Acute-graft-versus-host Disease, aGVHD, GVHD, GVHD, Acute
Conditions
Brief summary
This is a multi-center study to evaluate the safety, tolerability, PK, PD, and clinical activity of EQ001 in subjects with Acute Graft Versus Host Disease (aGVHD).
Detailed description
The study will enroll approximately 100 subjects in two (2) parts: Part A is an open label study and will enroll approximately 40 evaluable subjects with aGVHD across 4 cohorts. The total number of patients will depend on the number of dose escalations necessary to enable a decision to be made on the recommended dose to take forward into Part B of the study. The planned dose escalation will start with cohort 1, where subjects will receive EQ001 administered intravenously every two weeks for a total of 5 doses. Part B is a randomized, double-blind, placebo-controlled study and will enroll approximately 60 additional subjects, randomized in a 2:1 ratio to either active treatment EQ001 (40) or placebo (20). Subjects will receive either EQ001 or placebo administered intravenously every two weeks for a total of 5 doses.
Interventions
BIOLOGICALEQ001
Itolizumab \[Bmab 600\])
BIOLOGICALEQ001 Placebo
EQ001 Placebo
Sponsors
Biocon Limited
Equillium
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part B will be blinded to all study staff that has direct access to the subjects and the sponsor. The site's pharmacist or designee will be unblinded to prepare the study drug.
Intervention model description
Part A is an open label 3+3 dose escalation Part B is blinded and randomized 2:1
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subject at least 18 years of age for Part A, and at least 12 years of age for Part B. 2. Recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT) using myeloablative or non myeloablative conditioning regimens. 3. Have a clinical diagnosis of acute GVHD requiring systemic immune suppressive therapy. 4. Deemed by the investigator to be likely to comply with the planned procedure as required by the protocol for the duration of the study
Exclusion criteria
1. Presence of morphologic relapsed primary malignancy, treatment for relapse after alloHSCT was performed, or requirement for rapid immunosuppressive treatment withdrawal for early malignancy relapse. 2. Evidence of graft failure based on cytopenia(s), and as determined by the investigator. 3. Evidence of post-transplant lymphoproliferative disease. 4. Any prior therapy for acute GVHD, except for alloHSCT prophylaxis regimens or systemically administered corticosteroids. 5. As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect: the subject's participation in this clinical study, the subject's safety, or the reliability of the study data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Emergent Adverse Events | Study Day 85 | Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
| Overall Response Rate | Study Day 29 | Overall Response Rate (ORR) is defined as the number of subjects with a partial response (PR), very good partial response (VGPR), or complete response (CR) who are alive at Day 29. Subjects must not have received new systemic therapy for aGVHD before the Day 29 Visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum EQ001 Serum Drug Concentration, Cmin | Study Day 337 | Minimum EQ001 serum drug concentration prior to next dose, Cmin |
| Total EQ001 Exposure Across Time, AUC (From Zero to Infinity) | Study Day 337 | Total EQ001 exposure across time, AUC (from zero to infinity) |
| Half Life of EQ001, t1/2 | Study Day 337 | Half life of EQ001, t1/2 |
| Time to Maximum EQ001serum Concentration, Tmax | Day 337 | Time to maximum EQ001 serum concentration, Tmax |
| Clearance, Cl | Study Day 337 | Clearance, Cl |
| Inflammatory Markers | Study Day 337 | Including but not limited to: IL-1β, IL-2, IL-6, IL-17, IL-21, IL-22, IL-23, IFN-γ, and TGF-β, C-reactive protein |
| CD6 Receptor Expression Levels | Study Day 85 | CD6 receptor expression levels - percent of baseline |
| Volume of Distribution of EQ001, Vd | Study Day 337 | Volume of distribution of EQ001, Vd |
| Maximum EQ001 Serum Drug Concentration, Cmax | Study Day 337 | Maximum EQ001 serum drug concentration, Cmax |
Countries
United States
Participant flow
Pre-assignment details
Part B of the study was not conducted.
