A Phase 2/3 Study of GLASSIA for the Treatment of Acute GvHD

• Sponsor: Baxalta now part of Shire (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02956122
• Collaborator: Kamada, Ltd. (Industry)
• Enrollment: 1
• Location: 1
• Arms: 3
• Actual Duration (Months): 12.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease	Biological: GLASSIA; Drug: methylprednisolone or equivalent steroid; Biological: Albumin	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Two-Part, Multi-Center, Prospective, Phase 2/3 Clinical Study to Evaluate the Safety and Efficacy of GLASSIA as an Add-On Biopharmacotherapy to Conventional Steroid Treatment in Subjects With Acute Graft-Versus-Host Disease With Lower Gastrointestinal Involvement
• Actual Study Start Date: Apr 26, 2017
• Actual Primary Completion Date: May 3, 2018
• Actual Study Completion Date: May 3, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study Part 1 - All Participants - GLASSIA Participants to receive GLASSIA (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)	Biological: GLASSIA; GLASSIA [Alpha1-Proteinase Inhibitor (Human)]; Other Names: as alpha-1 antitrypsin A1PI alpha-1 proteinase inhibitor ; Drug: methylprednisolone or equivalent steroid; The conventional steroid treatment (methylprednisolone or equivalent steroid) will be supplied by the investigators per their institutional practice.
Experimental: Study Part 2 - GLASSIA Participants to receive GLASSIA (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)	Biological: GLASSIA; GLASSIA [Alpha1-Proteinase Inhibitor (Human)]; Other Names: as alpha-1 antitrypsin A1PI alpha-1 proteinase inhibitor ; Drug: methylprednisolone or equivalent steroid; The conventional steroid treatment (methylprednisolone or equivalent steroid) will be supplied by the investigators per their institutional practice.
Placebo Comparator: Study Part 2 - Albumin (Control) Participants to receive control (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)	Drug: methylprednisolone or equivalent steroid; The conventional steroid treatment (methylprednisolone or equivalent steroid) will be supplied by the investigators per their institutional practice.; Biological: Albumin; 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).; Other Names: Human Albumin

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. Incidence of Chronic Graft-versus-host Disease (GvHD) [Days 180 and 365]

   Incidence of chronic GvHD at Days 180 and 365 was reported.

5. 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.

6. 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.

7. 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.

8. Transplant-related Mortality [Days 28, 56, 100 and 180]

   Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant).

9. 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.

10. 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.

11. 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}]).

12. 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).

13. 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.

14. 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.

15. 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.

16. 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.

17. Number of Participants With Recurrence of Primary Malignancies [Baseline up to Day 365]

    Incidence of recurrence of primary malignancies was reported.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgia Cancer Center	Augusta	Georgia	United States	30912

Sponsors and Collaborators

• Baxalta now part of Shire
• Kamada, Ltd.

Investigators

• Study Director: Study Director, Shire

Study Documents (Full-Text)

• Study Protocol - Apr 19, 2017
• Statistical Analysis Plan - Sep 13, 2017

More Information

Publications

None provided.

• Responsible Party: Baxalta now part of Shire
• ClinicalTrials.gov Identifier: NCT02956122
• Other Study ID Numbers: 471501
• First Posted: Nov 6, 2016
• Last Update Posted: Jan 13, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Graft vs Host Disease; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Protease Inhibitors; Alpha 1-Antitrypsin

Study Results

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 Detail	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.

Arm/Group Title	GLASSIA
Arm/Group Description	Participants received an intravenous (IV) infusion of GLASSIA at a dose of 90 milligrams per kilogram (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 milligrams per kilogram per day (mg/kg/day) of methylprednisolone or equivalent steroid.
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	1 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Overall Response (OR) At Day 28
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Number [Percentage of participants]	100 10000%

2. Secondary Outcome

Title	Percentage of Participants Achieving Gastrointestinal (GI) Response at Day 28
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Number [Percentage of participants]	100 10000%

3. Secondary Outcome

Title	Percentage of Participants Achieving Overall Response at Day 56
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Number [Percentage of participants]	100 10000%

4. Secondary Outcome

Title	Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Stage 0	1 100%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	1 100%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	1 100%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	1 100%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	1 100%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	1 100%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	1 100%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	1 100%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%
Stage 0	1 100%
Stage 1	0 0%
Stage 2	0 0%
Stage 3	0 0%
Stage 4	0 0%

5. Secondary Outcome

Title	Incidence of Chronic Graft-versus-host Disease (GvHD)
Description	Incidence of chronic GvHD at Days 180 and 365 was reported.
Time Frame	Days 180 and 365

Outcome Measure Data

Analysis Population Description

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/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Day 180	0 0%
Day 365	0 0%

6. Secondary Outcome

Title	Duration of Overall Response (OR)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	0

7. Secondary Outcome

Title	Duration of Gastrointestinal (GI) Response
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	0

8. Secondary Outcome

Title	Overall Survival (OS) - Percentage of Participants With an Event
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis (SAF) set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Day 100	NA NaN
Day 180	NA NaN
Day 365	NA NaN

9. Secondary Outcome

Title	Transplant-related Mortality
Description	Transplant-related mortality was determined by the investigator (any deaths considered related to the transplant).
Time Frame	Days 28, 56, 100 and 180

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Day 28	0 0%
Day 56	0 0%
Day 100	0 0%
Day 180	0 0%

10. Secondary Outcome

Title	Failure-free Survival - Percentage of Participants With an Event
Description	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

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Day 100	100 10000%
Day 180	100 10000%

11. Secondary Outcome

Title	Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event
Description	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

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Day 28	100 10000%
Day 56	100 10000%
Day 100	100 10000%
Day 180	100 10000%
Day 365	100 10000%

12. Secondary Outcome

Title	Infection-related Mortality - Percentage of Participants With an Event
Description	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

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Day 28	0 0%
Day 56	0 0%
Day 100	0 0%
Day180	0 0%

13. Secondary Outcome

Title	Graft-versus-host Disease (GvHD)-Related Mortality - Percentage of Participants With an Event
Description	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

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Day 28	0 0%
Day 56	0 0%
Day 100	0 0%
Day 180	0 0%

14. Secondary Outcome

Title	All-cause Mortality - Percentage of Participants With an Event
Description	All-cause mortality was defined as the time from HSCT to death due to any cause.
Time Frame	Days 28, 56, 100 and 180

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Day 28	0 0%
Day 56	0 0%
Day 100	0 0%
Day180	0 0%

15. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs
Description	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

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Any Adverse Event	1 100%
Treatment-related AEs	0 0%
Serious adverse Events (SAEs)	0 0%
Treatment-related SAEs	0 0%
Temporally-associated AEs	0 0%

16. Secondary Outcome

Title	Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
Description	Clinical laboratory assessments such as hematology, clinical chemistry, lipid and coagulation panels and urinalysis were performed.
Time Frame	Baseline up to Day 56

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Count of Participants [Participants]	0 0%

17. Secondary Outcome

Title	Number of Participants With Clinically Significant Changes in Vital Signs
Description	Vital signs included body temperature, respiratory rate, pulse rate and systolic and diastolic blood pressure.
Time Frame	Baseline up to Day 56

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Count of Participants [Participants]	0 0%

18. Secondary Outcome

Title	Number of Participants With Recurrence of Primary Malignancies
Description	Incidence of recurrence of primary malignancies was reported.
Time Frame	Baseline up to Day 365

Outcome Measure Data

Analysis Population Description

SAF set consisted of all participants who received at least 1 dose of study treatment.

Arm/Group Title	GLASSIA
Arm/Group Description	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.
Measure Participants	1
Count of Participants [Participants]	0 0%

19. Secondary Outcome

Title	Area Under the Plasma Concentration Curve (AUC0-inf) From Time Zero to Infinity
Description	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

Outcome Measure Data

Analysis Population Description

PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.

Arm/Group Title	GLASSIA: Day 1: 90 mg/kg	GLASSIA: Day 13: 30 mg/kg	GLASSIA: Day 22: 120 mg/kg	GLASSIA: Day 50: 120 mg/kg
Arm/Group Description	Participants received an IV infusion of 90 mg/kg GLASSIA.	Participants received an IV infusion of 30 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.
Measure Participants	1	1	1	1
Number [Hour*milligrams per deciliter (h*mg/dL)]	61500	43500	126000	117000

20. Secondary Outcome

Title	Area Under the Plasma Concentration Curve From Time Zero to Time "t" AUC(0-t) of GLASSIA
Description	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

Outcome Measure Data

Analysis Population Description

PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.

Arm/Group Title	GLASSIA: Day 1: 90 mg/kg	GLASSIA: Day 13: 30 mg/kg	GLASSIA: Day 22: 120 mg/kg	GLASSIA: Day 50: 120 mg/kg
Arm/Group Description	Participants received an IV infusion of 90 mg/kg GLASSIA.	Participants received an IV infusion of 30 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.
Measure Participants	1	1	1	1
Number [h*mg/dL]	16300	11000	40400	33400

21. Secondary Outcome

Title	Systemic Clearance at Steady State (CLss) of GLASSIA
Description	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

Outcome Measure Data

Analysis Population Description

PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.

Arm/Group Title	GLASSIA: Day 13: 30 mg/kg	GLASSIA: Day 22: 120 mg/kg	GLASSIA: Day 50: 120 mg/kg
Arm/Group Description	Participants received an IV infusion of 30 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.
Measure Participants	1	1	1
Number [Deciliters per hour (dL/h)]	0.297	0.286	0.260

22. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of GLASSIA
Description	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

Outcome Measure Data

Analysis Population Description

PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.

