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

Hemophilia A Clinical Trial

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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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05856266
• Other study ID #: Sobi.HAEM89-007
• Secondary ID: 2022-502921-16-0
• Status: Terminated
• Phase: Phase 4
• Start date: August 24, 2023
• Est. completion date: December 6, 2023

Study information

• Verified date: December 2023
• Source: Swedish Orphan Biovitrum
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: December 6, 2023
• Est. primary completion date: December 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia B

Intervention

Procedure:
• Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US)
Ultrasound examination

Other:
• Haemophilia Joint Health Score (HJHS)
Functional joint examination

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum	IQVIA Pvt. Ltd

Countries where clinical trial is conducted

Bulgaria,  Croatia,  Czechia,  France,  Hungary,  Ireland,  Italy,  Romania,  Slovenia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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