<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02207894</url>
  </required_header>
  <id_info>
    <org_study_id>HZRM_ObsITI_4th Am.Version</org_study_id>
    <nct_id>NCT02207894</nct_id>
  </id_info>
  <brief_title>A Survey on the Success of Inhibitor Elimination Using Individualized Concentrate Selection and Controlled ITI</brief_title>
  <official_title>A Survey on the Success of Inhibitor Elimination Using Individualized Concentrate Selection and Controlled (High Dose) Immune Tolerance Induction (ITI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Haemophilia Centre Rhine Main</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Bonn</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Skane University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hopital Cardiologique Louis Pradel, Unité d'Hemostase Clinique Bron</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Haemophilia Centre Rhine Main</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research program is initiated to evaluate and document data on the success of ITI in 300&#xD;
      haemophilia A patients with newly developed or already existing FVIII-inhibitors (also&#xD;
      patients who might potentially have failed in earlier ITIs), which will be treated with ITI -&#xD;
      preferably high-dose based on individualized product selection, in order to improve&#xD;
      management of this potentially devastating complication of haemophilia treatment.&#xD;
&#xD;
      In order to investigate the role of in vitro tests on individual ITI success rate in patients&#xD;
      undergoing ITI, the inhibitor plasma samples can be assayed against different FVIII&#xD;
      concentrates using the following in vitro tests: Batch selection, Thrombin generation assay&#xD;
      (TGA), Thrombin Generation Test (TGT) to monitor FVIII efficacy, Epitope mapping,IgG&#xD;
      Subclasses specific for FVIII, Immunogenotyping.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As a result of many technological advances in the last two decades, current factor VIII&#xD;
      (FVIII) concentrates (both plasma-derived and recombinant products) are considered very safe&#xD;
      in terms of pathogen safety.&#xD;
&#xD;
      The development of inhibitors against FVIII or factor IX (FIX) is considered as a major&#xD;
      complication during replacement therapy of haemophiliacs.&#xD;
&#xD;
      Prospective studies of previously untreated patients (PUPs) have suggested that inhibitors&#xD;
      develop in up to 33% of patients with moderate to severe haemophilia A. Several strategies&#xD;
      are used to control bleedings in such patients, e.g. high-dose treatment with FVIII&#xD;
      concentrates, treatment with activated prothrombin complex concentrate (aPCC) or treatment&#xD;
      with activated factor VII (FVIIa).&#xD;
&#xD;
      Immune tolerance induction (ITI) in order to eradicate inhibitors in patients suffering from&#xD;
      an inhibitor to FVIII with high dose treatment of FVIII was first reported in 1977 by&#xD;
      Brackmann &amp; Gormsen in the so-called &quot;Bonn Protocol&quot; and was investigated from then on in a&#xD;
      series of clinical studies applying the same or a modified version of the &quot;Bonn Protocol&quot;.&#xD;
      During these investigations high dose FVIII treatment has been proven efficacious in inducing&#xD;
      immune tolerance and was shown to exert a long lasting effect in more than 80 % of the&#xD;
      patients treated.&#xD;
&#xD;
      The observational immune tolerance induction research program (ObsITI) will allow a&#xD;
      systematic prospective and retrospective data documentation and analysis on the success rate&#xD;
      of ITI by using individualized concentrate selection.&#xD;
&#xD;
      Pre-ITI-phase:&#xD;
&#xD;
      Aim of this evaluation is to assess current pre-ITI treatment strategies in inhibitor&#xD;
      patients from detection of inhibitor until start of ITI (early start vs. delayed start) and&#xD;
      the effect of pre-ITI treatment (prophylaxis and on-demand treatment in case of&#xD;
      bleeds/surgery) with bypassing agents (rFVIIa, NovoSeven®, aPCC, FEIBA®, emicizumab,&#xD;
      Hemlibra®) and / or FVIII on the titre at start of ITI, on the success rate of ITI, the&#xD;
      number of break-through bleeds and life-threatening bleeds.&#xD;
&#xD;
      ObsITI-Rescue ITI Study:&#xD;
&#xD;
      Patients who fail FVIII-stand-alone ITI or who are no candidates for FVIII-stand-alone ITI&#xD;
      and who are treated with ITI regimens including immunosuppressive agents can be included in&#xD;
      this sub-study. Aim of this study is to document ITI regimens including immunosuppressive&#xD;
      therapy (Rituximab, steroids, mycophenolate mofetil/MMF, sirolimus or other immunosuppressive&#xD;
      agents) combined with regular FVIII administration, potential drug related side effects,&#xD;
      outcome and duration of immune tolerance (relapse and recurrence of inhibitors).&#xD;
&#xD;
      Optional sub-studies:&#xD;
&#xD;
      In order to investigate the role of in vitro tests on individual ITI success rate in patients&#xD;
      undergoing ITI, the inhibitor plasma samples can be assayed against different FVIII&#xD;
      concentrates using the following in vitro tests:&#xD;
&#xD;
        1. Batch selection: The potential variation in inhibitor reactivity with different FVIII&#xD;
           concentrates/batches of the same concentrate can optionally be studied according to a&#xD;
           modified Oxford method (HZRM Hämophilie-Zentrum Rhein Main, Germany).&#xD;
&#xD;
        2. Thrombin generation assay (TGA): In this optional in vitro test the plasma samples from&#xD;
           an inhibitor patient can be spiked with different concentrates and the thrombin&#xD;
           generation will be measured using the TGA to evaluate the potential of different FVIII&#xD;
           concentrates to generate thrombin (Haemophilia Centre Malmö, Sweden).&#xD;
&#xD;
        3. Thrombin Generation Test (TGT): TGT will evaluate the correlation between clinical&#xD;
           bleeding phenotype of patients and their thrombin generation capacity before ITI in&#xD;
           order to predict the patients with the highest risk of bleeding. In vitro efficacy of&#xD;
           two FVIII doses (low and high) in the presence and absence of FEIBA® and emicizumab will&#xD;
           be evaluated (Louis Pradel Cardiology Hospital, Bron, France).&#xD;
&#xD;
        4. Epitope mapping / IgG Subclasses: The isotypic antibody epitopes on FVIII will be&#xD;
           identified in plasma samples from inhibitor patients. This will help to identify&#xD;
           relevant epitopes recognised by inhibitors in haemophilia A. This research program will&#xD;
           give an opportunity to comprehensively study various aspects of inhibitors and the&#xD;
           induction of immunetolerance in a relevant number of patients. Knowledge about relevant&#xD;
           epitopes from patient plasma rather than from model systems (i.e. monoclonal antibodies&#xD;
           or mouse models) will help to understand the immune response to FVIII and to develop&#xD;
           novel strategies to deplete inhibitors or inhibitor secreting B cells (Haemophilia&#xD;
           Centre, University Hospital Bonn, Germany). Plasma samples will also be tested for&#xD;
           IgG-subclasses specific for FVIII. Most inhibitors belong to the subclasses IgG1 and&#xD;
           IgG4. There are some indications that the ratio of IgG1 and IgG4 might influence ITI&#xD;
           outcome (Haemophilia Centre, University Hospital Bonn, Germany).&#xD;
&#xD;
        5. Immunogenotyping / HLA Genotyping: In addition, this study will investigate genetic risk&#xD;
           factors (gene defect responsible for haemophilia, HLA class II alleles, immune response&#xD;
           genes) as a potential variable with impact on course and outcome of ITI. Recently a&#xD;
           significantly higher inhibitor incidence has been found in patients (brothers) with&#xD;
           IL-10.G allele 134, TNFα - 308G&gt;A polymorphism within Hap and polymorphisms in the&#xD;
           CTLA-4-gene compared to those brothers without the above mentioned polymorphisms&#xD;
           (Haemophilia Centre, University Hospital Bonn, Germany).&#xD;
&#xD;
      If patients do not respond to FVIII stand-alone ITI and any immune modulating/&#xD;
      immunosuppressive agents are added to ITI,ITI courses can be followed up in the ObsITI-Rescue&#xD;
      ITI sub-study. Immunosuppressive therapy has to be documented as concomitant medication.&#xD;
      Follow up visits should be done in the same intervals as with stand-alone FVIII-ITI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>August 2006</start_date>
  <completion_date type="Anticipated">December 2027</completion_date>
  <primary_completion_date type="Anticipated">December 2026</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The efficacy of ITI, the primary endpoint of this observation, is defined according to the following criteria (The measure is a composite).: Inhibitor titre &lt;0.6 BU, Incremental recovery of FVIII in the normal range,Half-life of FVIII &gt; 7 hours.</measure>
    <time_frame>one year</time_frame>
    <description>The efficacy of ITI, the primary endpoint of this observation, is defined according to the following criteria (The measure is a composite):&#xD;
Inhibitor titre &lt;0.6 BU (at least 2 consecutive determinations)&#xD;
Incremental recovery of FVIII in the normal range (&gt; 80% of normal) with samples taken prior to and 15 or 30 minutes after FVIII treatment.&#xD;
Half-life of FVIII &gt; 7 hours (blood samples for FVIII determination should be taken prior to and 15 or 30 minutes, 1, 2, 4, 8 and either 12 or 24 hours after FVIII treatment.&#xD;
Complete Success:&#xD;
All three criteria above met.&#xD;
Partial Success:&#xD;
Two of the three criteria above met.&#xD;
Partial Response:&#xD;
One of the three criteria above met.&#xD;
Partial Failure of ITI-treatment:&#xD;
Inhibitor still present, but titre has decreased to &lt;5 BU.&#xD;
Complete Failure of ITI-treatment:&#xD;
None of the above mentioned criteria met, and the inhibitor titre is still ≥5 BU.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The following secondary endpoints will also be evaluated.The measure is a composite.</measure>
    <time_frame>one year</time_frame>
    <description>The following secondary endpoints will be evaluated:&#xD;
the success rates of the different types of products selected for ITI, especially those of pure and VWF-stabilized FVIII concentrates&#xD;
the maintenance in case of complete or partial ITI success&#xD;
the clinical relevance of the individual in vitro testing and batch selection, the selected type of concentrate will be correlated with the ITI success&#xD;
the adverse drug reactions and possibly ITI efficacy related events occurring during the ITI-treatment phase&#xD;
the compliance with the ITI-treatment regimen&#xD;
the time necessary to achieve complete or partial success of individualized ITI&#xD;
the impact of inhibitor titres at start of ITI and during the course of ITI, including the peak titre of the inhibitor&#xD;
the number of break-through bleeding events during the course of ITI-treatment.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Haemophilia A</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood, serum, white cells, plasma.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        all male patients with haemophilia A and inhibitor&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Based on the decision of the treating physicians in the participating centres, male&#xD;
             patients at any age suffering from severe (FVIII activity &lt; 1%), moderate (FVIII&#xD;
             activity &gt;1% - 5%), or mild (FVIII activity &gt; 5%) haemophilia A will be included into&#xD;
             this post marketing observation if relevant inhibitor levels (&gt; 0.6 BU) have been&#xD;
             detected, or - in case of an inhibitor level &lt;0.6 BU - with reduced recovery or&#xD;
             half-life of FVIII.&#xD;
&#xD;
          -  The observation is also open for patients who failed an earlier ITI attempt.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carmen Escuriola Ettingshausen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Director HZRM</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Carmen Escuriola Ettingshausen, MD</last_name>
    <phone>+4961059638909</phone>
    <email>carmen.escuriola@hzrm.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zeynep Gutowski, PhD</last_name>
    <phone>+4961059638954</phone>
    <email>zeynep.gutowski@hzrm.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Haemophilia centre Rhine Main (HZRM)</name>
      <address>
        <city>Mörfelden-Walldorf</city>
        <zip>64546</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carmen Escuriola Ettingshausen, MD</last_name>
      <phone>+4961059638909</phone>
      <email>carmen.escuriola@hzrm.de</email>
    </contact>
    <contact_backup>
      <last_name>Zeynep Gutowski, PhD</last_name>
      <phone>+4961059638954</phone>
      <email>zeynep.gutowski@hzrm.de</email>
    </contact_backup>
    <investigator>
      <last_name>Carmen Escuriola Ettingshausen, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.obsiti.de</url>
    <description>Click here for more information about this study:The Observational Immune Tolerance Induction (ObsITI) research program</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <last_update_submitted>March 2, 2023</last_update_submitted>
  <last_update_submitted_qc>March 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Haemophilia A, factor VIII, development of inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemophilia A</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02207894
org study id: HZRM_ObsITI_4th Am.Version
nct id: NCT02207894
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
This research program is initiated to evaluate and document data on the success of ITI in 300
      haemophilia A patients with newly developed or already existing FVIII-inhibitors (also
      patients who might potentially have failed in earlier ITIs), which will be treated with ITI -
      preferably high-dose based on individualized product selection, in order to improve
      management of this potentially devastating complication of haemophilia treatment.

      In order to investigate the role of in vitro tests on individual ITI success rate in patients
      undergoing ITI, the inhibitor plasma samples can be assayed against different FVIII
      concentrates using the following in vitro tests: Batch selection, Thrombin generation assay
      (TGA), Thrombin Generation Test (TGT) to monitor FVIII efficacy, Epitope mapping,IgG
      Subclasses specific for FVIII, Immunogenotyping.
As a result of many technological advances in the last two decades, current factor VIII
      (FVIII) concentrates (both plasma-derived and recombinant products) are considered very safe
      in terms of pathogen safety.

      The development of inhibitors against FVIII or factor IX (FIX) is considered as a major
      complication during replacement therapy of haemophiliacs.

      Prospective studies of previously untreated patients (PUPs) have suggested that inhibitors
      develop in up to 33% of patients with moderate to severe haemophilia A. Several strategies
      are used to control bleedings in such patients, e.g. high-dose treatment with FVIII
      concentrates, treatment with activated prothrombin complex concentrate (aPCC) or treatment
      with activated factor VII (FVIIa).

      Immune tolerance induction (ITI) in order to eradicate inhibitors in patients suffering from
      an inhibitor to FVIII with high dose treatment of FVIII was first reported in 1977 by
      Brackmann & Gormsen in the so-called "Bonn Protocol" and was investigated from then on in a
      series of clinical studies applying the same or a modified version of the "Bonn Protocol".
      During these investigations high dose FVIII treatment has been proven efficacious in inducing
      immune tolerance and was shown to exert a long lasting effect in more than 80 % of the
      patients treated.

      The observational immune tolerance induction research program (ObsITI) will allow a
      systematic prospective and retrospective data documentation and analysis on the success rate
      of ITI by using individualized concentrate selection.

      Pre-ITI-phase:

      Aim of this evaluation is to assess current pre-ITI treatment strategies in inhibitor
      patients from detection of inhibitor until start of ITI (early start vs. delayed start) and
      the effect of pre-ITI treatment (prophylaxis and on-demand treatment in case of
      bleeds/surgery) with bypassing agents (rFVIIa, NovoSeven®, aPCC, FEIBA®, emicizumab,
      Hemlibra®) and / or FVIII on the titre at start of ITI, on the success rate of ITI, the
      number of break-through bleeds and life-threatening bleeds.

      ObsITI-Rescue ITI Study:

      Patients who fail FVIII-stand-alone ITI or who are no candidates for FVIII-stand-alone ITI
      and who are treated with ITI regimens including immunosuppressive agents can be included in
      this sub-study. Aim of this study is to document ITI regimens including immunosuppressive
      therapy (Rituximab, steroids, mycophenolate mofetil/MMF, sirolimus or other immunosuppressive
      agents) combined with regular FVIII administration, potential drug related side effects,
      outcome and duration of immune tolerance (relapse and recurrence of inhibitors).

      Optional sub-studies:

      In order to investigate the role of in vitro tests on individual ITI success rate in patients
      undergoing ITI, the inhibitor plasma samples can be assayed against different FVIII
      concentrates using the following in vitro tests:

        1. Batch selection: The potential variation in inhibitor reactivity with different FVIII
           concentrates/batches of the same concentrate can optionally be studied according to a
           modified Oxford method (HZRM Hämophilie-Zentrum Rhein Main, Germany).

        2. Thrombin generation assay (TGA): In this optional in vitro test the plasma samples from
           an inhibitor patient can be spiked with different concentrates and the thrombin
           generation will be measured using the TGA to evaluate the potential of different FVIII
           concentrates to generate thrombin (Haemophilia Centre Malmö, Sweden).

        3. Thrombin Generation Test (TGT): TGT will evaluate the correlation between clinical
           bleeding phenotype of patients and their thrombin generation capacity before ITI in
           order to predict the patients with the highest risk of bleeding. In vitro efficacy of
           two FVIII doses (low and high) in the presence and absence of FEIBA® and emicizumab will
           be evaluated (Louis Pradel Cardiology Hospital, Bron, France).

        4. Epitope mapping / IgG Subclasses: The isotypic antibody epitopes on FVIII will be
           identified in plasma samples from inhibitor patients. This will help to identify
           relevant epitopes recognised by inhibitors in haemophilia A. This research program will
           give an opportunity to comprehensively study various aspects of inhibitors and the
           induction of immunetolerance in a relevant number of patients. Knowledge about relevant
           epitopes from patient plasma rather than from model systems (i.e. monoclonal antibodies
           or mouse models) will help to understand the immune response to FVIII and to develop
           novel strategies to deplete inhibitors or inhibitor secreting B cells (Haemophilia
           Centre, University Hospital Bonn, Germany). Plasma samples will also be tested for
           IgG-subclasses specific for FVIII. Most inhibitors belong to the subclasses IgG1 and
           IgG4. There are some indications that the ratio of IgG1 and IgG4 might influence ITI
           outcome (Haemophilia Centre, University Hospital Bonn, Germany).

        5. Immunogenotyping / HLA Genotyping: In addition, this study will investigate genetic risk
           factors (gene defect responsible for haemophilia, HLA class II alleles, immune response
           genes) as a potential variable with impact on course and outcome of ITI. Recently a
           significantly higher inhibitor incidence has been found in patients (brothers) with
           IL-10.G allele 134, TNFα - 308G>A polymorphism within Hap and polymorphisms in the
           CTLA-4-gene compared to those brothers without the above mentioned polymorphisms
           (Haemophilia Centre, University Hospital Bonn, Germany).

      If patients do not respond to FVIII stand-alone ITI and any immune modulating/
      immunosuppressive agents are added to ITI,ITI courses can be followed up in the ObsITI-Rescue
      ITI sub-study. Immunosuppressive therapy has to be documented as concomitant medication.
      Follow up visits should be done in the same intervals as with stand-alone FVIII-ITI.
observational model: Cohort
time perspective: Prospective
measure: The efficacy of ITI, the primary endpoint of this observation, is defined according to the following criteria (The measure is a composite).: Inhibitor titre <0.6 BU, Incremental recovery of FVIII in the normal range,Half-life of FVIII > 7 hours.
time frame: one year
description: The efficacy of ITI, the primary endpoint of this observation, is defined according to the following criteria (The measure is a composite):
Inhibitor titre <0.6 BU (at least 2 consecutive determinations)
Incremental recovery of FVIII in the normal range (> 80% of normal) with samples taken prior to and 15 or 30 minutes after FVIII treatment.
Half-life of FVIII > 7 hours (blood samples for FVIII determination should be taken prior to and 15 or 30 minutes, 1, 2, 4, 8 and either 12 or 24 hours after FVIII treatment.
Complete Success:
All three criteria above met.
Partial Success:
Two of the three criteria above met.
Partial Response:
One of the three criteria above met.
Partial Failure of ITI-treatment:
Inhibitor still present, but titre has decreased to <5 BU.
Complete Failure of ITI-treatment:
None of the above mentioned criteria met, and the inhibitor titre is still ≥5 BU.
measure: The following secondary endpoints will also be evaluated.The measure is a composite.
time frame: one year
description: The following secondary endpoints will be evaluated:
the success rates of the different types of products selected for ITI, especially those of pure and VWF-stabilized FVIII concentrates
the maintenance in case of complete or partial ITI success
the clinical relevance of the individual in vitro testing and batch selection, the selected type of concentrate will be correlated with the ITI success
the adverse drug reactions and possibly ITI efficacy related events occurring during the ITI-treatment phase
the compliance with the ITI-treatment regimen
the time necessary to achieve complete or partial success of individualized ITI
the impact of inhibitor titres at start of ITI and during the course of ITI, including the peak titre of the inhibitor
the number of break-through bleeding events during the course of ITI-treatment.
whole blood, serum, white cells, plasma.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Carmen Escuriola Ettingshausen, MD
role: Principal Investigator
affiliation: Director HZRM
last name: Carmen Escuriola Ettingshausen, MD
phone: +4961059638909
email: carmen.escuriola@hzrm.de
last name: Zeynep Gutowski, PhD
phone: +4961059638954
email: zeynep.gutowski@hzrm.de
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Germany
url: http://www.obsiti.de
description: Click here for more information about this study:The Observational Immune Tolerance Induction (ObsITI) research program
responsible party type: Sponsor
mesh term: Hemophilia A