A Clinical Trial to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2016-004366-25-FI
• Date of registration: 26/06/2017
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Clinical Trial to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
• Scientific title: A SINGLE-ARM, MULTICENTER PHASE IIIB CLINICAL TRIAL TO EVALUATE THE SAFETY AND TOLERABILITY OF PROPHYLACTIC EMICIZUMAB IN HEMOPHILIA A PATIENTS WITH INHIBITORS
• Date of first enrolment: 06/09/2017
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004366-25
• 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, Belgium, Brazil, Bulgaria, Canada, Colombia, Denmark, Dominican Republic, Finland, Germany, Guatemala, Hungary, Israel, Italy, Mexico, Netherlands, Panama, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Spain, Sweden, Switzerland, United Kingdom

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:
- As per the investigator's judgment, a willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the patient-reported outcome (PRO) questionnaires and bleed diaries through the use of an electronic device or paper
- Aged 12 years or older at the time of informed consent
- Body weight >=40 kg at the time of screening
- Diagnosis of congenital hemophilia A with persistent inhibitors against FVIII
- Documented treatment with bypassing agents or FVIII concentrates in the last 6 months (on-demand or prophylaxis). Prophylaxis needs to be discontinued the latest by a day before starting emicizumab
- Adequate hematologic, hepatic, and renal function
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method with a failure rate of <1% per year during the treatment period and for at least five elimination half-lives (24 weeks) after the last dose of emicizumab

Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 134
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion criteria:
- Inherited or acquired bleeding disorder other than hemophilia A
- Ongoing (or plan to receive during the study) immune tolerance induction (ITI) therapy (prophylaxis regimens with FVIII and/or bypassing agents must be discontinued prior to enrollment). Patients receiving ITI therapy will be eligible following the completion of a 72-hour washout period prior to the first emicizumab administration
- History of illicit drug or alcohol abuse within 12 months prior to screening, as per the investigator’s judgment
- High risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), as per the investigator’s judgment
- Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which antithrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
- Other conditions (e.g., certain autoimmune diseases) that may increase the risk of bleeding or thrombosis
- History of clinically significant hypersensitivity reaction associated with monoclonal antibody therapies or components of the emicizumab injection
- Known human immunodeficiency virus (HIV) infection with CD4 count <200 cells/µL within 6 months prior to screening
- Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of antiretroviral therapy
- Concurrent disease, treatment, or abnormality in clinical laboratory tests 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
- Receipt of:
•Emicizumab in a prior investigational study
•An investigational drug to treat or reduce the risk of hemophilic bleeds within five half-lives of last drug administration
•A non-hemophilia-related investigational drug within last 30 days or five half-lives, whichever is shorter
•Any concurrent investigational drug.
- Pregnancy or lactation, or intent to become pregnant during the study
- Positive serum pregnancy test result within 7 days prior to initiation of emicizumab (females only)



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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Hemophilia A
MedDRA version: 20.0 Level: LLT Classification code 10060612 Term: Hemophilia A System Organ Class: 100000004850
MedDRA version: 20.0 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System Organ Class: 100000004850

Intervention(s)

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

Primary Outcome(s)

Main Objective: To evaluate the overall safety and tolerability of prophylactic administration of emicizumab

Secondary Objective: •To evaluate the efficacy of prophylactic administration of emicizumab
•To evaluate the immunogenicity of emicizumab
•To obtain emicizumab PK data

Primary end point(s): 1. Incidence and severity of all adverse events including thromboembolic events, microangiopathic anemia or, TMA (e.g. hemolytic uremic syndrome), systemic hypersensitivity, anaphylaxis, and anaphylactoid events
2. Changes in physical examination findings, vital signs, and laboratory parameters

Timepoint(s) of evaluation of this end point: Up to 2 years

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Screening (Week-4 to Week 0), Week 1, Week 2, Week 3, Week 5, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24, at safety follow-up
2-3. Week 1, Month 3, Month 6, Month 12, Month 18, Month 24
4. Up to 2 years
5. Week 1, Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up
6. Week 1, Week 2, Week 3, and Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up

Secondary end point(s): 1. Number of bleeds over time
2. Hemophilia Adult Quality of Life Questionnaire (Haem-A-QoL) (>=18 y) or Hemophilia Quality of Life Short Form (Haemo-QoL-SF) (ages 12-17) scores over time
3. EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L) scores over time
4. Patient preference for the emicizumab regimen compared with the previous regimen used
5. The incidence and clinical significance of anti-emicizumab antibodies
6. Pharmacokinetics data for emicizumab at defined timepoints

Secondary ID(s)

MO39129

2016-004366-25-PT

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 06/09/2017
Contact: