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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03191799




Registration number
NCT03191799
Ethics application status
Date submitted
15/06/2017
Date registered
19/06/2017
Date last updated
16/06/2020

Titles & IDs
Public title
A Study 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
Secondary ID [1] 0 0
2016-004366-25
Secondary ID [2] 0 0
MO39129
Universal Trial Number (UTN)
Trial acronym
STASEY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hemophilia A 0 0
Condition category
Condition code
Blood 0 0 0 0
Clotting disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Emicizumab

Experimental: Emicizumab - Participants will receive initial weekly doses of prophylactic emicizumab subcutaneously for 4 weeks, followed by maintenance doses consisting of half the initial dose, administered subcutaneously for the remainder of the 2-year treatment period


Treatment: Drugs: Emicizumab
Initial dosing will be 3 mg/kg/week subcutaneously for 4 weeks; Maintenance dosing will follow at 1.5 mg/kg/week subcutaneously for the remainder of the 2-year treatment period

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of all adverse events (AEs) including thromboembolic events, microangiopathic hemolytic anemia or TMA (e.g. hemolytic uremic syndrome), systemic hypersensitivity, anaphylaxis, and anaphylactoid events - Incidence and severity of AEs will be monitored throughout the study to assess the safety and tolerability of emcizumab.
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [1] 0 0
Numbers of bleeds over time - To evaluate the efficacy of prophylactic administration of emicizumab, the number of bleeds over time will be recorded for all of the enrolled participants. The final analysis will be conducted when all participants have completed 2 years of treatment or have withdrawn, whichever occurs sooner. Participants, or their legally authorized representative, will be asked to report bleed information, including site and type of bleed, time of each individual bleed (day, start and stop time), and treatment for bleed.
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
Hemophilia Adult Quality of Life Questionnaire (Haem-A-QoL) (>= 18 y) - The Haem-A-QoL (>= 18 y) was designed for adult participants with hemophilia. It comprises 10 dimensions (physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, and partnerships and sexuality).
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
Hemophilia Quality of Life Short Form (Haemo-QoL-SF) (12-17 y) - The Haemo-QoL-SF (12-17 y) was designed as a series of age-related questionnaires to measure HRQoL in children and adolescents with hemophilia. This version covers nine dimensions considered relevant for children's HRQoL (physical health, feelings, view of yourself, family, friends, other people, sports, dealing with hemophilia, and treatment).
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L) - The EQ-5D-5L is a generic, self-reported, preference-based health utility measure that consists of six questions and is used to assess health status and inform pharmacoeconomic evaluations.
Timepoint [4] 0 0
Up to approximately 2 years
Secondary outcome [5] 0 0
Participant preference for the emicizumab regimen compared with the previous regimen, as measured by the EmiPref questionnaire - The EmiPref questionnaire asks participants to specify the treatment they would prefer to continue to receive after receiving treatment with their previous episodic or prophylactic regimen and subcutaneous (SC) emicizumab.
Timepoint [5] 0 0
Month 3
Secondary outcome [6] 0 0
Incidence and clinical significance of anti-emicizumab antibodies - Immunogenicity will be monitored by incidence and clinical significance of antibodies to emicizumab. For the assessment of anti-FVIII antibodies, functional assays for FVIII inhibitors that utilize a clotting readout (classic Bethesda or Nijmegen assay) cannot be used for participants on emicizumab therapy as emicizumab drives clotting even in the presence of FVIII inhibitors, causing a false-negative test result. After the first dose, local measurement of FVIII inhibitors, if indicated, requires use of an enzyme linked immunosorbent assay- (ELISA-) based test or a chromogenic Bethesda assay. At the discretion of the local investigator, any additional urgent request to assess FVIII inhibitors will need to be sent to a central laboratory.
Timepoint [6] 0 0
Up to approximately 2 years
Secondary outcome [7] 0 0
Ctrough of emicizumab - Ctrough is a measure of plasma concentration of a study drug at the end of of the dosage interval.
Timepoint [7] 0 0
Week 1, Week 2, Week 3, and Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up (up to approximately 2 years)
Secondary outcome [8] 0 0
Clearance of emicizumab - Clearance is the rate at which a study drug is removed from the body.
Timepoint [8] 0 0
Week 1, Week 2, Week 3, and Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up (up to approximately 2 years)
Secondary outcome [9] 0 0
Volume of distribution of emicizumab - Volume of distribution is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.
Timepoint [9] 0 0
Week 1, Week 2, Week 3, and Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up (up to approximately 2 years)
Secondary outcome [10] 0 0
Area under the plasma drug concentration-time curve (AUC) of emicizumab - AUC reflects the actual body exposure of a study drug after dosing.
Timepoint [10] 0 0
Week 1, Week 2, Week 3, and Week 5, Month 3, Month 6, Month 12, Month 18, Month 24, at safety follow-up (up to approximately 2 years)

