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- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT07578558
NAI for Sepsis With Persistent Lymphopenia
Phase 2, Randomized, Open-Label Clinical Trial Evaluating Nogapendekin Alfa Inbakicept in Combination With Standard of Care Versus Standard of Care Alone in Critically Ill Adults With Sepsis and Persistent Lymphopenia
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Sepsis is characterized by a biphasic immune response: an initial hyperinflammatory phase followed by a prolonged immunosuppressive phase with persistent lymphopenia. The majority of sepsis deaths (>70%) occur during the immunosuppressive phase rather than the initial hyperinflammatory phase. This acquired immunosuppression correlates with markedly increased 28-day mortality rates exceeding 40% and significantly elevated risk of secondary infections.
This study evaluates NAI, an IL-15 receptor agonist that promotes proliferation and activation of NK cells and CD8+ T cells, as a potential therapy to restore immune function in critically ill adults with sepsis and persistent lymphopenia (ALC <1,000 cells/µL on two consecutive measurements within 72 hours of sepsis diagnosis).
Study Arms:
- Experimental Arm: NAI 1.2 mg subcutaneous injection administered on Days 3 (or earlier than Day 3 if ALC is <700 cells/µL), Day 14, and Day 21 if needed for ALC <1,000 cells/µL, plus institutional standard of care for sepsis
- Control Arm: Institutional standard of care for sepsis alone Standard of care may include antimicrobial therapy, fluid resuscitation, vasopressor support, organ support, and mechanical ventilation as clinically indicated. Treatment will be discontinued if a participant has unacceptable toxicity, withdraws consent, or if the Investigator feels it is no longer in the participant's best interest to continue.
All participants will be followed for 90 days post the first dose of study treatment to capture late adverse events, rehospitalization, or mortality.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
- Nome: Tamra Madenwald
- E-mail: Tamra.Madenwald@immunitybio.com
Estude backup de contato
- Nome: Alex Golway
- Número de telefone: 516-225-0068
- E-mail: Alex.Golway@ImmunityBio.com
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion Criteria:
- Age 18 years or older at the time of informed consent
- Admitted to the ICU with a diagnosis of sepsis as defined by Sepsis-3 criteria: life-threatening organ dysfunction caused by a dysregulated host response to infection, operationalized as a Sequential Organ Failure Assessment (SOFA) score increase of 2 or more points
- Documented persistent lymphopenia defined as ALC <1,000 cells/µL on at least two consecutive measurements within 72 hours of sepsis diagnosis (measurements must be separated by at least 12 hours)
- Prior initiation of appropriate antimicrobial therapy per institutional guidelines
- Ability to obtain written informed consent from the participant or legally authorized representative
- Agreement to practice effective contraception for female participants of child-bearing potential and non-sterile males (for up to 7 months after completion of therapy)
Exclusion Criteria:
- Hematologic malignancies including leukemia, lymphoma, and myelodysplastic syndromes
- Prior CAR-T cell therapy or hematopoietic stem cell transplant (HSCT) within 3 months of screening
- Active cytokine release syndrome (CRS) at screening
- Current or recent (within 7 days) use of colony stimulating factors (G-CSF, GM-CSF)
- Lymphopenia attributable to chemotherapy, radiation therapy, or immunosuppressive medications administered within 30 days prior to screening
- High-dose immunosuppressive therapy (>0.5 mg/kg prednisone equivalent daily), excluding physiologic replacement and stress-dose hydrocortisone for septic shock
- Life expectancy less than 24 hours as assessed by the treating physician
- Active uncontrolled bleeding requiring >2 units of packed red blood cells in the preceding 24 hours
- Known HIV infection with CD4 count <350 cells/µL and detectable viral load
- Known active viral hepatitis (hepatitis B or C with detectable viral load)
- Advanced dementia or other conditions precluding meaningful participation
- Known hypersensitivity to any component of the investigational products
- Participation in another interventional trial with an investigational immunomodulatory agent within 30 days prior to screening
- Pregnant or breastfeeding
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: NAI + Standard of Care
NAI 1.2 mg subcutaneous injection administered on Days 3 (or earlier if ALC <700 cells/µL), Day 14, and Day 21 if needed for ALC <1,000 cells/µL, plus institutional standard of care for sepsis
|
IL-15 receptor agonist complex; 1.2 mg subcutaneous injection administered on Days 3 (or earlier if ALC <700 cells/µL), Day 14, and Day 21 if needed for ALC <1,000 cells/µL
Outros nomes:
Institutional standard of care for sepsis including antimicrobial therapy, fluid resuscitation, vasopressor support, organ support, and mechanical ventilation as clinically indicated
|
|
Comparador Ativo: Standard of Care Alone
Institutional standard of care for sepsis including antimicrobial therapy, fluid resuscitation, vasopressor support, and mechanical ventilation as clinically indicated
|
Institutional standard of care for sepsis including antimicrobial therapy, fluid resuscitation, vasopressor support, organ support, and mechanical ventilation as clinically indicated
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
28-day all-cause mortality rate
Prazo: 28 days
|
Proportion of participants who die from any cause within 28 days of randomization
|
28 days
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Change in absolute lymphocyte count (ALC)
Prazo: Baseline through Day 28
|
Change in ALC from baseline (Day 1 pre-dose) through Day 28
|
Baseline through Day 28
|
|
ICU re-admission rate
Prazo: Up to Day 90
|
Proportion of participants re-admitted to ICU after discharge by Day 90
|
Up to Day 90
|
|
Secondary infections
Prazo: Up to Day 90
|
Proportion of participants with secondary infections after discharge by Day 90
|
Up to Day 90
|
|
90-day all-cause mortality rate
Prazo: 90 days
|
Proportion of participants who die from any cause within 90 days of randomization
|
90 days
|
|
Safety and tolerability
Prazo: Through Day 30 after last dose
|
Incidence and severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and Grade ≥3 TEAEs graded per NCI CTCAE v6.0
|
Through Day 30 after last dose
|
Colaboradores e Investigadores
Patrocinador
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
- Citopenia
- Processos Patológicos
- Atributos da doença
- Doenças do sistema imunológico
- Infecções
- Síndrome da Resposta Inflamatória Sistêmica
- Inflamação
- Distúrbios leucocitários
- Doenças Hematológicas
- Síndromes de Deficiência Imunológica
- Leucopenia
- Choque
- Condições Patológicas, Sinais e Sintomas
- Doenças hemic e linfáticas
- Doença grave
- Sepse
- Linfopenia
- Choque, Séptico
- Administração de Serviços de Saúde
- Qualidade, acesso e avaliação da assistência médica
- Qualidade de assistência médica
- Indicadores de qualidade, assistência médica
- Padrão de atendimento
- Alt-803
Outros números de identificação do estudo
- ResQ2204-SEPSIS
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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