An 18-month Low-interventional Study to Assess Joint Health in Haemophilia A and B Patients on Prophylaxis With Efmoroctocog Alfa or Eftrenonacog Alfa (JOIN-us)

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

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.

Study Overview

• Status: Terminated
• Conditions: Hemophilia A; Hemophilia B
• Intervention / Treatment: Procedure: Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US); Other: Haemophilia Joint Health Score (HJHS)

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Study site 100
  • Sofia, Bulgaria
    • Study site 101
• Croatia
  • Zagreb, Croatia
    • Study site 102
  • Zagreb, Croatia
    • Study site 103
• Czechia
  • Brno, Czechia
    • Study site 108
  • Liberec, Czechia
    • Study site 107
  • Olomouc, Czechia
    • Study site 104
  • Praha, Czechia
    • Study site 105
  • Praha, Czechia
    • Study site 106
• France
  • Bordeaux, France
    • Study site 115
  • Caen, France
    • Study site 129
  • Chambéry, France
    • Study site 125
  • Clermont-Ferrand, France
    • Study site 110
  • Dijon, France
    • Study site 123
  • Lille, France
    • Study site 124
  • Lyon, France
    • Study site 111
  • Marseille, France
    • Study site 126
  • Nancy, France
    • Study site 120
  • Nantes, France
    • Study site 121
  • Nîmes, France
    • Study site 113
  • Paris, France
    • Study site 119
  • Paris, France
    • Study site 130
  • Poitiers, France
    • Study site 118
  • Reims, France
    • Study site 117
  • Rennes, France
    • Sudy site 122
  • Rouen, France
    • Study site 109
  • Strasbourg, France
    • Study site 112
  • Toulouse, France
    • Study site 128
  • Tours, France
    • Study site 114
• Hungary
  • Budapest, Hungary
    • Study site 131
• Ireland
  • Dublin, Ireland
    • Study site 132
  • Dublin, Ireland
    • Study site 133
• Italy
  • Bologna, Italy
    • Study site 136
  • Brescia, Italy
    • Study site 134
  • Catania, Italy
    • Study site 138
  • Milan, Italy
    • Study site 140
  • Palermo, Italy
    • Study site 137
  • Pisa, Italy
    • Study site 135
  • Vicenza, Italy
    • Study site 139
• Romania
  • Baia Mare, Romania
    • Study site 145
  • Bucharest, Romania
    • Study site 141
  • Craiova, Romania
    • Study site 143
  • Iaşi, Romania
    • Study site 146
  • Timişoara, Romania
    • Study site 142
• Slovenia
  • Ljubljana, Slovenia
    • Study site 147
• Spain
  • Alicante, Spain
    • Study site 150
  • Barcelona, Spain
    • Study site 152
  • Coruña, Spain
    • Study site 151
  • Madrid, Spain
    • Study site 149
  • Málaga, Spain
    • Study site 154
  • Oviedo, Spain
    • Study site 156
  • Salamanca, Spain
    • Study site 153
  • Valencia, Spain
    • Study site 157
  • Valladolid, Spain
    • Study site 155
  • Zaragoza, Spain
    • Study site 158
• United Kingdom
  • Belfast, United Kingdom
    • Study site 159

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Efmoroctocog alfa or eftrenonacog alfa; Efmoroctocog alfa or eftrenonacog alfa is prescribed and used according to usual clinical practice.	Procedure: Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US); Ultrasound examination; Other: Haemophilia Joint Health Score (HJHS); Functional joint examination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in total HEAD-US score up to month 18 (end of study - EOS)	HEAD-US is a standardized, fast, repeatable, and simple ultrasound scoring protocol for hemophiliac joints. The HEAD-US joint score will be calculated for the six index joints (elbows, knees, and ankles). The specific joint score is made up of three item scores: disease activity (synovitis), disease damage of articular surfaces, and disease damage of subchondral bone. The specific joint score is the sum of the three item scores for each specific joint. Its values range from 0 (minimum) to 8 (maximum). The total score represents the sum of item scores for abnormalities detected.	Baseline and month 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in HEAD-US score for hypertrophic synovium	HEAD-US is a standardized, fast, repeatable, and simple ultrasound scoring protocol for hemophiliac joints. The HEAD-US joint score will be calculated for the six index joints (elbows, knees, and ankles). The disease activity (synovitis) score rates the status of the hypertrophic synovium. Hypertrophic synovium is graded in three steps (0: absent/minimal; 1: mild/moderate [score=1], 2: severe [score=2]) based on the comprehensive evaluation of the joint recesses and the mean amount of synovial tissue contained in them.	Baseline, month 6, 12 and 18
Change from baseline in HEAD-US score for cartilage	HEAD-US is a standardized, fast, repeatable, and simple ultrasound scoring protocol for hemophiliac joints. The HEAD-US joint score will be calculated for the six index joints (elbows, knees, and ankles). Concerning the articular cartilage, the damage is graded in five steps (0: normal; 1: echotexture abnormalities and focal loss involving <25% of the target surface [score=1]; 2: partial/full-thickness loss of the cartilage involving at least 50% of the target surface [score=2]; 3: partial/full-thickness loss of the cartilage involving >50% of the target surface [score=3]; 4: complete cartilage destruction or absent visualization of the articular cartilage on the target surface [score=4]).	Baseline, month 6, 12 and 18
Change from baseline in HEAD-US score for bone	HEAD-US is a standardized, fast, repeatable, and simple ultrasound scoring protocol for hemophiliac joints. The HEAD-US joint score will be calculated for the six index joints (elbows, knees, and ankles). Damage of subchondral bone is scored using a three-grade scale (0: normal; 1: mild irregularities of the subchondral bone with/without initial osteophytes around the joint [score=1]; 2: deranged subchondral bone with/without erosions and presence of prominent osteophytes around the joint [score=2]).	Baseline, month 6, 12 and 18
Change from baseline in total Hemophilia Joint Health Score (HJHS) at month 18 (EOS)	The HJHS measures joint health, in the domain of body structure and function (i.e., impairment). The six index joints (elbows, knees, and ankles) will be examined and scored. The minimum score per joint is 0, the maximum score is 20. In addition, Gait is scored on a scale from 0 to 4 based on the number of skills that are not within the normal limits. The total score will be the sum of scores across all six joints plus the gait score (range from 0 to 124, with 0 being normal and 124 being the most severe disease).	Baseline and month 18
Number of target joints	A target joint is defined as a joint with three or more spontaneous bleeds into the joint within a consecutive 6-month period. The study will evaluate the presence, resolution, recurrence, and new development of target joints.	Baseline, month 6, 12 and 18
Location of target joints	A target joint is defined as a joint with three or more spontaneous bleeds into the joint within a consecutive 6-month period. The study will evaluate the presence, resolution, recurrence, and new development of target joints.	Baseline, month 6, 12 and 18
Total annualized bleeding rate (ABR)	For any bleeding episode, the following will be collected: bleeding episode circumstance (e.g., spontaneous, traumatic), bleeding episode location (e.g., muscle, joint, other), date of bleeding episode, dose (IU) and number of injections used to treat the bleed.	6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period
Joint ABR	For any bleeding episode, the following will be collected: bleeding episode circumstance (e.g., spontaneous, traumatic), bleeding episode location, date of bleeding episode, dose (IU) and number of injections used to treat the bleed.	6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period
Target joint ABR	For any bleeding episode, the following will be collected: bleeding episode circumstance (e.g., spontaneous, traumatic), bleeding episode location, date of bleeding episode, dose (IU) and number of injections used to treat the bleed.	6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period
Traumatic/spontaneous ABR	For any bleeding episode, the following will be collected: bleeding episode circumstance (e.g., spontaneous, traumatic), bleeding episode location (e.g., muscle, joint, other), date of bleeding episode, dose (IU) and number of injections used to treat the bleed.	6 months retrospective period to baseline, baseline to 6 months, 6-12 months, 12-18 months and entire study period
PROMIS physical function/activity short form 6b and 8a scores	Patient-Reported Outcomes Measurement Information System (PROMIS) is a validated system of reliable and precise measures of patient-reported health status. PROMIS measures cover physical, mental, and social health, use a 5-point Likert response scale and a recall period of the past 7 days. The Numeric Rating Scale measures for adults (6b) consist of a single item rating physical function on average over the past 7 days, ranging from 5 (without any difficulty) to 1 (unable to do). Lower scores mean a worse outcome. The Numeric Rating Scale measures for pediatric and parent proxy (8a) each consist of a single item rating physical activity on average over the past 7 days, ranging from 1 (no days) to 5 (6-7 days). Lower scores mean a worse outcome.	Baseline and 18 months
PROMIS pain intensity 3a and 1a scores	Patient-Reported Outcomes Measurement Information System (PROMIS) is a validated system of reliable and precise measures of patient-reported health status. PROMIS measures cover physical, mental, and social health, use a 5-point Likert response scale and a recall period of the past 7 days. The Numeric Rating Scale measures for adults (3a) consist of a single item rating pain over the past 7 days from 1 (had no pain) to 5 (very severe). Higher scores mean a worse outcome. The Numeric Rating Scale measures for pediatric and parent proxy (1a) each consist of a single item rating pain over the past 7 days, ranging from 0 (no pain) to 10 (worst pain you can think of). Higher scores mean a worse outcome.	Baseline and month 18
PROMIS pain interference short form 6a and 8a scores	Patient-Reported Outcomes Measurement Information System (PROMIS) is a validated system of reliable and precise measures of patient-reported health status. PROMIS measures cover physical, mental, and social health, use a 5-point Likert response scale and a recall period of the past 7 days. The Numeric Rating Scale measures (adult, pediatric, parent proxy) each consist of a single item rating pain interference with different activities over the past 7 days, ranging from 1 (not at all/never) to 5 (very much/almost always). Higher scores mean a worse outcome.	Baseline and month 18
IPAQ-SF scores	International Physical Activity Questionnaire - Short Form (IPAQ-SF). The IPAQ-SF is a validated, 7-day recall questionnaire measuring current levels of physical activity. Scoring of the IPAQ results in a continuous variable in the form of total MET-minutes per week, as well as categorization into high, moderate, or low physical activity level. Higher scores mean higher physical activity level (better outcome).	Baseline and month 18

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Collaborators: IQVIA Pvt. Ltd
• Investigators: Study Director: Stefan Lethagen, MD, PhD, Swedish Orphan Biovitrum AB (publ)

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Actual): December 6, 2023
• Study Completion (Actual): December 6, 2023

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Haemophilia; FIX; FVIII; Efmoroctocog alfa; Blood coagulation disorder; Coagulation protein disorder; Eftrenonacog alfa
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: Sobi.HAEM89-007; 2022-502921-16-00 (Other Identifier: EU Drug Regulatory Authorities Clinical Trial System)

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
• product manufactured in and exported from the U.S.: No