Factor VIII Deficiency
Conditions
Brief summary
The objective of the study is to assess the improvement of synovial hypertrophy during the 12 months of efanesoctocog alfa prophylaxis once per week (QW) in joints with existing evidence of synovial hypertrophy in participants with hemophilia A. The study duration for each participant is approximately 12 months.
Interventions
Pharmaceutical form:Lyophilized powder in a sterile vial that requires reconstitution with sterile water for injection (diluent)-Route of administration:Intravenous
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 3 in Taiwan, Canada and Australia, Phase 4 in US and Japan.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participant is diagnosed with moderate to severe hemophilia A (defined as less than or equal to (≤)5 percent (%) of endogenous FVIII clotting activity) at the time of consent/assent. Participant is more than or equal to (≥)12 years old at the time of consent/assent. Participant has existing synovial hypertrophy, defined as at least 1 eligible\* joint by the HEAD-US score (Synovitis score: 1 or 2) at the time of consent/assent. Participant has at least 1 eligible\* joint without planned future major orthopedic procedures (example, arthroscopic synovectomy, radioisotopic or chemical synoviorthesis), or major orthopedic procedures in the past 3 months prior to the screening visit (Visit 1). \*An eligible joint is a joint with existing synovial hypertrophy, as defined by a HEAD-US synovitis score of 1 or 2, considering hypertrophic synovium as an indication of the presence of synovitis Participant has received prophylactic treatment with hemophilia prophylaxis prescriptions in the last 12 months prior to the baseline visit (Visit 2). Participant is capable of understanding the written Informed Consent Form (ICF)/assent form, provides a signed and witnessed written ICF/assent form, and agrees to comply with the protocol requirements. If male, no contraceptive measures are required for this study. If female, is not pregnant or breastfeeding, and one of the following conditions applies: Is a women of nonchildbearing potential (WONCBP) Is a women of childbearing potential (WOCBP) and agrees to use a highly effective contraceptive method, with a failure rate of less than (\<)1 percent during the study treatment period (at least until the Week 52/ End of Treatment \[EoT\] visit). A WOCBP must have a negative serum pregnancy test at the screening visit (Visit 1)
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: Has other associated clotting disorders at the time of consent/assent. Is already under efanesoctocog alfa treatment. Has a current diagnosis of an factor VIII (FVIII) inhibitor, defined as inhibitor titer ≥0.60 BU/mL. Has ITI within the last 2 years prior to the baseline visit (Visit 2). Has been enrolled in a concurrent clinical interventional study or exposed to other investigational drug(s) within 3 months prior to screening for this study. Is currently in an institution because of regulatory or legal order (that is, is a prisoner or a patient who is legally institutionalized). Is not suitable for participation, whatever the reason, as judged by the investigator, including medical or clinical conditions, or patients potentially at risk of noncompliance to study procedures. Is an employee or family member of the investigator or site personnel. Is involved in a specific situation during study implementation or the course of the study that may raise ethics considerations. Has hypersensitivity to efanesoctocog alfa or its components or any of its excipients that, in the opinion of the investigator, contraindicates participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of joints with improvement in the Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) synovitis domain score | From Baseline up to Week 52 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of joints with the HEAD-US synovitis domain score that has remained unchanged or worsened | From Baseline up to Week 52 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
| Percentage of joints with the HEAD-US synovitis domain score that has remained unchanged or worsened | From Baseline up to Week 52 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
| Number of index joint type with the HEAD-US synovitis domain score that has improved, remained unchanged, or worsened | From Baseline up to Week 52 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
| Percentage of index joint type with the HEAD-US synovitis domain score that has improved, remained unchanged, or worsened | From Baseline up to Week 52 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
| Number of participants with at least 1 joint with the HEAD-US synovitis domain score that has improved, remained unchanged, or worsened | From Baseline up to Week 52 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
| Percentage of participants with at least 1 joint with the HEAD-US synovitis domain score that has improved, remained unchanged, or worsened | From Baseline up to Week 52 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
| Change from baseline in average HEAD-US synovitis domain score across all index joints | From Baseline up to Week 52 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
| Change from baseline in total/ domain scores of the HEAD-US | From Baseline up to Week 26 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
| Change from baseline in the distribution of joint HEAD-US synovitis score | From Baseline up to Week 52 | HEAD-US scoring system is a simplified ultrasound scanning procedure to image the elbow, knee, and ankle (index joints) and a scoring system based on an additive scale to define the joint status from disease activity and disease damage parameters to evaluate disease progression and monitor the results of treatment. |
| Change from baseline in total/ domain scores of magnetic resonance imaging (MRI) | From Baseline up to Week 52 | MRI will be used to detect changes in synovial hypertrophy in index joints of participants. |
| Change from baseline in patient-reported outcome (PRO) | From Baseline up to Week 52 | Change from baseline in PRO will be assessed by the EQ-5D 5-level (EQ-5D-5L), Patient-Reported Outcomes Measurement Information System - Short Form (PROMIS-SF) version 2.0 Pain Intensity 3a, PROMIS-SF version 1.1 Pain Interference 6a, and PROMIS-SF version 2.0 Physical Function 6b. |
| Patient reported treatment preference and satisfaction | At Week 52 | Patient reported treatment preference and satisfaction will be assessed through surveys and exit interviews. |
| Change from baseline in annualized bleeding rate (ABR) (spontaneous, traumatic) | At Week 52 | The ABR will be defined as (number of bleeding episodes occurring during the treatment period)/(duration of the treatment period \[days\]) × 365.25. |
| Change from baseline in annualized joint bleeding rate (AjBR) (spontaneous, traumatic) | At Week 52 | The AjBR will be defined as (number of joint bleeding episodes occurring during the treatment period)/(duration of the treatment period \[days\]) × 365.25. |
| Change from baseline in target joint resolution, recurrence, or development | At Week 52 | Change from baseline in target joint resolution, recurrence, or development will be assessed. |
| The occurrence of Adverse Events (AEs), all AEs leading to treatment discontinuation, Serious Adverse Events (SAEs), and Adverse Event of Special Interest (AESIs) | Up to Week 52 | The safety and tolerability of efanesoctocog alfa evaluated in all participants |
| Change from baseline in total/domain scores of the HJHS | From Baseline up to Week 26 | HJHS comprises an assessment of specific features, or items, of the 6 index joints and an assessment of global gait. For each of the 6 joints, the following items are scored: swelling (0 to 3), duration of swelling (0 to 1), muscle atrophy (0 to 2), crepitus on motion (0 to 2), flexion loss (0 to 3), extension loss (0 to 3), joint pain (0 to 2), and strength (0 to 4). The maximum score for an individual index joint is 20. Gait is scored from 0 to 4. The maximum HJHS total score is 124, with a higher score indicating worse joint health. |
Countries
Canada, Japan, Taiwan, United States
Contacts
Primary ContactTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed