Clinical trial NCT04293523: A 48-Month Study to Evaluate Long-Term Effectiveness of Elocta on Joint Health
Official title: A 48-Month, Multi-Centre, Observational Study to Evaluate Long-Term Effectiveness of Elocta on Joint Health
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Hemophilia A
Keywords: Joint health
HEAD-US
HJHS
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2020-03-03
Enrollment: 427
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with haemophilia A regardless of severity, of any gender and age, on factor treatment with Elocta according to usual clinical practice.

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.

Eligibility 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

Primary outcomes:
measure: Joint health: Target joint development
timeFrame: 48 months
measure: Joint health: Target joint resolution
timeFrame: 48 months
measure: Joint health: Target joint recurrence
timeFrame: 48 months
measure: Joint health: Annualised joint bleeding rate (AJBR) for treated bleeds
timeFrame: 48 months
Secondary outcomes:
measure: Disease Activity (hypertrophic synovium) and Disease Damage (Cartilage or Bone) scores for elbows, knees and ankles
timeFrame: 48 months
measure: Global Gait Score, and/or joint score items for elbows, knees and ankles.
timeFrame: 48 months
measure: Joint and physical evaluation for elbows, knees and ankles.
timeFrame: 48 months
Other outcomes:
measure: Effectiveness of Elocta: Annualised bleeding rate (ABR) for treated bleeds
timeFrame: 48 months
measure: Effectiveness of Elocta: Annualised bleeding rate (ABR) for all bleeds
timeFrame: 48 months
measure: Effectiveness of Elocta: Occurrence of zero (0) joint bleeds
timeFrame: 48 months
measure: Effectiveness of Elocta: Work productivity and impairment
timeFrame: 48 months
measure: Effectiveness of Elocta: Quality of Life
timeFrame: 48 months
measure: Effectiveness of Elocta: Physical activity level
timeFrame: 48 months
measure: Effectiveness of Elocta: Quality of Life
timeFrame: 48 months
measure: Effectiveness of Elocta: Severity of joint health
timeFrame: 48 months
measure: Effectiveness of Elocta: FVIII plasma levels
timeFrame: 48 months
measure: Effectiveness of Elocta: Usage of pain and anti-inflammatory medication
timeFrame: 48 months
measure: Effectiveness of Elocta: Usage of pain and anti-inflammatory medication
timeFrame: 48 months
measure: Usage of Elocta: Annualised injection frequency per subject
timeFrame: 48 months
measure: Usage of Elocta: Annualised factor consumption per subject
timeFrame: 48 months
measure: Usage of Elocta: Adherence
timeFrame: 48 months
measure: Exploratory Objective
timeFrame: 48 months
measure: Exploratory Objective: Impact of florio HAEMO on patients' sense of protection and their activity level
timeFrame: 48 months
measure: Exploratory Objective: Explore adherence to prescribed treatment regimen
timeFrame: 48 months
measure: Exploratory Objective: Explore relationship between predicted FVIII levels and physical activity
timeFrame: 48 months
measure: Exploratory Objective: Explore timing of bleeds in relation to predicted FVIII levels and physical activity
timeFrame: 48 months
measure: Exploratory Objective: Explore the use of Florio to characterise pain and well-being
timeFrame: 48 months
measure: Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health
timeFrame: 48 months
measure: Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health
timeFrame: 48 months
measure: Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health
timeFrame: 48 months
measure: Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health
timeFrame: 48 months
measure: Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health
timeFrame: 48 months
measure: Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health
timeFrame: 48 months
measure: Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health
timeFrame: 48 months
measure: Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health
timeFrame: 48 months
Locations:
city: Brno
country: Czechia
facility: University Hospital Brno
city: Ostrava
country: Czechia
facility: University Hospital Ostrava
city: Praha
country: Czechia
facility: Dept. of Pediatric Haematology and Oncology, University Hospital Motol
city: Tallinn
country: Estonia
facility: Lastehaigla, Tallinn (Tallinn Children´s Hospital)
city: Tallinn
country: Estonia
facility: The North Estonia Medical Centre Hematoloogiakeskus, Regionalhaigla
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital, New Children Hospital
city: Turku
country: Finland
facility: Turku University Central Hospital, Paediatric and adolescent haematology and oncology clinic
city: Berlin
country: Germany
facility: Charité-Universitätsmedizin Berlin Campus Virchow Klinikum
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn AöR, Institut für Experimentelle Hämatologie und Transfusionsmedizin
city: Frankfurt
country: Germany
facility: Hämostaseologie/Hämophiliezentrum, Medizinische Klinik 2 Institut für Transfusionsmedizin, Universitätsklinikum
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt - Klinik für Kinder- und Jugendmedizin
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf (UKE)
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hanover
country: Germany
facility: Werlhof-Institut für Hämostaseologie GmbH
city: Heidelberg
country: Germany
facility: SRH-Klinikum Heidelberg
city: Mörfelden-Walldorf
country: Germany
facility: HZRM Hämöphilie Zentrum Rhein Main
city: München
country: Germany
facility: Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital am Universitätsklinikum München
city: Thessaloníki
country: Greece
facility: Ippokrateio Hospital Thessaloniki (adult department)
city: Thessaloníki
country: Greece
facility: Ippokrateio Hospital Thessaloniki (pediatric department)
city: Bari
country: Italy
facility: University of Bari Aldo Moro (Centro Emofilia Policlinico - Pediatria U.O.)
city: Cesena
country: Italy
facility: AUSL Romagna Centro Emofilia U.O.C., Medicina Trasfusionale Dipartimento Patologia, Clinica Ospedale M. Bufalini
city: Genova
country: Italy
facility: Giannina Gaslini Institute
city: Milan
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Parma
country: Italy
facility: University Hospital of Parma, AOUP, Haemophilia Center
city: Rome
country: Italy
facility: Uo Malattie Emorragiche e Trombotiche Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Universitá Catolica del Sacro Coure
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino Regina Margherita
city: Groningen
country: Netherlands
facility: University Medical Center Groningen/UMCG
city: Muscat
country: Oman
facility: The Royal Hospital
city: Riyadh
country: Saudi Arabia
facility: Dr Suliman Al Habib Hospital Riyadh
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialised Hospital, KFSH Riyadh, Children
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital KFSH, Adults
city: Riyadh
country: Saudi Arabia
facility: Riyadh Military Hospital (P.S.M.C)
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana Division of Paediatrics
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Sant Johan De Deu
city: Cruces
country: Spain
facility: Hospital Universitario Cruces
city: Donostia
country: Spain
facility: Hospital Universitario Donostia
city: Murcia
country: Spain
facility: Hospital Virgen de la Arrixaca
city: Málaga
country: Spain
facility: Hospital Universitario Carlos Haya
city: Navarro
country: Spain
facility: Complejo Hospitalario de Navarra
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias (HUCA)
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro
city: Gothenburg
country: Sweden
facility: Hematologimottagning Sahlgrenska
city: Malmö
country: Sweden
facility: Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital Malmö
city: Bern
country: Switzerland
facility: Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor Inselspital
city: Lausanne
country: Switzerland
facility: Service et Laboratoire central d'hématologie, Adults
city: Saint Gallen
country: Switzerland
facility: Zentrum für Labormedizin
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich Klinik für Medizinische Onkologie und Hämatologie
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals University NHS Foundation Trust, Kent Haemophilia and Thrombosis Centre, Kent and Canterbury Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital, Royal London Hospital for Integrated Medicine
Study officials:
affiliation: Swedish Orphan Biovitrum AB
name: Study Physician
role: STUDY_DIRECTOR
References: