Clinical trial NCT02956122: A Phase 2/3 Study of GLASSIA for the Treatment of Acute GvHD
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Graft Versus Host Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Kamada, Ltd.
First posted: 2016-11-06
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Achieving Overall Response (OR) At Day 28
timeFrame: Day 28
Secondary outcomes:
measure: Percentage of Participants Achieving Gastrointestinal (GI) Response at Day 28
timeFrame: Day 28
measure: Percentage of Participants Achieving Overall Response at Day 56
timeFrame: Day 56
measure: Acute Graft-versus-host Disease (GvHD) Grading at Days 28, 56 and 180
timeFrame: Days 28, 56 and 180
measure: Incidence of Chronic Graft-versus-host Disease (GvHD)
timeFrame: Days 180 and 365
measure: Duration of Overall Response (OR)
timeFrame: Baseline up to Day 365
measure: Duration of Gastrointestinal (GI) Response
timeFrame: Baseline up to Day 365
measure: Overall Survival (OS) - Percentage of Participants With an Event
timeFrame: Days 100, 180 and 365
measure: Transplant-related Mortality
timeFrame: Days 28, 56, 100 and 180
measure: Failure-free Survival - Percentage of Participants With an Event
timeFrame: Days 100 and 180
measure: Graft-versus-host Disease (GvHD)-Free Survival - Percentage of Participants With an Event
timeFrame: Days 28, 56, 100, 180 and 365
measure: Infection-related Mortality - Percentage of Participants With an Event
timeFrame: Days 28, 56, 100 and 180
measure: Graft-versus-host Disease (GvHD)-Related Mortality - Percentage of Participants With an Event
timeFrame: Days 28, 56, 100 and 180
measure: All-cause Mortality - Percentage of Participants With an Event
timeFrame: Days 28, 56, 100 and 180
measure: Number of Participants With Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs and Temporally-associated AEs
timeFrame: From start of study drug administration up to 371 days
measure: Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments
timeFrame: Baseline up to Day 56
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Baseline up to Day 56
measure: Number of Participants With Recurrence of Primary Malignancies
timeFrame: Baseline up to Day 365
measure: Area Under the Plasma Concentration Curve (AUC0-inf) From Time Zero to Infinity
timeFrame: Day 1: through 48 hours; Day 13: through 48 hours; Day 22 and Day 50: through approximately 168 hours
measure: Area Under the Plasma Concentration Curve From Time Zero to Time "t" AUC(0-t) of GLASSIA
timeFrame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
measure: Systemic Clearance at Steady State (CLss) of GLASSIA
timeFrame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
measure: Maximum Observed Plasma Concentration (Cmax) of GLASSIA
timeFrame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
measure: Apparent Volume of Distribution at Steady State (Vss) of GLASSIA
timeFrame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
measure: Apparent Terminal Half-life (t1/2) of GLASSIA
timeFrame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
measure: Mean Residence Time (MRT) of GLASSIA
timeFrame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
measure: Trough Plasma Concentration at Steady State (Ctrough) of GLASSIA
timeFrame: Day 1: through 48 hours, Day 13: through 48 hours, Day 22 and Day 50: through approximately 168 hours
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Georgia Cancer Center
state: Georgia
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: