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

NCT02956122 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 471501
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Overall Response (OR) At 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.

  Day 28

Secondary Outcomes (25)

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

  Day 28

• Percentage of Participants Achieving Overall Response at Day 56

  Day 56

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

  Days 28, 56 and 180

• Incidence of Chronic Graft-versus-host Disease (GvHD)

  Days 180 and 365

• Duration of Overall Response (OR)

  Baseline up to Day 365

Study Arms (3)

Study Part 1 - All Participants - GLASSIA

EXPERIMENTAL

Participants to receive GLASSIA (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)

Biological: GLASSIA; Drug: methylprednisolone or equivalent steroid

Study Part 2 - GLASSIA

EXPERIMENTAL

Participants to receive GLASSIA (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)

Biological: GLASSIA; Drug: methylprednisolone or equivalent steroid

Study Part 2 - Albumin (Control)

PLACEBO COMPARATOR

Participants to receive control (intravenously) and methylprednisolone or equivalent steroid (either IV or oral per investigator discretion)

Drug: methylprednisolone or equivalent steroid; Biological: Albumin

Interventions

GLASSIA BIOLOGICAL

GLASSIA \[Alpha1-Proteinase Inhibitor (Human)\]

Also known as: as alpha-1 antitrypsin, A1PI, alpha-1 proteinase inhibitor

Study Part 1 - All Participants - GLASSIA; Study Part 2 - GLASSIA

methylprednisolone or equivalent steroid DRUG

The conventional steroid treatment (methylprednisolone or equivalent steroid) will be supplied by the investigators per their institutional practice.

Study Part 1 - All Participants - GLASSIA; Study Part 2 - Albumin (Control); Study Part 2 - GLASSIA

Albumin BIOLOGICAL

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).

Also known as: Human Albumin

Study Part 2 - Albumin (Control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants aged ≥18 years at the time of screening
• Recipient of an hematopoietic stem cell transplantation (HSCT)
• The disease indication for which the participant required HSCT must be in remission
• 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.
• 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 enrollment
• Evidence 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 test
• Females 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 protocol

You may not qualify if:

• Participant with manifestations of chronic GvHD
• Participant with acute/chronic GvHD overlap syndrome
• Participant whose GvHD developed after donor lymphocyte infusion
• 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
• Participant with evidence of recurrent malignancy
• Participant 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 study
• Participant with severe sepsis involving at least 1 organ failure
• Participant who is seropositive or positive in the nucleic acid test for human immunodeficiency virus (HIV)
• Participant with active hepatitis B or C
• 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
• If female, participant is pregnant or lactating at the time of enrollment, or has plans to become pregnant during the study
• Participant with a serious medical or psychiatric illness likely to interfere with participation in the study
• Participant is a family member or employee of the investigator

Sponsors & Collaborators

• Baxalta now part of Shire: lead
• Kamada, Ltd.: collaborator

Study Sites (1)

Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

alpha 1-Antitrypsin; Methylprednisolone; Albumins; Serum Albumin, Human

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Serum Albumin

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2016
• First Posted: November 7, 2016
• Study Start: April 26, 2017
• Primary Completion: May 3, 2018
• Study Completion: May 3, 2018
• Last Updated: January 13, 2021
• Results First Posted: April 24, 2019

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)