A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Participants From Birth to 12 Months of Age With Hemophilia A Without Inhibitors (HAVEN 7)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

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

Trial duration

9 Mar 2021 → ongoing

Decision date (initial)

2024-04-08

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

2023-505964-13-00

EudraCT number

2020-001733-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others, Pharmacodynamic, Pharmacokinetic

To evaluate the efficacy, safety, pharmacokinetic (PK) profile, pharmacodynamics (PD) parameters and immune response to treatment of emicizumab

Secondary objectives 1

1. Not applicable (N/A)

Conditions and MedDRA coding

Hemophilia A

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. No history of documented FVIII inhibitor (i.e., < 0.6 BU/mL), FVIII drug-elimination half-life < 6 hours, or FVIII recovery < 66%
2. 2. Mandatory receipt of vitamin K prophylaxis according to local standard practice
3. 3. Diagnosis of severe congenital hemophilia A (intrinsic FVIII level < 1%)
4. 4. A negative test for FVIII inhibitor (i.e., < 0.6 Bethesda units [BU]/mL) locally assessed during the 2-week screening period for all patients
5. 5. Previously untreated patients (PUPs) or minimally treated patient (MTPs) (i.e., up to 5 days of exposure with hemophilia-related treatments, such as plasma-derived FVIII, recombinant FVIII, fresh frozen plasma, cryoprecipitate, or whole blood products)
6. 6. Documentation of the details of the hemophilia-related treatments received since birth and documentation of the details of the bleeding episodes since birth

Exclusion criteria 6

1. 1. Inherited or acquired bleeding disorder other than severe hemophilia A
2. 2. Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study
3. 3. Current active severe bleed, such as intracranial hemorrhage (ICH)
4. 4. History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
5. 5. Patients who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA, such as thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome) in the investigator's judgment
6. 6. Previous or current treatment for thromboembolic disease or signs of thromboembolic disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 15

1. 1. Number of treated bleeds over time
2. 2. Number of all bleeds over time
3. 3. Number of treated spontaneous bleeds over time
4. 4. Number of treated joint bleeds over time
5. 5. Joint health, as assessed through use of the Hemophilia Joint Health Score (HJHS) and magnetic resonance imaging (MRI) score of specific joints at specified timepoints only during the 7-year long-term follow-up (LTFU) period
6. 6. Incidence and severity of adverse events, with severity determined according to WHO Toxicity Grading Scale
7. 7. Incidence of thromboembolic events and thrombotic microangiopathy (TMA)
8. 8. Change from baseline in physical examination findings
9. 9. Change from baseline in vital signs
10. 10. Incidence of laboratory abnormalities
11. 11. Incidence and severity of injection-site reactions
12. 12. Incidence of adverse events leading to study drug discontinuation
13. 13. Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events
14. 14. Plasma trough concentrations (Ctrough) of emicizumab prior to study drug administration
15. 15. Effect of emicizumab on PD parameters, including aPTT, thrombin generation (TG), and reported FVIII activity, as well as FIX antigen and FX antigen (emicizumab substrates) levels prior to study drug

Secondary endpoints 1

1. Not applicable

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 4

Locations

6 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 30 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