A Study to Evaluate Overall Health, Physical Activity and Joint Outcomes, in Participants with Severe or Moderate Hemophilia A without FVIII Inhibitors on Emicizumab Prophylaxis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

20 Apr 2022 → ongoing

Decision date (initial)

2024-06-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-505747-40-00

EudraCT number

2020-005092-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the impact of emicizumab treatment on joint health and health-related quality of life (HRQoL) outcomes as well as physical activity of participants with hemophilia A

Secondary objectives 2

1. To evaluate the safety of emicizumab
2. To evaluate the immune response to emicizumab

Conditions and MedDRA coding

Severe or Moderate Hemophilia A

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of severe congenital hemophilia A (intrinsic FVIII level <1%) or moderate congenital hemophilia A (intrinsic FVIII level ≤ 5%) if previously prescribed prophylaxis
2. A negative test for FVIII inhibitor (i.e., <0.6 BU) during screening period
3. 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
4. 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
5. Adequate hematologic, hepatic and renal function
6. 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 5

1. 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
2. Participants who have previously received emicizumab prophylaxis
3. Participants that plan to have joint replacement, joint procedure, synovectomy or synoviorthesis at screening
4. 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
5. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 11

1. 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
2. 2. Clinical joint status over time based on the Hemophilia Joint Health Score (HJHS v2.1), excluding gait assessment
3. 3. Joint status at screening and month 36 based on centrally reviewed International Prophylaxis Study Group (IPSG) score (with MRI)
4. 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
5. 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)
6. 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
7. 7. Change in the level of physical activity during the study as measured with a wearable activity tracker (Fitbit)
8. 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
9. 9. Change in the time and intensity level of physical activity as measured by the International Physical Activity Questionnaire Short Format (IPAQ-SF)
10. 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)
11. 11. Participant preference for emicizumab compared with previous FVIII regimen, as assessed through use of the Emicizumab Preference Survey (EmiPref) at month 6

Secondary endpoints 7

1. 1. Incidence and severity of adverse events, with severity determined according to World Health Organization (WHO) toxicity scale
2. 2. Incidence of thromboembolic events
3. 3. Incidence of thrombotic microangiopathy
4. 4. Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events
5. 5. Incidence and severity of injection-site reactions
6. 6. Prevalence of anti-drug antibodies (ADAs) against emicizumab at baseline and incidence of ADAs against emicizumab during the study
7. 7. Number and proportion of participants who develop anti-FVIII inhibitors (titer ≥ 0.6 BU/mL) at specified timepoints

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 7

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications