Incidence of Ultrasonographically Detected Articular Damage in Initially Healthy Joints of Patients With Hemophilia A Receiving Prophylactic Treatment With Emicizumab

Official title

Incidence of Ultrasonographically Detected Articular Damage in Initially Healthy Joints of Patients With Hemophilia A Receiving Prophylactic Treatment With Emicizumab. A Prospective Observational Study

Overview

Introduction: Prophylaxis with emicizumab has substantially improved hemorrhagic control in hemophilia A. However, the longitudinal incidence of ultrasonographically detected articular damage in initially healthy joints remains insufficiently characterized. Objective: To estimate the incidence of ultrasonographically detected articular damage in initially healthy joints among patients with hemophilia A receiving prophylaxis with emicizumab and to explore its association with relevant clinical variables. Methods: A prospective, longitudinal, observational study will be conducted in approximately 70 patients with hemophilia A receiving emicizumab, with an estimated recruitment of approximately 270 initially healthy joints. The study is purely observational and does not involve evaluation of the investigational product nor modification of the therapeutic regimen; dosing, administration intervals, and all clinical decisions regarding emicizumab will be determined exclusively at the discretion of the treating hematologist. Assessments will be performed at baseline and at 12 and 24 months. The unit of analysis will be the joint, including elbows, knees, and ankles without ultrasonographic evidence of articular damage and without a history of clinically evident hemarthrosis at study entry. The primary endpoint will be the occurrence of incident ultrasonographically detected articular damage, assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol. Secondary outcomes will include clinical joint health assessed by the Hemophilia Joint Health Score (HJHS), version 2.1; the frequency of joint hemarthroses measured by the annualized joint bleeding rate (AJBR); and habitual physical activity levels evaluated through age-specific validated questionnaires. Statistical analyses will account for intra-patient correlation among joints. Expected Results: A low to moderate incidence of ultrasonographically detected articular damage in initially healthy joints is anticipated during follow-up, providing clinically relevant information regarding structural joint preservation in patients with hemophilia A receiving emicizumab prophylaxis.

Interventions

• Other Hemophilia patients
  A prospective, longitudinal, observational study will be conducted in patients with hemophilia A receiving prophylaxis with emicizumab, with a 24-month follow-up period. Three assessments will be performed: at baseline, 12 months, and 24 months.

Primary outcome measures

• Measurement of Ultrasonographically Detected Articular Damage in Elbows, Knees, and Ankles [Time frame: Baseline visit, at 12 months, and at 24 months.]

Secondary outcome measures (5)

• Measurement of Clinical Joint Health in Knees, Ankles, and Elbows [Time frame: Baseline visit, at 12 months, and at 24 months.]
• Measurement of Joint Hemorrhagic Phenotype [Time frame: Baseline visit, at 12 months, and at 24 months.]
• Measurement of Physical Activity Level in patients under 18 years of age [Time frame: Baseline visit, at 12 months, and at 24 months.]
• Measurement of Physical Activity Level in Adult Patients [Time frame: Baseline visit, at 12 months, and at 24 months.]
• Measurement of Treatment Adherence [Time frame: Baseline visit, at 12 months, and at 24 months.]

Eligibility criteria

Inclusion criteria

• Confirmed diagnosis of hemophilia A;
• Receiving prophylactic treatment with emicizumab (Hemlibra®) according to routine clinical practice;
• Age ≥10 years at the time of study enrollment;
• Absence of ultrasonographic joint damage in at least one of the evaluated joints (elbows, knees, or ankles), defined as HEAD-US = 0 at baseline assessment;
• No documented history of clinically evident hemarthrosis in the corresponding joints from initiation of emicizumab prophylaxis to the study baseline evaluation;
• Ability to understand and complete study procedures (interviews, questionnaires, and clinical assessments), in accordance with the participant's age; and
• Provision of written informed consent; for minors, written informed consent from parents or legal guardians and assent from the minor participant, in accordance with applicable regulations.

Exclusion criteria

• Presence of ultrasonographic joint damage (HEAD-US ≥1) in all evaluated joints at the baseline visit;
• Documented history of clinically evident hemarthrosis in the joints under study;
• Prior major orthopedic surgery or arthroplasty in the evaluated joints;
• Presence of concomitant musculoskeletal pathology unrelated to hemophilia that could interfere with joint assessment (e.g., inflammatory arthritis, recent severe trauma);
• Inability to complete the planned 24-month follow-up or to undergo study assessments;
• Concurrent participation in another interventional study that could interfere with the joint health variables under evaluation; and
• Any clinical or social condition that, in the investigator's judgment, could compromise participant safety or the validity of the study data.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Spain · 1 center

• Universidad de Oviedo — Oviedo

Identifiers

NCT: NCT07420348 · HEmoJoint

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