Mother-and-child hemophilia A program

Hemophilia A Research Program (HARP): An Observational Intergenerational Cohort Study of Hemophilia A and Factor VIII Immunogenicity

See if following pregnant people with a severe hemophilia A genotype and their children from pregnancy through early childhood can identify factors linked to maternal bleeding and the child’s development of anti‑FVIII antibodies.

Quick facts

• Study type: Observational
• Enrollment: 500 (estimated)
• Sex: All
• Sponsor: University of Washington (Academic / other)
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT07414511 on ClinicalTrials.gov

What this trial studies

This is a national, longitudinal observational cohort that follows mother‑child pairs from pregnancy through at least the first two years of life to examine bleeding risks in mothers and inhibitor (anti‑FVIII antibody) development in children. The study aims to enroll about 120 pregnant individuals at risk of having a child with severe hemophilia A to yield roughly 50 affected mother‑child pairs, and invites blood relatives to improve genetic analyses. Participants receive usual clinical care from their health providers while the study collects clinical data and biological samples over time. The design is decentralized and multisite with a hybrid site at the University of Washington to support remote and occasional in‑person visits.

Who should consider this trial

Good fit: Ideal candidates are pregnant individuals aged 18 or older who are known to have or be at risk for a severe hemophilia A genotype and their newborns, with willing blood relatives to provide additional samples if available.

Not a fit: People who are not pregnant, who do not have or are not at risk for a severe hemophilia A genotype, or who cannot commit to longitudinal follow‑up are unlikely to gain direct benefit from participation.

Why it matters

Potential benefit: If successful, the study could help predict and reduce postpartum bleeding in affected mothers and identify early signs of inhibitor development in children so care can be personalized earlier.

How similar studies have performed: Prior studies have described inhibitor formation and bleeding risks, but longitudinal mother‑to‑child cohorts that begin before birth and follow both generations are relatively novel.

Eligibility criteria

Maternal Inclusion Criteria:

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
* 18 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.

Pediatric Continuation / Inclusion Criteria:

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.

Inclusion Criteria for Blood Relatives:

Blood relatives of the child may be offered participation if one of the following criteria are met:

* 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

Exclusion/Discontinuation Criteria:

Maternal: For the pregnant person, exclusion or discontinuation criteria are as follows:

* Genetic testing is negative for a severe hemophilia A genotype
* Prenatal clinical diagnostic testing that indicates there is no fetus affected with severe hemophilia A
* Presence of another clinically significant bleeding disorder
* Participation in another study for which any blood collection total would exceed safety limits defined in this study
* Will deliver outside the United States or plans for regular pediatric care for the child to be delivered outside the United States
* Is a prisoner
* Any other reason that, in the opinion of the investigator, would render the individual unsuitable for participation in the study
* Inability for study team to obtain translated study documents in time for participation if participant is not fluent in English

Pediatric: For the child, discontinuation criteria are as follows:

* Infant does not have severe hemophilia A defined by a baseline FVIII:C \< 0.01 IU/mL (or FVIII:C \< 1%) or does not have a genotype predicted to cause severe hemophilia A
* Mother or child did not have minimal required study samples or data collected before birth, around the time of delivery, or in the neonatal period
* Child has another clinically significant bleeding disorder
* Child has a clinically severe immune disorder
* Participation in another study for which any blood collection total would exceed safety limits defined in this study
* Any other reason that, in the opinion of the investigator, would render the individual unsuitable for participation in the study

Where this trial is running

Seattle, Washington

• University of Washington — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Jill M Johnsen, MD — University of Washington
• Study coordinator: Jill M Johnsen, MD

Conditions Hemophilia A; Hemophilia A, Severe; Factor VIII; FVIII Deficiency; Carrier of Hemophilia A; Inhibitors; Pregnancy; Maternal Blood Loss