A Phase 1 Study of Anitocabtagene Autoleucel for the Treatment of Subjects With Non-oncology Plasma Cell-related Diseases
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Arcellx, Inc.
- Enrollment
- 30
- Locations
- 14
- Primary Endpoint
- Assess safety profile, including any DLT and MTD (if applicable)
Study Overview
Brief Summary
A Phase 1 dose-escalation study designed to evaluate the safety, tolerability, and preliminary efficacy of anito-cel in subjects with generalized myasthenia gravis (GMG). Anitocabtagene autoleucel (anito-cel) is a BCMA-directed CAR-T cell therapy.
Detailed Description
This is a Phase 1 open-label, multi-center safety and dose-escalation study of anito-cel* in adult subjects with GMG (MGFA Grade 2 to 4a), in whom immunosuppressive therapy is clinically indicated in the judgement of the treating neurologist. The primary objective of this study is to assess the safety profile, including any DLT and identification of a MTD (if applicable), to support selection of the RP2D of anito-cel when administered to subjects with GMG.
The study will have the following sequential phases: screening, enrollment (leukapheresis), pretreatment with lymphodepletion (LD) chemotherapy, treatment with anito-cel and follow-up. Optional bridging therapy is allowed at investigator discretion while anito-cel is being manufactured.
Following a single infusion of anito-cel both safety and efficacy data will be assessed. The DLTs will be assessed in the first 28 days following anito-cel administration, and safety data will be collected throughout the study.
*Anitocabtagene autoleucel (anito-cel) drug product consists of autologous T cells that have been genetically modified ex vivo to express a D-domain Chimeric Antigen Receptor (CAR), followed by a cluster of differentiation 8 (CD8) hinge and transmembrane region that is fused to the intracellular signaling domains for 4-1BB and CD3ξ, that specifically recognizes B-cell maturation antigen (BCMA). The active substance of anitocabtagene autoleucel is CAR+ CD3+ T cells that have undergone ex vivo T-cell activation, gene transfer by replication-deficient lentiviral vector, and expansion.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subject must be 18 years of age or older
- •Must have MGFA clinical classification Grades 2-4A at time of screening
- •Subject must have clinically active disease and requiring ongoing therapy for GMG
- •MG-ADL score 6 and QMG score >10 at screening
- •GMG specific autoantibodies must be above the reference laboratory ULN
Exclusion Criteria
- •Subject is pregnant or breastfeeding
- •Treatment with Anti-CD20 agents, calcineurin inhibitors, FcRN inhibitors, azathioprine, mycophenolate mofetil, methotrexate, or cyclophosphamide within the specified time frame prior to leukapheresis or prior to anito-cel infusion
- •Previous treatment with any gene therapy, chimeric antigen receptor therapy or T cell engager
- •Previous thymectomy within 6 months of screening
- •Major chronic illness that is not well managed at the time of study entry and in the opinion of the investigator
Arms & Interventions
anito-cel
Single dose of anito-cel cells infused intravenously
Intervention: anito-cel (Biological)
anito-cel
Single dose of anito-cel cells infused intravenously
Intervention: Standard Lymphodepletion regimen (Drug)
Outcomes
Primary Outcomes
Assess safety profile, including any DLT and MTD (if applicable)
Time Frame: 24 months
Type, incidence, and severity of treatment-emergent adverse events (TEAEs), including DLT(s) and laboratory abnormalities
Selection of RP2D
Time Frame: 24 months
Evaluate the MTD and establish the RP2D
Secondary Outcomes
- Quantify Clinical Effect of Anito-cel in the Myasthenia Gravis Activities of Daily Living (MG ADL) score(24 months)
- Quantify Clinical Effect of Anito-cel in the Quantitative Myasthenia Gravis (QMG) score(24 months)
- Quantify Clinical Effect of Anito-cel in the Myasthenia Gravis Composite (MGC) scale.(24 months)
- Mean change in QMG score(24 months)
- Mean change in MG-ADL score(24 months)
- Mean change in MCG score(24 months)
- Mean change in MG-QoL15R score(24 months)
- Change in titer of myasthenia specific autoantibodies(24 months)
- PK Parameter for anito-cel: Cmax(Day 1 up to 24 months)
- PK Parameter for anito-cel: Tmax(Day 1 up to 24 months)
- PK Parameter for anito-cel: Area under the curve (AUC)(Day 1 up to 24 months)