Eligibility
Key inclusion criteria
- As per investigator's judgement, 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

- 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
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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; or, 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital; Haematology - Camperdown
Recruitment hospital [2] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Leuven
Country [2] 0 0
Brazil
State/province [2] 0 0
PR
Country [3] 0 0
Brazil
State/province [3] 0 0
RJ
Country [4] 0 0
Brazil
State/province [4] 0 0
SP
Country [5] 0 0
Canada
State/province [5] 0 0
Alberta
Country [6] 0 0
Canada
State/province [6] 0 0
Manitoba
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Colombia
State/province [8] 0 0
Localidad Puente Aranda
Country [9] 0 0
Colombia
State/province [9] 0 0
Medellin
Country [10] 0 0
Finland
State/province [10] 0 0
Helsinki
Country [11] 0 0
Germany
State/province [11] 0 0
Berlin
Country [12] 0 0
Germany
State/province [12] 0 0
Bonn
Country [13] 0 0
Germany
State/province [13] 0 0
Frankfurt/M.
Country [14] 0 0
Germany
State/province [14] 0 0
Leipzig
Country [15] 0 0
Germany
State/province [15] 0 0
Mörfelden-Walldorf
Country [16] 0 0
Germany
State/province [16] 0 0
München
Country [17] 0 0
Guatemala
State/province [17] 0 0
Guatemala
Country [18] 0 0
Hungary
State/province [18] 0 0
Budapest
Country [19] 0 0
Hungary
State/province [19] 0 0
Gyor
Country [20] 0 0
Hungary
State/province [20] 0 0
Pecs
Country [21] 0 0
India
State/province [21] 0 0
Karnataka
Country [22] 0 0
India
State/province [22] 0 0
Maharashtra
Country [23] 0 0
India
State/province [23] 0 0
WEST Bengal
Country [24] 0 0
India
State/province [24] 0 0
Pune
Country [25] 0 0
Israel
State/province [25] 0 0
Tel Hashomer
Country [26] 0 0
Italy
State/province [26] 0 0
Campania
Country [27] 0 0
Italy
State/province [27] 0 0
Emilia-Romagna
Country [28] 0 0
Italy
State/province [28] 0 0
Lazio
Country [29] 0 0
Italy
State/province [29] 0 0
Lombardia
Country [30] 0 0
Italy
State/province [30] 0 0
Piemonte
Country [31] 0 0
Italy
State/province [31] 0 0
Sicilia
Country [32] 0 0
Italy
State/province [32] 0 0
Toscana
Country [33] 0 0
Italy
State/province [33] 0 0
Veneto
Country [34] 0 0
Mexico
State/province [34] 0 0
Mexico CITY (federal District)
Country [35] 0 0
Mexico
State/province [35] 0 0
Mexico City
Country [36] 0 0
Netherlands
State/province [36] 0 0
Rotterdam
Country [37] 0 0
Netherlands
State/province [37] 0 0
Utrecht
Country [38] 0 0
Panama
State/province [38] 0 0
Panama City
Country [39] 0 0
Poland
State/province [39] 0 0
Warsaw
Country [40] 0 0
Portugal
State/province [40] 0 0
Coimbra
Country [41] 0 0
Portugal
State/province [41] 0 0
Lisboa
Country [42] 0 0
Portugal
State/province [42] 0 0
Porto
Country [43] 0 0
Romania
State/province [43] 0 0
Timisoara
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Altaj
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Moscow
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Saint Petersburg
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Samara
Country [48] 0 0
Saudi Arabia
State/province [48] 0 0
Riyadh
Country [49] 0 0
Spain
State/province [49] 0 0
Barcelona
Country [50] 0 0
Spain
State/province [50] 0 0
Madrid
Country [51] 0 0
Spain
State/province [51] 0 0
Malaga
Country [52] 0 0
Spain
State/province [52] 0 0
Sevilla
Country [53] 0 0
Spain
State/province [53] 0 0
Valencia
Country [54] 0 0
Sweden
State/province [54] 0 0
Göteborg
Country [55] 0 0
Sweden
State/province [55] 0 0
Solna
Country [56] 0 0
Switzerland
State/province [56] 0 0
Bern
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Birmingham
Country [58] 0 0
United Kingdom
State/province [58] 0 0
London
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Newcastle upon Tyne
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase IIIb, single arm, open-label, multi-center study to evaluate the safety and
tolerability of emicizumab in participants with congenital hemophilia A who have documented
inhibitors against Factor VIII (FVIII) at enrollment. Approximately 200 participants, aged 12
or older, will be enrolled in this study and are expected to be enrolled at approximately 85
sites globally. Participants will receive an initial weekly dose of prophylactic emicizumab
subcutaneously for 4 weeks, followed by a weekly maintenance dose subcutaneously for the
remainder of the 2-year treatment period.
Trial website
https://clinicaltrials.gov/show/NCT03191799
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications