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

April 26, 2024 updated by: EdiGene Inc.

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

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Phase 1 dose escalation (3+3): dose 1 and dose 2.
Other Names:
  • ET-901
Intravenous injection of fludarabine.
Other Names:
  • Fludarabine Phosphate for Injection
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
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.
0~28 day after treatment
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).
0 day to 24 months after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
0 to 16 weeks after treatment
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.
0 to 16 weeks after treatment
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.
0 to 16 weeks after treatment
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.
0 to 16 weeks after treatment
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.
0 to 16 weeks after treatment
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.
0 day to 24 months after treatment
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.
0 day to 24 months after treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
0 day to 24 months after treatment
PK characteristics (cont)
Time Frame: 0 day to 24 months after treatment
Evaluate main PK parameters of ATHENA CAR-T, including Tmax, unit day.
0 day to 24 months after treatment
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.
0 day to 24 months after treatment
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.
0 day to 24 months after treatment
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.
0 day to 24 months after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Xiaofei Shi, MD, The First Affiliated Hospital of Henan University of science and Technology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 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)

April 29, 2024

Last Update Submitted That Met QC Criteria

April 26, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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