Systemic Sclerosis, Idiopathic Inflammatory Myopathies, Rheumatoid Arthritis
Conditions
Keywords
Systemic Sclerosis, Idiopathic Inflammatory Myopathies, Rheumatoid Arthritis, CAR-T, BCMA, CD19
Brief summary
This trial is a Phase 1b, open-label, multi-center, clinical study of AZD0120, a BCMA/CD19 dual targeting CAR+ T-cell therapy, to evaluate the safety and tolerability in adult participants with systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), or difficult-to-treat rheumatoid arthritis (D2T RA).
Detailed description
This is a Phase 1b, open-label, multi-center, multi-cohort clinical study of AZD0120, a CD19/BCMA dual CAR T-cell therapy, to evaluate the safety in adult participants with systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM), or difficult-to-treat rheumatoid arthritis (D2T RA) for determination of the recommended phase 2 dose for each disease cohort. Approximately 9-12 participants will be evaluated per disease cohort.
Interventions
BIOLOGICALAZD0120
CD19/BCMA Autologous CAR T-cell therapy product
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multi-indication cohort
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Capable of giving signed informed consent. * Adequate physiological function and reserve at screening. * Able to comply with recommended medication washout period. * Participants who are suitable for the study as determined by medical evaluation and at the discretion of the investigator. * Willingness to remain on/start appropriate, highly effective methods of birth control or other acceptable criteria.
Exclusion criteria
* BMI at screening \< 18 or \> 35kg/m2. * Any prior CAR T exposure. * Unable or unwilling to remain within proximity (\~2 hours travel time) of the administering investigational site for the first 28 days post study drug administration. * Received a bone marrow or solid organ transplant at any time or on an active transplant waiting list. * Received any investigational drug within ≥ 5 half-lives or 4 weeks, whichever is longer, prior to screening. * Has certain heart conditions that could make it unsafe or unsuitable to take part in the study. * Requirement for supplemental oxygen at rest (except at night for sleep apnea) or mechanical ventilation. * Uncontrolled hypertension (\> 160/100 mmHg) or symptomatic hypertension. * Any central nervous system disease that may impact participants safety in the investigator's opinion. * Other concurrent autoimmune or autoinflammatory disease. Certain autoimmune/autoinflammatory diseases may be included after discussion with the medical monitor. * Evidence of clinically significant bleeding or active bleeding conditions within 90 days before screening * History of malignancy or ongoing treatment for prior malignancy. Certain malignancies may be excepted. * Known genetic inborn error of immunity and/or primary immunodeficiency. * Active viral, bacterial, or fungal infection, or any ongoing infection that requires systemic antimicrobial therapy in the 4 weeks prior to screening. * Seropositive for HIV. * Active viral hepatitis are excluded. * Active syphilis, positive for Treponema pallidum antibody. * Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis or lymphodepletion. * Not up-to-date on vaccinations per local/national health authority or institutional guidelines for immune-compromised individuals. * Known life threatening allergies, hypersensitivity, or intolerance to AZD0120 or its excipients, including dimethyl sulfoxide. * Contraindications or hypersensitivity to fludarabine and cyclophosphamide. * Major surgery, or has surgery planned during the study. * Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 1 year after receiving study treatment (whichever is later). * Plans to father a child while enrolled in this study or within 1 year after receiving study treatment (whichever is later). * Any issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to provide informed consent or any condition in the opinion of the investigator, participation would not be in the best interest of the participant. Other protocol-defined eligibility criteria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants and severity of dose limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs) | 1 year | Incidence and severity of DLTs and TEAEs to evaluate the safety of AZD0120 and to confirm the recommended Phase 2 dose (RP2D) in each indication SSc, IIM, or RA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cellular Kinetics - Cmax | 1 year | The maximum concentration of CAR T cells achieved in the body. |
| Cellular Kinetics - Tmax | 1 year | The time point at which the Cmax is reached |
| Cellular Kinetics - AUC | 1 year | The area under the concentration-time curve, which represents the total drug exposure over a specific period. |
| Cellular Kinetics - t½λz | 1 year | The terminal elimination half-life. |
| Cellular Kinetics - Clast | 1 year | The last observed quantifiable concentration of CAR T-cells. |
| Cellular Kinetics - Tlast | 1 year | The time to last quantifiable concentration. |
| Cellular Kinetics - AUClast | 1 year | The area under the concentration-time curve to the last measurable concentration. |
| Anti-drug antibodies (ADA) developed against AZD0120 from baseline | 1 year | Humoral immunogenicity assessment of AZD0120 in participants with SSc, IIM, or RA. |
| Proportion of participants with detectable replication competent lentivirus (RCL) at pre-specified post infusion timepoints. | 1 year | Incidence of vector-derived RCL in participant receiving AZD0120. |
| Change from baseline in the Disease Activity Score (DAS) 28-C-reactive protein (CRP). The DAS28-CRP is a measure from 0-10 with higher scores indicating greater disease activity. | 1 year | Disease activity measures in RA participants. |
| Change from baseline in modified Rodnan Skin Score (mRSS). The mRSS is a measure of skin thickness with a range of 0-51 with higher scores indicating more severe disease. | 1 year | Disease activity measures in SSc participants. |
| Change from baseline in the total improvement score (TIS). The TIS ranges from 0-100 with higher scores indicating greater improvement. | 1 year | Disease activity measures in IIM participants. |
Countries
Australia, Germany, Spain, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed