Clinical trial NCT06626919: A Phase 1 Study of Anitocabtagene Autoleucel for the Treatment of Subjects With Non-oncology Plasma Cell-related Diseases
Official title: A Phase 1 Study of Anitocabtagene Autoleucel for the Treatment of Subjects With Non-oncology Plasma Cell-related Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Muscular Diseases
Neuromuscular Manifestations
Autoimmune
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Myasthenia Gravis
Muscle Weakness
Keywords: ARC-311
CART
CAR-T
BCMA
Anito-cel
Generalized Myasthenia Gravis
gMG
MG
Myasthenia Gravis
non-oncology plasma cell
autoimmune
auto-antibody
chimeric antigen receptor
D-Domain chimeric antigen receptor
B-cell maturation antigen (BCMA)
anitocabtagene autoleucel
Lead sponsor: Arcellx, Inc.
Sponsor class: INDUSTRY
First posted: 2024-10-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Assess safety profile, including any DLT and MTD (if applicable)
timeFrame: 24 months
measure: Selection of RP2D
timeFrame: 24 months
Secondary outcomes:
measure: Quantify Clinical Effect of Anito-cel in the Myasthenia Gravis Activities of Daily Living (MG ADL) score
timeFrame: 24 months
measure: Quantify Clinical Effect of Anito-cel in the Quantitative Myasthenia Gravis (QMG) score
timeFrame: 24 months
measure: Quantify Clinical Effect of Anito-cel in the Myasthenia Gravis Composite (MGC) scale.
timeFrame: 24 months
measure: Mean change in QMG score
timeFrame: 24 months
measure: Mean change in MG-ADL score
timeFrame: 24 months
measure: Mean change in MCG score
timeFrame: 24 months
measure: Mean change in MG-QoL15R score
timeFrame: 24 months
measure: Change in titer of myasthenia specific autoantibodies
timeFrame: 24 months
measure: PK Parameter for anito-cel: Cmax
timeFrame: Day 1 up to 24 months
measure: PK Parameter for anito-cel: Tmax
timeFrame: Day 1 up to 24 months
measure: PK Parameter for anito-cel: Area under the curve (AUC)
timeFrame: Day 1 up to 24 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California, Irvine
state: California
Study officials:
References: