Hemophilia APhase 4SIPPETNCT01064284
Survey of Inhibitors in Plasma-Product Exposed Toddlers
A Phase 4 study testing PLASMA DERIVED Factor VIII and Recombinant FVIII in people with Hemophilia A, run by Fondazione Angelo Bianchi Bonomi at 48 sites in 14 countries.
Trial summary
The primary objective of the study is to assess the immunogenicity of VWF/FVIII and of rFVIII concentrates by determining the frequency of inhibitor development in previously untreated patients (PUPs) or minimally blood component-treated (MBCTPs) in the first 50 EDs or in the first 3 years from enrollment, whichever… Read more about this study
- Who is it for?
- Ages 1 minute to 6 years, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- PLASMA DERIVED Factor VIII and Recombinant FVIII
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 303 participants
- Where
- 48 sitesin 14 countries
- Study dates
- Jan 2010to May 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 minute to 6 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Male subjects
- Any ethnicity
- Age <6 years
- Severe haemophilia A (FVIII:C <1%), as confirmed at enrolment by the central laboratory.
- o Those patients diagnosed locally as severe but subsequently found to have FVIII levels >= 1% on testing at the central laboratory will be separately recorded in the screening list.
- Previously untreated (0 EDs to any FVIII concentrates or blood products) or minimally treated (<5 EDs) with blood components, namely whole blood, fresh frozen plasma, packed red blood cells, platelets or cryoprecipitate.
Show all 10Show fewer
- o Patients not meeting these criteria will be separately recorded in the screening list.
- Negative inhibitor measurement at both local and central laboratory at screening
- Ability to comply with study requirements
- Signed informed consent of legal tutors o Patients who will not accept to enter into the study or to be randomized will be separately recorded.
Who cannot join
- Previous history of FVIII inhibitor
- Other congenital or acquired bleeding defects
- Plasma FVIII level >= 1%, as assayed at the central laboratory
- o Those patients originally diagnosed locally as severe but subsequently found to have FVIII levels ranging from 1% to 2% on testing at the central laboratory will be separately recorded in the screening list.
- Concomitant congenital or acquired immunodeficiency
- Concomitant treatment with systemic immunosuppressive drugs
- Concomitant treatment with any investigational drug
Trial locations and contacts
48 sites in 14 countries.
48 sites in 14 countries
United States10 sites
Hemophilia and Thrombosis CenterUniversity of Colorado Denver - Anschutz Aurora
Aurora, Colorado, 80045
Rush Hemophilia & Trombophilia Center - Rush University Medical Center
Chicago, Illinois, 60612
City of Hope National Medical Center
Duarte, California, 91010
MeritCare Roger Maris Cancer Center, Pediatric Oncology
Fargo, North Dakota, 58102
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Mississippi Medical Center, Division of pediatric Hematology/Oncology
Jackson, Mississippi, 39216
Children's Mercy Hospital
Kansas City, Missouri, 64108
Hemophilia Treatment Center of Las Vegas
Las Vegas, Nevada, 89109
Children's Hospital Los Angeles (CHLA)
Los Angeles, California, 90027
Louisiana Center for Bleeding and Clotting Disorders, Tulane University Medical Center
New Orleans, Louisiana, 70112
India10 sites
Centre for Blood Disorders
Chennai, 600017
St. John's Medical College & Hospital
Karnataka, 560034
Kasturba Medical College, Manipal University
Karnataka, 576 104
Karnataka Hemophilia Care and Hematology Research Center
Karnataka, 577004
Kerala Institute of Medical Science (KIMS)
Kerala, 695 029
Lokmanya TilakMunicipal Medical College &General Hospital - Sion
Mumbai, 400022
All India Institute of Medical Sciences Department of Haematology
New Delhi, 110029
Sir Ganga Ram Hospital
New Delhi, 110060
Sahyadri Speciality Hospital
Pune, 411 004
Jehangir Clinical Development Centre, Department of Haematology, Jehangir Hospital Premises
Pune, 411-001
Mexico5 sites
Unidad Medica de Alta Especialidad (UMAE), Hospital de Pediatria. Centro Medico Nacional de Occidente Istituto Mexicano del Seguro Social
Jalisco, 44340
Instituto Nacional de Pediatria
México D.F., 04530
Hospital Infantil de Mexico Federico Gomez
México, D.F., 06720
Hospital Universitario Dr. Josè Eleuterio Gonzalez de la UANL, NL. Mexico
Monterrey, 64450
Hospital de Especialidades UMAE Istituto Mexicano del Seguro Social (IMSS)
Monterrey (Nuevo Leòn), 64330
Italy3 sites
Centro Emofilia e Trombosi "Angelo Bianchi Bonomi" Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano - Italy
Milan, 20122
Clinica Medica II - Azienda Ospedaliera di Padova - Centro Emofilia di Padova
Padova, 35128
Ematologia- UO Diagnostica Speciale e Terapia delle Malattie dell'Emostasi e della Trombosi- Università Sapienza - Policlinico Umberto I
Rome, 00161
Spain3 sites
Hospital Regional Universitario Carlos Haya
Málaga, 29011
Hospital Universitario Virgen del Rocio Unidad de Hemofilia
Seville, 41013
Hospital Universitario La Fe Unidad Coagulopatias Congenitas
Valencia, 46009
Turkey (Türkiye)3 sites
Cukurova Universitesi, Tip Fakultesi Pediatrik Hematoloji B.D.
Adana, 01330
Ege Üniversitesi Tip Fakültesi Cocuk Sağliği ve Hastalikari Anabilim Dali Pediatrik Hematoloji Bilim Dali
Bornova/Izmir, 35100
Istanbul Üniversitesi Cerrahpaşa Tip Fakültesi Pediatrik Hematoloji B.D.
Istanbul, 34300
Argentina2 sites
Fundacion de la Hemofilia
Buenos Aires, 3483
Hospital de Ninos Sor Maria Ludovica La Plata Servicio de Hematologia
La Plata, Buenos Aires, 1900
Austria2 sites
Landes- Frauen- und Kinderklinik Linz Abteilung für Kinder- und Jugendheilkunde
Linz, 4020
Medizinische Universität Wien, Dept. Paediatrics
Vienna, 1090
Brazil2 sites
Centro de Pesquisa Clinica HEMORIO - Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti
Rio de Janeiro, 20.211-030
Centro de Hematologia e Hemoterapia do e.s - Hemoes
Vitória, 29047-100
Chile2 sites
Hospital de Niños Dr. Luis Calvo Mackenna Centro Hemofílico
Santiago, 7500539
Centro de Hemofilicos del Hospital de Niños Roberto del Rio Instituto de Investigaciones Hematologicas
Santiago, 838-0418
Egypt2 sites
Paediatric Haematology department, Cairo University Pediatric Hospital
Cairo, 11432
Faculty of Medicine Ain Shams University Department Pediatrics
Cairo, 11566
Iran2 sites
Hemophilia Center - Hematoogy & Oncology Dept. Shiraz University of Medical Science Ayatollah Dastgheib Hospital
Shiraz
Comprehensive Care Center for Children with Hemophilia Mofid Children Hospital
Tehran, 15468-15514
Saudi Arabia1 site
Kinf Faisal Specilist Hospital and Research Center
Riyadh, 11211
South Africa1 site
Haemophilia Comprehensive Care Clinic, Area 454, Charlotte Maxeke Johannesburg Academic Hospital
Parktown
About this study
Official title: Inhibitor Development in Previously Untreated Patients (PUPs) or Minimally Blood Component-Treated Patients (MBCTPs) When Exposed to Plasma-derived Von Willebrand Factor-Containing Factor VIII (VWF/FVIII) Concentrates and to Recombinant Factor VIII (rFVIII) Concentrates: An Independent, International, Multicentre, Prospective, Controlled, Randomised, Open Label, Clinical Trial
The primary objective of the study is to assess the immunogenicity of VWF/FVIII and of rFVIII concentrates by determining the frequency of inhibitor development in previously untreated patients (PUPs) or minimally blood component-treated (MBCTPs) in the first 50 EDs or in the first 3 years from enrollment, whichever occurs first.
.
