Clinical Study of Targeting CD7 CAR-T Cells in the Treatment of Autoimmune Diseases

• ClinicalTrials.gov Identifier: NCT05239702
• Recruitment Status: Recruiting
• First Posted: February 15, 2022
• Last Update Posted: February 15, 2022
• Sponsor: Zhejiang University
• Collaborator: Yake Biotechnology Ltd.
• Information provided by (Responsible Party): He Huang, Zhejiang University

Study Description

Brief Summary:

A Clinical Study on the Safety and Effectiveness of Targeting CD7 Chimeric Antigen Receptor T Cells in the Treatment of Autoimmune Diseases

Condition or disease	Intervention/treatment	Phase
Crohn Disease; Ulcerative Colitis; Dermatomyositis; Still Disease; Autoimmune Diseases	Biological: CD7 CAR T-cells	Early Phase 1

Detailed Description:

Most patients with autoimmune diseases depend on hormones for life, and when poorly controlled, they are at risk of disability or even death. Studies have found that the abnormal T cell function of patients is closely related to the occurrence and development of the disease. Therefore, reducing the T cells in the patient's body or blocking the function has become the latest breakthrough in treatment. CD7 is a specific antigen on the surface of T cells. CD7 CAR-T can specifically attack T cells and has the potential to cure. In 2019, "Science Translational Medicine" magazine reported that the Marko Radic team demonstrated that CAR-T cells can achieve significant and long-lasting effects in the treatment of systemic lupus erythematosus (SLE) through animal experiments. In 2021, "NEJM" magazine reported the clinical efficacy of CAR-T cells in the treatment of SLE. In the same year, "Journal of Clinical Oncology" reported the clinical efficacy and safety of CD7 CAR-T cells in the treatment of T cell ALL.

Based on the current research status, we applied to clinical research on the treatment of refractory autoimmune diseases by targeting CD7 CAR-T cells. The selection criteria is patients with refractory autoimmune diseases. The purpose is to evaluate the safety and effectiveness of targeted CD7 CAR-T cell therapy through this clinical trial study, and to provide clinical evidence and experience reference for the application of CAR-T cell technology in the treatment of refractory autoimmune diseases.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 75 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Clinical Study on the Safety and Effectiveness of Targeting CD7 Chimeric Antigen Receptor T Cells in the Treatment of Autoimmune Diseases
• Estimated Study Start Date: February 28, 2022
• Estimated Primary Completion Date: December 1, 2024
• Estimated Study Completion Date: December 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Crohn Disease	Biological: CD7 CAR T-cells; Each subject receive CD7 CAR T-cells by intravenous infusion; Other Name: CD7 CAR-T cells injection
Experimental: Ulcerative Colitis	Biological: CD7 CAR T-cells; Each subject receive CD7 CAR T-cells by intravenous infusion; Other Name: CD7 CAR-T cells injection
Experimental: Dermatomyositis	Biological: CD7 CAR T-cells; Each subject receive CD7 CAR T-cells by intravenous infusion; Other Name: CD7 CAR-T cells injection
Experimental: Still Disease	Biological: CD7 CAR T-cells; Each subject receive CD7 CAR T-cells by intravenous infusion; Other Name: CD7 CAR-T cells injection
Experimental: Autoimmune Diseases	Biological: CD7 CAR T-cells; Each subject receive CD7 CAR T-cells by intravenous infusion; Other Name: CD7 CAR-T cells injection

Outcome Measures

Primary Outcome Measures :

1. Dose-limiting toxicity (DLT) [ Time Frame: Baseline up to 28 days after CD7 targeted CAR T-cells infusion ]
   Adverse events assessed according to NCI-CTCAE v5.0 criteria
2. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 2 years after CD7 targeted CAR T-cells infusion ]
   Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures :

1. Overall response rate (ORR) [ Time Frame: At Month 1, 3, 6, 12, 18, 24 ]
   Proportion of subjects with complete or partial remission
2. Best overall response, BOR [ Time Frame: At ≤3 month ]
   Assessment of ORR at ≤3 month
3. Concentration of CAR-T cells [ Time Frame: From admission to the end of the follow-up, up to 2 years ]
   In peripheral blood and bone marrow
4. Duration of remission, DOR [ Time Frame: 2 years post CD7 CAR-T cells infusion ]
   The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause
5. Overall survival (OS) [ Time Frame: From CD7 CAR-T infusion to death，up to 2 years ]
   The time from the cell reinfusion to death due to any cause

