Lupus Erythematosus, Systemic
Conditions
Keywords
AZD0120, SLE, Systemic Lupus Erythematosus, Lupus, Lupus Nephritis
Brief summary
This is a Phase 1b/2, single-arm, open-label, multi-center, clinical study of AZD0120, a CD19/BCMA dual CAR T cell therapy, to evaluate the safety, tolerability, and efficacy in adult participants with refractory Systemic Lupus Erythematosus.
Detailed description
The study will enrol adult participants with refractory Systemic Lupus Erythematosus (SLE) The study will be run in 2 parts; First part is Phase 1b during which the study aims to assess safety and tolerability of AZD0120 in patients in refractory SLE cohorts Second part is Phase 2, during which the study aims to assess safety, tolerability and efficacy of the selected dose, following Phase 1b completion, in patients with refractory SLE
Interventions
DRUGFludarabine
Lymphodepletion - specified dose prior to receiving AZD0120
BIOLOGICALAZD0120
Single infusion of AZD0120 on visit DAY 1 after completing required lymphodepleting chemotherapy..
DRUGCyclophosphamide
Lymphodepletion - specified dose prior to receiving AZD0120
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Drug: AZD0120 Single infusion of AZD0120
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
INCLUSION: 1. Males or females aged 18 through 70 years inclusive at the time of consent. 2. Written informed consent in accordance with federal, local, and institutional guidelines. 3. Must be able and willing to adhere to the study visit schedule and other protocol requirements 4. Adequate hepatic, renal, pulmonary, and cardiac function 5. Have a clinical diagnosis of SLE according to the EULAR/ American College of Rheumatology (ACR) 2019 criteria with a positive ANA ≥1:80 and a score ≥10. 6. Have used at least two standard immunosuppressants (including one biological agent). 7. SLEDAI-2K score ≥6 at screening. 8. Must include a significant SLE related organ involvement: arthritis, myositis, rash, alopecia, mucosal ulcers, pleurisy, pericarditis, vasculitis, or renal. 9. For lupus nephritis: Diagnosis of proliferative lupus nephritis based on a renal biopsy obtained within 6 months prior to signing the informed consent form or during the screening period Class III, IV or V LN according to the WHO 2003 ISN/RPS classification. EXCLUSION: 1. Have received prior treatment with CAR T therapy directed at any target. 2. Have received any therapy that is targeted to CD19 and/or BCMA 3. Received allogenic stem cell transplant or autologous stem cell transplant. 4. An active malignancy that is progressing or requires active treatment. 5. Primary immunodeficiency 6. Active viral or bacterial infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PHASE 1B: To evaluate the safety and tolerability of AZD0120 in participants with refractory systemic lupus erythematosus (SLE) | 2 years | The incidence and severity of adverse events (AEs) |
| PHASE 1B: Recommended Phase 2 Dose (RP2D) of AZD0120 in for Phase 2 | 2 years | To determine the recommended phase 2 dose (RP2D) of AZD0120 |
| PHASE 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE | 2 years | Proportion of participants achieving SRI-4 response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PHASE 1B & 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE | 2 years | Proportion of participants achieving SLE Responder Index 4 (SRI-4) response over time |
| PHASE 1B & 2: To characterize the cellular kinetics of AZD0120 in participants with refractory SLE | 2 years | The area under the concentration-time curve (AUC) from time zero (T0) to the last measurable concentration time point (AUClast) |
| PHASE 1B & 2: To assess immunogenicity of AZD0120 | 2 years | Presence of AZD0120 antibodies |
| PHASE 1B & 2: To determine whether replication-competent lentivirus is present in participants that receive AZD0120 | 2 years | Presence of replication-competent lentivirus (RCL) |
| PHASE 2: To further characterize the safety of AZD0120 in participants with refractory SLE | 2 years | Further characterization of the safety of AZD0120 by measuring the incidence and severity of Treatment Emergent Adverse Events (TEAEs) |
| PHASE 2: To assess changes from baseline for reported health-related quality of life, overall health status | 2 years | To assess changes from baseline for Changes in Lupus Quality of life (LupusQoL) |
Countries
Australia, Canada, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed