Clinical trial NCT06747156: A Study of mRNA Encoding CD19/CD3 T Cell Engager (ABO2203) in Patients With Refractory Autoimmune Diseases
Official title: A Clinical Study to Investigate Safety, Tolerability, and Preliminary Efficacy of mRNA Encoding CD19/CD3 T Cell Engager (ABO2203) in Patients With Refractory Autoimmune Diseases
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Autoimmune Diseases
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Suzhou Guangxin Biosciences Co., Ltd.
First posted: 2024-12-24
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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).

  1. Diagnosis of SLE defined as fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria of SLE.
  2. 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.
  3. 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.

     3. Inadequate response to SoCs (at least 2 of first-line treatment drugs, including glucocorticoids and immunosuppressants, etc.) or relapsed after the treatment.

     4. The results of clinical laboratory tests achieved during the screening period meet relevant criteria defined in the study protocol.

     5. 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.

     6. 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.

  6. 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.

  10. Received TNF-α antagonists, IL-6 antagonists, IL-1 antagonists, selective T cell co-stimulatory factor inhibitors, etc. within 48 weeks prior to screening.

  11. Received non biologic therapy within 4 weeks prior to screening or 5 known drug half-lives (whichever is shorter).

  12. History of severe allergies or known allergies to any active or inactive component of the study drug(s).

  13. A history of organ transplantation, bone marrow transplantation or hematopoietic stem cell transplantation.

Primary outcomes:
measure: The incidence, severity, and nature of treatment-emergent adverse events (TEAE)s.
timeFrame: from the first dose of study treatment to 30 days after the last dose of study treatment.
measure: The incidence, severity, and nature of serious TEAEs (TESAE)s .
timeFrame: from the first dose of study treatment to 30 days after the last dose of study treatment.
measure: The incidence, severity, and nature of TEAEs leading to interruption or early termination of study treatment.
timeFrame: from the first dose of study treatment to 30 days after the last dose of study treatment.
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital
Study officials:
affiliation: Ruijin Hospital
name: Chengde Yang
role: PRINCIPAL_INVESTIGATOR
References: