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NCT01523821

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

Completed Phase 1, PHASE2 Results posted Last updated 30 October 2018
What this trial tests

Phase 1, PHASE2 trial testing Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] in Graft-Versus-Host Disease (GVHD) Acute on Chronic in 20 participants. Completed in 15 January 2017.

Timeline
11 October 2013
Primary endpoint
15 January 2017
15 January 2017

Quick facts

Lead sponsorFred Hutchinson Cancer Center
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment20
Start date11 October 2013
Primary completion15 January 2017
Estimated completion15 January 2017
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Fred Hutchinson Cancer Center — full company profile →

Who can join

18 and older, any sex, with Graft-Versus-Host Disease (GVHD) Acute on Chronic. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number (Percentage) of Patients at Each Dosing Cohort Who Experience no Toxicity and in Whom Graft Versus Host Disease (GVHD) is Stable or Improved Primary · Adverse events were reported through 15 days after the last dose of AAT. GVHD response assessed at study day 28.

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

GroupValue95% CI
Cohort 1 (30 mg/kg)6
Cohort 2 (60 mg/kg)2
Cohort 3 (90 mg/kg)2
Number (Percentage) of Patients at Each Dosing Cohort Experiencing an Unexpected Serious Adverse Event (SAE) Secondary · 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 informat

GroupValue95% CI
Cohort 1 (30 mg/kg)2
Cohort 2 (60 mg/kg)0
Cohort 3 (90 mg/kg)0
Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Suspected Serious Adverse Reactions (Infusion Related Reactions) Secondary · Within 48 hours after each infusion

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

GroupValue95% CI
Cohort 1 (30 mg/kg)0
Cohort 2 (60 mg/kg)0
Cohort 3 (90 mg/kg)0
Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Thrombotic or Thrombo-embolic Events Secondary · Events were reported through 15 days after the last dose of AAT.

Events were assessed using the NCI CTCAE v4.0.

GroupValue95% CI
Cohort 1 (30 mg/kg)0
Cohort 2 (60 mg/kg)0
Cohort 3 (90 mg/kg)0
Number (Percentage) of Patients at Each Dosing Cohort With Occurrence of Infections Secondary · Infections were reported through 15 days after the last dose of AAT.

Infections were assessed using NCI CTCAE v4.0.

GroupValue95% CI
Cohort 1 (30 mg/kg)7
Cohort 2 (60 mg/kg)5
Cohort 3 (90 mg/kg)5
Number (Percentage) of Patients at Each Dosing Cohort With Progression of GVHD Secondary · 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.

GroupValue95% CI
Cohort 1 (30 mg/kg)4
Cohort 2 (60 mg/kg)5
Cohort 3 (90 mg/kg)4

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 (30 mg/kg)
Serious: 8/8 (100%)
Deaths: 6/8
Cohort 2 (60 mg/kg)
Serious: 5/6 (83%)
Deaths: 4/6
Cohort 3 (90 mg/kg)
Serious: 4/6 (67%)
Deaths: 4/6

Serious adverse events (7 terms)

ReactionSystemCohort 1 (30 mg/kg)Cohort 2 (60 mg/kg)Cohort 3 (90 mg/kg)
acute graft-versus-host diseaseImmune system disorders
infectionInfections and infestations
perirectal abbessGastrointestinal disorders
bowel perforationGastrointestinal disorders
liver failureHepatobiliary disorders
diffuse alveolar hemorrhageReproductive system and breast disorders
cranial hemorrhageNervous system disorders
Other adverse events (86 terms — click to expand)

ReactionSystemCohort 1 (30 mg/kg)Cohort 2 (60 mg/kg)Cohort 3 (90 mg/kg)
infectionInfections and infestations
thrombocytopeniaBlood and lymphatic system disorders
hypomagnesemiaMetabolism and nutrition disorders
weaknessMusculoskeletal and connective tissue disorders
anemiaBlood and lymphatic system disorders
hypokalemiaMetabolism and nutrition disorders
edema/fluid overloadCardiac disorders
fatigueGeneral disorders
neutropeniaBlood and lymphatic system disorders
elevated liver function testsHepatobiliary disorders
pain (all sites combined)General disorders
anxiety/stressPsychiatric disorders
insomniaGeneral disorders
acute graft versus host disease (GVHD)Immune system disorders
hyperglycemiaMetabolism and nutrition disorders
hypoglycemiaMetabolism and nutrition disorders
orthostatic hypotensionCardiac disorders
hypertensionCardiac disorders
blister/excoriationSkin and subcutaneous tissue disorders
rash/erythemaSkin and subcutaneous tissue disorders
depressionPsychiatric disorders
dry mouthGastrointestinal disorders
acute kidney injuryRenal and urinary disorders
hypogammaglobulinemiaBlood and lymphatic system disorders
leukocytosisBlood and lymphatic system disorders
HUS/microangiopathyBlood and lymphatic system disorders
hyponatremiaMetabolism and nutrition disorders
hypocalcemiaMetabolism and nutrition disorders
hypotensionCardiac disorders
tachycardiaCardiac disorders
dizzinessNervous system disorders
neuropathyNervous system disorders
tremorNervous system disorders
altered mental statusNervous system disorders
headacheNervous system disorders
constipationGastrointestinal disorders
nauseaGastrointestinal disorders
hemorrhoidsGastrointestinal disorders
gastroparesisGastrointestinal disorders
coughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: acute graft-versus-host disease, infection, perirectal abbess, bowel perforation, liver failure, diffuse alveolar hemorrhage, cranial hemorrhage.

Data from ClinicalTrials.gov NCT01523821 adverse events section.

Sponsor's own description

This phase I/II trial evaluates the efficacy and adverse effects of alpha 1 anti-trypsin (AAT) for the treatment of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Acute graft-versus-host disease: a bench-to-bedside update.
    Holtan SG, Pasquini M, Weisdorf DJ. · · 2014 · cited 152× · PMID 24914140 · DOI 10.1182/blood-2014-01-514786
  2. Achievement of Tolerance Induction to Prevent Acute Graft-vs.-Host Disease.
    Thangavelu G, Blazar BR. · · 2019 · cited 23× · PMID 30906290 · DOI 10.3389/fimmu.2019.00309
  3. Innate immune activation by tissue injury and cell death in the setting of hematopoietic stem cell transplantation.
    Brennan TV, Rendell VR, Yang Y. · · 2015 · cited 23× · PMID 25852683 · DOI 10.3389/fimmu.2015.00101
  4. T Helper Subsets, Peripheral Plasticity, and the Acute Phase Protein, α1-Antitrypsin.
    Baranovski BM, Freixo-Lima GS, Lewis EC, Rider P. · · 2015 · cited 13× · PMID 26583093 · DOI 10.1155/2015/184574
  5. Therapeutic targets and emerging treatment options in gastrointestinal acute graft-versus-host disease.
    Renteria AS, Levine JE, Ferrara JLM. · · 2016 · cited 3× · PMID 30057862 · DOI 10.1517/21678707.2016.1166949

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