Clinical trial NCT05856266: An 18-month Low-interventional Study to Assess Joint Health in Haemophilia A and B Patients on Prophylaxis With Efmoroctocog Alfa or Eftrenonacog Alfa
Official title: An 18-month Low-interventional Prospective, Multicentre Study to Assess Joint Outcomes in Patients With Haemophilia A or B on Prophylaxis With Efmoroctocog Alfa or Eftrenonacog Alfa
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hemophilia A
Hemophilia B
Keywords: Blood coagulation disorder
Coagulation protein disorder
Haemophilia
FVIII
FIX
Efmoroctocog alfa
Eftrenonacog alfa
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
Collaborators: name: IQVIA Pvt. Ltd
First posted: 2023-05-12
Enrollment: 10
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a low-interventional study, with the drugs being prescribed and used according to clinical practice.

The interventions in the study are the addition of the mandatory joint examinations HEAD-US (ultrasound) and HJHS (functional joint assessment).
Primary purpose: OTHER

Brief summary: The goal of this low-interventional study is to describe the overall joint health in patients with haemophilia A or haemophilia B prophylactically treated with rFVIIIFc or rFIXFc.

The main question it aims to answer is the:

• Evaluation of the overall joint status as detected by ultrasound in haemophilia A and B patients treated with rFVIIIFc or rFIXFc prophylaxis over the 18-month study period.

Participants will come to 6-monthly visits during the 18-month long study period and will perform an ultrasound with the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol at each visit. At baseline and end of study visits, the patients will be assessed with the clinical scoring system Haemophilia Joint Health Score (HJHS) and complete patient questionnaires. Retrospective data from patient medical records will also be collected for at least 6 months before enrolment in the study.

Detailed description: The main purpose of this study is to prospectively describe the joint health over an 18-month period of prophylactic treatment with rFVIIIFc or rFIXFc in patients with haemophilia A or haemophilia B in a real-world setting in Europe.

This is a low-interventional, multicentre study using point-of-care US examination for regular monitoring of joint health and detection of hypertrophic synovium, cartilage and bone damage. At the same time, clinical joint status will also be examined by HJHS. This study will evaluate the presence, resolution, recurrence, and new development of target joints. It will also describe bleeding episodes and evaluate the quality of life and physical activity with PROs. If patients are using the CE marked Florio HAEMO app in their routine clinical practice, they will be offered to participate in an optional sub-study that aims to explore possible correlations between the levels of physical activity, the estimated FVIII/FIX levels and bleeding occurrence.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 6 years
2. Diagnosis of haemophilia A or B
3. Having at least 6 months documented pre-study treatment data regarding treatment prescriptions and bleeding episodes prior to the baseline visit
4. Previous treatment for haemophilia A or B with any marketed recombinant and/or plasma-derived FVIII or FIX concentrate for at least 6 months
5. Start of prophylactic treatment with rFVIIIFc or rFIXFc prior to study enrollment or latest at the baseline visit, in accordance with local regulations
6. Signed and dated informed consent provided by the patient, or the patient's legally authorized representative for patients under the legal age. Assent should be obtained from paediatric patients in accordance with local regulations

Exclusion Criteria:

1. Any medical condition which in the opinion of the investigator makes the subject patient unsuitable for inclusion
2. Prophylactic treatment with non-factor therapy during the 6 months prior to enrolment
3. Presence of factor VIII or FIX inhibitory antibodies (inhibitors) (≥0.60 Bethesda Units \[BU\]/mL) at the latest available inhibitor test
4. Enrolment in a concurrent clinical interventional study, or intake of an IMP, within three months prior to inclusion in this study
5. Foreseeable inability to cooperate with given instructions or study procedures

