Graft Versus Host Disease
Conditions
Brief summary
The purpose of the study is to evaluate the safety and efficacy of GLASSIA as an add-on biopharmacotherapy to standard-of-care steroid treatment as the first-line treatment in participants with acute GvHD with lower GI involvement.
Interventions
BIOLOGICALGLASSIA
GLASSIA \[Alpha1-Proteinase Inhibitor (Human)\]
DRUGmethylprednisolone or equivalent steroid
The conventional steroid treatment (methylprednisolone or equivalent steroid) will be supplied by the investigators per their institutional practice.
BIOLOGICALAlbumin
The control vials contain human albumin 20% in 50 mL normal saline solution in glass vials (for non-United States (US) Countries), or Flexbumin 25% in 50 mL in normal saline solution in plastic IV bags (for US).
Sponsors
Kamada, Ltd.
Baxalta now part of Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants aged ≥18 years at the time of screening 2. Recipient of an hematopoietic stem cell transplantation (HSCT) 3. The disease indication for which the participant required HSCT must be in remission 4. Newly diagnosed acute graft-versus-host disease (GvHD), including lower Gastrointestinal (GI) involvement (modified International Bone Marrow Transplant Registry \[IBMTR\] Severity Stage 1 to 4 \[\>500 mL diarrhea/day\]), with or without other organ system involvement. 5. Willing to undergo or must have had a lower GI biopsy within 7 days of informed consent to confirm GI GvHD. Biopsy results are not needed to initiate treatment; however, if biopsy results are not consistent with aGvHD, treatment with GLASSIA will be discontinued. 6. Participants must be receiving systemic corticosteroids. Treatment with methylprednisolone/systemic steroids must have been initiated within 72 hours prior to the first dose of study treatment after enrollment 7. Evidence of myeloid engraftment (absolute neutrophil count ≥0.5 x 10\^9/L) 8. Lower GI GvHD manifested by diarrhea must have other causes of diarrhea ruled out (eg, negative for Clostridium difficile or cytomegalovirus \[CMV\] infection or oral magnesium administration) 9. Karnofsky Performance Score ≥50% 10. If female of childbearing potential, participant presents with a negative blood pregnancy test 11. Females of childbearing potential with a fertile male sexual partner must agree to employ adequate contraception for the duration of the study. 12. Males must use adequate contraception and must not donate sperm for the duration of the study. 13. Participant is willing and able to comply with the requirements of the protocol
Exclusion criteria
1. Participant with manifestations of chronic GvHD 2. Participant with acute/chronic GvHD overlap syndrome 3. Participant whose GvHD developed after donor lymphocyte infusion 4. Participant with myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to the first dose of study treatment, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant 5. Participant with evidence of recurrent malignancy 6. Participant with veno-occlusive disease (ie, sinusoidal obstruction syndrome) 7. Participant receiving GvHD treatment other than continued prophylaxis (eg, cyclosporine and/or mycophenolate mofetil, etc) or corticosteroid therapy. In addition, a participant who received the first dose of corticosteroid therapy for acute GvHD with lower GI involvement more than 72 hours before the first dose of study treatment is not eligible for the study 8. Participant with severe sepsis involving at least 1 organ failure 9. Participant who is seropositive or positive in the nucleic acid test for human immunodeficiency virus (HIV) 10. Participant with active hepatitis B or C 11. Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study 12. If female, participant is pregnant or lactating at the time of enrollment, or has plans to become pregnant during the study 13. Participant with a serious medical or psychiatric illness likely to interfere with participation in the study 14. Participant is a family member or employee of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Overall Response (OR) At Day 28 | Day 28 | OR was defined as graft-versus-host disease (GvHD) complete response (CR) + partial response (PR), defined as: - GvHD CR was complete resolution of all signs and symptoms of acute GvHD in all organs without intervening salvage and GvHD PR was improvement of 1 stage in 1 or more organs involved in GvHD without progression in other organs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Overall Response at Day 56 | Day 56 | Overall response was defined as graft-versus-host disease (GvHD) complete response (CR) + partial response (PR), defined as: - GvHD CR was complete resolution of all signs and symptoms of acute GvHD in all organs without intervening salvage - GvHD PR was improvement of 1 stage in 1 or more organs involved in GvHD without progression in other organs. |
| Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Days 28, 56 and 180 | Grading of GvHD was performed by the investigator according to the modified International Bone Marrow Transplant Registry (IBMTR) grading system which classifies the degree of involvement of each organ system by stage on a scale of 0 to 4. The degree of skin involvement was staged depending upon degree and severity of the lesions: Stage 1: Maculopapular rash over less than (\<) 25% of body area, Stage 2: Maculopapular rash over 25 to 50% of body area, Stage 3: Generalized erythroderma, Stage 4: Generalized erythroderma with bullous formation. Degree of GI involvement was staged based on severity of diarrhoea: Stage 1: 500 to 1000 mL/day,Stage 2: 1000 to 1500 mL/day, Stage 3: 1500 to 2000 mL/day, Stage 4: greater than (\>) 2000 mL/day OR pain OR ileus. Degree of liver involvement was staged based upon serum total bilirubin level as follows: Stage 1: 2 to 3 mg/dL, Stage 2: 3 to 6 mg/dL, Stage 3: 6 to 15 mg/dL, Stage 4: \>15 mg/dL. |
| Incidence of Chronic Graft-versus-host Disease (GvHD) | Days 180 and 365 | Incidence of chronic GvHD at Days 180 and 365 was reported. |
| Duration of Overall Response (OR) | Baseline up to Day 365 | OR was defined as GvHD CR + PR, defined as: - GvHD CR was complete resolution of all signs and symptoms of acute GvHD in all organs without intervening salvage - GvHD PR was improvement of 1 stage in 1 or more organs involved in GvHD without progression in other organs. Duration of OR was not assessed due to the termination of the study. |
| Duration of Gastrointestinal (GI) Response | Baseline up to Day 365 | GI response was defined as CR + PR, defined as: - GI CR was able to eat; not requiring parenteral nutrition, and passing primarily formed stools - GI PR was decrease in need for parenteral nutrition to \<= 50% of required calories; and reduction of stool volume by \>= 50%, without ileus. Duration of GI response was not assessed due to the termination of the study. |
| Overall Survival (OS) - Percentage of Participants With an Event | Days 100, 180 and 365 | OS was defined as the time from the date of randomization to the date of death due to any cause. |
| Transplant-related Mortality | Days 28, 56, 100 and 180 | Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant). |
| Failure-free Survival - Percentage of Participants With an Event | Days 100 and 180 | Failure-free survival was defined as the absence of all of the following criteria: Need for second-line treatment for acute GvHD, Non-relapse mortality (death during continuous complete remission) and recurrent malignancy. |
| Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event | Days 28, 56, 100, 180 and 365 | GVHD-free survival was defined as being alive without previous onset of acute GVHD or chronic GVHD requiring immunosuppressive therapy. |
| Infection-related Mortality - Percentage of Participants With an Event | Days 28, 56, 100 and 180 | Infection-related mortality was determined by the investigator (any deaths considered related to infection \[including infections related to hematopoietic stem cell transplant {HSCT}\]). |
| Graft-versus-host Disease (GvHD)-Related Mortality - Percentage of Participants With an Event | Days 28, 56, 100 and 180 | Graft-versus-host disease (GvHD)-related mortality was determined by the investigator (any deaths considered related to GvHD). |
| All-cause Mortality - Percentage of Participants With an Event | Days 28, 56, 100 and 180 | All-cause mortality was defined as the time from HSCT to death due to any cause. |
| Percentage of Participants Achieving Gastrointestinal (GI) Response at Day 28 | Day 28 | GI response was defined as complete response (CR) + partial response (PR), defined as: - GI CR was able to eat; not requiring parenteral nutrition, and passing primarily formed stools - GI PR was decrease in need for parenteral nutrition to less than or equal to (\<=) 50% of required calories; and reduction of stool volume by greater than or equal to (\>=) 50%, without ileus. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | Baseline up to Day 56 | Clinical laboratory assessments such as hematology, clinical chemistry, lipid and coagulation panels and urinalysis were performed. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Baseline up to Day 56 | Vital signs included body temperature, respiratory rate, pulse rate and systolic and diastolic blood pressure. |
| Number of Participants With Recurrence of Primary Malignancies | Baseline up to Day 365 | Incidence of recurrence of primary malignancies was reported. |