Read the detailed description
Patients meeting the enrollment criteria will be consecutively enrolled at each participating centre, randomized to be treated exclusively with a single FVIII product either plasma-derived or recombinant, and followed up until inhibitor development or until 50 exposure days (EDs) or 3 years from enrolment have elapsed, whichever comes first. Study products, belonging to the class of rFVIII concentrates and to the class of plasma-derived VWF/FVIII concentrates, will be provided for free to the patients for all the duration of the study
- Conditions
- Hemophilia A
- Being tested
- PLASMA DERIVED Factor VIII, Recombinant FVIII
- Keywords
- Hemophilia A, Factor VIII inhibitors, vWF/FVIII, rFVIII
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PLASMA DERIVED Factor VIIIDrug
Also called ALPHANATE
Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding
Recombinant FVIIIDrug
Also called ADVATE
Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding
| Study group | Role | What they receive |
|---|---|---|
| PLASMA DERIVED Factor VIII | Active comparator | Plasma-derived vWF/FVIII Receives: Drug: PLASMA DERIVED Factor VIII |
| rFVIII | Active comparator | Recombinant FVIII Receives: Drug: Recombinant FVIII |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Assess the Immunogenicity of Plasma Derived VWF/FVIII and rFVIII Concentrates by Determining the Frequency of Inhibitor Development in the First 50 EDs or in the First 3 Years From Enrolment, Whichever Comes First in PUPs and MBCTs
Expressed with the numebr of patients for each group who developed FVIII inhibitors.
PUPs: Previously Untreated Patients MBCTPs: Minimally Blood Component-Treated Patients
Measured: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
Secondary outcomes (7)
To Evaluate the Anamnestic Response of Inhibitor Patients
Measured: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Frequency of Transient Inhibitors
Number of participants for each group who developed transient inhibitors (this means, those inhibitors which disappeared spontaneously within 6 months without immunotolerance treatment).
Measured: In the 6 months after inhibitor development
To Evaluate the Modality of Occurrence of Inhibitors (Number of EDs)
Number of EDs: Number of Exposure Days (EDs) after which the inhibitors develop
Measured: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Modality of Occurrence of Inhibitors (Titre at Onset)
Inhibitor Titre at Onset
Measured: During 6 months of observation, from the inhibitor occurrence
To Evaluate Clinical Factors Potentially Associated to Inhibitor Development
Measured: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate Laboratory Factors Potentially Associated to Inhibitor Development
Measured: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Incidence of All Other Adverse Events Related and Not Related to the Products Used
Measured: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2010 (estimated)
- Study startJan 2010
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 303 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Angelo Bianchi Bonomi
- Sponsor type
- University, hospital or other
- Collaborators
- Sintesi Research Srl
- Responsible party
- Sponsor
- Investigators
- Pier M. Mannucci, Professor, Principal investigator, Fondazione Ca' Granda Ospedale Maggiore Policlinico MilanoFlora Peyvandi, Professor, Principal investigator, Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01064284
- Sponsor's protocol ID
- ABB - 09 - 001
- Other IDs
- 2009-011186-88, 2009
- Acronym
- SIPPET
- Status last verified
- Jul 2017
- First submitted
- 4 Feb 2010
- Last updated
- 25 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Individual participant data (IPD) are available to other researchers through the publication of an article.
Publications
Addiego J, Kasper C, Abildgaard C, Hilgartner M, Lusher J, Glader B, Aledort L. Frequency of inhibitor development in haemophiliacs treated with low-purity factor VIII. Lancet. 1993 Aug 21;342(8869):462-4. doi: 10.1016/0140-6736(93)91593-b.
PubMed 8102429Amano K, Arai M, Koshihara K, Suzuki T, Kagawa K, Nishida Y, Fukutake K. Autoantibody to factor VIII that has less reactivity to factor VIII/von Willebrand factor complex. Am J Hematol. 1995 Aug;49(4):310-7. doi: 10.1002/ajh.2830490409.
PubMed 7639276Auerswald G, Spranger T, Brackmann HH. The role of plasma-derived factor VIII/von Willebrand factor concentrates in the treatment of hemophilia A patients. Haematologica. 2003 Jun;88(6):EREP05.
PubMed 12826531Chalmers EA, Brown SA, Keeling D, Liesner R, Richards M, Stirling D, Thomas A, Vidler V, Williams MD, Young D; Paediatric Working Party of UKHCDO. Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A. Haemophilia. 2007 Mar;13(2):149-55. doi: 10.1111/j.1365-2516.2006.01418.x.
PubMed 17286767Courter SG, Bedrosian CL. Clinical evaluation of B-domain deleted recombinant factor VIII in previously untreated patients. Semin Hematol. 2001 Apr;38(2 Suppl 4):52-9. doi: 10.1016/s0037-1963(01)90109-x.
PubMed 11449336Dasgupta S, Repesse Y, Bayry J, Navarrete AM, Wootla B, Delignat S, Irinopoulou T, Kamate C, Saint-Remy JM, Jacquemin M, Lenting PJ, Borel-Derlon A, Kaveri SV, Lacroix-Desmazes S. VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors. Blood. 2007 Jan 15;109(2):610-2. doi: 10.1182/blood-2006-05-022756. Epub 2006 Sep 19.
PubMed 16985172Ehrenforth S, Kreuz W, Scharrer I, Linde R, Funk M, Gungor T, Krackhardt B, Kornhuber B. Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. Lancet. 1992 Mar 7;339(8793):594-8. doi: 10.1016/0140-6736(92)90874-3.
PubMed 1347102Goudemand J, Rothschild C, Demiguel V, Vinciguerrat C, Lambert T, Chambost H, Borel-Derlon A, Claeyssens S, Laurian Y, Calvez T; FVIII-LFB and Recombinant FVIII study groups. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. Blood. 2006 Jan 1;107(1):46-51. doi: 10.1182/blood-2005-04-1371. Epub 2005 Sep 15.
PubMed 16166584Gouw SC, van der Bom JG, Auerswald G, Ettinghausen CE, Tedgard U, van den Berg HM. Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study. Blood. 2007 Jun 1;109(11):4693-7. doi: 10.1182/blood-2006-11-056317. Epub 2007 Jan 11.
PubMed 17218379Gringeri A, Mantovani LG, Scalone L, Mannucci PM; COCIS Study Group. Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group. Blood. 2003 Oct 1;102(7):2358-63. doi: 10.1182/blood-2003-03-0941. Epub 2003 Jun 19.
PubMed 12816859Gringeri A, Monzini M, Tagariello G, Scaraggi FA, Mannucci PM; Emoclot15 Study Members. Occurrence of inhibitors in previously untreated or minimally treated patients with haemophilia A after exposure to a plasma-derived solvent-detergent factor VIII concentrate. Haemophilia. 2006 Mar;12(2):128-32. doi: 10.1111/j.1365-2516.2006.01201.x.
PubMed 16476086Guerois C, Laurian Y, Rothschild C, Parquet-Gernez A, Duclos AM, Negrier C, Vicariot M, Fimbel B, Fressinaud E, Fiks-Sigaud M, et al. Incidence of factor VIII inhibitor development in severe hemophilia A patients treated only with one brand of highly purified plasma-derived concentrate. Thromb Haemost. 1995 Feb;73(2):215-8.
PubMed 7792732Kreuz W, Gill JC, Rothschild C, Manco-Johnson MJ, Lusher JM, Kellermann E, Gorina E, Larson PJ; International Kogenate-FS Study Group. Full-length sucrose-formulated recombinant factor VIII for treatment of previously untreated or minimally treated young children with severe haemophilia A: results of an international clinical investigation. Thromb Haemost. 2005 Mar;93(3):457-67. doi: 10.1160/TH03-10-0643.
PubMed 15735795Lorenzo JI, Lopez A, Altisent C, Aznar JA. Incidence of factor VIII inhibitors in severe haemophilia: the importance of patient age. Br J Haematol. 2001 Jun;113(3):600-3. doi: 10.1046/j.1365-2141.2001.02828.x.
PubMed 11380444Lusher JM, Arkin S, Abildgaard CF, Schwartz RS. Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. Safety, efficacy, and development of inhibitors. Kogenate Previously Untreated Patient Study Group. N Engl J Med. 1993 Feb 18;328(7):453-9. doi: 10.1056/NEJM199302183280701.
