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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Estimé)
Phase
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Kirstin Liechty, Head of Clinical Operations, PhD
- Numéro de téléphone: 267-566-6081
- E-mail: kirstin.liechty@abelzeta.com
Sauvegarde des contacts de l'étude
- Nom: Yihong Liechty, Head of Clinical Operations, PhD
- Numéro de téléphone: 267-566-6081
- E-mail: kirstin.liechty@abelzeta.com
Lieux d'étude
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Arizona
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Gilbert, Arizona, États-Unis, 85234
- Research Site
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Key Inclusion Criteria:
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Able to sign and date the Informed Consent Form (ICF).
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Female or male, aged 18-70 years (inclusive) with body weight ≥40 kg.
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Have a clinical diagnosis of diffuse cutaneous SSc according to the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification.
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Disease duration between the onset of the first non-Raynaud's sign/symptom and ICF signing shall be ≤ 6 years.
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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%.
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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.
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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.
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Ability to taper steroids to protocol allowed doses
Exclusion Criteria:
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ppFVC<45% or ppDLco <40%.
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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.
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Presence of clinically significant abnormalities on chest high-resolution computed tomography (HRCT) that are UNRELATED to SSc.
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Cutaneous sclerosis that impedes venous access required for leukapheresis, lymphodepletion, C-CAR168 infusion, other study procedures and emergency rescue interventions.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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 |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Incidence and severity of treatment-emergent adverse events
Délai: Through Month 24
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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
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Proportion of Participants Achieving Response
Délai: Through Month 24
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Proportion of participants achieving a response per the revised Composite Response Index for Systemic Sclerosis (r-CRISS) |
Through Month 24
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Pharmacokinetics of C-CAR168 Utilizing Flow Cytometry
Délai: Through Month 24
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Characterize T-cell expansion and persistence utilizing flow cytometry |
Through Month 24
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Pharmacokinetics of C-CAR168 measured by quantitative polymerase chain reaction (qPCR)
Délai: Through Month 24
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Characterize CAR T-cell expansion and persistence using qPCR |
Through Month 24
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Proportion of Participants Progressed
Délai: Through Month 24
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Proportion of participants that progress meeting any of the protocol defined progression criteria |
Through Month 24
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Time to First Response
Délai: Through Month 24
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Time to participant meeting first response as defined in the protocol |
Through Month 24
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Duration of Response (DOR)
Délai: Through 24 months
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Time of response from first response until progression as defined in the protocol |
Through 24 months
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Yihong Yao, PhD, AbelZeta Inc.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- ABZT-413
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Description du régime IPD
Individual participant data collected during this study will not be made available to other researchers.
Informations sur les médicaments et les dispositifs, documents d'étude
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