ATHN 7: Hemophilia Natural History Study

This non-interventional, minimal risk cohort study will enroll and follow patients with
hemophilia A or B as they receive hemophilia treatment for 4 years. This is a pragmatic study
of real-world practices across a wide range of patients which will be ongoing as new
treatment products receive FDA approval and will be advantageous to the entire hemophilia
community. The total study duration is planned for 6 years.

The patients are seen at baseline, annually, and at study exit. Patients will also receive
routine quarterly follow-up phone calls from HTC staff to review medical history, bleed
events, and product treatment history. Other visits for unplanned events or for the change of
treatment product will be scheduled as necessary. All required study visits will be planned
to coincide with routine clinical care whenever possible. Co-enrollment in the ATHNdataset by
patients is required to participate in the study.

Please note - the treatment regimen will be at the discretion of the patients' hemophilia
caregivers. No treatment products are being provided by the study nor will the participants
be paid. However, inhibitor titer testing will be provided at no cost to patients by the
Center for Disease Control and Prevention (CDC).

The primary objective is to determine the safety of non-factor products, bypassing agents or
clotting factor replacement products when used for people with hemophilia with or without
inhibitors. Safety will be measured by those events listed in the European Haemophilia Safety
Surveillance (EUHASS).

Data collected will include eligibility, demographics, medical history, hemophilia history
(genotype and family history), inhibitor history and immune tolerance induction (ITI)
treatment regimen (if applicable), co-morbidities at baseline (i.e., HIV, Hepatitis C),
detailed treatment product(s) usage, bleeding events, surgical procedures, and EUHASS adverse
events and other adverse events of special interest. Data collection will also include
patient-reported outcome questionnaires regarding health-related quality of life, treatment
use and patient perceptions of treatment products.

Sub-studies

A number of sub-studies are planned with pharmaceutical sponsors to collect information from
patients about their specific product use. Participation in these sub-studies (Product
Specific Modules) is optional and sub-study visits will be planned to coincide with HTC
visits. The modules will collect information from patients about their perception and use of
treatment products, physical activity levels and other general health questions. This data
will be collected via questionnaire.

Data Collection System

All data collected will be entered into electronic case report forms (eCRFs) within the
secure ATHN System by HTC site personnel. All participating study sites will have in place a
current, executed Data Use and Business Associate Agreement (DUBAA) with ATHN.

Inclusion Criteria:

1. Congenital hemophilia A or B of any severity with or without inhibitors receiving a
current therapy, a non-factor product, or for whom use of a non-factor product is a
possibility;

2. Able to give informed consent (by patient or parent/authorized guardian); and

3. Co-enrollment in the ATHNdataset.

Exclusion Criteria:

1. Presence of any known bleeding disorder other than congenital hemophilia A or B;

2. Presence of concurrent hemophilia and a second hemostatic defect (low Von Willebrand
Factor (VWF) without Von Willebrand disease (VWD) diagnosis is not excluded); and

3. Unable or unwilling to comply with the study protocol.