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

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

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

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Diseases; Crohn Disease; Ulcerative Colitis; Dermatomyositis; Still Disease
• Intervention / Treatment: Biological: CD7 CAR T-cells

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 Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: He Huang, PhD; Phone Number: +8613605714822; Email: hehuangyu@126.com
• Study Contact Backup: Name: Yongxian Hu, PhD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: Yongxian Hu, PhD; Phone Number: +8615957162012; Email: huyongxian2000@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 28, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: February 13, 2022
• First Posted (Actual): February 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 13, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Dermatomyositis; CAR T-cell therapy; Ulcerative colitis; Crohn disease; CD7; Still disease; Refractory autoimmune disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Nervous System Diseases; Skin Diseases; Immune System Diseases; Gastrointestinal Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Gastroenteritis; Muscular Diseases; Neuromuscular Diseases; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Polymyositis; Myositis; Ulcer; Crohn Disease; Colitis; Colitis, Ulcerative; Dermatomyositis; Autoimmune Diseases
• Other Study ID Numbers: CD7-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No