]GTP1
Intervention description: Participants will receive semorinemab every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. Semorinemab will be administered Q4W in the OLE period.; Participants will receive placebo every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period.; [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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 272.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group
      study will evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of
      semorinemab in patients with moderate AD. The study consists of a screening period, a
      double-blind treatment period, an optional open-label extension (OLE) period, and a safety
      follow-up period. There may be up to two study cohorts.
    

Eligibility criteria:

        Inclusion Criteria:

          -  National Institute on Aging/Alzheimer's Association core clinical criteria for
             probable AD dementia

          -  Evidence of the AD pathological process, by a positive amyloid assessment either on
             CSF Aβ1-42 as measured on Elecsys β-Amyloid(1-42) Test System OR amyloid PET scan

          -  AD dementia of moderate severity, as defined by a screening MMSE score of 16-21
             points, inclusive, and a CDR-GS of 1 or 2

          -  Availability of a person with sufficient contact with the participant to be able to
             provide accurate information on the participant's cognitive, behavioral and functional
             ability

        Exclusion Criteria:

          -  Pregnant or breastfeeding

          -  Inability to tolerate MRI procedures or contraindication to MRI

          -  Contraindication to PET imaging

          -  Residence in a skilled nursing facility

          -  Any serious medical condition or abnormality in clinical laboratory tests that, 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 within the past 2 years

          -  Use of any experimental therapy within 90 days or 5 half-lives prior to screening,
             whichever is greater, or any passive immunotherapy against tau

          -  Use of any passive immunotherapy (immunoglobulin) against Aβ, unless the last dose was
             at least 1 year prior to screening or any active immunotherapy (vaccine) that is under
             evaluation to prevent or postpone cognitive decline

          -  Any other biologic therapy or previous treatment with medications specifically
             intended to treat Parkinsonian symptoms or any other non-AD 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): 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