| Area Under the Plasma Concentration Curve (AUC0-inf) From Time Zero to Infinity | Day 1: through 48 hours; Day 13: through 48 hours; Day 22 and Day 50: through approximately 168 hours | AUC of GLASSIA was reported. |
| Area Under the Plasma Concentration Curve From Time Zero to Time t AUC(0-t) of GLASSIA | Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours | AUC(0-t) of GLASSIA was reported. |
| Systemic Clearance at Steady State (CLss) of GLASSIA | Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours | CLss of GLASSIA was reported. |
| Maximum Observed Plasma Concentration (Cmax) of GLASSIA | Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours | Cmax of GLASSIA was reported. |
| Apparent Volume of Distribution at Steady State (Vss) of GLASSIA | Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours | Vss of GLASSIA was reported. |
| Apparent Terminal Half-life (t1/2) of GLASSIA | Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours | Apparent terminal half-life (hour), determined as ln2/lambda-z. lambda-z is the apparent terminal rate constant (one per hour), determined by linear regression of the terminal points of the log-linear concentration-time curve. Visual assessment will be used to identify the terminal linear phase of the concentration-time profile. A minimum of 3 data points will be used for determination. t1/2 of GLASSIA was reported. |
| Mean Residence Time (MRT) of GLASSIA | Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours | MRT of GLASSIA was not calculated. |
| Trough Plasma Concentration at Steady State (Ctrough) of GLASSIA | Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours | Ctrough of GLASSIA was not assessed due to the termination of the study. |
| Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs | From start of study drug administration up to 371 days | An AE was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome was fatal/results in death, life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. |
Countries
United States
Participant flow
Recruitment details
Study was conducted between 26 April 2017 (first participant first visit) and 03 May 2018 (last participant last visit).
Pre-assignment details
A total of 1 participant was enrolled and completed Part 1 (GLASSIA) of the study, and was analyzed for efficacy and safety with individual PK parameters estimated. Part 2 (GLASSIA versus albumin \[control\]) was not initiated following discontinuation of the study due to operational and business considerations.
Participants by arm
| Arm | Count |
|---|---|
| GLASSIA Participants received an IV infusion of GLASSIA at a dose of 90 mg/kg on Day 1 followed by 30 mg/kg every other day (Days 3 to 13), then followed by 120 mg/kg weekly (Days 15 to 50) along with 2 mg/kg/day of methylprednisolone or equivalent steroid. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | GLASSIA |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Percentage of Participants Achieving Overall Response (OR) At Day 28
OR was defined as graft-versus-host disease (GvHD) complete response (CR) + partial response (PR), defined as: - GvHD CR was complete resolution of all signs and symptoms of acute GvHD in all organs without intervening salvage and GvHD PR was improvement of 1 stage in 1 or more organs involved in GvHD without progression in other organs.
Time frame: Day 28
Population: Efficacy analysis set included all participants who were evaluated for overall response at Day 28. Participants who received at least 1 dose of study treatment and who had a lower GI biopsy that was consistent with acute GvHD were considered evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA | Percentage of Participants Achieving Overall Response (OR) At Day 28 | 100 Percentage of participants |
Secondary
Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180
Grading of GvHD was performed by the investigator according to the modified International Bone Marrow Transplant Registry (IBMTR) grading system which classifies the degree of involvement of each organ system by stage on a scale of 0 to 4. The degree of skin involvement was staged depending upon degree and severity of the lesions: Stage 1: Maculopapular rash over less than (\<) 25% of body area, Stage 2: Maculopapular rash over 25 to 50% of body area, Stage 3: Generalized erythroderma, Stage 4: Generalized erythroderma with bullous formation. Degree of GI involvement was staged based on severity of diarrhoea: Stage 1: 500 to 1000 mL/day,Stage 2: 1000 to 1500 mL/day, Stage 3: 1500 to 2000 mL/day, Stage 4: greater than (\>) 2000 mL/day OR pain OR ileus. Degree of liver involvement was staged based upon serum total bilirubin level as follows: Stage 1: 2 to 3 mg/dL, Stage 2: 3 to 6 mg/dL, Stage 3: 6 to 15 mg/dL, Stage 4: \>15 mg/dL.
