Severe Hemophilia ARESIST NAIVENCT01051544
Study of First TIME Immunotolerance Induction in Severe Hemophilia A Patients With Inhibitor at High Risk of Failure: Comparison With FVIII Concentrates With or Without Von Willebrand Factor - RES.I.S.T. Naive
A study testing FVIII Concentrates and FVIII/VWF concentrates in people with Severe Hemophilia A, run by City of Hope Medical Center.
Trial summary
This is a prospective, controlled, randomized, open label study, aimed at comparing FVIII/VWF concentrates with FVIII concentrates at 200 IU/kg daily in their ability to induce immune tolerance in Haemophilia A patients with high responding inhibitors and poor prognosis for success. 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?
- FVIII Concentrates and FVIII/VWF concentrates
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 25 Sep 2009to 25 Jun 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%);
- male, any age;
- high responders (peak inhibitor levels > 5 BU);
- any inhibitor level at study enrolment;
- ability and willingness to participate in the study;
- at least one of the following risk factors for ITI failure:
Show all 11Show fewer
- peak inhibitor titer > 200 BU
- titer at ITI start > 10 BU
- age > 7 years
- time between inhibitor occurrence and ITI > 2 years
- absence of high risk of cardiovascular, cerebrovascular or other thromboembolic events as deemed by the treating clinician.
Who cannot join
- concomitant systemic treatment with immunosuppressive drugs;
- concomitant experimental treatment;
- previous ITI attempt;
- previous history of myocardial infarction and/or cerebral stroke.
About this study
Official title: Randomised Study of First TIME Immunotolerance Induction in Patients With Severe Type A Haemophilia With Inhibitor at High Risk of Failure: Comparison of Induction of Immune Tolerance With FVIII Concentrates With or Without Von Willebrand Factor Acronym: RES.I.S.T.- Naive
This is a prospective, controlled, randomized, open label study, aimed at comparing FVIII/VWF concentrates with FVIII concentrates at 200 IU/kg daily in their ability to induce immune tolerance in Haemophilia A patients with high responding inhibitors and poor prognosis for success.
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 "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 the von Willebrand factor, and concentrates of FVIII without VWF (recombinant or plasma derived). Both types of concentrates are commonly used to induce immune tolerance in patients with Hemophilia A. Retrospective studies in subjects with hemophilia and inhibitors at risk for failing ITI, have indicated a higher rate of success if patients were treated with von Willebrand containing factor VIII concentrates. It is not known whether the addition of Von Willebrand factor offers an advantage to achieving immune tolerance.
- Conditions
- Severe Hemophilia A
- Being tested
- FVIII Concentrates, FVIII/VWF concentrates
- Keywords
- ITI, HAEMOPHILIA A, INHIBITORS, 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.
FVIII ConcentratesDrug
Also called Including but not limited to:, Advate, Beriate P, Hemofil M
Patients will be centrally randomized to receive a von Willebrand factor-free FVIII concentrate (recombinant or plasma-derived, monoclonally-purified). The choice of product brand will be based on physician / patients preferences.
FVIII/VWF concentratesDrug
Also called Including but not limited to:, Koate-DVI, 8Y, Optivate
Patients will be centrally randomized to receive a FVIII/VWF concentrate of 200 IU/Kg by one or two bolus injections daily.The choice of product brand will be based on physician / patients preferences.
| Study group | Role | What they receive |
|---|---|---|
| von Willebrand factor-free FVIII concentrates | Active comparator | Patients treated with FVIII concentrates Receives: Drug: FVIII Concentrates |
| FVIII/VWF concentrates | Active comparator | Patients treated with FVIII/VWF concentrates Receives: Drug: FVIII/VWF concentrates |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary end point is the success in inducing immune tolerance, defined as: the abolition of the inhibitor to < 0.6 BU within 33 months of ITI with a factor VIII recovery ≥ 66% and half-life ≥ 6 hrs, and measured after a 72-hour washout period.
Measured: 33 months
Secondary outcomes (4)
Absence of relapse, up to 12 months after achievement of Immune Tolerance
Measured: 12 months
Time to achieve partial or complete success as defined in the protocol.