Participants by arm
| Arm | Count |
|---|---|
| EQ001 Dose Escalation (Part A) 0.4mg/kg Open label EQ001 administered by intravenous infusion every two weeks for a total of 5 doses at 0.4mg/kg
EQ001: Itolizumab \[Bmab 600\] | 4 |
| EQ001 Dose Escalation (Part A) 0.8mg/kg Open label EQ001 administered by intravenous infusion every two weeks for a total of 5 doses at 0.8mg/kg
EQ001: Itolizumab \[Bmab 600\] | 17 |
| EQ001 Dose Escalation (Part A) 1.6mg/kg Open label EQ001 administered by intravenous infusion every two weeks for a total of 5 doses at 1.6mg/kg
EQ001: Itolizumab \[Bmab 600\] | 9 |
| Total | 30 |
Baseline characteristics
| Characteristic | EQ001 Dose Escalation (Part A) 0.4mg/kg | EQ001 Dose Escalation (Part A) 0.8mg/kg | EQ001 Dose Escalation (Part A) 1.6mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 44.3 years STANDARD_DEVIATION 18.03 | 60.1 years STANDARD_DEVIATION 10.86 | 54.6 years STANDARD_DEVIATION 12.98 | 56.3 years STANDARD_DEVIATION 13.22 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 14 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Female | 0 Participants | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 5 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 7 / 17 | 6 / 9 |
| other Total, other adverse events | 4 / 4 | 17 / 17 | 9 / 9 |
| serious Total, serious adverse events | 2 / 4 | 9 / 17 | 8 / 9 |
Outcome results
Primary
Number of Treatment Emergent Adverse Events
Number of participants with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: Study Day 85
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EQ001 Dose Escalation (Part A) 0.4mg/kg | Number of Treatment Emergent Adverse Events | 4 Participants |
| EQ001 Dose Escalation (Part A) 0.8mg/kg | Number of Treatment Emergent Adverse Events | 17 Participants |
| EQ001 Dose Escalation (Part A) 1.6mg/kg | Number of Treatment Emergent Adverse Events | 9 Participants |
Primary
Overall Response Rate
Overall Response Rate (ORR) is defined as the number of subjects with a partial response (PR), very good partial response (VGPR), or complete response (CR) who are alive at Day 29. Subjects must not have received new systemic therapy for aGVHD before the Day 29 Visit.
Time frame: Study Day 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EQ001 Dose Escalation (Part A) 0.4mg/kg | Overall Response Rate | 2 Participants |
| EQ001 Dose Escalation (Part A) 0.8mg/kg | Overall Response Rate | 10 Participants |
| EQ001 Dose Escalation (Part A) 1.6mg/kg | Overall Response Rate | 5 Participants |
Secondary
CD6 Receptor Expression Levels
CD6 receptor expression levels - percent of baseline
Time frame: Study Day 85
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EQ001 Dose Escalation (Part A) 0.4mg/kg | CD6 Receptor Expression Levels | 81.0 Percent of baseline | Standard Deviation 17.78 |
| EQ001 Dose Escalation (Part A) 0.8mg/kg | CD6 Receptor Expression Levels | 23.7 Percent of baseline | Standard Deviation 15.76 |
| EQ001 Dose Escalation (Part A) 1.6mg/kg | CD6 Receptor Expression Levels | 33.0 Percent of baseline | Standard Deviation 19.25 |
Secondary
Clearance, Cl
Clearance, Cl
Time frame: Study Day 337
Secondary
Half Life of EQ001, t1/2
Half life of EQ001, t1/2
Time frame: Study Day 337
Secondary
Inflammatory Markers
Including but not limited to: IL-1β, IL-2, IL-6, IL-17, IL-21, IL-22, IL-23, IFN-γ, and TGF-β, C-reactive protein
Time frame: Study Day 337
Secondary
Maximum EQ001 Serum Drug Concentration, Cmax
Maximum EQ001 serum drug concentration, Cmax
Time frame: Study Day 337
Secondary
Minimum EQ001 Serum Drug Concentration, Cmin
Minimum EQ001 serum drug concentration prior to next dose, Cmin
Time frame: Study Day 337
Secondary
Time to Maximum EQ001serum Concentration, Tmax
Time to maximum EQ001 serum concentration, Tmax
Time frame: Day 337
Secondary
Total EQ001 Exposure Across Time, AUC (From Zero to Infinity)
Total EQ001 exposure across time, AUC (from zero to infinity)
Time frame: Study Day 337
Secondary
Volume of Distribution of EQ001, Vd
Volume of distribution of EQ001, Vd
Time frame: Study Day 337