Clinical trial NCT05823675: Safety and Clinical Activity of Itolizumab in aGVHD
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acute Graft Versus Host Disease
Lead sponsor: Biotech Pharmaceutical Co., Ltd.
Sponsor class: OTHER
First posted: 2023-04-21
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment Emergent Adverse Events
timeFrame: Study Day 85
Secondary outcomes:
measure: Time to maximum Itolizumab serum concentration, Tmax
timeFrame: Study Day 85
measure: Maximum Itolizumab serum drug concentration, Cmax
timeFrame: Study Day 85
measure: Minimum Itolizumab serum drug concentration, Cmin
timeFrame: Study Day 85
measure: Total Itolizumab exposure across time, AUC
timeFrame: Study Day 85
measure: Half life of Itolizumab, t1/2
timeFrame: Study Day 85
measure: Volume of distribution of Itolizumab, Vd
timeFrame: Study Day 85
measure: Clearance, Cl
timeFrame: Study Day 85
measure: CD6 receptor expression levels on T cells
timeFrame: Study Day 85
measure: T cell subsets
timeFrame: Study Day 85
measure: Inflammatory Markers
timeFrame: Study Day 85
measure: Overall Response Rate (ORR)
timeFrame: Study Day 337
measure: Nonrelapse Mortality(NRM) Rate
timeFrame: Study Day 337
measure: cGVHD rate
timeFrame: Study Day 337
measure: Dose Reduction in Systemic Steroid Use
timeFrame: Study Day 337
measure: Incidence of ADA
timeFrame: Study Day 85
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Study officials:
affiliation: Chinese Academy of Medical Sciences
name: Erlie Jiang
role: PRINCIPAL_INVESTIGATOR
References: