C-CAR168, an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy, in Participants With Systemic Sclerosis (SSc) Refractory to Standard Therapy
A Multi-center, Phase 1b Clinical Study of an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy (C-CAR168) for the Treatment of Systemic Sclerosis (SSc) Refractory to Standard Therapy
This Phase 1b, multicenter, open-label study will evaluate the safety and efficacy of a single infusion of autologous anti-CD20/BCMA chimeric antigen receptor T cells (C-CAR168) following lymphodepleting chemotherapy in participants with refractory Systemic Sclerosis (SSc) who are not responding to standard therapy. Approximately 6-12 participants will undergo leukapheresis, lymphodepletion with fludarabine and cyclophosphamide, and infusion of C-CAR168. Participants will be followed for 24 months (2 years) to evaluate safety, CAR T-cell persistence, pharmacokinetics/pharmacodynamics, biomarkers, and preliminary efficacy results. Long-term safety follow-up for gene therapy-related events will continue for up to 15 years following CAR T-cell infusion.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Kirstin Liechty, Head of Clinical Operations, PhD
- Número de telefone: 267-566-6081
- E-mail: kirstin.liechty@abelzeta.com
Estude backup de contato
- Nome: Yihong Liechty, Head of Clinical Operations, PhD
- Número de telefone: 267-566-6081
- E-mail: kirstin.liechty@abelzeta.com
Locais de estudo
-
-
Arizona
-
Gilbert, Arizona, Estados Unidos, 85234
- Research Site
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Key Inclusion Criteria:
-
Able to sign and date the Informed Consent Form (ICF).
-
Female or male, aged 18-70 years (inclusive) with body weight ≥40 kg.
-
Have a clinical diagnosis of diffuse cutaneous SSc according to the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification.
-
Disease duration between the onset of the first non-Raynaud's sign/symptom and ICF signing shall be ≤ 6 years.
-
SSc Disease Activity meet all following criteria:
- Modified Rodnan Skin Score (mRSS) ≥15.
- Chest High Resolution Computed Tomography (HRCT) shows SSc related ground-glass opacities.
- Percent predicted forced vital capacity (ppFVC)<70% or precent predicted (diffusing capacity of the lungs for carbon monoxide) ppDLco<70%.
-
Positivity for at least one SSc-specific autoantibodies:
- anti-Scl70 antibody.
- anti-RNA polymerase III antibody.
- anti-centromere antibody.
- anti-Th/To antibody.
- and anti-U3RNP antibody.
-
Refractory to at least two prior standard-of-care regimens, including immunosuppressives and/or a biologic note: "Refractory" is defined as receiving each listed drug for ≥6 months with either no response, disease progression after transient remission, or persistent disease progression on treatment.
-
Ability to taper steroids to protocol allowed doses
Exclusion Criteria:
-
ppFVC<45% or ppDLco <40%.
-
Severe pulmonary arterial hypertension (PAH) as measured by screening echocardiogram (ECHO), or had documented mean positive airway pressure PAP (mPAP) > 45mmHg on recent right heart catheterization (RHC).
Note: RHC is not mandatory at screening, however participant with high-risk ECHO findings warrant close clinical vigilance, and participant with mPAP> 45mmHg at baseline shall not proceed with lymphodepletion.
-
Presence of clinically significant abnormalities on chest high-resolution computed tomography (HRCT) that are UNRELATED to SSc.
-
Cutaneous sclerosis that impedes venous access required for leukapheresis, lymphodepletion, C-CAR168 infusion, other study procedures and emergency rescue interventions.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: C-CAR168
Participants will receive: • Leukapheresis • Fludarabine • Cyclophosphamide • Single intravenous infusion of C-CAR168 |
Autologous anti-CD20/BCMA chimeric antigen receptor T-cell therapy administered as a single intravenous infusion |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Incidence and severity of treatment-emergent adverse events
Prazo: Through Month 24
|
Incidence and severity of treatment-emergent adverse events, serious adverse events, dose-limiting toxicities, CRS, ICANS, adverse events of special interest, and treatment- or procedure-related adverse events. |
Through Month 24
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Proportion of Participants Achieving Response
Prazo: Through Month 24
|
Proportion of participants achieving a response per the revised Composite Response Index for Systemic Sclerosis (r-CRISS) |
Through Month 24
|
|
Pharmacokinetics of C-CAR168 Utilizing Flow Cytometry
Prazo: Through Month 24
|
Characterize T-cell expansion and persistence utilizing flow cytometry |
Through Month 24
|
|
Pharmacokinetics of C-CAR168 measured by quantitative polymerase chain reaction (qPCR)
Prazo: Through Month 24
|
Characterize CAR T-cell expansion and persistence using qPCR |
Through Month 24
|
|
Proportion of Participants Progressed
Prazo: Through Month 24
|
Proportion of participants that progress meeting any of the protocol defined progression criteria |
Through Month 24
|
|
Time to First Response
Prazo: Through Month 24
|
Time to participant meeting first response as defined in the protocol |
Through Month 24
|
|
Duration of Response (DOR)
Prazo: Through 24 months
|
Time of response from first response until progression as defined in the protocol |
Through 24 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Yihong Yao, PhD, AbelZeta Inc.
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
Outros números de identificação do estudo
- ABZT-413
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Individual participant data collected during this study will not be made available to other researchers.
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .