Study of Modified Recombinant Factor VIII (OBI-1) in Subjects With Acquired Hemophilia A

• Sponsor: Baxalta now part of Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01178294
• Collaborator: (none)
• Enrollment: 29
• Locations: 12
• Arm: 1
• Actual Duration (Months): 35
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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 acquired hemophilia A.

Condition or Disease	Intervention/Treatment	Phase
Acquired Hemophilia A	Biological: OBI-1	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (OBI-1) in the Treatment of Acquired Hemophilia A Due to Factor VIII Inhibitory Auto-antibodies
• Actual Study Start Date: Nov 10, 2010
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Oct 9, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OBI-1 Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)	Biological: OBI-1; Intravenous infusion

Outcome Measures

Primary Outcome Measures

1. Percentage of Serious Bleeding Episodes Responsive to OBI-1 [24 hours after initiation of treatment]

   The initial serious ("qualifying") bleeding episode for each subject was analyzed for the primary efficacy outcome measure. A 'positive response' is defined as 'effective' (bleeding stopped with clinical control and FVIII levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' is defined as 'bleeding slightly reduced or unchanged and FVIII levels of less than 50%'. 'Not effective' is defined as 'bleeding worsening and FVIII levels of less than 50%'.

Secondary Outcome Measures

1. Overall Percentage of Serious Bleeding Episodes Successfully Controlled With OBI-1 Therapy, as Assessed by the Investigator [At the time of final treatment dosing (varied from participant to participant depending on bleeding episodes)]

   Treatment success was defined as control of qualifying bleeding episode at the time of final treatment dosing. A serious bleeding episode was considered 'successfully controlled' if the investigator had checked 'completed OBI-1 therapy as treatment success' on the eCRF.

2. Percentage of Serious Bleeding Episodes Responsive to OBI-1 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator [8 hours]

   A 'positive response' is defined as 'effective' (bleeding stopped with clinical control and FVIII levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' is defined as 'bleeding slightly reduced or unchanged and FVIII levels of less than 50%'. 'Not effective' is defined as 'bleeding worsening and FVIII levels of less than 50%'.

3. Percentage of Serious Bleeding Episodes Responsive to OBI-1 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator [16 hours]

   A 'positive response' is defined as 'effective' (bleeding stopped with clinical control and FVIII levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' is defined as 'bleeding slightly reduced or unchanged and FVIII levels of less than 50%'. 'Not effective' is defined as 'bleeding worsening and FVIII levels of less than 50%'.

4. Frequency of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes [Time of successful control of qualifying bleeding episode (varied from participant to participant)]

   'Frequency of infusions' was calculated as the 'average number of infusions per day'. 'Qualifying bleeding episode' was defined as the 'initial, serious bleeding episode'.

5. Total Dose of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes [Time of successful control of qualifying bleeding episode (varied from participant to participant)]

   'Qualifying bleeding episode' was defined as the 'initial, serious bleeding episode'.

6. Total Number of Infusions of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes [Time of successful control of qualifying bleeding episode (varied from participant to participant)]

   'Qualifying bleeding episode' was defined as the 'initial, serious bleeding episode'. A serious bleeding episode was considered 'successfully controlled' if the investigator had checked 'completed OBI-1 therapy as treatment success' on the eCRF.

7. Correlation Between Positive Response to OBI-1 Therapy at 8 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours [24 hours]

8. Correlation Between Response to OBI-1 Therapy at 16 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours [24 hours]

9. Correlation Between Response to OBI-1 Therapy at Specified Time Points and Eventual Control of Serious Bleeding Episodes at 24 Hours [24 hours]

10. 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 [Through 90 days ± 7 days following final OBI-1 dose]

11. Pharmacokinetics (PK) Analysis- Plasma Clearance [Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours]

    Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics.

12. PK Analysis- Volume of Distribution (Vd) at Steady State [Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours]

    Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics.

13. PK Analysis- Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Measurable Concentration [Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours]

    Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics. AUC was calculated as area under the percent activity-time curve.

14. PK Analysis- Terminal Half-life [Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours]

    Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics. Half-life was calculated as the time it took to reduce percent activity by half.

