A Clinical Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Patients from Birth to 12 Months of age with Hemophilia A Without Inhibitors

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2020-001733-12-NL
• Date of registration: 15/12/2020
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Clinical Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Patients from Birth to 12 Months of age with Hemophilia A Without Inhibitors
• Scientific title: A PHASE IIIb, MULTICENTER, OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE THE EFFICACY, SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SUBCUTANEOUS EMICIZUMAB IN PATIENTS FROM BIRTH TO 12 MONTHS OF AGE WITH HEMOPHILIA A WITHOUT INHIBITORS
• Date of first enrolment: 25/02/2021
• Target sample size: 50
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-001733-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, France, Germany, Israel, Italy, Netherlands, South Africa, Spain, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria:
• Age from birth to <= 12 months at time of informed consent
• Body weight >= 3 kg at time of informed consent
• Mandatory receipt of vitamin K prophylaxis according to local standard practice
• Diagnosis of severe congenital hemophilia A (intrinsic FVIII level < 1%)
• 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
• For PUPs or MTPs, 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
• Documentation of the details of the hemophilia-related treatments received since birth
• Documentation of the details of the bleeding episodes since birth
• For patients from birth to < 3 months of age at the time of study entry: no evidence of active ICH, as confirmed by a negative cranial ultrasound at screening irrespective of delivery mode
• Adequate hematologic, hepatic, and renal function

Are the trial subjects under 18? yes
Number of subjects for this age range: 50
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Exclusion criteria
• Inherited or acquired bleeding disorder other than severe hemophilia A
• Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use
• during the study
• Receipt of any of the following:
– An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 drug-elimination half-lives of last drug administration
– A non-hemophilia-related investigational drug within the last 30 days or 5 drug-elimination half-lives, whichever is shorter
– An investigational drug concurrently
– Prior use of emicizumab prophylaxis including investigational or commercial emicizumab
• Current active severe bleed, such as ICH
• Planned surgery during the study
• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
• Patients who are at high risk for 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
• Previous or current treatment for thromboembolic disease or signs of thromboembolic disease
• Any hereditary or acquired maternal condition that may predispose the patient to thrombotic events
• Other diseases (e.g., certain autoimmune diseases) that may increase risk of bleeding or thrombosis
• Known infection with HIV, hepatitis B virus, or hepatitis C virus
• Serious infection requiring antibiotics or antiviral treatments within 14 days prior to screening
• Concurrent disease, treatment, abnormality in clinical laboratory tests, vital signs measurements, or physical examination findings that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient’s safe participation in and completion of the study or interpretation of the study results
• Unwillingness of the parent or caregiver to allow receipt of blood or blood products, or any standard-of-care treatment for a life-threatening condition
• Any other medical, social, or other condition that may prevent adequate compliance with the study protocol in the opinion of the investigator



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hemophilia A
MedDRA version: 20.0 Level: LLT Classification code 10053753 Term: Hemophilia A without inhibitors System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: Hemlibra
Product Name: Hemlibra / Emicizumab
Product Code: RO5534262/ACE910
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EMICIZUMAB
CAS Number: 1610943-06-0
Current Sponsor code: RO553-4262
Other descriptive name: HEMLIBRA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Trade Name: Hemlibra
Product Name: Hemlibra / Emicizumab
Product Code: RO5534262/ACE910
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EMICIZUMAB
CAS Number: 1610943-06-0
Current Sponsor code: RO553-4262
Other descriptive name: HEMLIBRA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Secondary Objective: Not applicable

Main Objective: Main objectives:
• To evaluate the efficacy of emicizumab
• To evaluate the safety of emicizumab
• To characterize the emicizumab pharmacokinetic (PK) profile
• To investigate the effect of emicizumab on pharmacodynamics (PD) parameters
• To evaluate the immune response to treatment

Primary end point(s): Primary endpoints:
1. Number of treated bleeds over time
2. Number of all bleeds over time
3. Number of treated spontaneous bleeds over time
4. Number of treated joint bleeds over time
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 LTFU period
6. Incidence and severity of adverse events, with severity determined according to WHO Toxicity Grading Scale
7. Incidence of thromboembolic events
8. Incidence of thrombotic microangiopathy (TMA)
9. Change from baseline in physical examination findings
10. Change from baseline in vital signs
11. Incidence of laboratory abnormalities
12. Incidence and severity of injection-site reactions
13. Incidence of adverse events leading to drug discontinuation
14. Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events
15. Plasma trough concentrations (Ctrough) of emicizumab prior to study drug administration
16. aPTT levels prior to study drug administration
17. Thrombin generation (TG) prior to study drug administration
18. Reported FVIII activity prior to study drug administration
19. FIX antigen and FX antigen (emicizumab substrates) levels prior to study drug administration

Timepoint(s) of evaluation of this end point: 1-8. Up to 8 years
9-10. Baseline (Day 1) to 8 years
11-14. Up to 8 years
15-19. Every 2 weeks during Weeks 1-9 and every 4 weeks during Weeks 13-53

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

MO41787

2020-001733-12-DE

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 25/02/2021
Contact: