A Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Emicizumab in Patients with Hemophilia A

Phase 1

Conditions: Hemophilia A
MedDRA version: 20.0 Level: LLT Classification code 10018938 Term: Haemophilia A (Factor VIII) System Organ Class: 100000004850
MedDRA version: 20.0 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System Organ Class: 100000004850
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2016-001094-33-PL

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 48

Inclusion Criteria

•Aged >=12 years
•Body weight >= 40 kg at screening
•Have severe congenital hemophilia A or hemophilia A with FVIII inhibitors
•Patients using rFVIIa or willing to switch to rFVIIa as primary bypassing agent for the treatment of breakthrough bleeds
•FVIII inhibitor test during screening with titer results available prior to first administration of study drug
•Patients without FVIII inhibitors (< 0.6 Bethesda Units [BU]/milliliter
[mL], < 1.0 BU/mL only for laboratories with an historical sensitivity
cutoff for inhibitor detection of 1.0 BU/mL) who completed successful
immune tolerance induction (ITI) must have done so at least 5 years
before screening and must have no evidence of inhibitor recurrence
(permanent or temporary) indicated by detection of an inhibitor > 0.6
BU/mL (> 1.0 BU/mL only for laboratories with an historical sensitivity
cutoff for inhibitor detection of 1.0 BU/mL) since ITI
•For patients to be enrolled into PK run-in cohort: Current episodic treatment (FVIII or bypassing agents) at the time of entry into this study and documentation of details of episodic treatment for at least 24 weeks prior to entry into this study
•For patients to be enrolled into the expansion cohort: Documentation of details of prophylactic or episodic treatment and the number of bleeding episodes for at least 24 weeks prior to entry into this study. For patients on an episodic regimen, >= 5 bleeds in the prior 24 weeks, regardless of inhibitor status
•For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of < 1percent per year during the treatment period and for at least 5 elimination half-lives (24 weeks) after the last dose of study drug
•Adequate values of hematologic, hepatic, and renal function tests

Are the trial subjects under 18? yes
Number of subjects for this age range: 4
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 41
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

•Inherited or acquired bleeding disorder other than hemophilia A
•Ongoing or planned ITI therapy; patient in whom ITI has failed will be eligible with a 72-hour washout period prior to the first emicizumab administration
•History of illicit drug or alcohol abuse within 48 weeks prior to screening
•Patients who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), in the investigator’s judgment
•Previous (within the last 12 months) or current treatment for thromboembolic disease or signs of thromboembolic disease
•Other conditions (e.g., certain autoimmune diseases) that may currently increase the risk of bleeding or thrombosis
•History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
•Known HIV infection with cluster of differentiation 4 (CD4) counts < 200 cells/microliter (µL) (CD4 counts >= 200 cell/µL will be permitted)
•Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy
•Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study or pose an additional unacceptable risk in administering study drug to the patient
•Women with a positive serum pregnancy test or pregnant/lactating women
•Receipt of any of the following: emicizumab in a prior investigational study, an investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration, a non hemophilia related investigational drug within last 30 days or 5 half-lives, whichever is shorter, and any other investigational drug currently being administered or planned to be administered

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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