Ground Truth
Inclusion Criteria:Male or female participants aged ≥18 years at the time of screeningRecipient of an hematopoietic stem cell transplantation (HSCT)The disease indication for which the participant required HSCT must be in remissionNewly 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.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.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 enrollmentEvidence of myeloid engraftment (absolute neutrophil count ≥0.5 x 10^9/L)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)Karnofsky Performance Score ≥50%If female of childbearing potential, participant presents with a negative blood pregnancy testFemales of childbearing potential with a fertile male sexual partner must agree to employ adequate contraception for the duration of the study.Males must use adequate contraception and must not donate sperm for the duration of the study.Participant is willing and able to comply with the requirements of the protocolExclusion Criteria:Participant with manifestations of chronic GvHDParticipant with acute/chronic GvHD overlap syndromeParticipant whose GvHD developed after donor lymphocyte infusionParticipant 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 relevantParticipant with evidence of recurrent malignancyParticipant with veno-occlusive disease (ie, sinusoidal obstruction syndrome)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 studyParticipant with severe sepsis involving at least 1 organ failureParticipant who is seropositive or positive in the nucleic acid test for human immunodeficiency virus (HIV)Participant with active hepatitis B or CParticipant 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 studyIf female, participant is pregnant or lactating at the time of enrollment, or has plans to become pregnant during the studyParticipant with a serious medical or psychiatric illness likely to interfere with participation in the studyParticipant is a family member or employee of the investigator
Prediction
**Amended Eligibility Criteria (Version 3)**
**Inclusion Criteria:**
1.
Male or female participants aged ≥18 years at the time of screening.
2.
Recipient of an allogeneic 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) with lower gastrointestinal (GI) involvement (modified International Bone Marrow Transplant Registry [IBMTR] Severity Stage 1 to 4, defined as diarrhea >500 mL/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 acute GvHD, treatment with GLASSIA will be discontinued.
6.
Subjects 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 (e.g., negative for Clostridium difficile or cytomegalovirus [CMV] infection or oral magnesium administration).
9.
Karnofsky Performance Score ≥50%.
10.
If female of childbearing potential, subject 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.
Adequate contraception is defined as using hormonal contraceptives or an intrauterine device combined with at least one of the following forms of contraception: a diaphragm, cervical cap, or a condom.
12.
Males must use adequate contraception and must not donate sperm for the duration of the study.
Adequate contraception for the male subject and his female partner is defined as using hormonal contraceptives or an intrauterine device combined with at least one of the following forms of contraception: a diaphragm, cervical cap, or a condom.
13.
Subject is willing and able to comply with the requirements of the protocol.
**Exclusion Criteria:**
1.
Subject with manifestations of chronic GvHD.
2.
Subject with acute/chronic GvHD overlap syndrome.
3.
Subject whose GvHD developed after donor lymphocyte infusion.
4.
Subject 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.
Subject with evidence of recurrent malignancy.
6.
Subject with veno-occlusive disease (i.e., sinusoidal obstruction syndrome).
7.
Subject receiving GvHD treatment other than continued prophylaxis (e.g., cyclosporine and/or mycophenolate mofetil, etc.) or corticosteroid therapy.
In addition, a subject 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.
Subject with severe sepsis involving at least one organ failure.
9.
Subject who is seropositive or positive in the nucleic acid test for human immunodeficiency virus (HIV).
10.
Subject with active hepatitis B or C.
11.
Subject 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, subject is pregnant or lactating at the time of enrollment, or has plans to become pregnant during the study.
13.
Subject with a serious medical or psychiatric illness likely to interfere with participation in the study.
14.
Subject is a family member or employee of the investigator.