Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04205175 |
| Other study ID # |
19 00367 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2020 |
| Est. completion date |
October 2022 |
Study information
| Verified date |
March 2022 |
| Source |
Children's Hospital Los Angeles |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Hemophilia A is a severe, life-long, genetic bleeding disorder characterized by a deficiency
of factor VIII (FVIII), a crucial cofactor of the coagulation system. The mainstay of
hemophilia treatment is factor replacement therapy with FVIII clotting factor concentrates
(CFC) and these can be given episodically in response to bleeding or prophylactically to
prevent bleeding. The main adverse effect of FVIII CFC is the development of neutralizing
anti-drug antibodies termed inhibitors, and these render replacement therapy less effective
if they are low titer inhibitors or completely ineffective if they are of the high titer
variety. These so-called 'inhibitor patients' cannot rely on FVIII CFC for their treatment
and are treated with other CFC called bypassing agents such as activated prothrombin complex
concentrate (aPCC/Feiba). While these agents can be effective in some patients for
prophylaxis, they are not as effective for bleed prevention as FVIII CFC for patients without
inhibitors.Recently, emicizumab (Hemlibra, Roche), was developed and licensed for the
prevention of bleeding in patients with hemophilia A with and without inhibitors. However,
patients in the clinical trials for emicizumab have developed thrombotic adverse events and
only patients who received doses of Feiba of >100 IU/kg/24 hours for more than 24 hours
developed thrombosis.
As a result of the above data, recommendations have been to either avoid altogether in
patients on emicizumab, or to be very cautious about using it to treat breakthrough bleeding.
With this in mind, we propose to study the in vivo combination of Feiba in patients with
inhibitors on emicizumab.
Description:
Explanation of the study: Hemophilia A is a severe, life-long, genetic bleeding disorder
characterized by a deficiency of factor VIII (FVIII), a crucial cofactor of the coagulation
system. The mainstay of hemophilia treatment is factor replacement therapy with FVIII
clotting factor concentrates (CFC) and these can be given episodically in response to
bleeding or prophylactically to prevent bleeding. The main adverse effect of FVIII CFC is the
development of neutralizing anti-drug antibodies termed inhibitors, and these render
replacement therapy less effective if they are low titer inhibitors or completely ineffective
if they are of the high titer variety. These so-called 'inhibitor patients' cannot rely on
FVIII CFC for their treatment and are treated with other CFC called bypassing agents such as
activated prothrombin complex concentrate (aPCC/Feiba). While these agents can be effective
in some patients for prophylaxis, they are not as effective for bleed prevention as FVIII CFC
for patients without inhibitors.Recently, emicizumab (Hemlibra, Roche), was developed and
licensed for the prevention of bleeding in patients with hemophilia A with and without
inhibitors. However, patients in the clinical trials for emicizumab have developed thrombotic
adverse events and only patients who received doses of Feiba of >100 IU/kg/24 hours for more
than 24 hours developed thrombosis.
Rationale: As a result of the above data, recommendations have been to either avoid
altogether in patients on emicizumab, or to be very cautious about using it to treat
breakthrough bleeding. With this in mind, we propose to study the in vivo combination of
Feiba in patients with inhibitors on emicizumab.
Intervention: Administration of Feiba on the lower end of the licensed doses (or lower) and
running thrombin generation assay (TGA) in patients on emicizumab.
Objectives: To demonstrate the thrombin generation of the in vivo administration of Feiba at
various doses to patients with congenital hemophilia A and inhibitors who are on emicizumab
and to assess the safety of a single Feiba infusion in patients with congenital hemophilia A
with inhibitors.
Study population: Male patients with congenital hemophilia A of any severity and any age with
a history of high titer factor VIII inhibitor who are currently treated with emicizumab for a
minimum of 2 months without interruption.
Study methodology: Patients who agree to participate will be infused a single, weight-based
dose at each visit in the Infusion Center or the Outpatient Clinic. Depending on the thrombin
generation of each individual patient following the initial dose, the study team will
schedule the next infusion visit for subsequent Feiba dose.
Study endpoint: Once any patient on this trial achieves normal or near normal (within 10%)
thrombin generation, they will not receive subsequent Feiba infusions even if that occurs
after the lowest dose. Thus, no patient is expected to have excessive thrombin generation.
Statistics: The study will only employ descriptive statistics. The main outcome measure will
be to determine the dose of Feiba that most closely approximates normal thrombin generation
in patients with congenital hemophilia A with inhibitors who are on emicizumab.
Plans for analysis: the goal is to complete all study procedures within 12 months and have 2
months for data analysis and evaluation. Overall the goal is to complete the project
including a submission for an abstract and publication within 14 months from the start of
patient accrual.