Primary outcomes:
measure: Change From Baseline in Total HEAD-US Score up to Month 18 (End of Study - EOS)
timeFrame: Baseline and month 18
Secondary outcomes:
measure: Change From Baseline in HEAD-US Score for Hypertrophic Synovium
timeFrame: Baseline, month 6, 12 and 18
measure: Change From Baseline in HEAD-US Score for Cartilage
timeFrame: Baseline, month 6, 12 and 18
measure: Change From Baseline in HEAD-US Score for Bone
timeFrame: Baseline, month 6, 12 and 18
measure: Change From Baseline in Total Hemophilia Joint Health Score (HJHS) at Month 18 (EOS)
timeFrame: Baseline and month 18
measure: Number of Target Joints
timeFrame: Baseline, month 6, 12 and 18
measure: Location of Target Joints
timeFrame: Baseline, month 6, 12 and 18
measure: Total Annualized Bleeding Rate (ABR)
timeFrame: 6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period
measure: Joint ABR
timeFrame: 6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period
measure: Target Joint ABR
timeFrame: 6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period
measure: Traumatic/Spontaneous ABR
timeFrame: 6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period
measure: PROMIS Physical Function/Activity Short Form 6b and 8a Scores
timeFrame: Baseline and 18 months
measure: PROMIS Pain Intensity 3a and 1a Scores
timeFrame: Baseline and month 18
measure: PROMIS Pain Interference Short Form 6a and 8a Scores
timeFrame: Baseline and month 18
measure: IPAQ-SF Scores
timeFrame: Baseline and month 18
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Study site 100
city: Sofia
country: Bulgaria
facility: Study site 101
city: Zagreb
country: Croatia
facility: Study site 102
city: Zagreb
country: Croatia
facility: Study site 103
city: Brno
country: Czechia
facility: Study site 108
city: Liberec
country: Czechia
facility: Study site 107
city: Olomouc
country: Czechia
facility: Study site 104
city: Praha
country: Czechia
facility: Study site 105
city: Praha
country: Czechia
facility: Study site 106
city: Bordeaux
country: France
facility: Study site 115
city: Caen
country: France
facility: Study site 129
city: Chambéry
country: France
facility: Study site 125
city: Clermont-Ferrand
country: France
facility: Study site 110
city: Dijon
country: France
facility: Study site 123
city: Lille
country: France
facility: Study site 124
city: Lyon
country: France
facility: Study site 111
city: Marseille
country: France
facility: Study site 126
city: Nancy
country: France
facility: Study site 120
city: Nantes
country: France
facility: Study site 121
city: Nîmes
country: France
facility: Study site 113
city: Paris
country: France
facility: Study site 119
city: Paris
country: France
facility: Study site 130
city: Poitiers
country: France
facility: Study site 118
city: Reims
country: France
facility: Study site 117
city: Rennes
country: France
facility: Sudy site 122
city: Rouen
country: France
facility: Study site 109
city: Strasbourg
country: France
facility: Study site 112
city: Toulouse
country: France
facility: Study site 128
city: Tours
country: France
facility: Study site 114
city: Budapest
country: Hungary
facility: Study site 131
city: Dublin
country: Ireland
facility: Study site 132
city: Dublin
country: Ireland
facility: Study site 133
city: Bologna
country: Italy
facility: Study site 136
city: Brescia
country: Italy
facility: Study site 134
city: Catania
country: Italy
facility: Study site 138
city: Milan
country: Italy
facility: Study site 140
city: Palermo
country: Italy
facility: Study site 137
city: Pisa
country: Italy
facility: Study site 135
city: Vicenza
country: Italy
facility: Study site 139
city: Baia Mare
country: Romania
facility: Study site 145
city: Bucharest
country: Romania
facility: Study site 141
city: Craiova
country: Romania
facility: Study site 143
city: Iaşi
country: Romania
facility: Study site 146
city: Timişoara
country: Romania
facility: Study site 142
city: Ljubljana
country: Slovenia
facility: Study site 147
city: Alicante
country: Spain
facility: Study site 150
city: Barcelona
country: Spain
facility: Study site 152
city: Coruña
country: Spain
facility: Study site 151
city: Madrid
country: Spain
facility: Study site 149
city: Málaga
country: Spain
facility: Study site 154
city: Oviedo
country: Spain
facility: Study site 156
city: Salamanca
country: Spain
facility: Study site 153
city: Valencia
country: Spain
facility: Study site 157
city: Valladolid
country: Spain
facility: Study site 155
city: Zaragoza
country: Spain
facility: Study site 158
city: Belfast
country: United Kingdom
facility: Study site 159
Study officials:
affiliation: Swedish Orphan Biovitrum AB (publ)
name: Stefan Lethagen, MD, PhD
role: STUDY_DIRECTOR
References: