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).

Study Overview

• Status: Recruiting
• Conditions: Acute Graft Versus Host Disease
• Intervention / Treatment: Drug: Itolizumab; Drug: Methylprednisolone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xijuan Song; Phone Number: 010-51571020; Email: songxijuan@biotechplc.com

Study Locations

• China
  • Tianjin, China, 300020
    • Recruiting
    • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
    • Contact: Erlie Jiang

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itolizumab Dose Level 1; Itolizumab of 25 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.	Drug: Itolizumab; Subjects will receive Itolizumab concomitant within 72 hours of systematic Corticosteroids.; Other Names: T1h; Drug: Methylprednisolone; Methylprednisolone will be taperred as required; Other Names: Methylprednisolone Sodium Succinate
Experimental: Itolizumab Dose Level 2; Itolizumab of 50 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.	Drug: Itolizumab; Subjects will receive Itolizumab concomitant within 72 hours of systematic Corticosteroids.; Other Names: T1h; Drug: Methylprednisolone; Methylprednisolone will be taperred as required; Other Names: Methylprednisolone Sodium Succinate
Experimental: Itolizumab Dose Level 3; Itolizumab of 100 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.	Drug: Itolizumab; Subjects will receive Itolizumab concomitant within 72 hours of systematic Corticosteroids.; Other Names: T1h; Drug: Methylprednisolone; Methylprednisolone will be taperred as required; Other Names: Methylprednisolone Sodium Succinate
Experimental: Itolizumab Dose Level 4; Itolizumab of 150 mg administered by intravenous infusion every 2 weeks for a total of 5 doses.	Drug: Itolizumab; Subjects will receive Itolizumab concomitant within 72 hours of systematic Corticosteroids.; Other Names: T1h; Drug: Methylprednisolone; Methylprednisolone will be taperred as required; Other Names: Methylprednisolone Sodium Succinate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events	Number of subjects with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0	Study Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum Itolizumab serum concentration, Tmax	Time to maximum Itolizumab serum concentration	Study Day 85
Maximum Itolizumab serum drug concentration, Cmax	Maximum Itolizumab serum drug concentration	Study Day 85
Minimum Itolizumab serum drug concentration, Cmin	Minimum Itolizumab serum drug concentration	Study Day 85
Total Itolizumab exposure across time, AUC	Total Itolizumab exposure across time, AUC	Study Day 85
Half life of Itolizumab, t1/2	Half life of Itolizumab	Study Day 85
Volume of distribution of Itolizumab, Vd	Volume of distribution of Itolizumab	Study Day 85
Clearance, Cl	Clearance	Study Day 85
CD6 receptor expression levels on T cells	CD6 receptor expression levels	Study Day 85
T cell subsets	T cell subsets	Study Day 85
Inflammatory Markers	Including but not limited to:IL-2, IL-6, IL-8, IL-17, IFN-γ, TNF-α, CRP, TNFR1, ST2, REG3α, Elafin	Study Day 85
Overall Response Rate (ORR)	Percentage of subjects demonstrating a CR or PR.	Study Day 337
Nonrelapse Mortality(NRM) Rate	Proportion of subjects who died due to causes other than malignancy relapse	Study Day 337
cGVHD rate	Percentage of subjects demonstrating of cGVHD	Study Day 337
Dose Reduction in Systemic Steroid Use	Change from Baselinein Dose of Systemic Steroid Use	Study Day 337
Incidence of ADA	Precentage of subjects presenting anti-drug antibody	Study Day 85

Collaborators and Investigators

• Sponsor: Biotech Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Erlie Jiang, Institute of Hematology ＆ Blood Diseases Hospital，Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: March 16, 2023
• First Submitted That Met QC Criteria: April 10, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: BPL-ITO-aGVHD-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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