Safety and Clinical Activity of Itolizumab in aGVHD

Acute Graft Versus Host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05823675
• Other study ID #: BPL-ITO-aGVHD-1
• Status: Recruiting
• Phase: Phase 1
• Start date: May 19, 2023
• Est. completion date: February 2025

Study information

• Verified date: April 2023
• Source: Biotech Pharmaceutical Co., Ltd.
• Contact: Xijuan Song
• Phone: 010-51571020
• Email: songxijuan[@]biotechplc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: February 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Itolizumab
Subjects will receive Itolizumab concomitant within 72 hours of systematic Corticosteroids.
• Methylprednisolone
Methylprednisolone will be taperred as required

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Biotech Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to maximum Itolizumab serum concentration, Tmax	Time to maximum Itolizumab serum concentration	Study Day 85
Secondary	Maximum Itolizumab serum drug concentration, Cmax	Maximum Itolizumab serum drug concentration	Study Day 85
Secondary	Minimum Itolizumab serum drug concentration, Cmin	Minimum Itolizumab serum drug concentration	Study Day 85
Secondary	Total Itolizumab exposure across time, AUC	Total Itolizumab exposure across time, AUC	Study Day 85
Secondary	Half life of Itolizumab, t1/2	Half life of Itolizumab	Study Day 85
Secondary	Volume of distribution of Itolizumab, Vd	Volume of distribution of Itolizumab	Study Day 85
Secondary	Clearance, Cl	Clearance	Study Day 85
Secondary	CD6 receptor expression levels on T cells	CD6 receptor expression levels	Study Day 85
Secondary	T cell subsets	T cell subsets	Study Day 85
Secondary	Inflammatory Markers	Including but not limited to:IL-2, IL-6, IL-8, IL-17, IFN-?, TNF-a, CRP, TNFR1, ST2, REG3a, Elafin	Study Day 85
Secondary	Overall Response Rate (ORR)	Percentage of subjects demonstrating a CR or PR.	Study Day 337
Secondary	Nonrelapse Mortality(NRM) Rate	Proportion of subjects who died due to causes other than malignancy relapse	Study Day 337
Secondary	cGVHD rate	Percentage of subjects demonstrating of cGVHD	Study Day 337
Secondary	Dose Reduction in Systemic Steroid Use	Change from Baselinein Dose of Systemic Steroid Use	Study Day 337
Secondary	Incidence of ADA	Precentage of subjects presenting anti-drug antibody	Study Day 85