EMICIZUMAB for Hemophilia A

Inclusion criteria

• {"criterion_text":"- Diagnosis of severe congenital hemophilia A (intrinsic FVIII level <1%) or moderate congenital hemophilia A (intrinsic FVIII level ≤ 5%) if previously prescribed prophylaxis\n- A negative test for FVIII inhibitor (i.e., <0.6 BU) during screening period\n- No history of FVIII inhibitory antibodies (<0.6 BU/mL using the Bethesda assay) in the last 5 years. Participants who completed successful immune tolerance induction (ITI) at least 5 years before screening are eligible, provided they have had no evidence of inhibitor recurrence (permanent or temporary) as may be indicated by detection of an inhibitor, FVIII half-life <6 hours, or FVIII recovery < 66% since completing ITI\n- Participants who were on standard FVIII prophylaxis, defined as the regular administration of FVIII to prevent bleeding, for at least the last 24 weeks, can be enrolled regardless of the number of bleeds during this period\n- Adequate hematologic, hepatic and renal function\n- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 24 weeks after the final dose of emicizumab"}

Exclusion criteria

• {"criterion_text":"- Inherited or acquired bleeding disorder other than severe congenital hemophilia A (intrinsic FVIII level <1%) or moderate congenital hemophilia A (intrinsic FVIII level ≤ 5%) without FVIII inhibitors who were previously prescribed prophylaxis for at least 24 weeks\n- Participants who have previously received emicizumab prophylaxis\n- Participants that plan to have joint replacement, joint procedure, synovectomy or synoviorthesis at screening\n- Participants who had joint replacement, joint procedure, synovectomy or synoviorthesis: – Less than 2 years ago OR – More than 3 years ago and are still experiencing pain in the joint For participants who had joint replacement, joint procedure, synovectomy or synoviorthesis more than 2 years ago who are not experiencing pain in the joint, the participant may be enrolled but the specific joint in which the procedure was conducted will be excluded from the study\n- Participants who have conditions other than hemophilia A that can affect joint health and structure (e.g., osteoarthritis) or with severely impaired mobility due to conditions other than hemophilia A"}

Primary endpoints

• {"endpoint_text":"- 1. Joint status over time based on centrally reviewed Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) scores with a specific focus on the synovitis score in participants with synovitis","definition_or_measurement_approach":"Centrally reviewed HEAD-US ultrasound scoring focusing on synovitis score to assess joint status over time."}
• {"endpoint_text":"- 2. Clinical joint status over time based on the Hemophilia Joint Health Score (HJHS v2.1), excluding gait assessment","definition_or_measurement_approach":"Clinical assessment using HJHS v2.1 (excluding gait) to evaluate joint status changes over time."}
• {"endpoint_text":"- 3. Joint status at screening and month 36 based on centrally reviewed International Prophylaxis Study Group (IPSG) score (with MRI)","definition_or_measurement_approach":"Centrally reviewed IPSG scoring including MRI at screening and month 36 to assess joint status."}
• {"endpoint_text":"- 4. Number of problem joints and proportion of problem joints, defined as joints having chronic joint pain and/or limited range of movement due to compromised joint integrity (i.e., chronic synovitis and/or hemophilic arthropathy) with or without persistent bleeding, over time","definition_or_measurement_approach":"Count and proportion of joints meeting the definition (chronic pain and/or limited ROM due to compromised joint integrity) assessed over study visits."}
• {"endpoint_text":"- 5. Number of target joint bleeds over time (target joints are defined as joints with ≥ 3 bleeds occurring in the same joint during the last 24 weeks)","definition_or_measurement_approach":"Recording of bleeds with target joint definition (≥3 bleeds in same joint during last 24 weeks); tracked over time."}
• {"endpoint_text":"- 6. HRQoL, as assessed through use of the Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) Questionnaire over time with a focus on the following domains: risk perception of recreational activities, restrictions experienced in recreational activities, preoccupation with disease, impact of treatment burden on HRQoL, and pain severity","definition_or_measurement_approach":"HRQoL measured longitudinally using the CATCH Questionnaire focusing on specified domains."}
• {"endpoint_text":"- 7. Change in the level of physical activity during the study as measured with a wearable activity tracker (Fitbit)","definition_or_measurement_approach":"Physical activity level change measured with wearable activity tracker (Fitbit) across study period."}
• {"endpoint_text":"- 8. Change in daily step count, active minutes metabolic equivalents of tasks (METs), moderate to vigorous physical activity (MVPA; as per activity tracker default categorization), and type of physical activities","definition_or_measurement_approach":"Activity tracker-derived metrics (daily steps, active minutes, METs, MVPA categories, activity types) assessed for change over time."}
• {"endpoint_text":"- 9. Change in the time and intensity level of physical activity as measured by the International Physical Activity Questionnaire Short Format (IPAQ-SF)","definition_or_measurement_approach":"Self-reported time and intensity of physical activity via IPAQ-SF to evaluate changes."}
• {"endpoint_text":"- 10. Number of all bleeds (i.e., those treated and untreated with FVIII), treated bleeds, spontaneous bleeds, joint bleeds, treated joint bleeds, and target joint bleeds (i.e., bleed rate) over time (ABR) as assessed through use of the Bleed and Medication Questionnaire (BMQ)","definition_or_measurement_approach":"Bleed rates (ABR) and bleed types captured via the Bleed and Medication Questionnaire (BMQ) over time."}
• {"endpoint_text":"- 11. Participant preference for emicizumab compared with previous FVIII regimen, as assessed through use of the Emicizumab Preference Survey (EmiPref) at month 6","definition_or_measurement_approach":"Participant preference assessed at month 6 using the Emicizumab Preference Survey (EmiPref) comparing emicizumab to prior FVIII regimen."}

