A 48-Month Study to Evaluate Long-Term Effectiveness of Elocta on Joint Health (A-MORE)

A 48-Month, Multi-Centre, Observational Study to Evaluate Long-Term Effectiveness of Elocta on Joint Health

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: ELOCTA

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 Type: Observational
• Enrollment (Actual): 427

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia
    • University Hospital Brno
  • Ostrava, Czechia
    • University Hospital Ostrava
  • Praha, Czechia
    • Dept. of Pediatric Haematology and Oncology, University Hospital Motol
• Estonia
  • Tallinn, Estonia
    • Lastehaigla, Tallinn (Tallinn Children´s Hospital)
  • Tallinn, Estonia
    • The North Estonia Medical Centre Hematoloogiakeskus, Regionalhaigla
• Finland
  • Helsinki, Finland
    • Helsinki University Central Hospital, New Children Hospital
  • Turku, Finland
    • Turku University Central Hospital, Paediatric and adolescent haematology and oncology clinic
• Germany
  • Berlin, Germany
    • Charité-Universitätsmedizin Berlin Campus Virchow Klinikum
  • Bonn, Germany
    • Universitätsklinikum Bonn AöR, Institut für Experimentelle Hämatologie und Transfusionsmedizin
  • Frankfurt, Germany
    • Hämostaseologie/Hämophiliezentrum, Medizinische Klinik 2 Institut für Transfusionsmedizin, Universitätsklinikum
  • Frankfurt, Germany
    • Universitätsklinikum Frankfurt - Klinik für Kinder- und Jugendmedizin
  • Hamburg, Germany
    • Universitätsklinikum Hamburg-Eppendorf (UKE)
  • Hanover, Germany
    • Medizinische Hochschule Hannover
  • Hanover, Germany
    • Werlhof-Institut für Hämostaseologie GmbH
  • Heidelberg, Germany
    • SRH-Klinikum Heidelberg
  • Mörfelden-Walldorf, Germany
    • HZRM Hämöphilie Zentrum Rhein Main
  • München, Germany
    • Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital am Universitätsklinikum München
• Greece
  • Thessaloníki, Greece
    • Ippokrateio Hospital Thessaloniki (adult department)
  • Thessaloníki, Greece
    • Ippokrateio Hospital Thessaloniki (pediatric department)
• Italy
  • Bari, Italy
    • University of Bari Aldo Moro (Centro Emofilia Policlinico - Pediatria U.O.)
  • Cesena, Italy
    • AUSL Romagna Centro Emofilia U.O.C., Medicina Trasfusionale Dipartimento Patologia, Clinica Ospedale M. Bufalini
  • Genova, Italy
    • Giannina Gaslini Institute
  • Milan, Italy
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Parma, Italy
    • University Hospital of Parma, AOUP, Haemophilia Center
  • Rome, Italy
    • Uo Malattie Emorragiche e Trombotiche Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Universitá Catolica del Sacro Coure
  • Torino, Italy
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino Regina Margherita
• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen/UMCG
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • 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)
• Slovenia
  • Ljubljana, Slovenia
    • University Medical Centre Ljubljana Division of Paediatrics
• Spain
  • Barcelona, Spain
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Sant Johan De Deu
  • Cruces, Spain
    • Hospital Universitario Cruces
  • Donostia, Spain
    • Hospital Universitario Donostia
  • Murcia, Spain
    • Hospital Virgen de la Arrixaca
  • Málaga, Spain
    • Hospital Universitario Carlos Haya
  • Navarro, Spain
    • Complejo Hospitalario de Navarra
  • Oviedo, Spain
    • Hospital Universitario Central de Asturias (HUCA)
  • Palma De Mallorca, Spain
    • Hospital Universitario Son Espases
  • Sevilla, Spain
    • Hospital Universitario Virgen Del Rocio
  • Vigo, Spain
    • Hospital Álvaro Cunqueiro
• Sweden
  • Gothenburg, Sweden
    • Hematologimottagning Sahlgrenska
  • Malmö, Sweden
    • Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital Malmö
• Switzerland
  • Bern, Switzerland
    • Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor Inselspital
  • Lausanne, Switzerland
    • Service et Laboratoire central d'hématologie, Adults
  • Saint Gallen, Switzerland
    • Zentrum für Labormedizin
  • Zürich, Switzerland
    • Universitätsspital Zürich Klinik für Medizinische Onkologie und Hämatologie
• United Kingdom
  • Canterbury, United Kingdom
    • East Kent Hospitals University NHS Foundation Trust, Kent Haemophilia and Thrombosis Centre, Kent and Canterbury Hospital
  • London, United Kingdom
    • Great Ormond Street Hospital, Royal London Hospital for Integrated Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	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: efmoroctocog alfa; ELOCTATE; rFVIIIFc

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Joint health: Target joint development	Number of target joints	48 months
Joint health: Target joint resolution	Number of resolved target joints	48 months
Joint health: Target joint recurrence	Number of recurring target joints	48 months
Joint health: Annualised joint bleeding rate (AJBR) for treated bleeds	Number of joint bleeding events per year, for treated bleeds	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Activity (hypertrophic synovium) and Disease Damage (Cartilage or Bone) scores for elbows, knees and ankles	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.	48 months
Global Gait Score, and/or joint score items for elbows, knees and ankles.	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.	48 months
Joint and physical evaluation for elbows, knees and ankles.	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.	48 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of Elocta: Annualised bleeding rate (ABR) for treated bleeds	Number of bleeding events per year, for treated bleeds	48 months
Effectiveness of Elocta: Annualised bleeding rate (ABR) for all bleeds	Number of bleeding events per year, for all bleeds	48 months
Effectiveness of Elocta: Occurrence of zero (0) joint bleeds	Percentage (%) of study population with zero (0) joint bleeds	48 months
Effectiveness of Elocta: Work productivity and impairment	Assessed by WPAI-SHP questionnaire	48 months
Effectiveness of Elocta: Quality of Life	Assessed by Haemo-QoL/Haem-A-QoL questionnaire	48 months
Effectiveness of Elocta: Physical activity level	Assessed by the Saltin-Grimby scale	48 months
Effectiveness of Elocta: Quality of Life	Assessed by EQ-5D-5L/EQ-5D-Y questionnaire	48 months
Effectiveness of Elocta: Severity of joint health	Assessed by Patient Global Impression of Severity of Joint Health questionnaire	48 months
Effectiveness of Elocta: FVIII plasma levels	Percentage (%) of FVIII plasma level	48 months
Effectiveness of Elocta: Usage of pain and anti-inflammatory medication	Assessed by medication dose	48 months
Effectiveness of Elocta: Usage of pain and anti-inflammatory medication	Assessed by total number of exposure days per medication	48 months
Usage of Elocta: Annualised injection frequency per subject	Assessed by prescription	48 months
Usage of Elocta: Annualised factor consumption per subject	Assessed by prescription [IU/kg]	48 months
Usage of Elocta: Adherence	Investigator assessed (Percentage (%))	48 months
Exploratory Objective	Influence of different Elocta prophylaxis regimens on long term joint health	48 months
Exploratory Objective: Impact of florio HAEMO on patients' sense of protection and their activity level	Results from questionnaire on impact of florio HAEMO tools on patients' sense of protection and their activity level	48 months
Exploratory Objective: Explore adherence to prescribed treatment regimen	florio HAEMO captured treatment adherence scores	48 months
Exploratory Objective: Explore relationship between predicted FVIII levels and physical activity	florio HAEMO captured predicted FVIII levels, florio HAEMO captured physical activity (type, duration, heart rate and steps)	48 months
Exploratory Objective: Explore timing of bleeds in relation to predicted FVIII levels and physical activity	florio HAEMO captured bleed data (timing, location, cause, treated/untreated), florio HAEMO captured injection data (time, dose), florio HAEMO captured predicted FVIII levels	48 months
Exploratory Objective: Explore the use of Florio to characterise pain and well-being	florio HAEMO captured pain data (time, location, cause, intensity), florio HAEMO captured well-being data	48 months
Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Target joint development, resolution and recurrence	48 months
Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Annualised joint bleeding rate (AJBR) for treated bleeds	48 months
Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Ultrasound (HEAD-US)	48 months
Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Clinical joint scoring (HJHS)	48 months
Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Annualised bleeding rate (ABR) (based on bleeding episodes assessed according to local practice) for all bleeds	48 months
Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Occurrence of zero (0) joint bleeds	48 months
Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Quality of Life assessed by Haemo-QoL/Haem-A-QoL	48 months
Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Physical activity level assessed by the Saltin-Grimby scale	48 months

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Investigators: Study Director: Stefan Lethagen, MD, PhD, Swedish Orphan Biovitrum AB

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2020
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: February 20, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Joint health; HEAD-US; HJHS
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: Sobi.Elocta-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No