Trial Outcomes & Findings for Alpha 1 Anti-Trypsin (AAT) in Treating Patients With Acute Graft-Versus-Host Disease GVHD) (NCT NCT01523821)

Last Updated: 2018-10-30

Results Overview

Toxicity and adverse events were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All adverse events were reported regardless of attribution to alpha 1 anti-trypsin (AAT). GVHD response was defined per standard criteria for improvement, no change or progression of signs/symptoms in skin rash (% body surface area), GI (nausea, vomiting, anorexia, diarrhea, GI bleeding, abdominal cramping) and hepatic function (serum bilirubin levels). For this outcome measure, the requirement for additional GVHD treatment beyond AAT was not included in the criteria for response (i.e patients who may have required additional GVHD treatment before study day 28 were not automatically categorized as non-responders or as having progressive GVHD).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Adverse events were reported through 15 days after the last dose of AAT. GVHD response assessed at study day 28.

Results posted on

2018-10-30

Participant Flow

Patients signed IRB-approved consents during the period of 12/11/13 to 12/22/16. Treatment with alpha 1 anti-trypsin (AAT) typically started within 24 hours of consent. Patients were identified by clinical staff as needing additional treatment for acute graft versus his disease (GVHD) following initial therapy with corticosteroids.

Participant milestones

Participant milestones
Measure	Cohort 1 (30 mg/kg) AAT will administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 2 (60 mg/kg) AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 3 (90 mg/kg) AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]
Overall Study STARTED	8	6	6
Overall Study COMPLETED	8	6	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Alpha 1 Anti-Trypsin (AAT) in Treating Patients With Acute Graft-Versus-Host Disease GVHD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 (30 mg/kg) n=8 Participants AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 2 (60 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 3 (90 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Total n=20 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=93 Participants	4 Participants n=4 Participants	6 Participants n=27 Participants	18 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Age, Continuous	49 years n=93 Participants	40 years n=4 Participants	51 years n=27 Participants	48 years n=483 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	0 Participants n=4 Participants	6 Participants n=27 Participants	9 Participants n=483 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	6 Participants n=4 Participants	0 Participants n=27 Participants	11 Participants n=483 Participants
Region of Enrollment United States	8 participants n=93 Participants	6 participants n=4 Participants	6 participants n=27 Participants	20 participants n=483 Participants

PRIMARY outcome

Timeframe: Adverse events were reported through 15 days after the last dose of AAT. GVHD response assessed at study day 28.

Outcome measures

Outcome measures
Measure	Cohort 1 (30 mg/kg) n=8 Participants AAT will administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 2 (60 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 3 (90 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]
Number (Percentage) of Patients at Each Dosing Cohort Who Experience no Toxicity and in Whom Graft Versus Host Disease (GVHD) is Stable or Improved	6 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: SAEs were reported through 30 days after the last dose of alpha 1 anti-trypsin (AAT).

Serious adverse events included death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/ incapacity, or congenital anomaly/birth defect. Significant events that do not meet these criteria may be considered serious if they jeopardize the patient and require a medical intervention to prevent one of the outcomes above. An "unexpected" adverse event is defined as an event that is not identified in nature, severity or frequency in the current investigator brochure/package insert/product information.

Outcome measures

Outcome measures
Measure	Cohort 1 (30 mg/kg) n=8 Participants AAT will administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 2 (60 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 3 (90 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]
Number (Percentage) of Patients at Each Dosing Cohort Experiencing an Unexpected Serious Adverse Event (SAE)	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Within 48 hours after each infusion

Serious adverse reactions were assessed by the NCI CTCAE v4.0.

Outcome measures

Outcome measures
Measure	Cohort 1 (30 mg/kg) n=8 Participants AAT will administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 2 (60 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 3 (90 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]
Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Suspected Serious Adverse Reactions (Infusion Related Reactions)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Events were reported through 15 days after the last dose of AAT.

Events were assessed using the NCI CTCAE v4.0.

Outcome measures

Outcome measures
Measure	Cohort 1 (30 mg/kg) n=8 Participants AAT will administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 2 (60 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 3 (90 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]
Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Thrombotic or Thrombo-embolic Events	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Infections were reported through 15 days after the last dose of AAT.

Infections were assessed using NCI CTCAE v4.0.

Outcome measures

Outcome measures
Measure	Cohort 1 (30 mg/kg) n=8 Participants AAT will administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 2 (60 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 3 (90 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]
Number (Percentage) of Patients at Each Dosing Cohort With Occurrence of Infections	7 Participants	5 Participants	5 Participants

SECONDARY outcome

Timeframe: GVHD responses were assessed on day 28 after starting AAT therapy or at time of death if patient died before study day 28.

GVHD responses were assessed using criteria established by the Center for International Blood and Marrow Transplant Research and criteria from the Acute GVHD Activity Index. Patients who required additional systemic GVHD treatment beyond AAT before study day 28 were defined as having progressive GVHD.

Outcome measures

Outcome measures
Measure	Cohort 1 (30 mg/kg) n=8 Participants AAT will administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 2 (60 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 3 (90 mg/kg) n=6 Participants AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]
Number (Percentage) of Patients at Each Dosing Cohort With Progression of GVHD	4 Participants	5 Participants	4 Participants

Adverse Events

Cohort 1 (30 mg/kg)

Serious events: 8 serious events

Other events: 8 other events

Deaths: 6 deaths

Cohort 2 (60 mg/kg)

Serious events: 5 serious events

Other events: 6 other events

Deaths: 4 deaths

Cohort 3 (90 mg/kg)

Serious events: 4 serious events

Other events: 6 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 (30 mg/kg) n=8 participants at risk AAT will administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 2 (60 mg/kg) n=6 participants at risk AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]	Cohort 3 (90 mg/kg) n=6 participants at risk AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Alpha 1-Proteinase Inhibitor, Human 1 MG \[Glassia\]
Immune system disorders acute graft-versus-host disease	25.0% 2/8 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	66.7% 4/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	50.0% 3/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.
Infections and infestations infection	12.5% 1/8 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	16.7% 1/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	16.7% 1/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.
Gastrointestinal disorders perirectal abbess	12.5% 1/8 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.
Gastrointestinal disorders bowel perforation	12.5% 1/8 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.
Hepatobiliary disorders liver failure	12.5% 1/8 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.
Reproductive system and breast disorders diffuse alveolar hemorrhage	12.5% 1/8 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.
Nervous system disorders cranial hemorrhage	12.5% 1/8 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.	0.00% 0/6 • Adverse events were reported through 15 days after the last dose of AAT. Serious adverse events were reported if they occurred within 30 days after the last dose of AAT. All adverse events were collected regardless of attribution to AAT. Included are events that worsened from baseline.

Other adverse events

Additional Information

H. Joachim Deeg, MD

Fred Hutchinson Cancer Research Center

Phone: 206-667-5985

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place