Severe Hemophilia ARESIST EXPNCT01051076
Rescue Immunotolerance Study in Induction of Immune Tolerance (ITI)-Experienced Patients (RES.I.S.T. Experienced)
A study testing VWF/FVIII concentrates in people with Severe Hemophilia A, run by City of Hope Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to evaluate whether a concentrate containing both FVIII and von Willebrand Factor (VWF) given at a high dose will induce immune tolerance in subjects who have already experienced and failed ITI with VWF-free FVIII concentrates. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Severe Hemophilia A
- What is being tested?
- VWF/FVIII concentrates
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Nov 2009to 21 Oct 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- severe hemophilia A (FVIII<1%) with high responding inhibitors (peak levels >5 BU)
- male, any age;
- any inhibitor level at study enrollment;
- ability and willingness to participate to the study;
- previous ITI course of at least 9 months with a VWF-free FVIII concentrate at any dosage, such as recombinant FVIII and/or monoclonally purified FVIII.
Who cannot join
- concomitant systemic treatment with immunosuppressive drugs;
- concomitant experimental treatment;
- previous history of myocardial infarction and/or cerebral stroke
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: Immune Tolerance Induction Study in Patients With Severe Type A Haemophilia With Inhibitor After Failure of a Previous Induction of Immune Tolerance With FVII Concentrates Without Von Willebrand Factor Rescue
The purpose of this study is to evaluate whether a concentrate containing both FVIII and von Willebrand Factor (VWF) given at a high dose will induce immune tolerance in subjects who have already experienced and failed ITI with VWF-free FVIII concentrates. The treatment on this study is expected to last up to 33 months.
Read the detailed description
The presence of Factor VIII (FVIII) inhibitor prevents FVIII infusions from working properly and makes treatment of bleeding episodes very difficult. Having an inhibitor is a serious and life-threatening complication in patients with Hemophilia. The usual treatment of patients with FVIII inhibitors involves what is called "immune tolerance induction" (ITI). Immune Tolerance means that the body can accept infused FVIII and that FVIII is again effective in controlling bleeds. ITI involves giving high doses of FVIII regularly until the inhibitor disappears. This treatment is not always effective. The inhibitor persists in about 1 in 5 patients who undergo ITI.
There are 2 types of FVIII concentrates: FVIII concentrates derived from human plasma, which contain VWF, and concentrates of FVIII without VWF. Both types of concentrates are commonly used to induce immune tolerance in patients with Hemophilia A. Retrospective studies on subjects who were treated with VWF containing Factor VIII concentrates after failing ITI with pure factor VIII concentrates, have shown that tolerance can be achieved in a large percentage of patients. This study will access prospectively whether treatment with a FVIII concentrate containing VWF given at a high dose (200 units per kilogram) daily for up to 33 months is able to induce immune tolerance after previous attempts with concentrates containing only FVIII have failed.
- Conditions
- Severe Hemophilia A
- Being tested
- VWF/FVIII concentrates
- Keywords
- ITI, Haemophilia A, Inhibitors, Failed ITI, VWF/FVIII concentrates
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VWF/FVIII concentratesDrug
Also called Koate-DVI, Emoclot DI, Factane, 8Y
200 IU/Kg by one or two bolus injections daily. After successful confirmation the dose will be tailed off progressively until discontinuation. Patients will be treated with a VWF/FVIII concentrates according to physician/patients preference.
| Study group | Role | What they receive |
|---|---|---|
| Factor VIII and von Willebrand Factor | Experimental | Not described Receives: Drug: VWF/FVIII concentrates |
What is being measured
The primary outcome is the main question the study is designed to answer.
Achievement of an inhibitor titer of <0.6 BU/failure to achieve an inhibitor titer of <0.6 BU within 33 months, or failure to decrease inhibitor titer by at least 20% compared to titer in prior 6 months, beginning at 3 months after starting ITI
Primary end point is the achievement of an inhibitor titer of less than 0.6 BU or failure to achieve an inhibitor titer of less than 0.6 BU within 33 months of treatment, or failure to decrease the inhibitor titer by at least 20% compared to the titer in the prior 6 months, beginning at 3 months after starting ITI
Measured: 3 years
Secondary outcomes (3)
Time to achieve success- either partial or complete.
Measured: 33 months
Safety - assessment of adverse events through treatment and compliance with prolonged regimen.
Includes assessment and evaluation of adverse events occurring through treatment and compliance with a lengthy regimen
Measured: 33 months
Cost of care.
Direct cost will be calculated
Measured: Up to 45 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2010 (estimated)
- Study start3 Nov 2009
- Primary completion21 Oct 2020
- Study completion21 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Severe Hemophilia AStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Charta Foundation, Grifols Biologicals, LLC, CSL Behring, Biotest Pharmaceuticals Corporation, Grifols Therapeutics LLC
- Responsible party
- Sponsor
- Investigators
- Nadia P. Ewing, MD, Principal investigator, Clinical Professor of Pediatrics, City of Hope National Medical Center, Dept. of Pediatrics, 1500 E. Duarte Rd. Duarte, CA 91010
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01051076
- Sponsor's protocol ID
- 06200
- Other IDs
- 2008-007019-33, 2008
- Acronym
- RESIST EXP
- Status last verified
- Dec 2020
- First submitted
- 15 Jan 2010
- Last updated
- 23 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Berntorp E, Ekman M, Gunnarsson M, Nilsson IM. Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations. Haemophilia. 1996 Apr;2(2):95-9. doi: 10.1111/j.1365-2516.1996.tb00022.x.
PubMed 27214015Kreuz W, Steiner J, Auerswald G, Beeg T, Becker S. Successful immunetolerance therapy of FVIII-inhibitor in chldren after changing from high to intermediate purity FVIII concentrate. Ann Hematol 1996; 72 (suppl 1).
Gringeri A, Musso R, Mazzucconi MG, Piseddu G, Schiavoni M, Pignoloni P, Mannucci PM; RITS-FITNHES Study Group. Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response. Haemophilia. 2007 Jul;13(4):373-9. doi: 10.1111/j.1365-2516.2007.01484.x.
PubMed 17610550
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Tolerance Induction Study in Patients With Severe Type A Haemophilia With Inhibitor After Failure of a Previous Induction of Immune Tolerance With FVII Concentrates Without Von Willebrand Factor Rescue
- ClinicalTrials.gov ID
- NCT01051076
- Acronym / sponsor ID
- RESIST EXP / 06200
- Conditions
- Severe Hemophilia A
- Keywords
- ITI, Haemophilia A, Inhibitors, Failed ITI, VWF/FVIII concentrates
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- Charta Foundation, Grifols Biologicals, LLC, CSL Behring, Biotest Pharmaceuticals Corporation, Grifols Therapeutics LLC
- Study start
- 3 Nov 2009 (actual)
- Primary completion
- 21 Oct 2020 (actual)
- Study completion
- 21 Oct 2020 (actual)
- First posted
- 18 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate whether a concentrate containing both FVIII and von Willebrand Factor (VWF) given at a high dose will induce immune tolerance in subjects who have already experienced and failed ITI with VWF-free FVIII concentrates. The treatment on this study is expected to last up to 33 months.
Detailed description
The presence of Factor VIII (FVIII) inhibitor prevents FVIII infusions from working properly and makes treatment of bleeding episodes very difficult. Having an inhibitor is a serious and life-threatening complication in patients with Hemophilia. The usual treatment of patients with FVIII inhibitors involves what is called "immune tolerance induction" (ITI). Immune Tolerance means that the body can accept infused FVIII and that FVIII is again effective in controlling bleeds. ITI involves giving high doses of FVIII regularly until the inhibitor disappears. This treatment is not always effective. The inhibitor persists in about 1 in 5 patients who undergo ITI.