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Diagnosed as refractory Crohn disease, ulcerative colitis (collectively called Crohn's disease), and the conventional hormone therapy is not effective and (or) there is no effective treatment:

   1. At least 6 months before screening, diagnosed as Crohn's disease based on typical radiological results and/or typical histology.
   2. In addition to corticosteroids, after the use of immunosuppressive agents (usually azathioprine, methotrexate, and two biological agents (usually infliximab, adalimumab and/or setolizumab), the course of the disease is still Unsatisfactory. Patients should still have relapsed and refractory diseases after glucocorticoid and/or immunosuppressive treatment, or clearly show intolerance/toxicity to these drugs

2. Diagnosed as refractory dermatomyositis, and conventional hormone therapy is not effective and (or) ineffective treatment methods:

   1. At least 6 months before screening, confirmed or possible dermatomyositis according to Bohan and Peter criteria;
   2. At least it has no response to prednisone and other first-line immunosuppressants (such as methotrexate, mycophenolate mofetil, or azathioprine), or has obvious toxicity or intolerance to these therapies.

3. Refractory adult STILL disease

   1. Conform the diagnostic criteria for adult STILL disease (according to Yamaguchi et al., J. Rheumatology, 1992);
   2. After receiving non-steroidal anti-inflammatory drugs, glucocorticoids, anti-rheumatic drugs (DMARDs) and other treatments, there are still relapsed and refractory diseases, or clearly show that these drugs are intolerant/toxic.

4. Rheumatoid arthritis

   1. Conform the diagnostic criteria for rheumatoid arthritis in 2010 ACR classification criteria;
   2. Have received DMARDs or glucocorticoid therapy, but failed to achieve clinical remission, or clearly showed intolerance/toxicity to these drugs.

   The following screening can be performed by meeting any of the above 4 entry criteria

5. Estimated survival time> 12 weeks;
6. Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up;
7. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

• Subjects with any of the following exclusion criteria were not eligible for this trial:

  1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
  2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
  3. Pregnant (or lactating) women;
  4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
  5. Active infection of hepatitis B virus or hepatitis C virus;
  6. Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids);
  7. Those who have used any gene therapy products before.
  8. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
  9. Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl;
  10. Those who suffer from other uncontrolled diseases are not suitable to join the study;
  11. HIV infection;
  12. Any situation that the researchers believe may increase the risk of patients or interfere with the test results.

Contacts and Locations

Contacts

Contact: He Huang, PhD; +8613605714822; hehuangyu@126.com

Contact: Yongxian Hu, PhD; +8615957162012; huyongxian2000@aliyun.com

Locations

China, Zhejiang

The first affiliated hospital of medical college of zhejiang university; Recruiting

Hangzhou, Zhejiang, China, 310003

Contact: He Huang, PhD 86-13605714822 hehuangyu@126.com

Contact: Yongxian Hu, PhD +8615957162012 huyongxian2000@aliyun.com

Sponsors and Collaborators

Zhejiang University

Yake Biotechnology Ltd.

Investigators

• Principal Investigator: He Huang, PhD; First Affiliated Hospital of Zhejiang University

More Information

• Responsible Party: He Huang, The President of The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang University
• ClinicalTrials.gov Identifier: NCT05239702
• Other Study ID Numbers: CD7-002
• First Posted: February 15, 2022
• Last Update Posted: February 15, 2022
• Last Verified: February 2022

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

Keywords provided by He Huang, Zhejiang University:

CAR T-cell therapy; CD7; Crohn disease; Ulcerative colitis; Dermatomyositis; Still disease; Refractory autoimmune disease

Additional relevant MeSH terms:

Dermatomyositis; Crohn Disease; Colitis; Colitis, Ulcerative; Autoimmune Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colonic Diseases; Immune System Diseases; Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin Diseases