IASO207 Injection for Active Refractory Systemic Lupus Erythematosus (SLE)
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorPeking University People's Hospital
About this trial
This is a single-center, open-label, exploratory clinical study designed to evaluate the efficacy and safety of IASO207 Injection (in vivo CAR-T) in patients with active refractory systemic lupus erythematosus.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Subjects aged 18-75 years old, regardless of gender.
Subjects diagnosed with active refractory SLE: a) Confirmed by the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria or the 2012 Systemic Lupus Erythematosus Collaborative Clinic (SLICC) criteria for at least 24 weeks; b) SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥ 8, with at least 1 organ system having a BILAG-2004 A-class activity score at screening, or 2 organ systems having a BILAG-2004 B-class activity score; c) Previously treated with standardized glucocorticoids and at least two immunosuppressants/adjusters, antimalarial drugs or biologics for at least 3 months.
Positive for disease-related pathogenic antibodies: Anti-nuclear antibody (ANA) positive and/or anti-dsDNA positive and/or anti-Smith positive.
Allowed to use ≤ 20mg/d prednisone or equivalent dose of corticosteroids at screening, and use at a stable dose for at least 2 weeks. Note: Local or inhaled corticosteroids (or its immunomodulators) can be used concurrently;
Disqualifiers
Diagnosed with drug-induced SLE.
Complicated with other autoimmune diseases that may affect the assessment of the study, including but not limited to Sjögren's syndrome, psoriasis, rheumatoid arthritis.
Had a catastrophic antiphospholipid syndrome or developed a severe antiphospholipid syndrome within 1 year before screening.
The study disease involved neurological symptoms with a BILAG-2004 activity score of class A.
Trial design
Design model
Single group
Treatments tested in this trial
IASO207 Injection
DrugIASO207 is a third-generation replication-deficient self-inactivating lentiviral vector that carries the gene encoding a second-generation anti-human CD19 chimeric antigen receptor (CD19 CAR) containing the 4-1BB co-stimulatory factor. IASO207 has been engineered through surface modification of the lentiviral envelope to enable it to selectively bind and transduce T cells within the body, thereby directly generating CD19 CAR-T cells in vivo.
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: IASO207 InjectionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety endpoint - Adverse Events (AEs)
Incidence and severity of adverse events as assessed by NCI-CTCAE v5.0 (except CRS and ICANS assessed according to the criteria of 2019 ASTCT criteria).
Time frame
up to 2 years from IASO207 Injection infusion2
Safety endpoint - The incidence of dose-limiting toxicity (DLT)
Percentage of participants who experienced DLT within 28 days after IASO207 administration
Time frame
28 days from IASO207 Injection infusionSecondary outcomes
1
Efficacy endpoint - Response rate of SRI-4 after infusion
SLE Responder Index (SRI)-4 is defined as follows with all criteria compared with Baseline: 1. ≥ 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score. 2. No worsening of the overall condition (\< 0.3 point increase in Physician's Global Assessment \[PhGA\]). 3. No new British Isles Lupus Assessment Group (BILAG) A or more than 1 new BILAG B disease activity scores.
Time frame
up to 2 years from IASO207 Injection infusion2
Efficacy endpoint - lupus low disease activity state (LLDAS) rate through 2 years after infusion
Proportions of subjects achieving LLDAS at each time point
Time frame
up to 2 years from IASO207 Injection infusion3
Efficacy endpoint - Definitions of Remission in SLE (DORIS) rate through 2 years after infusion
Proportions of subjects achieving remission according to the DORIS as assessed by SLEDAI-2K Scale, PhGA score and concomitant medication use
Time frame
up to 2 years from IASO207 Injection infusion4
Efficacy endpoint - The changes in SLEDAI-2K scores
At each visit site, the patients were scored using the SLEDAI-2K, and then the changes in scores compared between each visit point and the baseline score were evaluated
Time frame
up to 2 years from IASO207 Injection infusionOther outcomes
1
Immunogenicity
Prevalence and titer of confirmed human anti-CAR antibodies in peripheral blood.
Time frame
up to 2 years from IASO207 Injection infusion2
Replication competent lentivirus (RCL)
Prevalence of replication-competent lentivirus (RCL) in peripheral blood.
Time frame
up to 2 years from IASO207 Injection infusion3
Virus shedding
Presence of viral shedding in body fluid samples (urine, feces, and saliva)
Time frame
Up to 7 days from IASO207 Injection infusionSponsors and contacts
Click on the lead sponsor to view all of their trials.
Peking University People's Hospital
Lead sponsor
Nanjing IASO Biotechnology Co., Ltd.
Collaborator
Source ClinicalTrials.gov