臨床研究等提出・公開システム

A phase 2/3, Multicenter, randOmized, Double-blind, placebo-controlled, stUdy to evaLuate the safety and efficacy of Alpha-1 AntiTrypsin for the prEvention of graft-versus-host disease in patients receiving hematopoietic cell transplant (MODULAATE Study) (MODULAATE)

The safety and efficacy of Alpha-1 Antitrypsin (AAT) for the prevention of graft-versus-host disease (GVHD) in patients receiving hematopoietic cell transplant (MODULAATE)

Akama Hideto

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo

JPN-CHIKEN@csl.com.au

Akama Hideto

CSL Behring K.K.

Aoyama Building, 1-2-3 Kita-Aoyama, Minato-ku, Tokyo

+81-3-4213-0191

JPN-CHIKEN@csl.com.au

Not Recruiting

June. 24, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

prevention purpose

1. Male or female participants, >=12 years of age (>= 18 years of age for participants at German sites only), undergoing HCT for hematological malignancies, including leukemia, lymphoma, multiple myeloma, myelodysplastic syndrome, and myeloproliferative neoplasms.
2. Planned myeloablative conditioning regimen.
3. Participants must have a related or unrelated donor as follows:
- Related donor must be a 6 / 6 match for human leukocyte antigen (HLA)-A, -B, at intermediate (or higher) resolution, and -DR beta 1 (DRB1) at high resolution using deoxyribonucleic acid (DNA)-based typing.
- Unrelated donor must be 7 / 8 or 8 / 8 match for HLA-A, -B, and -C at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing.

1. Prior autologous or allogeneic HCT.
2. T cell depleted transplant or planned use of anti-T cell antibody therapy either ex vivo or in vivo (ie, anti thymocyte globulin [ATG], alemtuzumab) for GVHD prophylaxis.
3. Planned umbilical cord blood transplant.
4. Planned use of cyclophosphamide after HCT for GVHD prophylaxis.
5. Planned haploidentical donor.

Both

Acute graft versus host disease

Part 1: Open-label, dose-finding phase (conducted outside Japan)
Cohorts 1 - 3: AAT 90 - 180 mg/kg to be administered intravenously as a loading dose on Day -1, followed by 60 - 120 mg/kg twice weekly (until Day 28), and once weekly thereafter (until Day 56).
Part 2: Double-blind, placebo-controlled part
Cohort 4: AAT 180 mg/kg (or placebo [a commercial albumin product diluted in 5% dextrose]) to be administered intravenously as a loading dose on Day -1, followed by 120 mg/kg twice weekly (until Day 56).

Grade II-IV aGVHD-free survival through 180 days after HCT

1. Incidence of lower gastrointestinal (GI) aGVHD or Grade III-IV aGVHD in any organ through 180 days after HCT
2. Incidence of severe infections defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) >= Grade 3 through 60 days after HCT
3. Incidence of Grade II-IV aGVHD or death through 100 and 180 days after HCT
4. Incidence of lower GI aGVHD through 60, 100, and 180 days after HCT
5. Incidence of severe infections defined by NCI-CTCAE >= Grade 3 through 100 and 180 days after HCT
6. Incidence of all-cause mortality, relapse-related and non-relapse-related mortality through 180, 365, and 730 days after HCT
7. Incidence of Grade III-IV aGVHD through 60, 100 and 180 days after HCT
8. Incidence of moderate to severe chronic GVHD through 180, 365, 545, and 730 days after HCT
9. Incidence of discontinuation of immune suppression through 180 and 365 days after HCT
10. Time to neutrophil engraftment
11. GVHD-relapse free survival through 365 and 730 days after HCT
12. Incidence of relapse of primary malignancies through 180, 365, and 730 days after HCT
13. Incidence of overall response, complete response and partial response among subjects with Grade II-IV aGVHD approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period
14. Incidence of investigational product-related AEs
15. Pharmacokinetic parameters

+81-11-716-1161

Dec. 21, 2021

Yes

CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com. Supporting information: Protocol and Statistical Analysis Plan (SAP) will also be provided. Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available. Access Criteria: Proposed research should seek to answer a previously unanswered important medical or scientific question. Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD. If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that have been appropriately anonymized will be available.

US/Australia/Germany/Italy/Spain/UK/Turkey/South Korea