Study of a new factor VIII replacement for patients with acquired hemophilia A

• Register: EUCTR
• Last refreshed on: 10 November 2014
• Main ID: EUCTR2011-000181-34-SE
• Date of registration: 07/02/2012
• Prospective Registration: Yes
• Primary sponsor: Baxter Innovations GmbH
• Public title: Study of a new factor VIII replacement for patients with acquired hemophilia A
• Scientific 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
• Date of first enrolment: 10/05/2012
• Target sample size: 28
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000181-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Canada, Germany, Hungary, India, Italy, Sweden, United Kingdom, United States

Contacts

• Name: Guido Wuerth, Clinical Operations
• Affiliation: Baxter Innovations GmbH

• Name: Guido Wuerth, Clinical Operations
• Affiliation: Baxter Innovations GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males or females =18 years of age.
2. Written informed consent from subject, trusted person or person who is legally authorized to sign on behalf of the subject (Legal representative in U.S.), depending on local regulations.
3. Subjects with acquired hemophilia with autoimmune inhibitors to human factor VIII with a clinical diagnosis established by the following criteria:
a) Prolonged activated partial thromboplastin time (aPTT)
b) Prothrombin time (PT) =ULN + 2 seconds and platelet count within normal range
c) Abnormal aPTT mixing study (patient normal control 1:1) consistent with a factor VIII inhibitor
d) Reduced factor VIII activity level (below 10%)
4. Has a serious bleeding episode, as documented by the investigator.
5. Be willing and able to follow all instructions and attend all study visits.
6. Subjects taking antithrombotics (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.
7. Life expectancy of at least 90 days prior to the onset of the bleeding episode.
8. Subjects of reproductive age will be required to use acceptable methods of birth control and, if female, undergo pregnancy testing as part of the screening process.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion criteria:
1. Hemodynamically unstable after blood transfusion, fluid resuscitation and pharmacologic or volume replacement pressor therapy.
2. Has an established reason for bleeding that is not correctable.
3. Bleeding episode assessed likely to resolve on its own if left untreated.
4. Anti-OBI-1 inhibitor that exceeds 20 BU (prospectively or retrospectively).
5. 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.
6. Prior history of bleeding disorder other than acquired hemophilia.
7. 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®).
8. Use of hemophilia medication: rFVIIa within 3 hours prior to OBI-1 administration, or aPCC treatment within 6 hours prior to OBI-1 administration.
9. Participation in any other clinical study within 30 days of the first OBI-1 treatment.
10. 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.
11. Is currently pregnant, or breastfeeding or planning to become pregnant or father a child during the study.
12. 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.
13. Inability or unwillingness to comply with the study design, protocol requirements, or the follow-up procedures.
14. Patient of majority age under legal protection.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acquired Haemophilia A
MedDRA version: 16.0 Level: LLT Classification code 10053761 Term: Acquired hemophilia with anti FVIII, XI, or XIII System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

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
Concentration unit: U unit(s)
Concentration type: range
Concentration number: 350-650

Primary Outcome(s)

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.

Secondary Objective: 1)To determine the proportion of serious bleeding episodes controlled with OBI-1.
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 all serious bleeding episodes.
4)To assess the correlation between response to anti-OBI-1 therapy at specified assessment time points and eventual control of serious bleeding episodes.
5)To assess the correlation between the preinfusion anti-OBI-1 inhibitor titer, the total dose of OBI-1, the outcome at 24 hours and the eventual control of the bleeding episode.
6)To assess the anti-OBI-1 inhibitor level preinfusion, at specified time points during treatment, and at 90 days post final infusion.
7)To evaluate the safety of OBI-1.
8)To assess drug exposure using extensive(non-bleeding state) or sparse sampling(bleeding state), and a population PK approach with sparse data in subjects treated with OBI-1.

Main Objective: Main objectives:
To evaluate the efficacy of OBI-1 for the treatment of serious bleeding episodes in subjects with acquired hemophilia with autoimmune inhibitors to human factor VIII.

Timepoint(s) of evaluation of this end point: At 24 hours

Secondary Outcome(s)

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) Drug exposure will be determined by means of population PK analysis for the sparse (bleeding state data) and compartmental analysis for the complete (non-bleeding) data. At least the following PK parameters will be estimated: Cl, Vd, area under the concentration-time curve (AUC) and Cmax/Dose.

Safety endpoints:
1) TEAEs and serious adverse events (SAEs) throughout the study.
2) Biochemistry, hematology, urinalyses and vital signs.
3) Anti-human factor VIII antibody titer.
4) Anti-OBI-1 antibody titer.
5) Anti-host cell protein (BHK) antibody titer.

Timepoint(s) of evaluation of this end point: Efficacy:
1)-5)Each dose or q8h to 24h;24h;each dose or q12h from 24- 120h;each dose or q24h thereafter until last OBI-1 dose or withdrawal.
6)screening; 10-20min;each dose or q8h to 24h;24h;each dose or q12h from 24-120h;each dose or q24h thereafter until last OBI-1 dose or withdrawal;optional:last OBI-1 dose
Safety:
1)Ongoing basis throughout study including follow-up
2)Vital signs:screening;10-20min after end of first dose; each dose or q8h up to 24h;24h;each dose or q12h from 24h-120h;each dose or q24h thereafter until last OBI-1 dose or withdrawal;follow-up
Analyses:screening;at each dose or q8h to 24h;24h;follow-up
3)-4)Screening;q5 days during treatment;follow-up
5)Screening;follow-up

Secondary ID(s)

NCT01178294

OBI-1-301

2011-000181-34-GB

Source(s) of Monetary Support

Baxter Innovations GmbH