There are 2 types of FVIII concentrates: FVIII concentrates derived from human plasma, which contain VWF, and concentrates of FVIII without VWF. Both types of concentrates are commonly used to induce immune tolerance in patients with Hemophilia A. Retrospective studies on subjects who were treated with VWF containing Factor VIII concentrates after failing ITI with pure factor VIII concentrates, have shown that tolerance can be achieved in a large percentage of patients. This study will access prospectively whether treatment with a FVIII concentrate containing VWF given at a high dose (200 units per kilogram) daily for up to 33 months is able to induce immune tolerance after previous attempts with concentrates containing only FVIII have failed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Factor VIII and von Willebrand Factor | Experimental | Drug: VWF/FVIII concentrates |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- severe hemophilia A (FVIII<1%) with high responding inhibitors (peak levels >5 BU)
- male, any age;
- any inhibitor level at study enrollment;
- ability and willingness to participate to the study;
- previous ITI course of at least 9 months with a VWF-free FVIII concentrate at any dosage, such as recombinant FVIII and/or monoclonally purified FVIII.
Key exclusion criteria (3 listed)
- concomitant systemic treatment with immunosuppressive drugs;
- concomitant experimental treatment;
- previous history of myocardial infarction and/or cerebral stroke
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 |
|---|---|---|
| VWF/FVIII concentratesAlso: Koate-DVI, Emoclot DI, Factane, 8Y200 IU/Kg by one or two bolus injections daily. After successful confirmation the dose will be tailed off progressively until discontinuation. Patients will be treated with a VWF/FVIII concentrates according to physician/patients preference. | Drug | Factor VIII and von Willebrand Factor |
Primary outcome
Achievement of an inhibitor titer of <0.6 BU/failure to achieve an inhibitor titer of <0.6 BU within 33 months, or failure to decrease inhibitor titer by at least 20% compared to titer in prior 6 months, beginning at 3 months after starting ITI
Time frame: 3 years
Primary end point is the achievement of an inhibitor titer of less than 0.6 BU or failure to achieve an inhibitor titer of less than 0.6 BU within 33 months of treatment, or failure to decrease the inhibitor titer by at least 20% compared to the titer in the prior 6 months, beginning at 3 months after starting ITI
3 secondary outcomes
Time to achieve success- either partial or complete.
Time frame: 33 months
Safety - assessment of adverse events through treatment and compliance with prolonged regimen.
Time frame: 33 months
Cost of care.
Time frame: Up to 45 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2021.
- Background: PubMed 27214015Berntorp E, Ekman M, Gunnarsson M, Nilsson IM. Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations. Haemophilia. 1996 Apr;2(2):95-9. doi: 10.1111/j.1365-2516.1996.tb00022.x.
- BackgroundKreuz W, Steiner J, Auerswald G, Beeg T, Becker S. Successful immunetolerance therapy of FVIII-inhibitor in chldren after changing from high to intermediate purity FVIII concentrate. Ann Hematol 1996; 72 (suppl 1).
- Background: PubMed 17610550Gringeri A, Musso R, Mazzucconi MG, Piseddu G, Schiavoni M, Pignoloni P, Mannucci PM; RITS-FITNHES Study Group. Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response. Haemophilia. 2007 Jul;13(4):373-9. doi: 10.1111/j.1365-2516.2007.01484.x.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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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.
Nadia P. Ewing, MD principal investigator
Clinical Professor of Pediatrics, City of Hope National Medical Center, Dept. of Pediatrics, 1500 E. Duarte Rd. Duarte, CA 91010
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing VWF/FVIII concentrates in people with Severe Hemophilia A, run by City of Hope Medical Center at 1 site in United States.
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 5 inclusion and 3 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 23 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Achievement of an inhibitor titer of <0.6 BU/failure to achieve an inhibitor titer of <0.6 BU within 33 months, or failure to decrease inhibitor titer by at least 20% compared to titer in prior 6 months, beginning at 3 months after starting ITI (time frame: 3 years). 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 NCT01051076, which also lists 3 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 23 Aug 2021.