A 48-Month Study to Evaluate Long-Term Effectiveness of Elocta on Joint Health
- Registration Number
- NCT04293523
- Lead Sponsor
- Swedish Orphan Biovitrum
- Brief Summary
This is a 48-month observational, prospective, multicentre study. The overall aim of the study is to evaluate the long-term effectiveness of Elocta treatment on joint health in patients treated prophylactically with Elocta in a real-world setting.
- Detailed Description
Haemophilia A is a rare genetic disorder estimated to occur in one out of 10,000 live births, characterized by a deficiency in coagulation factor VIII causing impaired haemostasis and prolonged bleeding episodes. Moderate haemophilia, defined as \< 5%, and severe haemophilia, defined as \< 1% of normal factor VIII activity result in frequent and spontaneous bleeds into muscles and joints, commonly the elbows, knees, and ankles. Bleeding into joints can cause acute pain and swelling and can result in reduced joint range of motion, long-term cartilage damage and debilitating haemophilic arthropathy. Early use of prophylaxis with factor VIII replacement is recommended following diagnosis of haemophilia A to maintain joint health and prevent joint destruction. However, despite the use of prophylaxis many patients still experience joint bleeds which may lead to joint deterioration over time. The risk of joint bleeds increases with the amount of time spent below certain FVIII trough levels, e.g. 1, 3 or 5 IU/dL. Thus, there is probably a relation between the intensity of the prophylactic treatment regimen and joint health. Elocta is an extended half-life rFVIII product (EHL rFVIII), with a slower clearance as compared to conventional FVIII products. Treatment with Elocta will therefore provide the treater with a greater flexibility for individualizing prophylaxis as compared to conventional FVIII. Higher trough levels can be reached with Elocta without increasing factor usage or injection frequency. The treater can instead choose to reduce the injection frequency or the factor consumption without lowering trough levels.
Patients may limit their physical activities due to fear of bleeding if they are unaware of their current FVIII level. Patient apps and wearables are now available which allow patients to view their predicted FVIII levels, and capture health-related data (such as bleedings, pain, well-being, physical activity levels etc.). This data can be shared with the treating physician supporting the planning to individualize the patient's factor treatment based on current lifestyle, health status and physical activity levels. Florio, a certified medical device used as part of routine clinical practice, is such an app, and the data output and patient feedback on their activity levels and sense of protection while using Florio will be analysed as exploratory objectives in this study.
The main purpose of this study is to evaluate the effectiveness of Elocta on joint health over a long observation period (48 months). The study will also explore the influence on long term joint health of different Elocta prophylaxis regimens leading to different trough levels and if the extent of patients' physical activity levels can be associated with predicted FVIII levels.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 427
- Provided signed and dated informed consent by the patient, or the patient's legally authorized representative(s) for patients under the legal age, before any study-related activities are undertaken. Assent should be obtained from paediatric patients according to local regulations
- Have a diagnosis of haemophilia A
- At enrolment on prophylactic treatment with Elocta, independent of participation in the study
- Enrolment in another concurrent clinical interventional study, or intake of an Investigational Medicinal Product (IMP), within three months prior to inclusion in this study
- Presence of factor VIII antibodies (inhibitors) (≥0.60 Bethesda Unit [BU]/mL) at the latest available inhibitor test
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Hemophilia A patients ELOCTA All patients diagnosed with haemophilia A regardless of severity, on factor treatment with Elocta according to usual clinical practice.
- Primary Outcome Measures
Name Time Method Joint health: Target joint recurrence 48 months Number of recurring target joints
Joint health: Annualised joint bleeding rate (AJBR) for treated bleeds 48 months Number of joint bleeding events per year, for treated bleeds
Joint health: Target joint resolution 48 months Number of resolved target joints
Joint health: Target joint development 48 months Number of target joints
- Secondary Outcome Measures
Name Time Method Joint and physical evaluation for elbows, knees and ankles. 48 months The WFH Physical Examination Score (AKA Gilbert Score) will be used. Joint evaluation (pain, bleeding, physical examination and radiologic evaluation) and physical evaluation (swelling, muscle atrophy, axial deformity, crepitus on motion, range of motion, flexion contracture, and instability). A higher score indicates a worse outcome.
Disease Activity (hypertrophic synovium) and Disease Damage (Cartilage or Bone) scores for elbows, knees and ankles 48 months The Haemophilia Early Arthropathy Detection with UltraSound (HEAD-US) protocol will be used. The total score represents the sum of item scores for abnormalities detected. Its values range from 0 (minimum) to 8 (maximum). A higher score indicates a worse outcome.
Global Gait Score, and/or joint score items for elbows, knees and ankles. 48 months The Haemophilia Joint Health Score (HJHS) system will be used. Global Gait Score, and/or Joint score items (swelling, duration of swelling, muscle atrophy, axial alignment, crepitus on motion, flexion loss, instability, extension loss, joint pain, strength, gait) for elbows, knees and ankles.
The minimum score per joint is 0, the maximum score is 20. The overall total joint score (range 0-120) is the sum of the 6 six index joint (elbows, knees and ankles) scores. A higher score indicates a worse outcome.
Trial Locations
- Locations (53)
The Royal Hospital
🇴🇲Muscat, Oman
University Hospital Brno
🇨🇿Brno, Czechia
University Hospital Ostrava
🇨🇿Ostrava, Czechia
Dept. of Pediatric Haematology and Oncology, University Hospital Motol
🇨🇿Praha, Czechia
Lastehaigla, Tallinn (Tallinn Children´s Hospital)
🇪🇪Tallinn, Estonia
The North Estonia Medical Centre Hematoloogiakeskus, Regionalhaigla
🇪🇪Tallinn, Estonia
Helsinki University Central Hospital, New Children Hospital
🇫🇮Helsinki, Finland
Turku University Central Hospital, Paediatric and adolescent haematology and oncology clinic
🇫🇮Turku, Finland
Charité-Universitätsmedizin Berlin Campus Virchow Klinikum
🇩🇪Berlin, Germany
Universitätsklinikum Bonn AöR, Institut für Experimentelle Hämatologie und Transfusionsmedizin
🇩🇪Bonn, Germany
Hämostaseologie/Hämophiliezentrum, Medizinische Klinik 2 Institut für Transfusionsmedizin, Universitätsklinikum
🇩🇪Frankfurt, Germany
Universitätsklinikum Frankfurt - Klinik für Kinder- und Jugendmedizin
🇩🇪Frankfurt, Germany
Universitätsklinikum Hamburg-Eppendorf (UKE)
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hanover, Germany
Werlhof-Institut für Hämostaseologie GmbH
🇩🇪Hanover, Germany
SRH-Klinikum Heidelberg
🇩🇪Heidelberg, Germany
HZRM Hämöphilie Zentrum Rhein Main
🇩🇪Mörfelden-Walldorf, Germany
Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital am Universitätsklinikum München
🇩🇪München, Germany
Ippokrateio Hospital Thessaloniki (adult department)
🇬🇷Thessaloníki, Greece
Ippokrateio Hospital Thessaloniki (pediatric department)
🇬🇷Thessaloníki, Greece
University of Bari Aldo Moro (Centro Emofilia Policlinico - Pediatria U.O.)
🇮🇹Bari, Italy
AUSL Romagna Centro Emofilia U.O.C., Medicina Trasfusionale Dipartimento Patologia, Clinica Ospedale M. Bufalini
🇮🇹Cesena, Italy
Giannina Gaslini Institute
🇮🇹Genova, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
University Hospital of Parma, AOUP, Haemophilia Center
🇮🇹Parma, Italy
Uo Malattie Emorragiche e Trombotiche Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Universitá Catolica del Sacro Coure
🇮🇹Rome, Italy
Azienda Ospedaliera Città della Salute e della Scienza di Torino Regina Margherita
🇮🇹Torino, Italy
University Medical Center Groningen/UMCG
🇳🇱Groningen, Netherlands
Dr Suliman Al Habib Hospital Riyadh
🇸🇦Riyadh, Saudi Arabia
King Faisal Specialised Hospital, KFSH Riyadh, Children
🇸🇦Riyadh, Saudi Arabia
King Faisal Specialist Hospital KFSH, Adults
🇸🇦Riyadh, Saudi Arabia
Riyadh Military Hospital (P.S.M.C)
🇸🇦Riyadh, Saudi Arabia
University Medical Centre Ljubljana Division of Paediatrics
🇸🇮Ljubljana, Slovenia
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Sant Johan De Deu
🇪🇸Barcelona, Spain
Hospital Universitario Cruces
🇪🇸Cruces, Spain
Hospital Universitario Donostia
🇪🇸Donostia, Spain
Hospital Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario Carlos Haya
🇪🇸Málaga, Spain
Complejo Hospitalario de Navarra
🇪🇸Navarro, Spain
Hospital Universitario Central de Asturias (HUCA)
🇪🇸Oviedo, Spain
Hospital Universitario Son Espases
🇪🇸Palma De Mallorca, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Alvaro Cunqueiro
🇪🇸Vigo, Spain
Hematologimottagning Sahlgrenska
🇸🇪Gothenburg, Sweden
Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital Malmö
🇸🇪Malmö, Sweden
Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor Inselspital
🇨🇭Bern, Switzerland
Service et Laboratoire central d'hématologie, Adults
🇨🇭Lausanne, Switzerland
Zentrum für Labormedizin
🇨🇭Saint Gallen, Switzerland
Universitätsspital Zürich Klinik für Medizinische Onkologie und Hämatologie
🇨🇭Zürich, Switzerland
East Kent Hospitals University NHS Foundation Trust, Kent Haemophilia and Thrombosis Centre, Kent and Canterbury Hospital
🇬🇧Canterbury, United Kingdom
Great Ormond Street Hospital, Royal London Hospital for Integrated Medicine
🇬🇧London, United Kingdom