Time frame: Days 28, 56 and 180
Population: Efficacy analysis set included all participants who were evaluated for overall response at Day 28. Participants who received at least 1 dose of study treatment and who had a lower GI biopsy that was consistent with acute GvHD were considered evaluable.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of skin Involvement | Stage 2 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of skin Involvement | Stage 3 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of GI Involvement | Stage 0 | 1 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of GI Involvement | Stage 3 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of GI Involvement | Stage 4 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of skin Involvement | Stage 2 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of skin Involvement | Stage 3 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of skin Involvement | Stage 4 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of GI Involvement | Stage 0 | 1 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of skin Involvement | Stage 3 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of skin Involvement | Stage 0 | 1 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of skin Involvement | Stage 1 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of skin Involvement | Stage 1 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of skin Involvement | Stage 4 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of GI Involvement | Stage 1 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of GI Involvement | Stage 2 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of liver Involvement | Stage 0 | 1 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of liver Involvement | Stage 1 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of liver Involvement | Stage 2 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of liver Involvement | Stage 3 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 28: Degree of liver Involvement | Stage 4 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of skin Involvement | Stage 0 | 1 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of GI Involvement | Stage 1 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of GI Involvement | Stage 2 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of GI Involvement | Stage 3 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of GI Involvement | Stage 4 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of liver Involvement | Stage 0 | 1 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of liver Involvement | Stage 1 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of liver Involvement | Stage 2 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of liver Involvement | Stage 3 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 56: Degree of liver Involvement | Stage 4 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of skin Involvement | Stage 0 | 1 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of skin Involvement | Stage 1 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of skin Involvement | Stage 2 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of skin Involvement | Stage 4 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of GI Involvement | Stage 0 | 1 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of GI Involvement | Stage 1 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of GI Involvement | Stage 2 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of GI Involvement | Stage 3 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of GI Involvement | Stage 4 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of liver Involvement | Stage 0 | 1 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of liver Involvement | Stage 1 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of liver Involvement | Stage 2 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of liver Involvement | Stage 3 | 0 Participants |
| GLASSIA | Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180 | Day 180: Degree of liver Involvement | Stage 4 | 0 Participants |
Secondary
All-cause Mortality - Percentage of Participants With an Event
All-cause mortality was defined as the time from HSCT to death due to any cause.
Time frame: Days 28, 56, 100 and 180
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLASSIA | All-cause Mortality - Percentage of Participants With an Event | Day 28 | 0 Percentage of participants |
| GLASSIA | All-cause Mortality - Percentage of Participants With an Event | Day 56 | 0 Percentage of participants |
| GLASSIA | All-cause Mortality - Percentage of Participants With an Event | Day 100 | 0 Percentage of participants |
| GLASSIA | All-cause Mortality - Percentage of Participants With an Event | Day180 | 0 Percentage of participants |
Secondary
Apparent Terminal Half-life (t1/2) of GLASSIA
Apparent terminal half-life (hour), determined as ln2/lambda-z. lambda-z is the apparent terminal rate constant (one per hour), determined by linear regression of the terminal points of the log-linear concentration-time curve. Visual assessment will be used to identify the terminal linear phase of the concentration-time profile. A minimum of 3 data points will be used for determination. t1/2 of GLASSIA was reported.
Time frame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
Population: PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA | Apparent Terminal Half-life (t1/2) of GLASSIA | 152 Hour (h) |
| GLASSIA: Day 13: 30 mg/kg | Apparent Terminal Half-life (t1/2) of GLASSIA | 117 Hour (h) |
| GLASSIA: Day 22: 120 mg/kg | Apparent Terminal Half-life (t1/2) of GLASSIA | 317 Hour (h) |
| GLASSIA: Day 50: 120 mg/kg | Apparent Terminal Half-life (t1/2) of GLASSIA | 247 Hour (h) |
Secondary
Apparent Volume of Distribution at Steady State (Vss) of GLASSIA
Vss of GLASSIA was reported.
Time frame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
Population: PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA | Apparent Volume of Distribution at Steady State (Vss) of GLASSIA | 50.9 Deciliter (dL) |
| GLASSIA: Day 13: 30 mg/kg | Apparent Volume of Distribution at Steady State (Vss) of GLASSIA | 123 Deciliter (dL) |
| GLASSIA: Day 22: 120 mg/kg | Apparent Volume of Distribution at Steady State (Vss) of GLASSIA | 91.1 Deciliter (dL) |
Secondary
Area Under the Plasma Concentration Curve (AUC0-inf) From Time Zero to Infinity
AUC of GLASSIA was reported.
Time frame: Day 1: through 48 hours; Day 13: through 48 hours; Day 22 and Day 50: through approximately 168 hours
Population: PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA | Area Under the Plasma Concentration Curve (AUC0-inf) From Time Zero to Infinity | 61500 Hour*milligrams per deciliter (h*mg/dL) |
| GLASSIA: Day 13: 30 mg/kg | Area Under the Plasma Concentration Curve (AUC0-inf) From Time Zero to Infinity | 43500 Hour*milligrams per deciliter (h*mg/dL) |
| GLASSIA: Day 22: 120 mg/kg | Area Under the Plasma Concentration Curve (AUC0-inf) From Time Zero to Infinity | 126000 Hour*milligrams per deciliter (h*mg/dL) |
| GLASSIA: Day 50: 120 mg/kg | Area Under the Plasma Concentration Curve (AUC0-inf) From Time Zero to Infinity | 117000 Hour*milligrams per deciliter (h*mg/dL) |
Secondary
Area Under the Plasma Concentration Curve From Time Zero to Time t AUC(0-t) of GLASSIA
AUC(0-t) of GLASSIA was reported.
Time frame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
Population: PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA | Area Under the Plasma Concentration Curve From Time Zero to Time t AUC(0-t) of GLASSIA | 16300 h*mg/dL |
| GLASSIA: Day 13: 30 mg/kg | Area Under the Plasma Concentration Curve From Time Zero to Time t AUC(0-t) of GLASSIA | 11000 h*mg/dL |
| GLASSIA: Day 22: 120 mg/kg | Area Under the Plasma Concentration Curve From Time Zero to Time t AUC(0-t) of GLASSIA | 40400 h*mg/dL |
| GLASSIA: Day 50: 120 mg/kg | Area Under the Plasma Concentration Curve From Time Zero to Time t AUC(0-t) of GLASSIA | 33400 h*mg/dL |
Secondary
Duration of Gastrointestinal (GI) Response
GI response was defined as CR + PR, defined as: - GI CR was able to eat; not requiring parenteral nutrition, and passing primarily formed stools - GI PR was decrease in need for parenteral nutrition to \<= 50% of required calories; and reduction of stool volume by \>= 50%, without ileus. Duration of GI response was not assessed due to the termination of the study.
Time frame: Baseline up to Day 365
Population: Efficacy analysis set included all participants who were evaluated for overall response at Day 28. Participants who received at least 1 dose of study treatment and who had a lower GI biopsy that was consistent with acute GvHD were considered evaluable. Here, number of participants analyzed refer to the participants evaluable for this outcome.
Secondary
Duration of Overall Response (OR)
OR was defined as GvHD CR + PR, defined as: - GvHD CR was complete resolution of all signs and symptoms of acute GvHD in all organs without intervening salvage - GvHD PR was improvement of 1 stage in 1 or more organs involved in GvHD without progression in other organs. Duration of OR was not assessed due to the termination of the study.
Time frame: Baseline up to Day 365
Population: Efficacy analysis set included all participants who were evaluated for overall response at Day 28. Participants who received at least 1 dose of study treatment and who had a lower GI biopsy that was consistent with acute GvHD were considered evaluable. Here, number of participants analyzed refer to the participants evaluable for this outcome.
Secondary
Failure-free Survival - Percentage of Participants With an Event
Failure-free survival was defined as the absence of all of the following criteria: Need for second-line treatment for acute GvHD, Non-relapse mortality (death during continuous complete remission) and recurrent malignancy.
Time frame: Days 100 and 180
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLASSIA | Failure-free Survival - Percentage of Participants With an Event | Day 100 | 100 Percentage of participants |
| GLASSIA | Failure-free Survival - Percentage of Participants With an Event | Day 180 | 100 Percentage of participants |
Secondary
Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event
GVHD-free survival was defined as being alive without previous onset of acute GVHD or chronic GVHD requiring immunosuppressive therapy.
