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UG3HL165064

Cooperative Agreement

Overview

Grant Description
A Severe Hemophilia A Intergenerational Cohort Research Program for the Study of Factor VIII Immunogenicity - Project Summary

We propose to establish a Hemophilia A Analytical Cohort Research Program (HARP) to support the development of an intergenerational precision medicine program for the study of Factor VIII (FVIII) immunogenicity in severe Hemophilia A.

The first major aim of HARP is to form a new longitudinal antenatal/neonatal/pediatric severe Hemophilia A cohort to study the development of FVIII inhibitors. The cohort will encompass at least 50 mother-baby pairs, following first genetic carrier mothers and then their babies with severe Hemophilia A over at least the first two years of life.

HARP will be responsible for the overall project coordination, administration, data and biospecimen management, and biostatistics/data analytical support for the program.

The second major aim of HARP is to enable the development of the HARP Shareable Resource comprised of well-annotated data and biological samples collected over the course of the program accessible through a portal, F8PORTAL.ORG, and a linked biorepository. These resources will be made available to community researchers.

As part of Aim 2, protocols will be developed by the HARP Protocols Expert Panel (PEP) in conjunction with the Consortium of Clinical Centers to support research in four HARP scientific emphasis areas (SEAs):

1. Maternal Antenatal Research
2. Perinatal Research
3. Neonatal/Pediatric Multi-Omics and Immunology Research
4. Hemophilia-Event Driven Neonatal/Pediatric Multi-Omics and Immunology Research

The third major aim of HARP is to perform hypothesis-testing research in each of the four scientific emphasis areas.

For the Maternal Antenatal SEA, we will deeply characterize the mother's expression of FVIII and the antenatal environment to test our hypothesis that the mother's Hemophilia carrier phenotype modulates inhibitor development by influencing exposure to FVIII tolerizing proteins and future bleeding risk of the infant.

For the Perinatal SEA, we hypothesize that perinatal exposure to FVIII via expression of F8 gene products is critical in modulating the FVIII immune response and propose to investigate this via genetic methods in the neonate and maternal/cord blood.

For the Neonatal/Pediatric -Omics and Immunology SEA, we hypothesize that environmental, genetic, and persistent maternal factors promote perturbations in the immune system leading to an FVIII immune response. We propose to rigorously investigate these factors using genetic, immunologic, and -omics evaluation beginning in neonates and following through early life.

Finally, we propose to investigate FVIII antibody affinity, epitope, and peptide presentation to test our hypothesis that immunologic and/or inflammatory events occurring around FVIII exposure influence production of FVIII-IGG1 and ultimately inhibitors for the Hemophilia event-driven SEA.

Together, this proposal seeks to provide rigorous scientific and clinical data with biospecimens and expert support for a communal resource to drive innovative investigations of FVIII immunogenicity.
Funding Goals
NOT APPLICABLE
Place of Performance
Seattle, Washington 981950001 United States
Geographic Scope
Single Zip Code
Analysis Notes
Amendment Since initial award the total obligations have increased 278% from $1,791,855 to $6,768,642.
University Of Washington was awarded HARP: Hemophilia A Cohort for FVIII Immunogenicity Cooperative Agreement UG3HL165064 worth $6,768,642 from National Heart Lung and Blood Institute in September 2022 with work to be completed primarily in Seattle Washington United States. The grant has a duration of 3 years and was awarded through assistance program 93.837 Cardiovascular Diseases Research. The Cooperative Agreement was awarded through grant opportunity An Intergenerational Precision Medicine Research Program for the Study of Factor VIII Immunogenicity in Severe Hemophilia A: Hemophilia A Analytical Cohort Research Program (UG3/UH3 Clinical Trial Not Allowed).

Status
(Ongoing)

Last Modified 9/20/24

Period of Performance
9/21/22
Start Date
8/31/25
End Date
93.0% Complete

Funding Split
$6.8M
Federal Obligation
$0.0
Non-Federal Obligation
$6.8M
Total Obligated
100.0% Federal Funding
0.0% Non-Federal Funding

Activity Timeline

Interactive chart of timeline of amendments to UG3HL165064

Subgrant Awards

Disclosed subgrants for UG3HL165064

Transaction History

Modifications to UG3HL165064

Additional Detail

Award ID FAIN
UG3HL165064
SAI Number
UG3HL165064-551385651
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NH00 NIH NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Funding Office
75NH00 NIH NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Awardee UEI
HD1WMN6945W6
Awardee CAGE
1HEX5
Performance District
WA-07
Senators
Maria Cantwell
Patty Murray

Budget Funding

Federal Account Budget Subfunction Object Class Total Percentage
National Heart, Lung, and Blood Institute, National Institutes of Health, Health and Human Services (075-0872) Health research and training Grants, subsidies, and contributions (41.0) $4,303,323 100%
Modified: 9/20/24