A Study of mRNA Encoding CD19/CD3 T Cell Engager (ABO2203) in Patients With Refractory Autoimmune Diseases

Shanghai Jiao Tong University

Status and phase

Not yet enrolling

Early Phase 1

Conditions

Autoimmune Diseases

Treatments

Drug: ABO2203 Injection

Study type

Interventional

Funder types

Other

Identifiers

NCT06747156

ABO2203-001

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, as well as preliminary efficacy of mRNA encoding CD19/CD3 T cell engager (ABO2203) in patients with refractory autoimmune diseases who received inadequate response or relapsed from standard of care (SoC). The trial included dose escalation and dose expansion parts.

Enrollment

26 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. ≥18 years of age at time of informed consent. 2. Diagnosis of autoimmune diseases according to the corresponding disease classification criteria, including but not limited to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), and idiopathic inflammatory myopathy (IIM).
2. Diagnosis of SLE defined as fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria of SLE.
3. Diagnosis of lupus nephritis (LN): active, biopsy-proven LN Class III or IV ± V by 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria.
  
  Active SLE disease, as demonstrated by a SLE disease activity index (SLEDAI-2K) total score of ≥6 with a clinical score of ≥4.
4. Diagnosis of RA: meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA.
  
  Moderate or severe active RA disease, as demonstrated by minimum of 6 swollen (SJC) and 6 tender joints (TJC) on a 66/68 joint count, ESR≥28mm/h, and CRP>7.0mg/L at the screening visit.
  1. Inadequate response to SoCs (at least 2 of first-line treatment drugs, including glucocorticoids and immunosuppressants, etc.) or relapsed after the treatment.
  2. The results of clinical laboratory tests achieved during the screening period meet relevant criteria defined in the study protocol.
  3. Received relevant background SoCs at least 12 weeks prior to screening, and with a stable dose at least 4 weeks prior to the enrollment, it must be planned that the background SoC treatment remains at the stable dose throughout the study period.
  4. Sufficient organ function.
  Exclusion Criteria:
1. Criteria for relevant autoimmune diseases, e.g., SLE: Active severe or unstable lupus-associated neuropsychiatric SLE. LN: Active central nervous system (CNS) lupus RA: experienced surgery in joint or intraarticular glucocorticoid therapy within 8 weeks prior to screening; experienced inflammatory joint disease other than RA.
2. Active infection, including tuberculosis, active or relapsed peptic ulcer, etc.
3. Severe hypogammaglobulinemia or IgA deficiency. 4. Active hepatitis or with a history of severe liver disease. 5. History of rapid allergic reactions, eczema or asthma that cannot be controlled by topical corticosteroids.
4. Severe cardiovascular diseases. 7. History of cancer within past 5 years. 8. Have other serious medical conditions. 9. Received any of B cell targeted therapies within 48 weeks prior to screening.
5. Received TNF-α antagonists, IL-6 antagonists, IL-1 antagonists, selective T cell co-stimulatory factor inhibitors, etc. within 48 weeks prior to screening.
6. Received non biologic therapy within 4 weeks prior to screening or 5 known drug half-lives (whichever is shorter).
7. History of severe allergies or known allergies to any active or inactive component of the study drug(s).
8. A history of organ transplantation, bone marrow transplantation or hematopoietic stem cell transplantation.