Arm/Group Title	GLASSIA: Day 1: 90 mg/kg	GLASSIA: Day 13: 30 mg/kg	GLASSIA: Day 22: 120 mg/kg	GLASSIA: Day 50: 120 mg/kg
Arm/Group Description	Participants received an IV infusion of 90 mg/kg GLASSIA.	Participants received an IV infusion of 30 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.
Measure Participants	1	1	1	1
Number [Milligrams per deciliter (mg/dl)]	339	262	390	409

23. Secondary Outcome

Title	Apparent Volume of Distribution at Steady State (Vss) of GLASSIA
Description	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

Outcome Measure Data

Analysis Population Description

PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.

Arm/Group Title	GLASSIA: Day 13: 30 mg/kg	GLASSIA: Day 22: 120 mg/kg	GLASSIA: Day 50: 120 mg/kg
Arm/Group Description	Participants received an IV infusion of 30 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.
Measure Participants	1	1	1
Number [Deciliter (dL)]	50.9	123	91.1

24. Secondary Outcome

Title	Apparent Terminal Half-life (t1/2) of GLASSIA
Description	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

Outcome Measure Data

Analysis Population Description

PK Analysis set included all participants in the SAF set who have at least 1 PK or stool sample collected.

Arm/Group Title	GLASSIA: Day 1: 90 mg/kg	GLASSIA: Day 13: 30 mg/kg	GLASSIA: Day 22: 120 mg/kg	GLASSIA: Day 50: 120 mg/kg
Arm/Group Description	Participants received an IV infusion of 90 mg/kg GLASSIA.	Participants received an IV infusion of 30 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.
Measure Participants	1	1	1	1
Number [Hour (h)]	152	117	317	247

25. Secondary Outcome

Title	Mean Residence Time (MRT) of GLASSIA
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GLASSIA: Day 1: 90 mg/kg	GLASSIA: Day 13: 30 mg/kg	GLASSIA: Day 22: 120 mg/kg	GLASSIA: Day 50: 120 mg/kg
Arm/Group Description	Participants received an IV infusion of 90 mg/kg GLASSIA.	Participants received an IV infusion of 30 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.
Measure Participants	0	0	0	0

26. Secondary Outcome

Title	Trough Plasma Concentration at Steady State (Ctrough) of GLASSIA
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GLASSIA: Day 1: 90 mg/kg	GLASSIA: Day 13: 30 mg/kg	GLASSIA: Day 22: 120 mg/kg	GLASSIA: Day 50: 120 mg/kg
Arm/Group Description	Participants received an IV infusion of 90 mg/kg GLASSIA.	Participants received an IV infusion of 30 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.	Participants received an IV infusion of 120 mg/kg GLASSIA.
Measure Participants	0	0	0	0

Adverse Events

Time Frame	From the start of drug administration up to 371 days
Arm/Group Title	GLASSIA
Arm/Group Description	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.
All Cause Mortality
	GLASSIA
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	GLASSIA
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	GLASSIA
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
Anaemia	1/1 (100%)	2
Cardiac disorders
Sinus tachycardia	1/1 (100%)	1
Eye disorders
Vision blurred	1/1 (100%)	1
Gastrointestinal disorders
Toothache	1/1 (100%)	1
Gastrooesophageal reflux disease	1/1 (100%)	1
Dry mouth	1/1 (100%)	1
Tongue ulceration	1/1 (100%)	1
General disorders
Injection site reaction	1/1 (100%)	1
Fatigue	1/1 (100%)	2
Localised oedema	1/1 (100%)	1
Infections and infestations
Sinusitis	1/1 (100%)	1
Mucosal infection	1/1 (100%)	1
Cellulitis	1/1 (100%)	1
Investigations
Platelet count decreased/	1/1 (100%)	1
Weight decreased	1/1 (100%)	1
Blood cholesterol increased	1/1 (100%)	1
White blood cell count decreased	1/1 (100%)	3
Bilirubin conjugated increased	1/1 (100%)	2
Lymphocyte count decreased	1/1 (100%)	1
Neutrophil count decreased	1/1 (100%)	1
Metabolism and nutrition disorders
Hyperglycaemia	1/1 (100%)	6
Hypocalcaemia	1/1 (100%)	1
Hypokalaemia	1/1 (100%)	2
Hypomagnesaemia	1/1 (100%)	2
Hypoalbuminaemia	1/1 (100%)	1
Hypophosphataemia	1/1 (100%)	1
Hypercalcaemia	1/1 (100%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/1 (100%)	1
Myalgia	1/1 (100%)	2
Nervous system disorders
Peripheral motor neuropathy	1/1 (100%)	1
Amnesia	1/1 (100%)	1
Headache	1/1 (100%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/1 (100%)	1
Oropharyngeal pain	1/1 (100%)	2
Nasal congestion	1/1 (100%)	1
Dyspnoea	1/1 (100%)	2
Skin and subcutaneous tissue disorders
Pruritus	1/1 (100%)	1
Dry skin	1/1 (100%)	1
Eczema	1/1 (100%)	1
Vascular disorders
Hot flush	1/1 (100%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonmentor termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.