A Study to Evaluate the Safety and Efficacy of ATHENA CAR-T in Subjects With Systemic Lupus Erythematosus

A Phase 1 Study to Evaluate the Safety and Efficacy of ATHENA CAR-T in Subjects With Moderate or Severe Systemic Lupus Erythematosus

The goal of this clinical trial is to test ATHENA CAR-T injection in adults with moderate to severe Systemic Lupus Erythematosus. The main question it aims to answer is:

• To evaluate the safety and tolerability of ATHENA CAR-T.

After screening, participants will be subjected to lymphodepletion regimen. After recovery, participants will be injected with ATHENA CAR-T injection and followed up to 24 months.

Study Overview

• Status: Not yet recruiting
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Biological: ATHENA CAR-T; Drug: Fludarabine; Drug: Cyclophosphamide

Detailed Description

This study is a single center, one-arm, open label, phase I study aimed at evaluate the safety and effectiveness of ATHENA CAR-T treating moderate to severe SLE patients.

A traditional "3+3" design is used with two doses. DLT is monitored. Safety and effectiveness are followed up until 24 months post infusion of ATHENA CAR-T. Besides safety monitoring, efficacy is evaluated via SLEDAI-2000, BILAG-2004, PGA.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chao Liu; Phone Number: 8039 (86)-10-80733899; Email: cliu@edigene.com
• Study Contact Backup: Name: Yiding Zhao, PhD; Phone Number: 8103 (86)-10-80733899; Email: ydzhao@edigene.com

Study Locations

• China
  • Henan
    • Luoyang, Henan, China, 471003
      • The First Affiliated Hospital of Henan University of Science And Technology
      • Contact: Muchen Liu; Phone Number: (86)-13663884080

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or Female, between 18 and 56 years old;
• diagnosed with SLE according to 2019 EULAR/ACR SLE classifications;
• anti-Nuclear Antigen Ab positive (titer NLT 1:80) and/or dsDNA ab positive and/or Anti-Sm ab positive at screening;
• at screening, SLEDAI-2000 scoring NLT 8 points, if low complement scoring and/or anti-dsDNA ab scoring is available, the SLEDAI-2000 scoring except low complement and anti-dsDNA ab should be NLT 6 points;
• should be subjected to at least 6 months of standard treatment for SLE, and disease active at least two months before screening;
• good organ functions;
• trial participants whose partner is fertile agree to use effective contraceptives til 24 months post transfusion, fertile female participants should have negative urine/blood pregnancy test results (participants who were sterilized or menopause for MT 12 months is not considered fertile);
• voluntary participates this trial and can comprehend and sign ICF.

Exclusion Criteria:

• Had or has active malignancy;
• had been subjected to treatment by CD19 targeted therapy or CAR-T therapy or any gene therapy;
• within 8 weeks before screening, had CNS disease caused by SLE or non-SLE diseases;
• within 8 weeks before screening, had lupus crisis;
• has following kidney diseases: within 8 weeks before randomization, had SLE with serious kidney involvement or need treatment using medications prohibited by protocol to treat active nephritis, or need hemodialysis or need treatment by prednisone MT 100mg/d for longer than 14d or equivalent therapy;
• had serious allergy to any lymphodepletion medication or ingredients of ATHENA CAR-T;
• has uncontrolled fungi, bacterial or viral infection or other infections investigator deemed not suitable to participate in the study;
• combined with other autoimmune disease that needs treatment;
• pregnant or lactating women;
• has other factors that deemed not suitable by investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATHENA CAR-T Arm; A conditioning chemotherapy regimen will be administered followed by investigational treatment of ATHENA CAR-T	Biological: ATHENA CAR-T; Phase 1 dose escalation (3+3): dose 1 and dose 2.; Other Names: ET-901; Drug: Fludarabine; Intravenous injection of fludarabine.; Other Names: Fludarabine Phosphate for Injection; Drug: Cyclophosphamide; Intravenous injection of cyclophosphamide.; Other Names: Cyclophosphamide for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity	Dose Limiting Toxicity (DLT) is defined as AEs related to ATHENA CART from infusion till 28 days post infusion.	0~28 day after treatment
Frequency of AEs, SAEs, lab abnormalities, AESIs	Monitor grade and frequency of Adverse Events (AEs), Severe Adverse Events (SAEs), abnormal laboratory findings and Adverse Events of Special Interest (AESI).	0 day to 24 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Percent of patients achieved SRI-4	Measure percentage of patients who achieved SRI-4 (Systemic Lupus Erythematosus Responder Index-4) at week 4,8,12,16. SRI-4 response is achieved if SLEDAI-2000 score is lowered NLT 4pt compared to baseline, BILAG-2004 has no new A grade or NMT 1 new B grade, and PGA is not worsen (increase LT 0.3 compare to baseline).	0 to 16 weeks after treatment
Efficacy: Patients SLEDAI-2000 change compared with baseline	Compare patients' SLEDAI-2000 (Systemic Lupus Erythematosus Disease Activity Index 2000) value at baseline and week 4,8,12,16. SLEDAI-2000 is an index of range 0 to 105. Higher score indicates stronger disease activity, a score NLT 15 means strong SLE activity.	0 to 16 weeks after treatment
Efficacy: Patients BILAG-2004 change compared with baseline	Compare patients' BILAG-2004 (British Isles Lupus Assessment Group index 2004) value at baseline and week 4,8,12,16. Each organ system is graded from A to E, A indicate high disease activity while grade E indicate no disease activity now and then. A is assigned 9 points and E is assigned 0 points.	0 to 16 weeks after treatment
Efficacy: Percent of patients' PGA not worsen	Measure percentage of patients whose PGA (Physician Global Assessment) is not worsen (increase LT 0.3 compare to baseline) at week 4,8,12,16. PGA is ranged 0 to 3, score 0 means no disease activity while score 3 means strong disease activity.	0 to 16 weeks after treatment
Percent of patients responded by BILAG-2004	Measure percentage of patients who responded by BILAG-2004 (no new A grade or NMT 1 new B grade) at week 4,8,12,16.	0 to 16 weeks after treatment
Efficacy: Immunologic parameters	Evaluate the change of immunological parameters. Including of concentration of IgG, IgA, IgM, C3, C4, unit g/L.	0 day to 24 months after treatment
Efficacy: Immunologic parameters (cont)	Evaluate the change of immunological parameters. Including concentration of anti-dsDNA antibody, unit IU/ml.	0 day to 24 months after treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK characteristics	Evaluate main PK parameters of ATHENA CAR-T, including Cmax, unit CAR+ T cell/l.	0 day to 24 months after treatment
PK characteristics (cont)	Evaluate main PK parameters of ATHENA CAR-T, including Tmax, unit day.	0 day to 24 months after treatment
PK characteristics (cont)	Evaluate main PK parameters of ATHENA CAR-T, including AUC0-28d and AUC0-last, both unit are day*CAR+T cell/l.	0 day to 24 months after treatment
PD characteristics	Evaluate change of CD19+ cell number, unit CD19 cell/l, before and after infusion of ATHENA CAR-T.	0 day to 24 months after treatment
PD characteristics (cont)	Evaluate change of serum cytokine level, including but not limited to TNF-alpha and IFN-gamma, unit pg/ml, before and after infusion of ATHENA CAR-T.	0 day to 24 months after treatment

Collaborators and Investigators

• Sponsor: EdiGene Inc.
• Collaborators: The First Affiliated Hospital of Henan University of Science and Technology; Changping Laboratory
• Investigators: Principal Investigator: Xiaofei Shi, MD, The First Affiliated Hospital of Henan University of Science And Technology

Study record dates

Study Major Dates

• Study Start (Estimated): July 24, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 16, 2024
• First Posted (Actual): April 18, 2024

Study Record Updates

• Last Update Posted (Actual): June 17, 2024
• Last Update Submitted That Met QC Criteria: June 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Adult moderate to serve SLE
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Fludarabine phosphate
• Other Study ID Numbers: EDI-901-SLE01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share IPD.

Drug and device information, study documents

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