Study Stopped
complete per PI
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
RESIST NAIVE
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
2 other identifiers
interventional
N/A
0 countries
N/A
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Sep 2009
Longer than P75 for not_applicable
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 25, 2009
CompletedFirst Submitted
Initial submission to the registry
January 15, 2010
CompletedFirst Posted
Study publicly available on registry
January 18, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 25, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 25, 2020
CompletedDecember 17, 2020
December 1, 2020
10.8 years
January 15, 2010
December 15, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
33 months
Secondary Outcomes (4)
Absence of relapse, up to 12 months after achievement of Immune Tolerance
12 months
Time to achieve partial or complete success as defined in the protocol.
33 months
Safety Compliance to treatment
33 months
Cost of Care
12 months
Study Arms (2)
von Willebrand factor-free FVIII concentrates
ACTIVE COMPARATORPatients treated with FVIII concentrates
FVIII/VWF concentrates
ACTIVE COMPARATORPatients treated with FVIII/VWF concentrates
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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:
- 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.
You may not qualify if:
- concomitant systemic treatment with immunosuppressive drugs;
- concomitant experimental treatment;
- previous ITI attempt;
- previous history of myocardial infarction and/or cerebral stroke.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- Charta Foundationcollaborator
- Grifols Biologicals, LLCcollaborator
- CSL Behringcollaborator
- Biotest Pharmaceuticals Corporationcollaborator
- Grifols Therapeutics LLCcollaborator
Related Publications (3)
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.
PMID: 27214015BACKGROUNDKreutz W: Immune tolerance induction (ITI) in Haemophilia A-patients with inhibitors - the choice of concentrate affecting success. Haematologica2001; 86 (S4):16-20
BACKGROUNDGringeri 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.
PMID: 17610550BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nadia P Ewing, MD
Clinical Professor of Pediatrics, City of Hope National Medical Center, Dept. of Pediatrics, 1500 E. Duarte Rd. Duarte, CA 91010
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 15, 2010
First Posted
January 18, 2010
Study Start
September 25, 2009
Primary Completion
June 25, 2020
Study Completion
June 25, 2020
Last Updated
December 17, 2020
Record last verified: 2020-12