PubMed 8421474
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhibitor Development in Previously Untreated Patients (PUPs) or Minimally Blood Component-Treated Patients (MBCTPs) When Exposed to Plasma-derived Von Willebrand Factor-Containing Factor VIII (VWF/FVIII) Concentrates and to Recombinant Factor VIII (rFVIII) Concentrates: An Independent, International, Multicentre, Prospective, Controlled, Randomised, Open Label, Clinical Trial
- ClinicalTrials.gov ID
- NCT01064284
- Acronym / sponsor ID
- SIPPET / ABB - 09 - 001
- Conditions
- Hemophilia A
- Keywords
- Hemophilia A, Factor VIII inhibitors, vWF/FVIII, rFVIII
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 303 participants (actual)
- Lead sponsor
- Fondazione Angelo Bianchi BonomiUniversity, hospital or other
- Collaborators
- Sintesi Research Srl
- Study start
- Jan 2010
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 8 Feb 2010 (estimated)
- Results
- Posted 7 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to assess the immunogenicity of VWF/FVIII and of rFVIII concentrates by determining the frequency of inhibitor development in previously untreated patients (PUPs) or minimally blood component-treated (MBCTPs) in the first 50 EDs or in the first 3 years from enrollment, whichever occurs first.
.
Detailed description
Patients meeting the enrollment criteria will be consecutively enrolled at each participating centre, randomized to be treated exclusively with a single FVIII product either plasma-derived or recombinant, and followed up until inhibitor development or until 50 exposure days (EDs) or 3 years from enrolment have elapsed, whichever comes first. Study products, belonging to the class of rFVIII concentrates and to the class of plasma-derived VWF/FVIII concentrates, will be provided for free to the patients for all the duration of the study
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PLASMA DERIVED Factor VIII | Active comparator | Drug: PLASMA DERIVED Factor VIIIPlasma-derived vWF/FVIII |
| rFVIII | Active comparator | Drug: Recombinant FVIIIRecombinant FVIII |
Who may qualify
- Ages
- 1 minute to 6 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- Male subjects
- Any ethnicity
- Age <6 years
- Severe haemophilia A (FVIII:C <1%), as confirmed at enrolment by the central laboratory.
- o Those patients diagnosed locally as severe but subsequently found to have FVIII levels >= 1% on testing at the central laboratory will be separately recorded in the screening list.
Key exclusion criteria (7 listed)
- Previous history of FVIII inhibitor
- Other congenital or acquired bleeding defects
- Plasma FVIII level >= 1%, as assayed at the central laboratory
- o Those patients originally diagnosed locally as severe but subsequently found to have FVIII levels ranging from 1% to 2% on testing at the central laboratory will be separately recorded in the screening list.
- Concomitant congenital or acquired immunodeficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PLASMA DERIVED Factor VIIIAlso: ALPHANATEMaximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding | Drug | PLASMA DERIVED Factor VIII |
| Recombinant FVIIIAlso: ADVATEMaximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding | Drug | rFVIII |
Primary outcome
To Assess the Immunogenicity of Plasma Derived VWF/FVIII and rFVIII Concentrates by Determining the Frequency of Inhibitor Development in the First 50 EDs or in the First 3 Years From Enrolment, Whichever Comes First in PUPs and MBCTs
Time frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
Expressed with the numebr of patients for each group who developed FVIII inhibitors. PUPs: Previously Untreated Patients MBCTPs: Minimally Blood Component-Treated Patients
7 secondary outcomes
To Evaluate the Anamnestic Response of Inhibitor Patients
Time frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Frequency of Transient Inhibitors
Time frame: In the 6 months after inhibitor development
To Evaluate the Modality of Occurrence of Inhibitors (Number of EDs)
Time frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Modality of Occurrence of Inhibitors (Titre at Onset)
Time frame: During 6 months of observation, from the inhibitor occurrence
To Evaluate Clinical Factors Potentially Associated to Inhibitor Development
Time frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate Laboratory Factors Potentially Associated to Inhibitor Development
Time frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Incidence of All Other Adverse Events Related and Not Related to the Products Used
Time frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8102429Addiego J, Kasper C, Abildgaard C, Hilgartner M, Lusher J, Glader B, Aledort L. Frequency of inhibitor development in haemophiliacs treated with low-purity factor VIII. Lancet. 1993 Aug 21;342(8869):462-4. doi: 10.1016/0140-6736(93)91593-b.
- Background: PubMed 7639276Amano K, Arai M, Koshihara K, Suzuki T, Kagawa K, Nishida Y, Fukutake K. Autoantibody to factor VIII that has less reactivity to factor VIII/von Willebrand factor complex. Am J Hematol. 1995 Aug;49(4):310-7. doi: 10.1002/ajh.2830490409.
