A-MORE: A 48-Month Study to Evaluate Long-Term Effectiveness of Elocta on Joint Health
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Hemophilia A patients All patients diagnosed with haemophilia A regardless of severity, on factor treatment with Elocta according to usual clinical practice. |
Drug: ELOCTA
Extended half-life factor VIII product
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Joint health: Target joint development [48 months]
Number of target joints
- Joint health: Target joint resolution [48 months]
Number of resolved target joints
- 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
Secondary Outcome Measures
- 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.
- 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.
Other Outcome Measures
- Effectiveness of Elocta: Annualised bleeding rate (ABR) for treated bleeds [48 months]
Number of bleeding events per year, for treated bleeds
- Effectiveness of Elocta: Annualised bleeding rate (ABR) for all bleeds [48 months]
Number of bleeding events per year, for all bleeds
- Effectiveness of Elocta: Occurrence of zero (0) joint bleeds [48 months]
Percentage (%) of study population with zero (0) joint bleeds
- Effectiveness of Elocta: Work productivity and impairment [48 months]
Assessed by WPAI-SHP questionnaire
- Effectiveness of Elocta: Quality of Life [48 months]
Assessed by Haemo-QoL/Haem-A-QoL questionnaire
- Effectiveness of Elocta: Physical activity level [48 months]
Assessed by the Saltin-Grimby scale
- Effectiveness of Elocta: Quality of Life [48 months]
Assessed by EQ-5D-5L/EQ-5D-Y questionnaire
- Effectiveness of Elocta: Severity of joint health [48 months]
Assessed by Patient Global Impression of Severity of Joint Health questionnaire
- Effectiveness of Elocta: FVIII plasma levels [48 months]
Percentage (%) of FVIII plasma level
- Effectiveness of Elocta: Usage of pain and anti-inflammatory medication [48 months]
Assessed by medication dose
- Effectiveness of Elocta: Usage of pain and anti-inflammatory medication [48 months]
Assessed by total number of exposure days per medication
- Usage of Elocta: Annualised injection frequency per subject [48 months]
Assessed by prescription
- Usage of Elocta: Annualised factor consumption per subject [48 months]
Assessed by prescription [IU/kg]
- Usage of Elocta: Adherence [48 months]
Investigator assessed (Percentage (%))
- Exploratory Objective [48 months]
Influence of different Elocta prophylaxis regimens on long term joint health
- Exploratory Objective: Impact of florio HAEMO on patients' sense of protection and their activity level [48 months]
Results from questionnaire on impact of florio HAEMO tools on patients' sense of protection and their activity level
- Exploratory Objective: Explore adherence to prescribed treatment regimen [48 months]
florio HAEMO captured treatment adherence scores
- Exploratory Objective: Explore relationship between predicted FVIII levels and physical activity [48 months]
florio HAEMO captured predicted FVIII levels, florio HAEMO captured physical activity (type, duration, heart rate and steps)
- Exploratory Objective: Explore timing of bleeds in relation to predicted FVIII levels and physical activity [48 months]
florio HAEMO captured bleed data (timing, location, cause, treated/untreated), florio HAEMO captured injection data (time, dose), florio HAEMO captured predicted FVIII levels
- Exploratory Objective: Explore the use of Florio to characterise pain and well-being [48 months]
florio HAEMO captured pain data (time, location, cause, intensity), florio HAEMO captured well-being data
- Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health [48 months]
Target joint development, resolution and recurrence
- Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health [48 months]
Annualised joint bleeding rate (AJBR) for treated bleeds
- Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health [48 months]
Ultrasound (HEAD-US)
- Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health [48 months]
Clinical joint scoring (HJHS)
- Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health [48 months]
Annualised bleeding rate (ABR) (based on bleeding episodes assessed according to local practice) for all bleeds
- Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health [48 months]
Occurrence of zero (0) joint bleeds
- Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health [48 months]
Quality of Life assessed by Haemo-QoL/Haem-A-QoL
- Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health [48 months]
Physical activity level assessed by the Saltin-Grimby scale
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Brno | Brno | Czechia | ||