Measured: 33 months
Safety Compliance to treatment
Measured: 33 months
Cost of Care
Measured: 12 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 start25 Sep 2009
- Primary completion25 Jun 2020
- Study completion25 Jun 2020
Why it stopped: complete per PI
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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 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
- NCT01051544
- Sponsor's protocol ID
- 06201
- Other IDs
- 2008-007016-15, 2008
- Acronym
- RESIST NAIVE
- Status last verified
- Dec 2020
- First submitted
- 15 Jan 2010
- Last updated
- 17 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
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 27214015Kreutz W: Immune tolerance induction (ITI) in Haemophilia A-patients with inhibitors - the choice of concentrate affecting success. Haematologica2001; 86 (S4):16-20
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 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Study of First TIME Immunotolerance Induction in Patients With Severe Type A Haemophilia With Inhibitor at High Risk of Failure: Comparison of Induction of Immune Tolerance With FVIII Concentrates With or Without Von Willebrand Factor Acronym: RES.I.S.T.- Naive
- ClinicalTrials.gov ID
- NCT01051544
- Acronym / sponsor ID
- RESIST NAIVE / 06201
- Conditions
- Severe Hemophilia A
- Keywords
- ITI, HAEMOPHILIA A, INHIBITORS, VWF/FVIII Concentrates
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: complete per PI
- Enrolment
- 0 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
- 25 Sep 2009 (actual)
- Primary completion
- 25 Jun 2020 (actual)
- Study completion
- 25 Jun 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.
This is a prospective, controlled, randomized, open label study, aimed at comparing FVIII/VWF concentrates with FVIII concentrates at 200 IU/kg daily in their ability to induce immune tolerance in Haemophilia A patients with high responding inhibitors and poor prognosis for success.
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 "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 the von Willebrand factor, and concentrates of FVIII without VWF (recombinant or plasma derived). Both types of concentrates are commonly used to induce immune tolerance in patients with Hemophilia A. Retrospective studies in subjects with hemophilia and inhibitors at risk for failing ITI, have indicated a higher rate of success if patients were treated with von Willebrand containing factor VIII concentrates. It is not known whether the addition of Von Willebrand factor offers an advantage to achieving immune tolerance.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| von Willebrand factor-free FVIII concentrates | Active comparator | Drug: FVIII ConcentratesPatients treated with FVIII concentrates |
| FVIII/VWF concentrates | Active comparator | Drug: FVIII/VWF concentratesPatients treated with FVIII/VWF concentrates |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- severe hemophilia A (FVIII<1%);
- male, any age;
- high responders (peak inhibitor levels > 5 BU);
- any inhibitor level at study enrolment;
- ability and willingness to participate in the study;
Key exclusion criteria (4 listed)
- concomitant systemic treatment with immunosuppressive drugs;
- concomitant experimental treatment;
- previous ITI attempt;
- 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 |
|---|---|---|
| FVIII ConcentratesAlso: Including but not limited to:, Advate, Beriate P, Hemofil MPatients will be centrally randomized to receive a von Willebrand factor-free FVIII concentrate (recombinant or plasma-derived, monoclonally-purified). The choice of product brand will be based on physician / patients preferences. | Drug | von Willebrand factor-free FVIII concentrates |
| FVIII/VWF concentratesAlso: Including but not limited to:, Koate-DVI, 8Y, OptivatePatients will be centrally randomized to receive a FVIII/VWF concentrate of 200 IU/Kg by one or two bolus injections daily.The choice of product brand will be based on physician / patients preferences. | Drug | FVIII/VWF concentrates |
Primary outcome
Primary end point is the success in inducing immune tolerance, defined as: the abolition of the inhibitor to < 0.6 BU within 33 months of ITI with a factor VIII recovery ≥ 66% and half-life ≥ 6 hrs, and measured after a 72-hour washout period.
Time frame: 33 months
4 secondary outcomes
Absence of relapse, up to 12 months after achievement of Immune Tolerance
Time frame: 12 months
Time to achieve partial or complete success as defined in the protocol.
Time frame: 33 months
Safety Compliance to treatment
Time frame: 33 months
Cost of Care
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
- 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.
- BackgroundKreutz W: Immune tolerance induction (ITI) in Haemophilia A-patients with inhibitors - the choice of concentrate affecting success. Haematologica2001; 86 (S4):16-20
- 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.
- 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
Questions about this trial
What is this clinical trial studying?
A study testing FVIII Concentrates and FVIII/VWF concentrates in people with Severe Hemophilia A, run by City of Hope Medical Center.
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 11 inclusion and 4 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: withdrawn, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Primary end point is the success in inducing immune tolerance, defined as: the abolition of the inhibitor to < 0.6 BU within 33 months of ITI with a factor VIII recovery ≥ 66% and half-life ≥ 6 hrs, and measured after a 72-hour washout period. (time frame: 33 months). 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 NCT01051544, 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 17 Dec 2020.