- Background: PubMed 12826531Auerswald G, Spranger T, Brackmann HH. The role of plasma-derived factor VIII/von Willebrand factor concentrates in the treatment of hemophilia A patients. Haematologica. 2003 Jun;88(6):EREP05.
- Background: PubMed 17286767Chalmers EA, Brown SA, Keeling D, Liesner R, Richards M, Stirling D, Thomas A, Vidler V, Williams MD, Young D; Paediatric Working Party of UKHCDO. Early factor VIII exposure and subsequent inhibitor development in children with severe haemophilia A. Haemophilia. 2007 Mar;13(2):149-55. doi: 10.1111/j.1365-2516.2006.01418.x.
- Background: PubMed 11449336Courter SG, Bedrosian CL. Clinical evaluation of B-domain deleted recombinant factor VIII in previously untreated patients. Semin Hematol. 2001 Apr;38(2 Suppl 4):52-9. doi: 10.1016/s0037-1963(01)90109-x.
- Background: PubMed 16985172Dasgupta S, Repesse Y, Bayry J, Navarrete AM, Wootla B, Delignat S, Irinopoulou T, Kamate C, Saint-Remy JM, Jacquemin M, Lenting PJ, Borel-Derlon A, Kaveri SV, Lacroix-Desmazes S. VWF protects FVIII from endocytosis by dendritic cells and subsequent presentation to immune effectors. Blood. 2007 Jan 15;109(2):610-2. doi: 10.1182/blood-2006-05-022756. Epub 2006 Sep 19.
- Background: PubMed 1347102Ehrenforth S, Kreuz W, Scharrer I, Linde R, Funk M, Gungor T, Krackhardt B, Kornhuber B. Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs. Lancet. 1992 Mar 7;339(8793):594-8. doi: 10.1016/0140-6736(92)90874-3.
- Background: PubMed 16166584Goudemand J, Rothschild C, Demiguel V, Vinciguerrat C, Lambert T, Chambost H, Borel-Derlon A, Claeyssens S, Laurian Y, Calvez T; FVIII-LFB and Recombinant FVIII study groups. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. Blood. 2006 Jan 1;107(1):46-51. doi: 10.1182/blood-2005-04-1371. Epub 2005 Sep 15.
- Background: PubMed 17218379Gouw SC, van der Bom JG, Auerswald G, Ettinghausen CE, Tedgard U, van den Berg HM. Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study. Blood. 2007 Jun 1;109(11):4693-7. doi: 10.1182/blood-2006-11-056317. Epub 2007 Jan 11.
- Background: PubMed 12816859Gringeri A, Mantovani LG, Scalone L, Mannucci PM; COCIS Study Group. Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group. Blood. 2003 Oct 1;102(7):2358-63. doi: 10.1182/blood-2003-03-0941. Epub 2003 Jun 19.
- Background: PubMed 16476086Gringeri A, Monzini M, Tagariello G, Scaraggi FA, Mannucci PM; Emoclot15 Study Members. Occurrence of inhibitors in previously untreated or minimally treated patients with haemophilia A after exposure to a plasma-derived solvent-detergent factor VIII concentrate. Haemophilia. 2006 Mar;12(2):128-32. doi: 10.1111/j.1365-2516.2006.01201.x.
- Background: PubMed 7792732Guerois C, Laurian Y, Rothschild C, Parquet-Gernez A, Duclos AM, Negrier C, Vicariot M, Fimbel B, Fressinaud E, Fiks-Sigaud M, et al. Incidence of factor VIII inhibitor development in severe hemophilia A patients treated only with one brand of highly purified plasma-derived concentrate. Thromb Haemost. 1995 Feb;73(2):215-8.
- Individual participant dataSharing planned: Yes. Individual participant data (IPD) are available to other researchers through the publication of an article.
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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pier M. Mannucci, Professor principal investigator
Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano
Flora Peyvandi, Professor principal investigator
Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano
48 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PLASMA DERIVED Factor VIII and Recombinant FVIII in people with Hemophilia A, run by Fondazione Angelo Bianchi Bonomi at 48 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States, India, Mexico, Italy, Spain and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To Assess the Immunogenicity of Plasma Derived VWF/FVIII and rFVIII Concentrates by Determining the Frequency of Inhibitor Development in the First 50 EDs or in the First 3 Years From Enrolment, Whichever Comes First in PUPs and MBCTs (time frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01064284, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2017.