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

Lupus Erythematosus, Systemic Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06373991
• Other study ID #: EDI-901-SLE01
• Status: Recruiting
• Phase: Phase 1
• Start date: April 24, 2024
• Est. completion date: April 30, 2027

Study information

• Verified date: April 2024
• Source: EdiGene Inc.
• Contact: Chao Liu
• Phone: (86)-10-80733899
• Email: cliu[@]edigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: April 30, 2027
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic

Intervention

Biological:
• ATHENA CAR-T
Phase 1 dose escalation (3+3): dose 1 and dose 2.

Drug:
• Fludarabine
Intravenous injection of fludarabine.
• Cyclophosphamide
Intravenous injection of cyclophosphamide.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan

Sponsors (3)

Lead Sponsor	Collaborator
EdiGene Inc.	Changping Laboratory, The First Affiliated Hospital of Henan University of Science and Technology

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PK characteristics	Evaluate main PK parameters of ATHENA CAR-T, including Cmax, unit CAR+ T cell/l.	0 day to 24 months after treatment
Other	PK characteristics (cont)	Evaluate main PK parameters of ATHENA CAR-T, including Tmax, unit day.	0 day to 24 months after treatment
Other	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
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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