Hemophilia A Research Program

NCT07414511 | Recruiting DMC

• 2 other identifiers: STUDY000204651UG3HL165064-01
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

This study longitudinally observes the intergenerational (mother-child) continuum in hemophilia A from pregnancy through early childhood. Because the study follows mother-child pairs, the study includes both a maternal cohort and a pediatric cohort. Each cohort has a primary goal: for the mother with a severe hemophilia genotype, the overarching primary goal is to understand the risks for pregnancy-associated bleeding and postpartum hemorrhage (PPH); for the child, the overarching primary goal is to understand the risks, timing, and circumstances of development of anti-FVIII antibodies. From a longitudinal perspective, risks for both bleeding in the mother and anti-FVIII antibody development in the child are expected to be influenced over time by genetic and environmental factors that begin early in (or before) pregnancy. Enrollment of blood relatives is offered to improve power to better understand inherited contributions to bleeding and inhibitor development in the mother-baby pairs.

Conditions

Factor VIII (FVIII); FVIII Deficiency; Maternal Blood Loss; Bleeding Disorder; Hemorrhage, Postpartum; Hemophilia A; Hemophilia A, Severe; Carrier of Hemophilia A; Inhibitors; Pregnancy; Pregnancy Complications; Alloimmunization; X-Linked

Keywords

Pregnancy; Inhibitor; Bleeding; Bleeding Disorder; Maternal Child Health; Hemophilia; Hemophilia A; Hemophilia A Carrier; Hemophilia A Symptomatic Carrier; Coagulation; Factor VIII

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint(s)/Outcome(s)

  The study primary endpoints/outcomes for the maternal and pediatric cohorts are as follows: • Maternal: Rates of primary PPH, defined as * estimated or quantified blood loss \> 1,000 mL in the first 24 hours PP, or * unplanned transfusion of blood products related to blood loss in the first 24 hours PP. As a subset of primary PPH, severe primary PPH is defined as * estimated or quantified blood loss \> 1,500 mL or requirement of \> 2 units packed red blood cells within 24 hours PP, or * primary PPH with estimated or quantified blood loss \> 1,000 mL and evidence of maternal hemodynamic instability (tachycardia, hypotension) or end organ damage with no other etiology (oliguria, creatinine \> 0.8, etc.). • Pediatric: Rate of development of humoral immune response to FVIII and proportion that progress to clinical inhibitors, defined as * clinical FVIII inhibitor, or * detection of an antibody specific to FVIII.

  For mother-child pairs, from enrollment until the child with severe hemophilia A is at least 2 years old*, or until a study discontinuation criteria is met. *This is the minimum duration, the mother-child pairs will be followed for as long as feasible.

Secondary Outcomes (1)

• Secondary Endpoint(s)/Outcome(s)

  For mother-child pairs, from enrollment until the child with severe hemophilia A is at least 2 years old*, or until a study discontinuation criteria is met. *This is the minimum duration, the mother-child pairs will be followed for as long as feasible.

Study Arms (3)

Maternal Cohort

Inclusion Criteria (mother): * Currently pregnant and prior to 37 weeks gestation * Known or at-risk of having a severe hemophilia A genotype * Pregnant with a fetus at-risk of inheriting severe hemophilia A * Ability to understand and willingness to provide informed consent * 18 years of age or older

Pediatric Cohort Continuation Criteria (Child)

* Severe hemophilia A defined by a baseline factor VIII activity (FVIII:C) \<0.01 international units (IU)/mL (or FVIII:C \< 1%) or a genotype predicted to result in severe hemophilia A * Born to a pregnant mother participating in the study * Absence of discontinuation criteria

Blood Relatives of the Child (may be offered participation)

* First-degree blood relatives (e.g., father, sibling) of the child * Second-degree blood relatives (e.g., aunt, uncle, grandparent, half-sibling) of the child * Any more distant male or female blood relative whose data or samples may be informative for the planned genetic studies of hemophilia and inhibitors

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

To accomplish the goal of following 50 mother-child pairs with a child affected by severe hemophilia A from pregnancy through at least the first 2 years of life, we expect to enroll approximately 120 pregnant mothers with a pregnancy at-risk of being affected by severe hemophilia A. Blood relatives of the child can also enroll.

You may qualify if:

• Pregnant individuals who meet the following criteria are eligible for enrollment as study participants:
• Currently pregnant and prior to 37 weeks gestation
• Known to have or at-risk of having a severe hemophilia A genotype
• Pregnant with at least one fetus at-risk of inheriting severe hemophilia A
• Ability to understand and willingness to provide informed consent
• years of age or older
• Before the 38th week of pregnancy, enrolled participants must meet all the following criteria to continue to remain in the study:
• The pregnant mother has a severe hemophilia A genotype.
• A fetus is determined to have a \>/= 25% risk of inheriting severe hemophilia A, or prenatal testing indicates a fetus is affected by severe hemophilia A.
• No other discontinuation criteria have been identified.
• Eligibility of the child to continue is assessed by age 8 weeks. Mother-child pairs in which a child meets the following criteria will remain in the study:
• Severe hemophilia A defined by a baseline FVIII:C \< 0.01 IU/mL (or FVIII:C \< 1%) or a genotype predicted to cause severe hemophilia A
• Born to a mother participating in the study
• Thereafter, mothers and their children will continue in the study as long as no new discontinuation criteria occur.
• Blood relatives of the child may be offered participation if one of the following criteria are met:

Sponsors & Collaborators

• University of Washington: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• RTI International: collaborator
• Emory University: collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (14)

• Fein SB, Labiner-Wolfe J, Shealy KR, Li R, Chen J, Grummer-Strawn LM. Infant Feeding Practices Study II: study methods. Pediatrics. 2008 Oct;122 Suppl 2:S28-35. doi: 10.1542/peds.2008-1315c.

  PMID: 18829828 BACKGROUND

• Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.

  PMID: 11556941 BACKGROUND

• Kadir RA, Economides DL, Sabin CA, Pollard D, Lee CA. Assessment of menstrual blood loss and gynaecological problems in patients with inherited bleeding disorders. Haemophilia. 1999 Jan;5(1):40-8. doi: 10.1046/j.1365-2516.1999.00285.x.

  PMID: 10215946 BACKGROUND

• Young JE, Grabell J, Tuttle A, Bowman M, Hopman WM, Good D, Rydz N, Mahlangu JN, James PD. Evaluation of the self-administered bleeding assessment tool (Self-BAT) in haemophilia carriers and correlations with quality of life. Haemophilia. 2017 Nov;23(6):e536-e538. doi: 10.1111/hae.13354. Epub 2017 Sep 26. No abstract available.

  PMID: 28949433 BACKGROUND

• Deforest M, Grabell J, Albert S, Young J, Tuttle A, Hopman WM, James PD. Generation and optimization of the self-administered bleeding assessment tool and its validation as a screening test for von Willebrand disease. Haemophilia. 2015 Sep;21(5):e384-8. doi: 10.1111/hae.12747. Epub 2015 Jul 14.

  PMID: 26179127 BACKGROUND

• Lavin M, Christopherson P, Grabell J, Abshire T, Flood V, Haberichter SL, Lillicrap D, O'Donnell JS, Montgomery RR, James PD. Longitudinal bleeding assessment in von Willebrand disease utilizing an interim bleeding score. J Thromb Haemost. 2022 Oct;20(10):2246-2254. doi: 10.1111/jth.15807. Epub 2022 Jul 26.

  PMID: 35780487 BACKGROUND

• James PD, Mahlangu J, Bidlingmaier C, Mingot-Castellano ME, Chitlur M, Fogarty PF, Cuker A, Mancuso ME, Holme PA, Grabell J, Satkunam N, Hopman WM, Mathew P; Global Emerging HEmostasis Experts Panel (GEHEP). Evaluation of the utility of the ISTH-BAT in haemophilia carriers: a multinational study. Haemophilia. 2016 Nov;22(6):912-918. doi: 10.1111/hae.13089.

  PMID: 27868369 BACKGROUND

• van Hoorn ES, Teela L, Kuijlaars IAR, Fischer K, Gouw SC, Cnossen MH, Haverman L; for SYMPHONY consortium and Dutch research group for PROMIS implementation in inherited bleeding disorders. Harmonizing patient-reported outcome measurements in inherited bleeding disorders with PROMIS. Haemophilia. 2023 Jan;29(1):357-361. doi: 10.1111/hae.14694. Epub 2022 Nov 17. No abstract available.

  PMID: 36395776 BACKGROUND

• Slopen N, Loucks EB, Appleton AA, Kawachi I, Kubzansky LD, Non AL, Buka S, Gilman SE. Early origins of inflammation: An examination of prenatal and childhood social adversity in a prospective cohort study. Psychoneuroendocrinology. 2015 Jan;51:403-13. doi: 10.1016/j.psyneuen.2014.10.016. Epub 2014 Oct 25.