15. Number of Participants Who Developed de Novo Anti-OBI-1 Antibody Titers [Through 90 days ± 7 days following final OBI-1 dose]

16. Number of Participants Who Developed an Anti-host Cell Protein Baby Hamster Kidney (BHK) Antibody Titer [Through 90 days ± 7 days following final OBI-1 dose]

Other Outcome Measures

1. Anti-human Factor VIII Antibody Titer [Through 90 days ± 7 days following final OBI-1 dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent from subject, trusted person or person who is legally authorized to sign on behalf of the participant (Legal Representative in U.S.), depending on local regulations

• Participants with acquired hemophilia with autoimmune inhibitory antibodies to human factor VIII with a clinical diagnosis established by the following criteria: a) Prolonged activated partial thromboplastin time (aPTT), b) Prothrombin time (PT) ≤ upper limit of normal (ULN) + 2 seconds and platelet count within normal range, c) Abnormal aPTT mixing study (patient-normal control 1:1) consistent with a factor VIII inhibitors reduced factor VIII activity level (below 10%)

• Has a serious bleeding episode, as documented by the investigator

• Be willing and able to follow all instructions and attend all study visits

• 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

• Life expectancy, prior to onset of the hemorrhagic episode, of at least 90 days

• Participants of reproductive age must use acceptable methods of contraception and if female, undergo pregnancy testing as part of the screening process

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)

• Has an established reason for bleeding that is not correctable

• Bleeding episode assessed likely to resolve on its own if left untreated

• Anti-OBI-1 inhibitor that exceeds 20 Bethesda Units (BU) (prospectively or retrospectively)

• Subsequent bleeding episode at the site of the initial qualifying bleeding episode within two weeks following the final OBI-1 dose for the initial qualifying bleeding episode, or subsequent bleeding episode at a different site than the initial qualifying bleeding episode within 1 week following the final OBI-1 dose for the initial qualifying bleeding episode will not be considered "new" qualifying bleeding episodes

• Prior history of bleeding disorder other than acquired hemophilia.

• Known major sensitivity to therapeutic products of pig 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®)

• Use of hemophilia medication: rFVIIa within 3 hours prior to OBI-1 administration or aPCC treatment within 6 hours prior to OBI-1 administration

• Participation in any other clinical study 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 currently pregnant, breastfeeding, or planning to become pregnant or father a child during the study

• 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

• Inability or unwillingness to comply with the study design, protocol requirements, or the follow-up procedures

• Participant of majority age under legal protection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana Hemophilia and Thrombosis Center	Indianapolis	Indiana	United States	46260
2	Louisiana Center for Bleeding & Clotting Disorders	New Orleans	Louisiana	United States	70112-2699
3	National Institutes of Health - Warren G. Magnuson Clinical Center	Bethesda	Maryland	United States	20892-1508
4	Tufts Medical Center	Boston	Massachusetts	United States	02111
5	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
6	University of North Carolina at Chapel Hill Hospital	Chapel Hill	North Carolina	United States	27599-7305
7	The Pennsylvania State University and Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
8	Vanderbilt University Medical Center, Hemostasis/Hemophilia Clinic	Nashville	Tennessee	United States	37232-9830
9	Maisonneuve-Rosemont Hospital	Montreal	Quebec	Canada	H1T 2M4
10	Apollo Hospitals	Chennai	Tamil Nadu	India	600006
11	Royal Free Hospital-Katharine Dormandy Haemophilia Centre and Thrombosis Unit	London	England	United Kingdom	NW3 2QG
12	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	Hampshire/England	United Kingdom	RG249NA

Sponsors and Collaborators

• Baxalta now part of Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Baxalta now part of Shire
• ClinicalTrials.gov Identifier: NCT01178294
• Other Study ID Numbers: OBI-1-301
• First Posted: Aug 10, 2010
• Last Update Posted: May 13, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by Baxalta now part of Shire: haemophilia A; blood coagulation disorders; coagulation protein disorder; hemophilia A; Acquired Hemophilia A; hematologic diseases; hemorrhagic disorders
• Additional relevant MeSH terms: Hemophilia A

Study Results

Participant Flow

Recruitment Details	Enrollment was conducted at 12 clinical sites in 4 countries (USA, Canada, UK, India). Eight sites enrolled subjects under Protocol OBI-1-301 only. Two US sites enrolled subjects under the expanded access protocol OBI-1-301a and subsequently under protocol OBI-1-301. Another 2 US sites enrolled subjects under OBI-1-301a only.
Pre-assignment Detail	29 subjects were enrolled and all were treated with OBI-1. Data from the expanded access subjects (Protocol 301a, n= 4) are included with the data from subjects enrolled under Protocol OBI-1-301 (n=25). 10 subjects discontinued prematurely and 18 completed the study. For one subject, the completion status could not be verified.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Period Title: Overall Study
STARTED	29
COMPLETED	18
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Overall Participants	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.8 (13.28)
Sex: Female, Male (Count of Participants)
Female	10 34.5%
Male	19 65.5%
Region of Enrollment (Count of Participants)
United States	16 55.2%
Canada	5 17.2%
United Kingdom	4 13.8%
India	4 13.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Serious Bleeding Episodes Responsive to OBI-1
Description	The initial serious ("qualifying") bleeding episode for each subject was analyzed for the primary efficacy outcome measure. A 'positive response' is defined as 'effective' (bleeding stopped with clinical control and FVIII levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' is defined as 'bleeding slightly reduced or unchanged and FVIII levels of less than 50%'. 'Not effective' is defined as 'bleeding worsening and FVIII levels of less than 50%'.
Time Frame	24 hours after initiation of treatment

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT) population = 29 subjects with initial serious bleeding episodes

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	29
Measure Initial Serious Bleeding Episodes	29
Number (95% Confidence Interval) [percentage of serious bleeding episodes]	100

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	OBI-1
	Comments	Summary statistics for the percentage of participants with serious bleeding episodes responsive at 24 hours after the initiation of treatment are presented, along with the 95% confidence interval (two-sided 95% Clopper-Pearson confidence interval).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	one-sided binomial exact test
	Comments

2. Secondary Outcome

Title	Overall Percentage of Serious Bleeding Episodes Successfully Controlled With OBI-1 Therapy, as Assessed by the Investigator
Description	Treatment success was defined as control of qualifying bleeding episode at the time of final treatment dosing. A serious bleeding episode was considered 'successfully controlled' if the investigator had checked 'completed OBI-1 therapy as treatment success' on the eCRF.
Time Frame	At the time of final treatment dosing (varied from participant to participant depending on bleeding episodes)

Outcome Measure Data

Analysis Population Description

ITT population = 29 subjects with initial serious bleeding episodes (BEs)

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	29
Measure Initial Serious Bleeding Episodes	29
Number (95% Confidence Interval) [percentage of serious bleeding episodes]	86.2

3. Secondary Outcome

Title	Percentage of Serious Bleeding Episodes Responsive to OBI-1 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator
Description	A 'positive response' is defined as 'effective' (bleeding stopped with clinical control and FVIII levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' is defined as 'bleeding slightly reduced or unchanged and FVIII levels of less than 50%'. 'Not effective' is defined as 'bleeding worsening and FVIII levels of less than 50%'.
Time Frame	8 hours

Outcome Measure Data

Analysis Population Description

21 subjects of the ITT population (n=29) had responses available at 8 hours after initial infusion of OBI-1.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	21
Measure Responses Available at 8 hrs	21
Number (95% Confidence Interval) [percentage of serious bleeding episodes]	95.2

4. Secondary Outcome

Title	Percentage of Serious Bleeding Episodes Responsive to OBI-1 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator
Description	A 'positive response' is defined as 'effective' (bleeding stopped with clinical control and FVIII levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' is defined as 'bleeding slightly reduced or unchanged and FVIII levels of less than 50%'. 'Not effective' is defined as 'bleeding worsening and FVIII levels of less than 50%'.
Time Frame	16 hours

Outcome Measure Data

Analysis Population Description

19 subjects of the ITT population (n=29) had responses available at 16 hours after initial infusion of OBI-1.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	19
Measure Responses Available at 16 hrs	19
Number (95% Confidence Interval) [percentage of serious bleeding episodes]	100

5. Secondary Outcome

Title	Frequency of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes
Description	'Frequency of infusions' was calculated as the 'average number of infusions per day'. 'Qualifying bleeding episode' was defined as the 'initial, serious bleeding episode'.
Time Frame	Time of successful control of qualifying bleeding episode (varied from participant to participant)

Outcome Measure Data

Analysis Population Description

The analysis was performed in 25 of 29 participants in the ITT population whose 'qualifying' bleeding episode was controlled successfully.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	25
Mean (Standard Deviation) [average number of infusions per day]	2.10 (1.109)

6. Secondary Outcome

Title	Total Dose of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes
Description	'Qualifying bleeding episode' was defined as the 'initial, serious bleeding episode'.
Time Frame	Time of successful control of qualifying bleeding episode (varied from participant to participant)

Outcome Measure Data

Analysis Population Description

The analysis was performed in 25 of 29 participants in the ITT population whose 'qualifying' bleeding episode was controlled successfully.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	25
Mean (Standard Deviation) [dose in U/kg]	2683.2 (2928.61)

