Phase 2 Study of AV-1959R in Individuals With Preclinical Alzheimer's Disease
A Phase II, Randomized, Double-Blind Study to Evaluate Safety, Tolerability, Immunogenicity, and Amyloid-Lowering Effect of Amyloid-β Vaccine, AV-1959R, in Individuals With Preclinical Alzheimer's Disease.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
- Nome: Roman Kniazev
- Número de telefone: 7145963981
- E-mail: rkniazev@immed.org
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
Male or female participants 55 to 80 years of age, inclusive, at screening. Signed informed consent before initiation of study-related procedures.
Cognitively unimpaired participants with preclinical Alzheimer's disease meeting all of the following:
CDR global score = 0 at screening. MMSE score ≥26 at screening, with education adjustment. Plasma p-tau217/Aβ1-42 ratio ≥0.00738. Vision and hearing sufficient to comply with study procedures, in the investigator's judgment.
Stable concomitant medications for management of existing medical conditions, as appropriate.
Women must be of non-childbearing potential as defined in the protocol. Men must meet protocol-defined contraception and sperm donation requirements. Ability, in the investigator's opinion, to understand the study and comply with study requirements.
Exclusion Criteria:
Screening MRI showing clinically significant abnormalities, including protocol-defined infarcts, excessive microbleeds, leptomeningeal hemosiderosis, superficial siderosis, or ARIA-E.
Contraindication to MRI. Serious illness requiring systemic treatment and/or hospitalization within 4 weeks before study entry.
Clinically relevant cardiovascular, respiratory, gastrointestinal, endocrine, immunologic, hematologic, neurologic, or other systemic disease that could interfere with participation or follow-up.
Insulin-dependent diabetes. Clinically significant ECG abnormalities, including protocol-defined conduction abnormalities or QTc abnormalities.
Pre-existing autoimmune disease. History of seizure disorder, except protocol-permitted use of certain antiepileptic medications for chronic pain.
Any medical, psychological, or social condition that may interfere with participation, compliance, or safety.
Participation in another investigational drug study or use of an investigational drug within 30 days or 5 half-lives, whichever is longer, before dosing.
Prior amyloid-beta or tau immunotherapy, including vaccine or monoclonal antibody, within 1 year before screening.
Recent use of protocol-defined immunomodulatory or growth-stimulating agents. Chronic use of protocol-defined anticoagulants or antiplatelet agents; aspirin is permitted.
Parenteral use of immunoglobulin preparations, blood products, or plasma derivatives.
History of severe local or systemic vaccine reactions or significant allergic reactions.
Clinically significant laboratory abnormalities at screening. Positive testing for HIV-1/2, hepatitis B surface antigen, or hepatitis C virus.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: AV-1959R
Participants will receive AV-1959R 100 micrograms with adjuvant by intramuscular injection at Weeks 0, 4, and 44.
|
Investigational amyloid-beta vaccine, AV-1959R, 100 micrograms, administered intramuscularly with adjuvant at Weeks 0, 4, and 44.
|
|
Comparador de Placebo: Placebo
Participants will receive placebo with adjuvant by intramuscular injection at Weeks 0, 4, and 44.
|
Placebo administered by intramuscular injection with adjuvant at Weeks 0, 4, and 44.
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Prazo: From first study intervention through Week 78
|
Number and percentage of participants with treatment-emergent adverse events.
|
From first study intervention through Week 78
|
|
Incidence of ARIA-E and ARIA-H
Prazo: Through Week 78
|
Number and percentage of participants with MRI-detected amyloid-related imaging abnormalities, including ARIA-E and ARIA-H.
|
Through Week 78
|
|
Clinically Significant Changes in Safety Assessments
Prazo: Through Week 78
|
Number and percentage of participants with clinically significant changes in vital signs, ECG, laboratory assessments, physical examinations, or neurological examinations.
|
Through Week 78
|
|
Change From Baseline in C-SSRS Score
Prazo: Baseline through Week 78
|
Change from baseline in Columbia-Suicide Severity Rating Scale score comparing AV-1959R and placebo groups.
|
Baseline through Week 78
|
|
Serum Anti-Amyloid-Beta Antibody Levels
Prazo: Baseline through Week 78
|
Serum anti-amyloid-beta antibody levels following vaccination, comparing AV-1959R and placebo groups.
|
Baseline through Week 78
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
T-cell responses to MultiTEP and amyloid-beta
Prazo: Baseline through Week 78
|
Assessment of MultiTEP-specific T-cell responses and autoreactive anti-amyloid-beta T-cell responses, comparing AV-1959R and placebo groups.
|
Baseline through Week 78
|
|
Change From Baseline in Global Brain Amyloid Burden
Prazo: Baseline to Week 78
|
Change from baseline in global brain amyloid burden measured by amyloid PET using the Centiloid scale, comparing the AV-1959R and placebo groups.
|
Baseline to Week 78
|
|
Change From Baseline in Plasma p-tau217/Aβ1-42 Ratio
Prazo: Baseline through Week 78
|
Change from baseline in plasma Lumipulse p-tau217/Aβ1-42 ratio, comparing the AV-1959R and placebo groups.
|
Baseline through Week 78
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Change From Baseline in CDR-SB Score
Prazo: Baseline to Week 78
|
Change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, comparing the AV-1959R and placebo groups.
|
Baseline to Week 78
|
|
Change From Baseline in Plasma Amyloid Biomarkers
Prazo: Baseline through Week 78
|
Change from baseline in plasma Aβ42, Aβ40, and Aβ42/Aβ40 ratio, comparing the AV-1959R and placebo groups.
|
Baseline through Week 78
|
|
Change From Baseline in Plasma Tau Biomarkers
Prazo: Baseline through Week 78
|
Change from baseline in plasma BD-tau, MTBR-tau243, total tau, p-tau181, p-tau231, and p-tau217.
|
Baseline through Week 78
|
|
Change From Baseline in Plasma Neurofilament Light Chain
Prazo: Baseline through Week 78
|
Change from baseline in plasma neurofilament light chain (NfL).
|
Baseline through Week 78
|
|
Change From Baseline in Plasma GFAP
Prazo: Baseline through Week 78
|
Change from baseline in plasma glial fibrillary acidic protein (GFAP).
|
Baseline through Week 78
|
|
Change From Baseline in Brain Tau Burden
Prazo: Baseline to Week 78
|
Change from baseline in pathological tau accumulation measured by quantitative tau PET imaging, comparing the AV-1959R and placebo groups.
|
Baseline to Week 78
|
|
Changes in T-Cell and B-Cell Receptor Repertoires and Lineages
Prazo: Baseline through Week 78
|
Exploratory analysis of changes in T-cell receptor and B-cell receptor repertoires and T-cell and B-cell lineages in response to vaccination.
|
Baseline through Week 78
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Michael Agadjanyan, Institute for Molecular Medicine
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças Cerebrais
- Doenças do Sistema Nervoso Central
- Doenças do Sistema Nervoso
- Transtornos Mentais, Desordem Mental
- Condições Patológicas, Anatômicas
- Distúrbios Neurocognitivos
- Demência
- Tauopatias
- Doenças Neurodegenerativas
- Condições Patológicas, Sinais e Sintomas
- Doença de Alzheimer
- Placa, Amilóide
Outros números de identificação do estudo
- US-AV1959R-201
Plano para dados de participantes individuais (IPD)
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Descrição do plano IPD
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