Time frame: Days 28, 56, 100, 180 and 365
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLASSIA | Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event | Day 28 | 100 Percentage of participants |
| GLASSIA | Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event | Day 56 | 100 Percentage of participants |
| GLASSIA | Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event | Day 100 | 100 Percentage of participants |
| GLASSIA | Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event | Day 180 | 100 Percentage of participants |
| GLASSIA | Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event | Day 365 | 100 Percentage of participants |
Secondary
Graft-versus-host Disease (GvHD)-Related Mortality - Percentage of Participants With an Event
Graft-versus-host disease (GvHD)-related mortality was determined by the investigator (any deaths considered related to GvHD).
Time frame: Days 28, 56, 100 and 180
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLASSIA | Graft-versus-host Disease (GvHD)-Related Mortality - Percentage of Participants With an Event | Day 28 | 0 Percentage of participants |
| GLASSIA | Graft-versus-host Disease (GvHD)-Related Mortality - Percentage of Participants With an Event | Day 56 | 0 Percentage of participants |
| GLASSIA | Graft-versus-host Disease (GvHD)-Related Mortality - Percentage of Participants With an Event | Day 100 | 0 Percentage of participants |
| GLASSIA | Graft-versus-host Disease (GvHD)-Related Mortality - Percentage of Participants With an Event | Day 180 | 0 Percentage of participants |
Secondary
Incidence of Chronic Graft-versus-host Disease (GvHD)
Incidence of chronic GvHD at Days 180 and 365 was reported.
Time frame: Days 180 and 365
Population: Efficacy analysis set included all participants who were evaluated for overall response at Day 28. Participants who received at least 1 dose of study treatment and who had a lower GI biopsy that was consistent with acute GvHD were considered evaluable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLASSIA | Incidence of Chronic Graft-versus-host Disease (GvHD) | Day 180 | 0 Participants |
| GLASSIA | Incidence of Chronic Graft-versus-host Disease (GvHD) | Day 365 | 0 Participants |
Secondary
Infection-related Mortality - Percentage of Participants With an Event
Infection-related mortality was determined by the investigator (any deaths considered related to infection \[including infections related to hematopoietic stem cell transplant {HSCT}\]).
Time frame: Days 28, 56, 100 and 180
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLASSIA | Infection-related Mortality - Percentage of Participants With an Event | Day 28 | 0 Percentage of participants |
| GLASSIA | Infection-related Mortality - Percentage of Participants With an Event | Day 56 | 0 Percentage of participants |
| GLASSIA | Infection-related Mortality - Percentage of Participants With an Event | Day 100 | 0 Percentage of participants |
| GLASSIA | Infection-related Mortality - Percentage of Participants With an Event | Day180 | 0 Percentage of participants |
Secondary
Maximum Observed Plasma Concentration (Cmax) of GLASSIA
Cmax of GLASSIA was reported.
Time frame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
Population: PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA | Maximum Observed Plasma Concentration (Cmax) of GLASSIA | 339 Milligrams per deciliter (mg/dl) |
| GLASSIA: Day 13: 30 mg/kg | Maximum Observed Plasma Concentration (Cmax) of GLASSIA | 262 Milligrams per deciliter (mg/dl) |
| GLASSIA: Day 22: 120 mg/kg | Maximum Observed Plasma Concentration (Cmax) of GLASSIA | 390 Milligrams per deciliter (mg/dl) |
| GLASSIA: Day 50: 120 mg/kg | Maximum Observed Plasma Concentration (Cmax) of GLASSIA | 409 Milligrams per deciliter (mg/dl) |
Secondary
Mean Residence Time (MRT) of GLASSIA
MRT of GLASSIA was not calculated.
Time frame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
Population: PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected. Her, the number of participants analyzed refer to the participants evaluable for this outcome at specified time point.
Secondary
Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs
An AE was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome was fatal/results in death, life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
Time frame: From start of study drug administration up to 371 days
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GLASSIA | Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs | Any Adverse Event | 1 Participants |
| GLASSIA | Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs | Treatment-related AEs | 0 Participants |
| GLASSIA | Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs | Serious adverse Events (SAEs) | 0 Participants |
| GLASSIA | Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs | Treatment-related SAEs | 0 Participants |
| GLASSIA | Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs | Temporally-associated AEs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
Clinical laboratory assessments such as hematology, clinical chemistry, lipid and coagulation panels and urinalysis were performed.