| 2 | University Hospital Ostrava | Ostrava | Czechia | ||
| 3 | Dept. of Pediatric Haematology and Oncology, University Hospital Motol | Praha | Czechia | ||
| 4 | Lastehaigla, Tallinn (Tallinn Children´s Hospital) | Tallinn | Estonia | ||
| 5 | The North Estonia Medical Centre Hematoloogiakeskus, Regionalhaigla | Tallinn | Estonia | ||
| 6 | Helsinki University Central Hospital, New Children Hospital | Helsinki | Finland | ||
| 7 | Turku University Central Hospital, Paediatric and adolescent haematology and oncology clinic | Turku | Finland | ||
| 8 | Charité-Universitätsmedizin Berlin Campus Virchow Klinikum | Berlin | Germany | ||
| 9 | Universitätsklinikum Bonn AöR, Institut für Experimentelle Hämatologie und Transfusionsmedizin | Bonn | Germany | ||
| 10 | Hämostaseologie/Hämophiliezentrum, Medizinische Klinik 2 Institut für Transfusionsmedizin, Universitätsklinikum | Frankfurt | Germany | ||
| 11 | Universitätsklinikum Frankfurt - Klinik für Kinder- und Jugendmedizin | Frankfurt | Germany | ||
| 12 | Universitätsklinikum Hamburg-Eppendorf (UKE) | Hamburg | Germany | ||
| 13 | Medizinische Hochschule Hannover | Hanover | Germany | ||
| 14 | Werlhof-Institut für Hämostaseologie GmbH | Hanover | Germany | ||
| 15 | SRH-Klinikum Heidelberg | Heidelberg | Germany | ||
| 16 | HZRM Hämöphilie Zentrum Rhein Main | Mörfelden-Walldorf | Germany | ||
| 17 | Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital am Universitätsklinikum München | München | Germany | ||
| 18 | Ippokrateio Hospital Thessaloniki (adult department) | Thessaloníki | Greece | ||
| 19 | Ippokrateio Hospital Thessaloniki (pediatric department) | Thessaloníki | Greece | ||
| 20 | University of Bari Aldo Moro (Centro Emofilia Policlinico - Pediatria U.O.) | Bari | Italy | ||
| 21 | AUSL Romagna Centro Emofilia U.O.C., Medicina Trasfusionale Dipartimento Patologia, Clinica Ospedale M. Bufalini | Cesena | Italy | ||
| 22 | Giannina Gaslini Institute | Genova | Italy | ||
| 23 | Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico | Milan | Italy | ||
| 24 | University Hospital of Parma, AOUP, Haemophilia Center | Parma | Italy | ||
| 25 | Uo Malattie Emorragiche e Trombotiche Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Universitá Catolica del Sacro Coure | Rome | Italy | ||
| 26 | Azienda Ospedaliera Città della Salute e della Scienza di Torino Regina Margherita | Torino | Italy | ||
| 27 | University Medical Center Groningen/UMCG | Groningen | Netherlands | ||
| 28 | Dr Suliman Al Habib Hospital Riyadh | Riyadh | Saudi Arabia | ||
| 29 | King Faisal Specialised Hospital, KFSH Riyadh, Children | Riyadh | Saudi Arabia | ||
| 30 | King Faisal Specialist Hospital KFSH, Adults | Riyadh | Saudi Arabia | ||
| 31 | Riyadh Military Hospital (P.S.M.C) | Riyadh | Saudi Arabia | ||
| 32 | University Medical Centre Ljubljana Division of Paediatrics | Ljubljana | Slovenia | ||
| 33 | Hospital de la Santa Creu i Sant Pau | Barcelona | Spain | ||
| 34 | Hospital Vall d'Hebron | Barcelona | Spain | ||
| 35 | Sant Johan De Deu | Barcelona | Spain | ||
| 36 | Hospital Universitario Cruces | Cruces | Spain | ||
| 37 | Hospital Universitario Donostia | Donostia | Spain | ||
| 38 | Hospital Virgen de la Arrixaca | Murcia | Spain | ||
| 39 | Hospital Universitario Carlos Haya | Málaga | Spain | ||
| 40 | Complejo Hospitalario de Navarra | Navarro | Spain | ||
| 41 | Hospital Universitario Central de Asturias (HUCA) | Oviedo | Spain | ||
| 42 | Hospital Universitario Son Espases | Palma De Mallorca | Spain | ||
| 43 | Hospital Universitario Virgen del Rocío | Sevilla | Spain | ||
| 44 | Hospital Alvaro Cunqueiro | Vigo | Spain | ||
| 45 | Hematologimottagning Sahlgrenska | Gothenburg | Sweden | ||
| 46 | Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital Malmö | Malmö | Sweden | ||
| 47 | Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor Inselspital | Bern | Switzerland | ||
| 48 | Service et Laboratoire central d'hématologie, Adults | Lausanne | Switzerland | ||
| 49 | Zentrum für Labormedizin | Saint Gallen | Switzerland | ||
| 50 | Universitätsspital Zürich Klinik für Medizinische Onkologie und Hämatologie | Zürich | Switzerland | ||
| 51 | East Kent Hospitals University NHS Foundation Trust, Kent Haemophilia and Thrombosis Centre, Kent and Canterbury Hospital | Canterbury | United Kingdom | ||
| 52 | Great Ormond Street Hospital, Royal London Hospital for Integrated Medicine | London | United Kingdom |
Sponsors and Collaborators
- Swedish Orphan Biovitrum
Investigators
- Study Director: Elena Santagostino, MD, Swedish Orphan Biovitrum AB
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Sobi.Elocta-005