Safety Study of CC312 in Autoimmune Disease Patients

NCT06888960 | Recruiting Early Phase 1

• 1 other identifier: CC312-I-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, multiple-dose escalation, Investigator-Initiated Trial (IIT) clinical trial designed to evaluate the safety and tolerability of CC312 in adult patients with relapsed and refractory autoimmune diseases. The trial also assesses pharmacokinetics (PK) and preliminary efficacy. CC312 is a trispecific T cell engager (TriTE) that targets the B cell surface antigen CD19, the T cell antigen CD3, and the T cell co-stimulatory molecule CD28. Given its mechanism of action, which is similar to the "biopharmaceutical version" of CAR-T, there is a higher risk of cytokine release syndrome (CRS) at the onset of infusion administration. Therefore, a lower priming dose will be administered before the therapeutic dosing phase to mitigate this risk and ensure safety, followed by a therapeutic dose to achieve and maintain efficacy. The study is divided into three dose groups, with 3-6 subjects enrolled in each group, resulting in a total of 9-18 subjects in the study. A "3+3" dose escalation design is employed to systematically evaluate the safety and determine the optimal dose of CC312.

Conditions

Systemic Lupus Erythematosus (SLE); Idiopathic Inflammatory Myopathy (IIM); Systemic Sclerosis (SSc); Rheumatoid Arthritis (RA); Primary Immune Thrombocytopenia (ITP); Autoimmune Hemolytic Anemia

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  Hematological DLT is defined as a Grade 4 toxic reaction (excluding lymphopenia) that is not attributable to the underlying disease and persists for more than 29 days. Non-hematological DLT refers to any Grade ≥4 toxicities that may be associated with CC312 treatment, or Grade 3 toxicities that may be associated with CC312 treatment and persist for ≥7 days during the DLT observation period following CC312 infusion.

  2 years

• Adverse events (AE)/serious adverse events (SAE)

  All adverse events will be evaluated and graded according to the severity criteria of CTCAE (Common Terminology Criteria for Adverse Events) version 5.0, with the exception of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which will be assessed using the ASTCT (American Society for Transplantation and Cellular Therapy) standard.

  2 years

Secondary Outcomes (15)

• Maximum Serum Concentration (Cmax) of CC312

  2 years

• Area Under the Concentration-time Curve (AUC) of CC312

  2 years

• Minimum Concentration (Cmin) of CC312

  2 years

• Counts of peripheral B cells

  2 years

• Cytokine Indicators

  2 years

Study Arms (1)

CC312

EXPERIMENTAL

The patient received CC312 via intravenous administration.

Biological: CC312

Interventions

CC312 BIOLOGICAL

After a 28-day screening period, subjects who meet the inclusion and exclusion criteria will be enrolled for baseline assessments and biological sample collection prior to the guided administration period. The guided dose of CC312 will be administered via IV infusion on Day -3, followed by safety and tolerability assessments on the third day after the initial administration (i.e., Day -1). The therapeutic dose of CC312 will be administered via IV infusion on Day 1, with subsequent infusions scheduled on Day 4, Day 8, Day 11, Day 15, Day 18, Day 22, and Day 25. Comprehensive safety and tolerability assessments will be conducted at each of these time points.

CC312

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who fully understand the objectives, nature, methods of the study, and possible adverse reactions, voluntarily participate as subjects, and sign the informed consent form (ICF).
• Age ≥18 years (inclusive, based on the time of signing ICF), male or female.
• For SLE:
• Subjects who are diagnosed with SLE according to the 2019 European League Against Rheumatism (EULAR)/1997 American College of Rheumatology (ACR) diagnostic classification criteria;
• SLEDAI-2000 score of ≥ 8 points and at least one BILAG grade A or two BILAG grade B under standard treatment conditions;
• Meet one of the following conditions: antinuclear antibody (ANA) determined to be positive during the screening period, or anti-dsDNA antibodies higher than normal levels at screening, or anti-Sm antibodies higher than normal levels at screening;
• Before the first dose of the investigational drug, subjects must have received at least one of the following standard treatments for 12 weeks, and the dose must have been stable for at least 30 days (dose reduction is allowed and dose increase is not allowed ). Standard treatment regimen refers to the stable use of any of the following (alone or in combination): a. Antimalarial (hydroxychloroquine) monotherapy; b. Antimalarials in combination with oral corticosteroids (OCS, e.g., prednisone or other hormones at equivalent doses) and/or immunosuppressants (including mycophenolate mofetil, cyclophosphamide, leflunomide, methotrexate, tacrolimus, ciclosporin, azathioprine, Tripterygium wilfordii); c. OCS and/or immunosuppressant combination therapy. If the subject is receiving OCS (e.g., prednisone or other hormones at equivalent doses), the following criteria must be met: at screening and during the screening period, the maximum dose of OCS is 30 mg/day of prednisone (or other hormones at equivalent doses); other drugs and traditional Chinese medicines that affect immunity may be continued at the discretion of the investigator.
• For IIM:
• According to the 2017 EULAR/ACR Classification Criteria, diagnosed as possible or definite IIM-possible IIM: with a score of 5.5 points without biopsy; definite IIM: with a score of 6.7 points with biopsy;
• Meeting one of the following criteria: During or before the screening period, confirmed to have at least one positive myositis-specific autoantibody (MSA), myositis-associated autoantibody (MAA), or ANA;
• Conventional treatment is ineffective or the disease relapses after remission. Conventional treatment is defined as: the use of glucocorticoids (prednisone \>1 mg/kg/d or equivalent dose) and/or at least one immunomodulatory drug: such as antimalarial drugs, azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, tacrolimus, ciclosporin, and/or biological drug products: such as rituximab and belimumab.
• For IIM:
• Subjects who are diagnosed with SSc according to the 2013 EULAR/ACR diagnostic classification criteria;
• Meets one of the following criteria: positive ANA confirmed during or before the screening period, or at least one positive SSc-related antibody profile (such as Scl70, Th/To, RP11/12, U3RNP autoantibodies);
• Conventional treatment is ineffective or the disease relapses after remission. Conventional treatment is defined as: using glucocorticoids (prednisone \> 0.5 mg/kg/d or equivalent dose) and cyclophosphamide, and any of the following immunomodulatory drugs: such as antimalarial drugs, azathioprine, mycophenolate mofetil, methotrexate, leflunomide, tacrolimus, ciclosporin, and/or biological agents: such as rituximab and belimumab, with a cumulative treatment duration \> 6 months.

You may not qualify if:

• Subjects who have severe lupus nephritis (defined as urinary protein \>6 g/24 h or serum creatinine \>2.5 mg/dL or 221 μmol/L), or required treatment of active nephritis with protocol-prohibited drugs, or required hemodialysis or received prednisone ≥100 mg/d or equivalent glucocorticoid therapy for ≥14 days within 8 weeks before screening.
• Subjects who have central nervous system diseases caused by SLE or not caused by SLE within 8 weeks before screening (including but not limited to epilepsy, psychosis, posterior reversible encephalopathy syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis, etc.).
• Pulmonary arterial hypertension associated with SSc requiring treatment; or rapidly progressive SSc-related lower gastrointestinal tract (small and large intestine) involvement (requiring parenteral nutrition), active antral vascular ectasia; previous renal crisis caused by SSc.
• Significant organ transplantation (e.g., heart, lung, kidney, liver) or history of hematopoietic stem cell/bone marrow transplantation.
• Concomitant presence of two or more immune diseases requiring systemic treatment, if the investigator deems the subject unsuitable for enrollment.
• IgA deficiency (serum IgA level \<10 mg/dL).
• Have participated in any other clinical trials (including cell or gene therapy) within 4 weeks before screening or within 5 half-lives of the investigational product (whichever is longer).
• Have received CAR-T therapy within 6 months before screening.
• Have received B-cell depleting drug rituximab or equivalent treatments (targeting CD19, CD20, BAFF, etc.) within 1 month before screening, unless it can be demonstrated that B cells have returned to pre-treatment levels or within the normal range.
• Have received anti-SLE treatments (e.g., Saphnelo) other than standard therapy within 3 months before screening or within 5 half-lives of the investigational product (whichever is longer).
• Have received a live/attenuated vaccine within 4 weeks before screening or plans to receive a live/attenuated vaccine during the study.
• Active infection.
• History of Grade 3-4 (CTCAE v5.0) allergic reaction to another monoclonal antibody treatment, or known allergy to any component or excipient of the CC312 drug product (including recombinant proteins, polysorbate 80, etc.); patients with a ≤Grade 3 allergy lasting \<24h may participate in this study after discussion with the investigator.
• Acknowledgement of or evidence of illicit drug use, drug abuse, or alcoholism.
• History of any of the following cardiovascular diseases within 6 months before screening: NYHA Class III or IV heart failure, myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmia, any ventricular arrhythmia, or other clinically significant heart disease.

Sponsors & Collaborators

• CytoCares Inc: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, China, 300030, China

RECRUITING

Related Publications (3)

• Murimi-Worstell IB, Lin DH, Kan H, Tierce J, Wang X, Nab H, Desta B, Alexander GC, Hammond ER. Healthcare Utilization and Costs of Systemic Lupus Erythematosus by Disease Severity in the United States. J Rheumatol. 2021 Mar;48(3):385-393. doi: 10.3899/jrheum.191187. Epub 2020 Jul 1.

  PMID: 32611669 BACKGROUND

• Fortuna G, Brennan MT. Systemic lupus erythematosus: epidemiology, pathophysiology, manifestations, and management. Dent Clin North Am. 2013 Oct;57(4):631-55. doi: 10.1016/j.cden.2013.06.003.

  PMID: 24034070 BACKGROUND

• Cooper GS, Bynum ML, Somers EC. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun. 2009 Nov-Dec;33(3-4):197-207. doi: 10.1016/j.jaut.2009.09.008. Epub 2009 Oct 9.

  PMID: 19819109 BACKGROUND

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Myositis; Scleroderma, Systemic; Arthritis, Rheumatoid; Purpura, Thrombocytopenic, Idiopathic; Anemia, Hemolytic, Autoimmune

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Skin Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Anemia, Hemolytic; Anemia

Central Study Contacts

CEO

CONTACT

021-50582090; yingfeng.huang@cytocares.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2025
• First Posted: March 21, 2025
• Study Start: November 8, 2024
• Primary Completion (Estimated): November 8, 2026
• Study Completion (Estimated): November 8, 2026
• Last Updated: September 17, 2025

Record last verified: 2025-09

Locations

CN (1)