7. Secondary Outcome

Title	Total Number of Infusions of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes
Description	'Qualifying bleeding episode' was defined as the 'initial, serious bleeding episode'. A serious bleeding episode was considered 'successfully controlled' if the investigator had checked 'completed OBI-1 therapy as treatment success' on the eCRF.
Time Frame	Time of successful control of qualifying bleeding episode (varied from participant to participant)

Outcome Measure Data

Analysis Population Description

The analysis was performed in 25 of 29 participants in the ITT population whose 'qualifying' bleeding episode was controlled successfully.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	25
Mean (Standard Deviation) [infusions per participant]	15.4 (12.64)

8. Secondary Outcome

Title	Correlation Between Positive Response to OBI-1 Therapy at 8 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Of 21 subjects in the ITT population (n=29) with responses available at 8 hours after initial infusion of OBI-1, 20 had a positive response.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	21
Number [subjects with eventual bleed control]	17

9. Secondary Outcome

Title	Correlation Between Response to OBI-1 Therapy at 16 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

All 19 subjects in the ITT population (n=29) who had responses available at 16 hours after initial infusion of OBI-1 had a positive response.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	19
Number [subjects with eventual bleed control]	17

10. Secondary Outcome

Title	Correlation Between Response to OBI-1 Therapy at Specified Time Points and Eventual Control of Serious Bleeding Episodes at 24 Hours
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

29 subjects (ITT population) had responses available at 24 hours after initial infusion of OBI-1.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	29
Number [participants with bleeds controlled]	25 86.2%

11. Secondary Outcome

Title	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	Through 90 days ± 7 days following final OBI-1 dose

Outcome Measure Data

Analysis Population Description

Because of expected sparseness of positive anti-OBI-1 antibody titers, formal statistical analyses of correlation were not performed.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	0

12. Secondary Outcome

Title	Pharmacokinetics (PK) Analysis- Plasma Clearance
Description	Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics.
Time Frame	Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours

Outcome Measure Data

Analysis Population Description

PK population (= all subjects in the ITT population who consent to PK draws and have factor VIII levels measured at the central reference laboratory)

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	5
Chromogenic FVIII activity assay	11.80 (13.44)
One-stage FVIII activity assay	18.07 (21.78)

13. Secondary Outcome

Title	PK Analysis- Volume of Distribution (Vd) at Steady State
Description	Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics.
Time Frame	Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	5
Chromogenic FVIII activity assay	53.8 (52.9)
One-stage FVIII activity assay	65.1 (45.1)

14. Secondary Outcome

Title	PK Analysis- Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Measurable Concentration
Description	Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics. AUC was calculated as area under the percent activity-time curve.
Time Frame	Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	5
Chromogenic FVIII activity assay	599 (459)
One-stage FVIII activity assay	423 (340)

15. Secondary Outcome

Title	PK Analysis- Terminal Half-life
Description	Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics. Half-life was calculated as the time it took to reduce percent activity by half.
Time Frame	Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	5
Chromogenic FVIII activity assay	3.3 (0.4)
One-stage FVIII activity assay	3.5 (1.0)

16. Secondary Outcome

Title	Number of Participants Who Developed de Novo Anti-OBI-1 Antibody Titers
Time Frame	Through 90 days ± 7 days following final OBI-1 dose

Outcome Measure Data

Analysis Population Description

28 eligible subjects with acquired hemophilia A in the ITT population (n=29), of whom 18 had no detectable anti-porcine FVIII inhibitor titers at baseline (<0.6 BU) and 10 had detectable anti-porcine FVIII antibody titers at baseline (>=0.6 BU)

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	28
Number [participants]	5 17.2%

17. Secondary Outcome

Title	Number of Participants Who Developed an Anti-host Cell Protein Baby Hamster Kidney (BHK) Antibody Titer
Time Frame	Through 90 days ± 7 days following final OBI-1 dose

Outcome Measure Data

Analysis Population Description

21 subjects in the ITT population (n=29) with available baseline and follow-up test results

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	21
Number [participants]	0 0%

18. Other Pre-specified Outcome

Title	Anti-human Factor VIII Antibody Titer
Time Frame	Through 90 days ± 7 days following final OBI-1 dose

Outcome Measure Data

Analysis Population Description

Anti-human factor VIII antibody titer data were presented in subject data listings. No statistical test was planned for anti-human factor VIII antibody titer.

Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Measure Participants	0

Adverse Events

Time Frame	Through 90 days ± 7 days following final OBI-1 dose
Adverse Event Reporting Description	Subjects were monitored for adverse events from the time the subject presented with the initial bleeding episode until the end of the follow-up period.
Arm/Group Title	OBI-1
Arm/Group Description	Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
All Cause Mortality
	OBI-1
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	OBI-1
	Affected / at Risk (%)	# Events
Total	13/29 (44.8%)
Cardiac disorders
Atrial fibrillation	1/29 (3.4%)	1
Gastrointestinal disorders
Esophagitis	1/29 (3.4%)	1
Gastrointestinal hemorrhage	1/29 (3.4%)	1
Intestinal hemorrhage	1/29 (3.4%)	1
General disorders
Asthenia	1/29 (3.4%)	1
Hepatobiliary disorders
Cholangitis	1/29 (3.4%)	1
Immune system disorders
Anaphylactic reaction	1/29 (3.4%)	1
Infections and infestations
Pneumonia	3/29 (10.3%)	3
Sepsis	2/29 (6.9%)	2
Systemic mycosis	1/29 (3.4%)	1
Urinary tract infection	1/29 (3.4%)	1
Injury, poisoning and procedural complications
Fall	1/29 (3.4%)	1
Tracheostomy malfunction	1/29 (3.4%)	1
Vascular pseudoaneurysm	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/29 (3.4%)	3
Joint swelling	1/29 (3.4%)	2
Hemarthrosis	1/29 (3.4%)	1
Nervous system disorders
Dizziness	1/29 (3.4%)	1
Brain edema	1/29 (3.4%)	1
Intracranial hemorrhage	2/29 (6.9%)	2
Transient ischemic attack	1/29 (3.4%)	1
Grand mal convulsion	1/29 (3.4%)	1
Renal and urinary disorders
Renal failure	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/29 (3.4%)	1
Vascular disorders
Hematoma	1/29 (3.4%)	2
Other (Not Including Serious) Adverse Events
	OBI-1
	Affected / at Risk (%)	# Events
Total	27/29 (93.1%)
Blood and lymphatic system disorders
Anemia	6/29 (20.7%)	6
Cardiac disorders
Cardiac failure congestive	2/29 (6.9%)	2
Gastrointestinal disorders
Abdominal pain	2/29 (6.9%)	3
Abdominal pain upper	2/29 (6.9%)	3
Constipation	12/29 (41.4%)	12
Diarrhea	7/29 (24.1%)	7
Mouth ulceration	2/29 (6.9%)	2
Nausea	4/29 (13.8%)	5
Vomiting	2/29 (6.9%)	2
General disorders
Chest pain	2/29 (6.9%)	2
Fatigue	2/29 (6.9%)	2
Peripheral edema	6/29 (20.7%)	7
Pyrexia	3/29 (10.3%)	5
Infections and infestations
Bacteremia	2/29 (6.9%)	2
Bacteriuria	2/29 (6.9%)	2
Candidiasis	3/29 (10.3%)	3
Sepsis	3/29 (10.3%)	3
Oral candidiasis	3/29 (10.3%)	3
Urinary tract infection	2/29 (6.9%)	2
Investigations
Antibody test positive	2/29 (6.9%)	2
Troponin I increased	2/29 (6.9%)	2
Metabolism and nutrition disorders
Decreased appetite	3/29 (10.3%)	3
Hypoglycemia	2/29 (6.9%)	2
Hypokalemia	7/29 (24.1%)	11
Hypomagnesemia	2/29 (6.9%)	2
Hypophosphatemia	2/29 (6.9%)	2
Musculoskeletal and connective tissue disorders
Muscle hemorrhage	2/29 (6.9%)	3
Pain in extremity	2/29 (6.9%)	2
Psychiatric disorders
Depression	2/29 (6.9%)	2
Insomnia	4/29 (13.8%)	6
Respiratory, thoracic and mediastinal disorders
Wheezing	2/29 (6.9%)	3
Skin and subcutaneous tissue disorders
Ecchymosis	3/29 (10.3%)	3
Pruritus	2/29 (6.9%)	2
Vascular disorders
Hypertension	3/29 (10.3%)	4
Hypotension	2/29 (6.9%)	2

Limitations/Caveats

Due to the low number of subjects available for evaluation, statistical tests could only be performed for the primary outcome measure. The results of all other outcome measures are descriptive.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

For this study, PIs are restricted from independently publishing results before completion of a single multicenter publication or one year after study completion, whichever occurs first. Baxter requires a review of results communications (eg, for confidential information) ≥30 days prior to submission or communication. Baxter may request an additional delay of ≤60 days (eg, if a patentable invention is disclosed).