Clinical Trials Logo

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
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
See also
  Status Clinical Trial Phase
Completed NCT03834727 - Characterizing the Impact and Treatment of Reproductive Tract Bleeding on Women and Post-menarchal Girls With Bleeding Disorders
Completed NCT03191799 - A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors Phase 3
Completed NCT01599819 - BAX 855 Dose-Escalation Safety Study Phase 1
Terminated NCT04541628 - Safety & Efficacy of Encapsulated Allogeneic FVIII Cell Therapy in Haemophilia A Phase 1/Phase 2
Completed NCT02847637 - A Clinical Trial to Evaluate Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants Without Inhibitors Phase 3
Completed NCT04072237 - Study of Coagulation Faction VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia Phase 1
Completed NCT04085458 - Study to Gain More Information on How Safe and Effective Jivi Works in Patients With Severe Hemophilia A (Post-marketing Investigation) Phase 4
Completed NCT04565236 - A Post Approval Commitment Study to Gain More Information on How Safe and Effective KOVALTRY is in Chinese Children, Adolescents /Adults With Severe Hemophilia A Phase 4
Recruiting NCT05987449 - A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A Phase 1/Phase 2
Active, not recruiting NCT04621916 - Preventing Inhibitor Recurrence Indefinitely Phase 4
Not yet recruiting NCT02888223 - Pharmacokinetic Study of SCT800 in Previously Treated Patients With Hemophilia A Phase 1
Completed NCT02528968 - National Study of a Pharmacokinetic-Focused Educational Package for Patients With Severe Haemophilia A N/A
Completed NCT02225483 - Phenotypic Heterogeneity in Hemophilia A: An Investigation of the Role of Platelet Function N/A
Completed NCT02199717 - An Institutional Pilot Study to Investigate Physical Activity Patterns in Boys With Hemophilia N/A
Completed NCT01217255 - Comparing the Burden of Illness of Hemophilia in the Developing and the Developed World
Terminated NCT00995046 - Individually Tailored Prophylaxis in Patients With Severe Hemophilia A N/A
Completed NCT00969319 - Effekt-2 - Efficacy and Safety of Long-term Treatment With KOGENATE® FS in Latin America N/A
Completed NCT00868530 - Study Evaluating On-Demand Treatment Of Xyntha In Chinese Subjects Phase 3
Completed NCT00839202 - Activity and Content of Factor VIII (FVIII) in Human Plasma: The Assessment of a Novel Immunoassay N/A
Completed NCT00629837 - Pharmacokinetics and Safety of a Single Intravenous Infusion of BAY 79-4980 Phase 1