Safety and Clinical Activity of Itolizumab in aGVHD

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Itolizumab in Subjects With Newly Diagnosed Acute Graft Versus Host Disease

To evaluate the safety, tolerability, PK, PD, and clinical activity of Itolizumab in subjects with Newly diagnosed Acute Graft Versus Host Disease(aGVHD).

The study will enroll approximately 44 subjects in three parts:

Part 1 is an open label 3+3 single dose escalation phase and will enroll approximately 30 subjects with aGVHD across 4 cohorts, where subjects will receive Itolizumab administered intravenously for 1 dose.

Part 2 is an open label phase and subjects from part 1 will receive Itolizumab administered intravenously every two weeks for a total of 4 doses.

Part 3 is a randomized phase and will enroll approximately 14 additional subjects, randomized in a 1:1 ratio to one of the 2 recommended doses provided by Part 1 and Part 2. Subjects will receive Itolizumab administered intravenously every two weeks for a total of 5 doses.

Inclusion Criteria:

• Male or female subject at least 18 years of age.
• Has received allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• Clinical diagnosis of Grade II-IV aGVHD per MAGIC guideline requiring systemic immune suppressive therapy.
• Initiation of systemic steroids therapy ≤ 72 hours.
• Negative result of serum HCG within 72 hours before enrollment for female with potential fertility.
• Have a life expectancy of 10 weeks or more.
• Able to understand and comply with the planned procedure as required by the protocol, and sign a written informed consent form (ICF).

Exclusion Criteria:

• Has received more than 1 allo-HSCT.
• Presence of morphologic relapsed primary malignancy, treatment for relapse after alloHSCT was performed, or requirement for rapid immunosuppressive treatment withdrawal for early malignancy relapse.
• Evidence of graft failure based on cytopenia(s), and as determined by the investigator.
• Evidence of post-transplant lymphoproliferative disease.
• Any prior therapy for acute GVHD, except for alloHSCT prophylaxis regimens or systemically administered corticosteroids.
• aGVHD induced by donor lymphocyte infusion(DLI).
• Clinically or suspected diagnosed of cGVHD or overlap syndrome.
• Unresolved toxicity or complications due to allo-HSCT,other than aGVHD.
• Any clinical or laboratory abnormalities that is likely to negatively affect the reliability of the study safety data, as determined by the investigator.
• Presence of any uncontrolled active infections, which was defined as hemodynamic instability due to sepsis or worsening of new symptoms, signs, or imaging findings due to infection.
• Presence of any uncontrolled and active infections.
• Presence of active and uncontrolled viral infections at screening.
• History of active tuberculosis within 6 months prior to screening or negative result of interferon-gamma release assay at screening.
• History of class III or IV congestive heart failure per New York Heart Association, clinically significant or uncontrolled unstable angina or myocardial infarction, cerebrovascular accident, or pulmonary embolism within 6 months prior to screening.
• Severe impaired renal function at screening (serum creatinine > 1.5 ULN or creatinine clearance < 30mL/min).
• Presence of persistent bilirubin abnormalities induced by hepatic sinusoidal obstruction, hepatic veno-occlusive disease, non-GVHD or progressive organ dysfunction at screening.
• Serum ALT and AST > 4 ULN at screening.
• Absolute lymphocyte count < 0.5×109/L at screening.
• Any major surgical procedures performed within 4 weeks prior to screening, that is likely to negatively affect the evaluation of the study safety data, as determined by the investigator.
• Any malignant tumor other than the transplanted tumor within 5 years before screening.
• Suspected allergic to the experimental drug product or any of its excipients.
• Currently pregnant, breastfeeding,or planning to become pregnant or not using reliable method to avoid pregnancy during study and within 3 months after the last study treatment.
• As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect the reliability of the study data.