Congenital Hemophilia A with factor VIII inhibitors MedDRA version: 14.1 Level: LLT Classification code 10018938 Term: Haemophilia A (Factor VIII) System Organ Class: 100000004850
Conditions
Interventions
Product Name: OBI-1
Product Code: OBI-1
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: obyoctocog alfa
CAS Number: 1339940-90-7
Current Sponsor code: OBI-1
Oth
Sponsors
Baxter Innovations GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Males or females = 6 years of age. 2) Written informed consent from subject or subject’s legal representative. 3) Subjects with congenital hemophilia A with a human factor VIII inhibitor =30 BU assessed within 30 days prior to study entry and no documented human factor VIII inhibitor >30 BU within the prior 90 days.. 4) 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. 5) Has an anti-OBI-1 titer =10 BU. 6) Has any serious or life-threatening bleeding episode; or requires a major or minor surgical procedure that could lead to a serious bleeding episode if not well controlled. 7) Is willing and able to follow all instructions and attend all study visits. 8) Has no other significant hemostatic abnormality and: a) Platelets >100,000/mm^3 b) Prothrombin time =65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1) 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). 2) Bleeding episode assessed likely to resolve on its own if left untreated. 3) Prior history of bleeding disorder other than congenital hemophilia A. 4) Known major sensitivity (anaphylactoid reactions) to therapeutic products of porcine or hamster origin; 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®). 5) Received any other investigational treatment within 30 days of the first OBI-1 treatment. 6) Anticipated need for treatment or device during the study that may interfere with the evaluation of the safety or efficacy of OBI-1, whose safety or efficacy may be affected by OBI-1. 7) Is planning to father a child during the study. 8) Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the subject’s safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study. 9) Inability or unwillingness to comply with the study design, protocol requirements, or the follow-up procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of OBI-1 for the treatment of serious bleeding episodes in subjects with congenital hemophilia A with inhibitors to human factor VIII and with a history of inadequate response to bypassing agents. ;Secondary Objective: 1) To determine the proportion of serious bleeding episodes controlled with OBI-1 therapy 2) To assess the efficacy of OBI-1 at designated time points after the initiation of therapy 3) To determine the frequency, total dose and total number of infusions of OBI-1 required to control serious bleeding episodes 4) To assess the correlations between response to OBI-1 therapy at specified assessment time points and eventual control of serious bleeding episodes. 5) To assess the correlations between the pre-infusion anti-OBI-1 inhibitor titer, the total dose of OBI-1, the outcome at 24 hours and the eventual control of the bleeding disorder 6) To assess the anti-OBI-1 inhibitor level pre-infusion, at specified time points during treatment and at the end of the follow-up period at 90 days post final infusion 7) To evaluate the safety of OBI-1 8) To assess the simple recovery and elimination rate parameters of OBI-1 in subjects with inhibitors treated with OBI-1 therapy;Primary end point(s): The primary efficacy endpoint is the proportion of serious bleeding episodes responsive to OBI-1 therapy at 24 hours after the initiation of treatment. Response to OBI-1 therapy will be based on assessment of effectiveness and factor VIII blood levels.;Timepoint(s) of evaluation of this end point: 24 hours after initiation of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: 1. The overall proportion of serious bleeding episodes successfully controlled with OBI-1 therapy, as assessed by the investigator. 2. The proportion of bleeding episodes responsive to OBI-1 therapy at designated assessment time points after the initiation of therapy, as assessed by the investigator. 3. Frequency, total dose, and total number of infusions of OBI-1 required to successfully control qualifying bleeding episodes. 4. Correlation between response to OBI-1 therapy at specified time points and eventual control of serious bleeding episodes. 5. 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. 6. Correlation between the pre-infusion anti-OBI-1 antibody titers and the recovery of OBI-1. Safety endpoints: 7. TEAEs and serious adverse events (SAEs) throughout the study. 8. Biochemistry, hematology, urinalyses and vital signs. 9. Anti-human factor VIII antibody titer. 10. Anti-OBI-1 antibody titer. 11. Anti-host cell protein (BHK) antibody titer.;Timepoint(s) of evaluation of this end point: Efficacy: 1,3,4,5,6. Ongoing basis throughout study 2. 24h after end of first dose;each dose or q8h to 24h, q12h from 24-120h and q24h thereafter until last OBI-1 dose or withdrawal;all f-up visits Safety: 7. 0, 10-20min and 24h after end of first dose;at each dose or q8h to 24h, q12h from 24-120h and q24h thereafter until last OBI-1 dose or withdrawal;all f-up visits;termination 8. Biochemistry, hematology and urinalyses: screening;24h after end of first dose;f-up visits 2-5; Vital signs: screening;10-20min and 24h after end of first dose;at each dose or q8h to 24h, q12h from 24-120h and q24h thereafter until last OBI-1 dose or withdrawal;all f-up visits 9-10: Screening;q5 days during treatment and healing;all f-up visits;termination 11: Screening;f-up visit 5;termination | — |
Countries
Canada, South Africa, United Kingdom, United States
Contacts
Public ContactGuido Wuerth, Clinical Operations
Baxter Innovations GmbH
Outcome results
None listed