A Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of emicizumab in patients with mild or moderate hemophilia A without FVIII inhibitors

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

24 Jun 2020 → 8 Dec 2025

Decision date (initial)

2024-07-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

External identifiers

EU CT number

2023-506610-52-00

EudraCT number

2019-002179-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Others, Pharmacokinetic

Safety: 1. To evaluate safety profile of emicizumab in patients with non-severe hemophilia A without inhibitors Primary Efficacy: 2. To evaluate the efficacy of emicizumab on the basis of number of treated bleeds over time

Secondary objectives 3

1. Secondary Efficacy: 1. To evaluate the efficacy of emicizumab on basis of number of all bleeds, joint bleeds over time, target joint bleeds over time, spontaneous bleeds over time, joint health, health-related quality of life, preference for emicizumab compared with previous FVIII treatment, effect of emicizumab prophylaxis on physical activity compared with physical activity at baseline and menstruation heaviness and menstruation-related quality of life in female patients
2. Pharmacokinetic: 2. To characterize emicizumab pharmacokinetic profile
3. Immunogenicity: 3. To evaluate immune response to emicizumab

Conditions and MedDRA coding

Mild or moderate hemophilia A without FVIII inhibitors

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of mild (FVIII level between > 5% and < 40%) or moderate (FVIII level between >= 1% and <= 5%) congenital Hemophilia A without FVIII inhibitors
2. Weight >= 3 kg
3. Need for prophylaxis based on investigator assessment
4. A negative test for inhibitor (i.e., < 0.6 BU/mL) within 8 weeks prior to enrollment
5. No documented inhibitor (i.e., < 0.6 BU/mL), FVIII half-life < 6 hours, or FVIII recovery < 66% in the last 5 years
6. Documentation of the details of prophylactic or episodic FVIII treatment and of number of bleeding episodes for at least the last 24 weeks prior to enrollment

Exclusion criteria 6

1. Inherited or acquired bleeding disorder other than mild (FVIII level between > 5% and < 40%) or moderate (FVIII level between >= 1% and <= 5%) congenital hemophilia A
2. History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the investigator’s judgment
3. Previous (within the last 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease
4. History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
5. Planned surgery during the emicizumab loading dose phase Surgeries in patients on emicizumab from Week 5 onwards are allowed
6. Known HIV infection with CD4 counts < 200 cells/micro L

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. 1.Incidence and severity of adverse events, with severity determined according to WHO Toxicity Grading Scale
2. 2. Incidence of thromboembolic events and thrombotic microangiopathy
3. 3. Incidence of laboratory abnormalities, injection-site reactions, adverse events leading to drug discontinuation, severe hypersensitivity, anaphylaxis, anaphylactoid events
4. 4. Change from baseline in physical examination findings, vital signs and ECG parameters
5. 5. Number of treated bleeds over time

Secondary endpoints 9

1. 1. Number of all bleeds (i.e., those treated and untreated with FVIII), joint bleeds, target joint bleeds and spontaneous bleeds over time
2. 2. Joint health, as assessed through use of the Hemophilia Joint Health Score at specified timepoints
3. 3. Health-related quality of life, as assessed through use of the Comprehensive Assessment Tool of Challenges in Hemophilia Questionnaire over time
4. 4. Preference for emicizumab compared with previous FVIII regimen, as assessed through use of the Emicizumab Preference Survey
5. 5. Effect of emicizumab prophylaxis treatment on physical activity compared with physical activity at baseline
6. 6. Effect of emicizumab prophylaxis treatment on menstruation heaviness and menstruation-related quality of life in female patients, as assessed through the use of the Menstrual Bleeding Questionnaire (MBQ) and the Menstruation Diary (MD) with the Pictorial Blood Assessment Chart (PBAC)
7. 7. Plasma concentration of emicizumab at specified timepoints
8. 8. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
9. 9. Number and proportion of patients who develop anti-FVIII inhibitors (titer>= 0.6 BU/mL) at specified timepoints

Investigational products

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

Test 2

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 6

Locations

3 EU/EEA countries · 5 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 29 files

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

Application history

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