Hemophilia A
Conditions
Keywords
hemophilia A, haemophilia A, blood coagulation disorders, hemorrhagic disorders, coagulation protein disorder, hematologic diseases, congenital hemophilia A
Brief summary
This study is to test whether the study drug (OBI-1) is safe and effective for the treatment of serious bleeding episodes in people with congenital hemophilia A.
Interventions
BIOLOGICALOBI-1
intravenous infusion, up to every 2-3 hours for the first 24 hours of treatment
Sponsors
Baxalta now part of Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent/assent from participant and/or participant's parent or legal representative. * Participants with congenital hemophilia A with human factor VIII inhibitor ≤30 BU assessed within 90 days prior to study entry. * Has previously or is currently demonstrating suboptimal hemostatic response to bypassing agents for treatment of bleeding episodes; suboptimal response is determined by the investigator , but minimally includes no or minimal evidence of response after at least two doses of bypassing agents, either for the current or a historic bleeding episode. * Has an anti-OBI-1 titer ≤ 10 BU * Has any serious or life-threatening bleeding episode; or requires a surgical procedure that could lead to a serious bleeding episode if not well controlled. * Is willing and able to follow all instructions and attend all study visits. * Has no other significant hemostatic abnormality and: * Platelets ≥100,000/mm-cubed * Prothrombin time \< 15 seconds * INR \< 1.3 * Participants taking anti-thrombotics (such as clopidogrel, heparin or heparin analogue) may be included provided three half-lives of the agent have elapsed since the last dose of the agent.
Exclusion criteria
* Hemodynamically unstable after blood transfusion, fluid resuscitation and pharmacologic or volume replacement pressor therapy. This hemodynamic instability is characterized by symptomatic hypotension resulting in vital organ dysfunction, such as cardiac ischemia, oliguria (urine volume \<0.5 mL/kg in the previous six hours), central nervous system hypoperfusion manifested by mental status change such as confusion (unless head injury or intracranial hemorrhage is present), pulmonary compromise, and/or acidosis (manifested by pH and lactate levels). * Bleeding episode assessed likely to resolve on its own if left untreated. * Use of hemophilia medication: recombinant factor VIIa within 3 hours prior to OBI-1 administration or activated prothrombin complex concentrate (aPCC) treatment within 6 hours prior to OBI-1 administration * Prior history of bleeding disorder other than congenital hemophilia A * Known major sensitivity (anaphylactoid reactions) to porcine or hamster products. Examples include therapeutics of porcine origin (e.g. previously marketed porcine factor VIII, Hyate-C®) and recombinant therapeutics prepared from hamster cells (e.g. Humira®, Advate® and Enbrel®). * Received any other investigational treatment within 30 days of the first OBI-1 treatment. * Anticipated need for treatment or device during the study that may interfere with the evaluation of the safety or efficacy of OBI-1, or whose safety or efficacy may be affected by OBI-1. * Is planning to father a child during the study * Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the participant's safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study. * Inability or unwillingness to comply with the study design, protocol requirements, or the follow-up procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Serious Bleeding Episodes Responsive to OBI-1 | 24 hours after initiation of treatment | This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, the study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within the OBI-1-302 study (Congenital Hemophilia A). |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Bleeding Episodes Responsive to OBI-1 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator | Through 90 days ± 7days following final OBI-1 dose |
| Frequency of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes. | Through 90 days ± 7days following final OBI-1 dose |
| Total Dose of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes. | Through 90 days ± 7days following final OBI-1 dose |
| Total Number of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes. | Through 90 days ± 7days following final OBI-1 dose |
| Correlation Between Response to OBI-1 Therapy at Specified Time Points and Eventual Control of Serious Bleeding Episodes. | Through 90 days ± 7days following final OBI-1 dose |
| Correlation Between the Pre-infusion Anti-OBI-1 Antibody Titers, the Total Dose of OBI-1, the Outcome at 24 Hours and the Eventual Control of the Bleeding Episode. | Frame: Through 90 days ± 7days following final OBI-1 dose |
| Overall Proportion of Serious Bleeding Episodes Successfully Controlled With OBI-1 Therapy, as Assessed by the Investigator. | Through 90 days ± 7days following final OBI-1 dose |
| Recovery and Elimination Rate Parameters of OBI-1 in Subjects With Inhibitors Treated With OBI-1 Therapy. | Through 90 days ± 7days following final OBI-1 dose |
| Efficacy Assessment of OBI-1 in Participants With Anti-human Factor VIII Titers >30 Bethesda Units (BU) | Through 90 days ± 7days following final OBI-1 dose |
| Anti-human Factor VIII Antibody Titer. | Through 90 days ± 7days following final OBI-1 dose |
| Anti-OBI-1 Antibody Titer. | Through 90 days ± 7days following final OBI-1 dose |
| Anti-host Cell Protein Baby Hamster Kidney (BHK) Antibody Titer. | Through 90 days ± 7days following final OBI-1 dose |
| Correlation Between the Pre-infusion Anti-OBI-1 Antibody Titers and the Recovery of OBI-1. | Through 90 days ± 7days following final OBI-1 dose |
Countries
South Africa, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OBI-1 OBI-1: intravenous infusion, up to every 2-3 hours for the first 24 hours of treatment | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Proportion of Serious Bleeding Episodes Responsive to OBI-1
This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, the study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within the OBI-1-302 study (Congenital Hemophilia A).
Time frame: 24 hours after initiation of treatment
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Anti-host Cell Protein Baby Hamster Kidney (BHK) Antibody Titer.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Anti-human Factor VIII Antibody Titer.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Anti-OBI-1 Antibody Titer.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Correlation Between Response to OBI-1 Therapy at Specified Time Points and Eventual Control of Serious Bleeding Episodes.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Correlation Between the Pre-infusion Anti-OBI-1 Antibody Titers and the Recovery of OBI-1.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Correlation Between the Pre-infusion Anti-OBI-1 Antibody Titers, the Total Dose of OBI-1, the Outcome at 24 Hours and the Eventual Control of the Bleeding Episode.
Time frame: Frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Efficacy Assessment of OBI-1 in Participants With Anti-human Factor VIII Titers >30 Bethesda Units (BU)
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Frequency of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Overall Proportion of Serious Bleeding Episodes Successfully Controlled With OBI-1 Therapy, as Assessed by the Investigator.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Proportion of Bleeding Episodes Responsive to OBI-1 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Recovery and Elimination Rate Parameters of OBI-1 in Subjects With Inhibitors Treated With OBI-1 Therapy.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Total Dose of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).
Secondary
Total Number of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes.
Time frame: Through 90 days ± 7days following final OBI-1 dose
Population: This study was terminated early and only enrolled one participant. Due to concerns that the participant would be at risk of being re-identified, study results are not posted. The decision to terminate this study was not related to any safety and/or efficacy concern of OBI-1 in the indication described within this study (Congenital Hemophilia A).