A Study to Investigate the Safety, Tolerability, and Efficacy of AZD0120 in Adults With Refractory SLE

A Phase 1b/2 Study of AZD0120, a Chimeric Antigen Receptor T-cell (CAR T) Therapy Targeting CD19 and B-cell Maturation Antigen (BCMA) in Subjects With Refractory Systemic Lupus Erythematosus (SLE)

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.

Study Overview

• Status: Recruiting
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Biological: AZD0120; Drug: Cyclophosphamide; Drug: Fludarabine

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

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Darlinghurst, Australia, 2010
    • Not yet recruiting
    • Research Site
  • Melbourne, Australia, 3000
    • Not yet recruiting
    • Research Site
• Canada
  • Toronto, Canada, M5T 2S8
    • Not yet recruiting
    • Research Site
• United States
  • California
    • San Francisco, California, United States, 94143
      • Not yet recruiting
      • Research Site
    • Stanford, California, United States, 94304-2201
      • Not yet recruiting
      • Research Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Suspended
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Research Site
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Withdrawn
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Research Site
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Research Site
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Research Site
    • Syracuse, New York, United States, 13202-2240
      • Recruiting
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7280
      • Not yet recruiting
      • Research Site
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Not yet recruiting
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Research Site
    • Seattle, Washington, United States, 98195
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD0120; Single dose of AZD0120	Biological: AZD0120; Single infusion of AZD0120 on visit DAY 1 after completing required lymphodepleting chemotherapy..; Other Names: GC012F; Drug: Cyclophosphamide; Lymphodepletion - specified dose prior to receiving AZD0120; Drug: Fludarabine; Lymphodepletion - specified dose prior to receiving AZD0120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PHASE 1B: To evaluate the safety and tolerability of AZD0120 in participants with refractory systemic lupus erythematosus (SLE)	The incidence and severity of adverse events (AEs)	2 years
PHASE 1B: Recommended Phase 2 Dose (RP2D) of AZD0120 in for Phase 2	To determine the recommended phase 2 dose (RP2D) of AZD0120	2 years
PHASE 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE	Proportion of participants achieving SRI-4 response	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PHASE 1B & 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE	Proportion of participants achieving SLE Responder Index 4 (SRI-4) response over time	2 years
PHASE 1B & 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE	Proportion of participants achieving remission in SLE (DORIS) remission over time	2 years
PHASE 1B & 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE	Proportion of participants achieving Lupus Low Disease Activity State (LLDAS) over time	2 years
PHASE 1B & 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE	Proportion of participants achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response over time	2 years
PHASE 1B & 2: To evaluate the efficacy of AZD0120 in participants with refractory SLE	Time from AZD0120 infusion and time from response to first disease flare	2 years
PHASE 1B & 2: To characterize the cellular kinetics of AZD0120 in participants with refractory SLE	The area under the concentration-time curve (AUC) from time zero (T0) to the last measurable concentration time point (AUClast)	2 years
PHASE 1B & 2: To characterize the cellular kinetics of AZD0120 in participants with refractory SLE	Area under the blood concentration-time curve from time zero to 28 days after dosing (AUC(0-28D))	2 years
PHASE 1B & 2: To characterize the cellular kinetics of AZD0120 in participants with refractory SLE	The last measurable concentration of AZD0120 (Clast)	2 years
PHASE 1B & 2: To characterize the cellular kinetics of AZD0120 in participants with refractory SLE	Maximum observed blood concentration (Cmax)	2 years
PHASE 1B & 2: To characterize the cellular kinetics of AZD0120 in participants with refractory SLE	Terminal half-life of a drug during its elimination phase in pharmacokinetics (t1/2λz)	2 years
PHASE 1B & 2: To characterize the cellular kinetics of AZD0120 in participants with refractory SLE	Time of the last measurable (quantifiable) concentration of a AZD0120 (Tlast)	2 years
PHASE 1B & 2: To characterize the cellular kinetics of AZD0120 in participants with refractory SLE	Time of maximum observed blood concentration (Tmax)	2 years
PHASE 1B & 2: To assess immunogenicity of AZD0120	Presence of AZD0120 antibodies	2 years
PHASE 1B & 2: To determine whether replication-competent lentivirus is present in participants that receive AZD0120	Presence of replication-competent lentivirus (RCL)	2 years
PHASE 2: To further characterize the safety of AZD0120 in participants with refractory SLE	Further characterization of the safety of AZD0120 by measuring the incidence and severity of Treatment Emergent Adverse Events (TEAEs)	2 years
PHASE 2: To assess changes from baseline for reported health-related quality of life, overall health status	To assess changes from baseline for Changes in Lupus Quality of life (LupusQoL)	2 years
PHASE 2: To assess changes from baseline for reported health-related quality of life, overall health status	To assess changes from baseline for FUNCTIONAL ASSESSMENT OF CHRONIC ILLNESS THERAPY (FACIT)	2 years

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: March 12, 2025
• First Submitted That Met QC Criteria: March 20, 2025
• First Posted (Actual): March 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Lupus; SLE; Systemic Lupus Erythematosus; Lupus Nephritis; AZD0120
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: D8313C00001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No