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

• ClinicalTrials.gov Identifier: NCT06373991
• Recruitment Status: Recruiting
• First Posted: April 18, 2024
• Last Update Posted: April 29, 2024
• Sponsor: EdiGene Inc.
• Collaborators: The First Affiliated Hospital of Henan University of Science and Technology; Changping Laboratory
• Information provided by (Responsible Party): EdiGene Inc.

Tracking Information

• First Submitted Date: April 9, 2024
• First Posted Date: April 18, 2024
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: April 24, 2024
• Estimated Primary Completion Date: April 30, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 16, 2024)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 16, 2024)

• Efficacy: Percent of patients achieved SRI-4 [ Time Frame: 0 to 16 weeks after treatment ]
  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).
• Efficacy: Patients SLEDAI-2000 change compared with baseline [ Time Frame: 0 to 16 weeks after treatment ]
  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.
• Efficacy: Patients BILAG-2004 change compared with baseline [ Time Frame: 0 to 16 weeks after treatment ]
  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.
• Efficacy: Percent of patients' PGA not worsen [ Time Frame: 0 to 16 weeks after treatment ]
  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.
• Percent of patients responded by BILAG-2004 [ Time Frame: 0 to 16 weeks after treatment ]
  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.
• Efficacy: Immunologic parameters [ Time Frame: 0 day to 24 months after treatment ]
  Evaluate the change of immunological parameters. Including of concentration of IgG, IgA, IgM, C3, C4, unit g/L.
• Efficacy: Immunologic parameters (cont) [ Time Frame: 0 day to 24 months after treatment ]
  Evaluate the change of immunological parameters. Including concentration of anti-dsDNA antibody, unit IU/ml.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 16, 2024)

• PK characteristics [ Time Frame: 0 day to 24 months after treatment ]
  Evaluate main PK parameters of ATHENA CAR-T, including Cmax, unit CAR+ T cell/l.
• PK characteristics (cont) [ Time Frame: 0 day to 24 months after treatment ]
  Evaluate main PK parameters of ATHENA CAR-T, including Tmax, unit day.
• PK characteristics (cont) [ Time Frame: 0 day to 24 months after treatment ]
  Evaluate main PK parameters of ATHENA CAR-T, including AUC0-28d and AUC0-last, both unit are day*CAR+T cell/l.
• PD characteristics [ Time Frame: 0 day to 24 months after treatment ]
  Evaluate change of CD19+ cell number, unit CD19 cell/l, before and after infusion of ATHENA CAR-T.
• PD characteristics (cont) [ Time Frame: 0 day to 24 months after treatment ]
  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.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

Brief Summary

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.

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
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lupus Erythematosus, Systemic

Intervention

• Biological: ATHENA CAR-T
  Phase 1 dose escalation (3+3): dose 1 and dose 2.
  Other Name: ET-901
• Drug: Fludarabine
  Intravenous injection of fludarabine.
  Other Name: Fludarabine Phosphate for Injection
• Drug: Cyclophosphamide
  Intravenous injection of cyclophosphamide.
  Other Name: Cyclophosphamide for Injection

Study Arms

Experimental: ATHENA CAR-T Arm

A conditioning chemotherapy regimen will be administered followed by investigational treatment of ATHENA CAR-T

Interventions:

• Biological: ATHENA CAR-T
• Drug: Fludarabine
• Drug: Cyclophosphamide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 16, 2024): 12
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2027
• Estimated Primary Completion Date: April 30, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Chao Liu; (86)-10-80733899 ext 8039; cliu@edigene.com

Contact: Yiding Zhao, PhD; (86)-10-80733899 ext 8103; ydzhao@edigene.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT06373991
• Other Study ID Numbers: EDI-901-SLE01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: No plan to share IPD.

• Current Responsible Party: EdiGene Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: EdiGene Inc.
• Original Study Sponsor: Same as current

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

• PRS Account: EdiGene Inc.
• Verification Date: April 2024