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

Hemophilia A Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04293523
• Other study ID #: Sobi.Elocta-005
• Status: Active, not recruiting
• Start date: March 30, 2020
• Est. completion date: April 2026

Study information

• Verified date: April 2024
• Source: Swedish Orphan Biovitrum
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 427
• Est. completion date: April 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Drug:
• ELOCTA
Extended half-life factor VIII product

Locations

Country	Name	City	State
Czechia	University Hospital Brno	Brno
Czechia	University Hospital Ostrava	Ostrava
Czechia	Dept. of Pediatric Haematology and Oncology, University Hospital Motol	Praha
Estonia	Lastehaigla, Tallinn (Tallinn Children´s Hospital)	Tallinn
Estonia	The North Estonia Medical Centre Hematoloogiakeskus, Regionalhaigla	Tallinn
Finland	Helsinki University Central Hospital, New Children Hospital	Helsinki
Finland	Turku University Central Hospital, Paediatric and adolescent haematology and oncology clinic	Turku
Germany	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
Greece	Ippokrateio Hospital Thessaloniki (adult department)	Thessaloníki
Greece	Ippokrateio Hospital Thessaloniki (pediatric department)	Thessaloníki
Italy	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
Netherlands	University Medical Center Groningen/UMCG	Groningen
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)	Riyadh
Slovenia	University Medical Centre Ljubljana Division of Paediatrics	Ljubljana
Spain	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 Universitario Carlos Haya	Málaga
Spain	Hospital Virgen de la Arrixaca	Murcia
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
Sweden	Hematologimottagning Sahlgrenska	Gothenburg
Sweden	Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital Malmö	Malmö
Switzerland	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
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum

Countries where clinical trial is conducted

Czechia,  Estonia,  Finland,  Germany,  Greece,  Italy,  Netherlands,  Saudi Arabia,  Slovenia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effectiveness of Elocta: Annualised bleeding rate (ABR) for treated bleeds	Number of bleeding events per year, for treated bleeds	48 months
Other	Effectiveness of Elocta: Annualised bleeding rate (ABR) for all bleeds	Number of bleeding events per year, for all bleeds	48 months
Other	Effectiveness of Elocta: Occurrence of zero (0) joint bleeds	Percentage (%) of study population with zero (0) joint bleeds	48 months
Other	Effectiveness of Elocta: Work productivity and impairment	Assessed by WPAI-SHP questionnaire	48 months
Other	Effectiveness of Elocta: Quality of Life	Assessed by Haemo-QoL/Haem-A-QoL questionnaire	48 months
Other	Effectiveness of Elocta: Physical activity level	Assessed by the Saltin-Grimby scale	48 months
Other	Effectiveness of Elocta: Quality of Life	Assessed by EQ-5D-5L/EQ-5D-Y questionnaire	48 months
Other	Effectiveness of Elocta: Severity of joint health	Assessed by Patient Global Impression of Severity of Joint Health questionnaire	48 months
Other	Effectiveness of Elocta: FVIII plasma levels	Percentage (%) of FVIII plasma level	48 months
Other	Effectiveness of Elocta: Usage of pain and anti-inflammatory medication	Assessed by medication dose	48 months
Other	Effectiveness of Elocta: Usage of pain and anti-inflammatory medication	Assessed by total number of exposure days per medication	48 months
Other	Usage of Elocta: Annualised injection frequency per subject	Assessed by prescription	48 months
Other	Usage of Elocta: Annualised factor consumption per subject	Assessed by prescription [IU/kg]	48 months
Other	Usage of Elocta: Adherence	Investigator assessed (Percentage (%))	48 months
Other	Exploratory Objective	Influence of different Elocta prophylaxis regimens on long term joint health	48 months
Other	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
Other	Exploratory Objective: Explore adherence to prescribed treatment regimen	florio HAEMO captured treatment adherence scores	48 months
Other	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
Other	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
Other	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
Other	Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Target joint development, resolution and recurrence	48 months
Other	Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Annualised joint bleeding rate (AJBR) for treated bleeds	48 months
Other	Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Ultrasound (HEAD-US)	48 months
Other	Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Clinical joint scoring (HJHS)	48 months
Other	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
Other	Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Occurrence of zero (0) joint bleeds	48 months
Other	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
Other	Exploratory Objective: Influence of different Elocta prophylaxis regimens on long term joint health	Physical activity level assessed by the Saltin-Grimby scale	48 months
Primary	Joint health: Target joint development	Number of target joints	48 months
Primary	Joint health: Target joint resolution	Number of resolved target joints	48 months
Primary	Joint health: Target joint recurrence	Number of recurring target joints	48 months
Primary	Joint health: Annualised joint bleeding rate (AJBR) for treated bleeds	Number of joint bleeding events per year, for treated bleeds	48 months
Secondary	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
Secondary	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
Secondary	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