System Lupus Erythematosus(SLE)
Conditions
Keywords
ACE1831, SLE, Refractory Systemic lupus erythematosus (SLE), gamma delta T (gdT) cell
Brief summary
ACE1831 is an off-the-shelf, allogeneic gamma delta T (gdT) cell therapy derived from healthy donors, that is under investigation for the treatment in subjects with Relapsed/Refractory Systemic lupus erythematosus (SLE)
Interventions
DRUGACE1831
ACE1831 is allogeneic gamma delta T (gdT) cell therapy. Subjects will receive ACE1831 dose based on the assigned dose escalation cohort.
Subjects assigned to receive lymphodepleting preconditioning (LDC) will receive chemotherapy cyclophosphamide ahead of ACE1831 administration.
Sponsors
Tongji Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or female 18 to 60 years (inclusive) * History of meeting the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, or the 1997 ACR criteria, or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) * Presence of anti-dsDNA antibodies and/or anti-nuclear antibodies (ANA) and/or anti-Smith (anti-Sm) antibodies positive * SLE is in the moderate to severe active phase with the SLEDAI-2000 score ≥ 8 * At least one British Isle Lupus Rating Group Index (BILAG-2004) Class A (severe manifestation) or two Class B (moderate manifestation) organ scores, or both * Inadequate response to glucocorticoids and at least 2 of treatments used for at least 3 months * Women of childbearing potential and their partners must agree to use at least 1 highly effective method of contraception throughout the study period and for 1 year after treatment * Signed informed consent
Exclusion criteria
* Severe lupus nephritis requiring prohibited medications for active nephritis treatment，or hemodialysis, or eGFR \< 50 ml/min/1.73m² * Central nervous system disease caused by SLE or other conditions * Significant medical history that would pose a risk to the patients safety from the investigator's opinion, or patients medical condition could worsen during the study * Malignancies within 5 years * Presence of active, recurrent, chronic infection requiring treatment , or latent infection (HBV, HCV, HIV, TB, syphilis) * Received any B-cell depletion biologic therapy * Received immunosuppressive small molecule drug therapy， or other systemic corticosteroid therapy ， or prednisone * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the safety and tolerability of ACE1831 in subjects with Refractory Systemic lupus erythematosus | 24 weeks after last dose of ACE1831 | To assess the incidence of Adverse Events (AEs), \[AEs including Treatment Emergent AEs, Serious AEs (SAEs), AEs of Special Interests (AESIs), and dose limiting toxicities (DLTs)\] (unit: number of AEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the efficacy of ACE1831： Changes in SLE disease activity Index (SLEDAI-2000) score | 24 weeks after last dose of ACE1831 | Changes of SLE disease activity Index (SLEDAI-2000) score |
| To assess the efficacy of ACE1831 (secondary efficacy)：Changes in PGA | 24 weeks after last dose of ACE1831 | Changes in Physician's Global Assessment (PGA) of disease activity score (Visual Activity Score,scale range 0 - 100) |
| To assess the efficacy of ACE1831 : Changes in SGA | Time Frame: 24 weeks after last dose of ACE1831 | Changes in Subject's Global Assessment (SGA) of disease activity score (Visual Activity Score,scale range 0 - 100) |
| To assess the efficacy of ACE1831 ：Changes in LupusQOL | 24 weeks after last dose of ACE1831 | Changes of Lupus Qualituy of Life(LupusQOL) total score |
| To assess the efficacy of ACE1831 ：Changes in EQ-5D-5L score | 24 weeks after last dose of ACE1831 | Changes of European Quality of Life Five Dimension Five Level questionnaire(EQ-5D-5L )score |
| To assess the efficacy of ACE1831 ：Changes in SF-12 score | 24 weeks after last dose of ACE1831 | Changes in Quality of Life Questionnaire (QOL) Short Form 12 (SF-12) total score |
| To assess the efficacy of ACE1831: LLDAS rate | 24 weeks after last dose of ACE1831 | Proportions of subjects achieving LLDAS by timepoint |
| To assess the efficacy of ACE1831: DORIS | 24 weeks after last dose of ACE1831 | Proportions of subjects who achieved remission according to the DORIS by timepoint |
| To assess the efficacy of ACE1831: SRI-4 response rate | 24 weeks after last dose of ACE1831 | Proportion of participants who achieved Systemic Lupus Erythematosus Responder Index -4 (SRI-4) response |
| Persistence of ACE1831 after administration | 8 weeks after last dose of ACE1831 | Half-life of ACE1831 |
| Measure the pharmacodynamics change of ACE1831 | 24 weeks after last dose of ACE1831 | Immunoglobulin, cytokines, lymphocytecount , autoantibody titers, complement C3 and C4 levels, C-reactive protein, erythrocyte sedimentation rate, etc |
| Immunogenicity | 24 weeks after last dose of ACE1831 | Titration of anti-ACE1831 antibodies after administration |
| To assess the efficacy of ACE1831 ：Changes in BILAG-2004 score | 24 weeks after last dose of ACE1831 | Changes of BILAG-2004 score |
Other
| Measure | Time frame |
|---|---|
| To assess the efficacy of ACE1831： single-cell sequencing | 24 weeks after last dose of ACE1831 |
Countries
China
Contacts
Primary ContactLingli Dong
Backup ContactZiwei Hu
Outcome results
None listed