Time frame: Baseline up to Day 56
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GLASSIA | Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | 0 Participants |
Secondary
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs included body temperature, respiratory rate, pulse rate and systolic and diastolic blood pressure.
Time frame: Baseline up to Day 56
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GLASSIA | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Secondary
Number of Participants With Recurrence of Primary Malignancies
Incidence of recurrence of primary malignancies was reported.
Time frame: Baseline up to Day 365
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GLASSIA | Number of Participants With Recurrence of Primary Malignancies | 0 Participants |
Secondary
Overall Survival (OS) - Percentage of Participants With an Event
OS was defined as the time from the date of randomization to the date of death due to any cause.
Time frame: Days 100, 180 and 365
Population: Safety analysis (SAF) set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLASSIA | Overall Survival (OS) - Percentage of Participants With an Event | Day 100 | NA Percentage of participants |
| GLASSIA | Overall Survival (OS) - Percentage of Participants With an Event | Day 180 | NA Percentage of participants |
| GLASSIA | Overall Survival (OS) - Percentage of Participants With an Event | Day 365 | NA Percentage of participants |
Secondary
Percentage of Participants Achieving Gastrointestinal (GI) Response at Day 28
GI response was defined as complete response (CR) + partial response (PR), defined as: - GI CR was able to eat; not requiring parenteral nutrition, and passing primarily formed stools - GI PR was decrease in need for parenteral nutrition to less than or equal to (\<=) 50% of required calories; and reduction of stool volume by greater than or equal to (\>=) 50%, without ileus.
Time frame: Day 28
Population: Efficacy analysis set included all participants who were evaluated for overall response at Day 28. Participants who received at least 1 dose of study treatment and who had a lower GI biopsy that was consistent with acute GvHD were considered evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA | Percentage of Participants Achieving Gastrointestinal (GI) Response at Day 28 | 100 Percentage of participants |
Secondary
Percentage of Participants Achieving Overall Response at Day 56
Overall response was defined as graft-versus-host disease (GvHD) complete response (CR) + partial response (PR), defined as: - GvHD CR was complete resolution of all signs and symptoms of acute GvHD in all organs without intervening salvage - GvHD PR was improvement of 1 stage in 1 or more organs involved in GvHD without progression in other organs.
Time frame: Day 56
Population: Efficacy analysis set included all participants who were evaluated for overall response at Day 28. Participants who received at least 1 dose of study treatment and who had a lower GI biopsy that was consistent with acute GvHD were considered evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA | Percentage of Participants Achieving Overall Response at Day 56 | 100 Percentage of participants |
Secondary
Systemic Clearance at Steady State (CLss) of GLASSIA
CLss of GLASSIA was reported.
Time frame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
Population: PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLASSIA | Systemic Clearance at Steady State (CLss) of GLASSIA | 0.297 Deciliters per hour (dL/h) |
| GLASSIA: Day 13: 30 mg/kg | Systemic Clearance at Steady State (CLss) of GLASSIA | 0.286 Deciliters per hour (dL/h) |
| GLASSIA: Day 22: 120 mg/kg | Systemic Clearance at Steady State (CLss) of GLASSIA | 0.260 Deciliters per hour (dL/h) |
Secondary
Transplant-related Mortality
Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant).
Time frame: Days 28, 56, 100 and 180
Population: SAF set consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GLASSIA | Transplant-related Mortality | Day 28 | 0 Participants |
| GLASSIA | Transplant-related Mortality | Day 56 | 0 Participants |
| GLASSIA | Transplant-related Mortality | Day 100 | 0 Participants |
| GLASSIA | Transplant-related Mortality | Day 180 | 0 Participants |
Secondary
Trough Plasma Concentration at Steady State (Ctrough) of GLASSIA
Ctrough of GLASSIA was not assessed due to the termination of the study.
Time frame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
Population: PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected. Here, number of participants analyzed refer to the participants evaluable for this outcome at specified time point.