CAR-T Cells Targeting Autoimmune Diseases

• ClinicalTrials.gov Identifier: NCT05459870
• Recruitment Status: Recruiting
• First Posted: July 15, 2022
• Last Update Posted: July 19, 2022
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborator: Guilin Hospital of Chinese Traditional and Western Medicine
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: July 12, 2022
• First Posted Date: July 15, 2022
• Last Update Posted Date: July 19, 2022
• Estimated Study Start Date: July 31, 2022
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 12, 2022)

Safety of 4SCAR T cells in patients with autoimmune diseases [ Time Frame: 12 weeks ]

Safety of 4SCAR T cells in patients with autoimmune diseases using CTCAE 5 standard to evaluate the level of adverse events

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 12, 2022)

• B cell and immunoglobulin suppression activity of 4SCAR T cells in patients with autoimmune diseases [ Time Frame: 1 year ]
  scale of CAR copies (for efficacy)
• B cell and immunoglobulin suppression activity of 4SCAR T cells in patients with autoimmune diseases [ Time Frame: 1 year ]
  immunoglobulin levels (for efficacy)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CAR-T Cells Targeting Autoimmune Diseases
• Official Title: CAR-T Cells Targeting B Cell Related Autoimmune Diseases
• Brief Summary: The purpose of this study is to assess the feasibility, safety and efficacy of CAR-T cell therapy in patients with autoimmune disease. Another goal of the study is to learn more about the safety and function of the CAR-T cells and their persistency in autoimmune disease patients.

Detailed Description

Autoimmune disease refers to the disease in which the immune system reacts to the host's own body and causes damage to tissues and organs. At present, the pathogenesis of various autoimmune diseases is still not well understood, but an imbalanced immune tolerance plays a key role in this process.

An ideal therapy to autoimmune disease should eradicate pathogenic autoimmune cells but retain the protective immunity. The chimeric antigen receptor-modified T (CAR-T) cell technology has proven to be highly effective in targeting B cell malignancies, and the treatment-induced B cell and antibody deficiencies have implications for treating autoantibody-related autoimmune diseases. Studies have shown that CAR-T cells targeting B cell surface molecules can kill autoreactive B lymphocytes in pemphigus vulgaris (PV) and systemic lupus erythematosus (SLE) patients. Thus, CAR-T cell technology targeting B cells has potential in treating autoimmune diseases including PV, SLE, autoimmune hemolytic anemia, Sjogren's syndrome etc..

CD19-specific CAR is based on activation of intracellular signalijng domains of T cells by the extracellular single chain variable fragment (scFv) antibody against CD19. The activated CAR-T cells can target and kill B cells. The investigation plans to use genetically modified T cells to express a 4th generation lentiviral anti-CD19 CAR with an inducible caspase 9 self-withdrawal gene (4SCAR) to increase the safety of this specific approach. Besides targeting CD19, specific CARs targeting other B cell surface molecules including BCMA, CD138, and BAFF-R will also be included in the treatment regimen. Based on accumulated experiences, the 4SCAR T cells have shown high safety profile without serious cytokine release syndrome (CRS) or neural toxicities in patients. Through this trial, the safety and long term efficacy of the B cell-specific 4SCAR T cell therapy will be evaluated, providing clinical evidence supporting the application of 4SCAR-T cell technology in the treatment of autoimmune diseases.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Autoimmune Diseases

Intervention

Biological: 4SCAR T cells

Infusion of 4SCAR T cells at 10^6 cells/kg body weight via IV

Study Arms

Experimental: 4SCAR T Cell Therapy for autoimmune diseases

Intervention: Biological: 4SCAR T cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 12, 2022): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2026
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. age older than 18 years.
2. expression of B cell surface molecules.
3. the KPS score over 80 points, and survival time is more than 3 months.
4. greater than Hgb 80 g/L.
5. no contraindications to blood cell collection.

Exclusion Criteria:

1. accompanied with other active diseases and difficult to assess treatment response.
2. bacterial, fungal, or viral infection, unable to control.
3. living with HIV.
4. active HBV or HCV infection.
5. pregnant and nursing mothers.
6. under systemic steroid treatment within a week of the treatment.
7. prior failed CAR-T treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Lung-Ji Chang, PhD; 86-0755-86725195; c@szgimi.org

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05459870
• Other Study ID Numbers: GIMI-IRB-22010
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Guilin Hospital of Chinese Traditional and Western Medicine
• Investigators: Not Provided
• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: July 2022