Clinical trial NCT05765006: CD19-CART(Relma-cel) for Moderate to Severe Active Systemic Lupus Erythematosus
Official title: A Phase I Dose-escalation Study Evaluate the Safety Tolerability Pharmacokinetics(PK) and Pharmacodynamics(PD) of Relma-cel in Subjects With Moderate to Severe Active Systemic Lupus Erythematosus (SLE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Keywords: Relma-cel
Systemic lupus erythematosus
CD19-CART
Lead sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-03-13
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase I, open-label, single-arm, multicenter study to asess the safety tolerability pharmacokinetics and pharmacodynamics of Relma-cel in moderate or severe active systemic lupus erythematosus (SLE) subjects in China.

Detailed description: This is a phase I, open-label, single-arm, multicenter study to asess the safety tolerability pharmacokinetics(PK) and pharmacodynamics(PD) of Relma-cel in moderate or severe active systemic lupus erythematosus (SLE) subjects in China.

There will be 4 dose level (15x106 CAR+ T cells as the back up dose ,25x106 CAR+ T cells as the starting dose 、50x106 CAR+ T cells and 100x106(or 150 x106CAR+ T cells）Dose escalation, to evaluate the safety、 tolerability of Relma-cel in adult subjects of SLE and determine RP2D .

Eligibility criteria: Inclusion Criteria:

1. Sign an informed consent form (ICF) voluntarily.
2. At the time of signing the ICF, you must be between 18 and 70 years old (inclusive), male or female.
3. A diagnosis of SLE according to the 1997 revised criteria of the American College of Rheumatology (ACR).
4. The history of SLE prior to screening was at least 6 months, and the disease remained active at least 2 months after the use of a stable standard SLE regimen prior to screening.

Standard treatment regimen refers to the steady use of any of the following (alone or in combination) : corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), and other immunosuppressants or immunomodulators including azathioprine, Mycophenolate Mofetil, cyclophosphamide, methotrexate, leflunomide, tacrolimus, and cyclosporine.

Oral corticosteroids must meet the following requirements:

1. Prednisone (or equivalent) ≥7.5 mg/ day, and ≤30 mg/ day.
2. There is no minimum daily dose requirement for corticosteroids when used in combination with immunosuppressants.
3. At least 8 weeks of treatment prior to screening, and the dose must be kept stable for \> 2 weeks.

5. Screening is positive for antinuclear antibodies, and/or anti-DS-DNA antibodies, and/or anti-Smith antibodies.

6. SELENA-SLEDAI score ≥8 during the screening period. Score ≥6 for SELENA-SLEDAI clinical symptoms (except for low complement and/or anti-DS-DNA antibodies) if low complement and/or anti-DS-DNA antibody score is present.

Exclusion Criteria:

1. Severe lupus nephritis (defined as proteinuria \> 6 g/24h or serum creatinine \> 2.5 mg/dL or 221 μmol/L), treatment with active nephritis with Prohibited drugs, hemodialysis, or prednisone ≥100 within 8 weeks prior to screening mg/d or equivalent glucocorticoid therapy ≥14 days.
2. Prior to screening, other lupus crises, such as active central nervous system lupus, severe hemolytic anemia, severe thrombocytopenic purpura, severe agranulocytosis, severe myocardial damage, severe lupus pneumonia or pulmonary hemorrhage, severe lupus hepatitis, and severe vasculitis.
3. Clinically significant central nervous system diseases or pathological changes not caused by lupus prior to screening, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, convulsions/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
4. Combined with other autoimmune diseases, systematic treatment is needed.
5. History of major organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
6. IgA deficiency was present during screening (serum IgA level \< 10 mg/dL)

Primary outcomes:
measure: DLT rate
timeFrame: 3 months
measure: determine RP2D
timeFrame: 3 months
Secondary outcomes:
measure: SELENA-SLEDAI （Safety of Estrogens in Systemic Lupus Erythematosus National Assessment） score； 0 to 4 is basically no disease activity; 5 to 9 is light activity; 10 to 14 is moderate activity;≥15 is considered heavy activity.
timeFrame: 3 months
measure: BILAG -2004（updated version of british isles lupus assessment group ） level；The BILAG 2004 index categorizes disease activity into 5 different levels from A-E.Grade A represents very active disease.
timeFrame: 3 months
measure: PGA (physician global assessment) score,The PGA scale ranges from "no disease activity" (0) to the "most severe disease activity" (3).the score is between 0 to 3.
timeFrame: 3 months
measure: Autoantibody detection
timeFrame: 3 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Relma-cel Medical
Study officials:
affiliation: Wuhan Union Hospital, China
name: yu Hu
role: PRINCIPAL_INVESTIGATOR
affiliation: Wuhan Union Hospital, China
name: heng Mei
role: PRINCIPAL_INVESTIGATOR
affiliation: Renji Hospital Shanghai Jiaotong University School of Medical
name: liangjing Lv
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kaufman JL, Deak ST, Erdman W. Radionuclide scans to define patterns of occult myonecrosis. N J Med. 1986 Feb;83(2):101-3. No abstract available.