  PMID: 25462912 BACKGROUND

• Robles TF. Annual Research Review: Social relationships and the immune system during development. J Child Psychol Psychiatry. 2021 May;62(5):539-559. doi: 10.1111/jcpp.13350. Epub 2020 Nov 8.

  PMID: 33164229 BACKGROUND

• Wang E, Glazer KB, Howell EA, Janevic TM. Social Determinants of Pregnancy-Related Mortality and Morbidity in the United States: A Systematic Review. Obstet Gynecol. 2020 Apr;135(4):896-915. doi: 10.1097/AOG.0000000000003762.

  PMID: 32168209 BACKGROUND

• Soucie JM, Miller CH, Dupervil B, Le B, Buckner TW. Occurrence rates of haemophilia among males in the United States based on surveillance conducted in specialized haemophilia treatment centres. Haemophilia. 2020 May;26(3):487-493. doi: 10.1111/hae.13998. Epub 2020 Apr 24.

  PMID: 32329553 BACKGROUND

• Knapp EA, Kress AM, Parker CB, Page GP, McArthur K, Gachigi KK, Alshawabkeh AN, Aschner JL, Bastain TM, Breton CV, Bendixsen CG, Brennan PA, Bush NR, Buss C, Camargo CA Jr, Catellier D, Cordero JF, Croen L, Dabelea D, Deoni S, D'Sa V, Duarte CS, Dunlop AL, Elliott AJ, Farzan SF, Ferrara A, Ganiban JM, Gern JE, Giardino AP, Towe-Goodman NR, Gold DR, Habre R, Hamra GB, Hartert T, Herbstman JB, Hertz-Picciotto I, Hipwell AE, Karagas MR, Karr CJ, Keenan K, Kerver JM, Koinis-Mitchell D, Lau B, Lester BM, Leve LD, Leventhal B, LeWinn KZ, Lewis J, Litonjua AA, Lyall K, Madan JC, McEvoy CT, McGrath M, Meeker JD, Miller RL, Morello-Frosch R, Neiderhiser JM, O'Connor TG, Oken E, O'Shea M, Paneth N, Porucznik CA, Sathyanarayana S, Schantz SL, Spindel ER, Stanford JB, Stroustrup A, Teitelbaum SL, Trasande L, Volk H, Wadhwa PD, Weiss ST, Woodruff TJ, Wright RJ, Zhao Q, Jacobson LP, Influences On Child Health Outcomes OBOPCFE. The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort. Am J Epidemiol. 2023 Aug 4;192(8):1249-1263. doi: 10.1093/aje/kwad071.

  PMID: 36963379 BACKGROUND

• Johnsen JM, Fletcher SN, Dove A, McCracken H, Martin BK, Kircher M, Josephson NC, Shendure J, Ruuska SE, Valentino LA, Pierce GF, Watson C, Cheng D, Recht M, Konkle BA. Results of genetic analysis of 11 341 participants enrolled in the My Life, Our Future hemophilia genotyping initiative in the United States. J Thromb Haemost. 2022 Sep;20(9):2022-2034. doi: 10.1111/jth.15805. Epub 2022 Jul 17.

  PMID: 35770352 BACKGROUND

Related Links

• HARP Website
• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

Biological samples consisting of primary samples and derivative samples from the following sources: blood, stool, hair, cord blood, umbilical cord, placenta, amniotic fluid, cheek swab, saliva, vaginal swab, placenta. Derivatives are planned to include DNA, RNA, proteins, cells, and small molecules.

MeSH Terms

Conditions

Hemophilia A; Pregnancy Complications; Hemostatic Disorders; Postpartum Hemorrhage; Hemorrhage; Thrombosis

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis

Study Officials

• Jill M Johnsen, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

• Grier Page, PhD

  RTI International

  PRINCIPAL INVESTIGATOR

• Shannon Meeks, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jill M Johnsen, MD

CONTACT

206 568-2230; jjohnsen@uw.edu

G Shellye Horowitz, MA

CONTACT

Shellye@uw.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Division of Hematology and Oncology

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: February 17, 2026
• Study Start: July 31, 2024
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Study protocol and informed consents will be available on request starting Nov 2024 and will be on study website in 2026. The Clinical data will be available to qualified researchers with approved applications upon completion of primary analysis in late 2029. Results will be presented in meetings, published in journals, and shared widely with the community.
• Access Criteria: Qualified researchers will apply for approval from the HARP Research Access Committee, expected to form in late 2029.

Locations

US (1)