Hemophilia A Without Inhibitor
Conditions
Keywords
hemophilia A, eloctate, Emicizumab, inhibitor
Brief summary
This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which Eloctate will be compared with Emicizumab, using adaptive design, to prevent inhibitors in patients with severe hemophilia A.
Detailed description
This is a multi-center randomized phase III clinical trial, the Inhibitor Prevention Trial, in which consecutive hemostatic agents will be compared using adaptive design to prevent inhibitors in patients with severe hemophilia A. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. The INHIBIT Clinical Trials Platform includes two linked trials, the Inhibitor Prevention Trial (Prevention Trial) and the Inhibitor Eradication Trial (Eradication Trial) that will be conducted at up to 41 U.S. hemophilia treatment centers (HTCs) affiliated with universities. The Inhibitor Prevention Trial is a 48-week randomized phase III trial, in which 66 previously untreated patients (PUPs) with severe hemophilia A will be enrolled. Subjects will include children from 4 months of age up to 4 years of age who have not been previously treated with clotting factor. Once enrolled, subjects who meet all the inclusion and none of the exclusion criteria will be randomized to preemptive weekly Eloctate (rFVIIIFc) vs. weekly Emicizumab (Hemlibra) to prevent inhibitor formation, defined as anti-FVIII \>= 0.6 BU. Blood draws will be minimized to 6 timepoints, pre, 4, 12, 24, 36, and 48 weeks, and validated for small volumes, 3.8 cc (¾ tsp) each. The Inhibitor Prevention Trial is considered greater than minimal risk as study drug is given before the first bleed and special inhibitor studies are obtained. (NB: The Inhibitor Prevention Trial (PRO19040140) is linked to the Inhibitor Eradication Trial (PRO19070080), as part of the INHIBIT Clinical Trials Platform, with both trials will be conducted efficiently in the same hemophilia treatment centers (HTCs), with the same MDs, coordinators, visit frequency, blood sampling, and assays.
Interventions
DRUGEloctate Injectable Product
This is a factor VIII-Fc fusion protein.
DRUGEmicizumab Injection [Hemlibra]
This is a bispecific monoclonal antibody FVIII mimic.
Sponsors
Health Resources and Services Administration (HRSA)
Margaret Ragni
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
This is a phase III open-label, randomized controlled trial comparing two drugs in the prevention of hemophilia inhibitor formation.
Eligibility
Sex/Gender
MALE
Age
4 Months to 4 Years
Healthy volunteers
No
Inclusion criteria
1. Male children \>= 4 months and up to 4 years of age. 2. Severe hemophilia A (FVIII \< 0.01 U/ml). 3. No evidence of an inhibitor i.e. anti-FVIII \< 0.6 B.U. 4. No more than 3 FVIII exposures (Factor VIII concentrate, cryoprecipitate, or fresh frozen plasma), including circumcision.
Exclusion criteria
1. Acquired hemophilia or any bleeding disorder other than hemophilia A. 2. Treatment with clotting factor or emicizumab previously. 3. Use of an experimental drug(s). 4. Surgery anticipated in the next 48 weeks. 5. Life expectancy less than 5 years. 6. Parent/caretaker unable or unwilling to keep a personal diary of bleeding frequency and study drug treatment, make monthly visits and blood draws at weeks 4, 12, 24, 36, and 48. 7. Other illness, condition or reason in the opinion of the investigator that would make the patient unsuitable for the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inhibitor Formation | 48 weeks | The proportion developing anti-FVIII inhibitors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding Events | 48 weeks | The number of bleeding events:hematoma, joint, central nervous system, other bleeds. |
| FVIII Trough Level | 48 weeks | The FVIII trough activity by chromogenic assay |
| Human Leukocyte Antigen (HLA) Haplotype | 48 weeks | The number of HLA haplotype variants. |
| FVIII Mutation | 48 weeks | The number of FVIII mutation variants. |
| Number of FVIII Exposures | 48 weeks | Number of FVIII exposures, |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eloctate Arm A: Eloctate 65 IU/kg will be administered weekly by intravenous infusion in previously untreated children with severe hemophilia A beginning before the first bleed and continued up to 48 weeks.
Eloctate Injectable Product: This is a factor VIII-Fc fusion protein. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study closed due to poor enrollment. | 1 |
Baseline characteristics
| Characteristic | Eloctate |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 1 years |
| Anti-FVIII level > 0.6 BU | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Number and Type of Bleeds in the last year | 0 Bleeds |
| Number of FVIII exposures | 0 FVIII exposures |
| Prior Circumcision, | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Inhibitor Formation
The proportion developing anti-FVIII inhibitors.
Time frame: 48 weeks
Population: Only patient was enrolled on study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Eloctate | Inhibitor Formation | 1 Participants |
Secondary
Bleeding Events
The number of bleeding events:hematoma, joint, central nervous system, other bleeds.
Time frame: 48 weeks
Population: Only patient was enrolled on study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eloctate | Bleeding Events | 1 bleeding events |
Secondary
FVIII Mutation
The number of FVIII mutation variants.
Time frame: 48 weeks
Population: specimen collected, discarded with out analysis due to study being close dearly due to low enrollment
Secondary
FVIII Trough Level
The FVIII trough activity by chromogenic assay
Time frame: 48 weeks
Population: specimen collected, discarded with out analysis due to study being close dearly due to low enrollment
Secondary
Human Leukocyte Antigen (HLA) Haplotype
The number of HLA haplotype variants.
Time frame: 48 weeks
Population: specimen collected, discarded with out analysis due to study being close dearly due to low enrollment
Secondary
Number of FVIII Exposures
Number of FVIII exposures,
Time frame: 48 weeks
Population: Only patient was enrolled on study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eloctate | Number of FVIII Exposures | 2 FVIII exposures |