Secondary endpoints

• {"endpoint_text":"- 1. Incidence and severity of adverse events, with severity determined according to World Health Organization (WHO) toxicity scale","definition_or_measurement_approach":"AE incidence and severity recorded; severity graded per WHO toxicity scale."}
• {"endpoint_text":"- 2. Incidence of thromboembolic events","definition_or_measurement_approach":"Recording and counting of thromboembolic events during the study."}
• {"endpoint_text":"- 3. Incidence of thrombotic microangiopathy","definition_or_measurement_approach":"Recording and counting of thrombotic microangiopathy events during the study."}
• {"endpoint_text":"- 4. Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events","definition_or_measurement_approach":"Recording and counting of severe hypersensitivity/anaphylaxis/anaphylactoid events."}
• {"endpoint_text":"- 5. Incidence and severity of injection-site reactions","definition_or_measurement_approach":"Recording incidence and severity of injection-site reactions during treatment."}
• {"endpoint_text":"- 6. Prevalence of anti-drug antibodies (ADAs) against emicizumab at baseline and incidence of ADAs against emicizumab during the study","definition_or_measurement_approach":"ADA presence at baseline and incidence during study measured by laboratory immunogenicity assays."}
• {"endpoint_text":"- 7. Number and proportion of participants who develop anti-FVIII inhibitors (titer ≥ 0.6 BU/mL) at specified timepoints","definition_or_measurement_approach":"Monitoring for development of anti-FVIII inhibitors (titer ≥0.6 BU/mL) at prespecified timepoints using Bethesda assay."}

Germany

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

28-06-2024

Processing Time Days

18

Number Of Sites

2

Number Of Participants

4

Hungary

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

26-06-2024

Processing Time Days

16

Number Of Sites

1

Number Of Participants

13

Italy

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

08-07-2024

Processing Time Days

28

Number Of Sites

4

Number Of Participants

12

Spain

Earliest CTIS Part Ii Submission Date

10-06-2024

Latest Decision Or Authorization Date

27-06-2024

Processing Time Days

17

Number Of Sites

5

Number Of Participants

16

Primary sponsor

Full Name

F. Hoffmann-La Roche AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Fortrea Inc.

Responsibilities

Global CRO

Name

Iqvia Inc.

Responsibilities

Monitoring

Third parties

• {"country":"Belgium","full_name":"S-Clinica","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Inc.","duties_or_roles":"Monitoring","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Umotif Limited","duties_or_roles":"ePRO","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Global CRO","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Worldcare Clinical LLC","duties_or_roles":"Imaging","organisation_type":"Pharmaceutical company"}