Hemophilia ANCT01541527
Non Neutralizing Antibodies: Prevalence and Characterization
An observational study of Hemophilia A, run by University Hospital, Montpellier at 1 site in France.
Trial summary
Antibodies (Abs) directed against factorVIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Anti-FVIII Abs inhibiting pro-coagulant properties of the molecule are named inhibitors whereas Abs directed towards non-functional epitopes are named non-neutralizing antibodies (NNA). Read more about this study
- Who is it for?
- Ages 6 years and older, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- blood test
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2012to Aug 2013
- Phase
- Observational
- 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 6 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Study population: severe, moderate and mild HA patients (sex: Male and age > 6 years)
Who may be able to join
- male with Age > 6 years
- Severe, moderate or mild treated HA patients with negative inhibitor titer (<0.6UB)
- An information form will be presented to the patient or his/her legal representative by the physician who includes the patient in the study protocol
- Patient with national insurance
Who cannot join
- Patient without his agreement for this study
- Patient deprived of freedom
- Patient without national insurance
Trial locations and contacts
1 site in 1 country.
France1 site
CHU de Montpellier- Centre administratif André Benech
Montpellier, 3400
About this study
Official title: Prevalence and Epitope Specificity of Non-neutralizing Antibodies in Haemophilia A Patients Without Inhibitors, Immunogenicity of B Domain: A Prospective Study
Antibodies (Abs) directed against factorVIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Anti-FVIII Abs inhibiting pro-coagulant properties of the molecule are named inhibitors whereas Abs directed towards non-functional epitopes are named non-neutralizing antibodies (NNA). These NNA are poorly studied and their prevalence is ill-defined.
In a recent retrospective study the investigators evaluated, in a cohort of 210 patients without inhibitor, the NNA prevalence and the NNA epitope specificity against the heavy chain (HC)or the light chain(LC). For the first time, the investigators used two x-MAP based assays: the first to determine the specificity of anti-FVIII Abs against the HC or the LC, the second to display Abs directed towards the B domain. NNA were found in 38 out of 210 patients (18).
Read more
Among this NNA positive population, 74% and 13% of patients had anti-FVIII Abs against both chains. The proportion of NNA directed towards the B domain was 18%.
Considering an approximate inhibitor prevalence of 30% and a NNA prevalence of 19% in severe HA patients, approximately 50% of severe HA patients develop an immune response against infused FVIII. Due to their unclear relevance, the NNA detection does not yet belong to the routine clinical practice.
However, in 2006, Dimichele advancedf a hypothesis concerning the influence of NNA on the variations in the kinectics of FVIII observed in certain patients.
The mechanism explaining the role of these NNA in the FVIII in the FVIII kinectics has not still been demonstrated.
The investigators propose to perform a multicentre prospective study with the aim to confirm, in severe, moderate and mild HA treated patietns, the NNA prevalence observed in our retrospective study, to study the evolution over time of the epitopemapping of these NNA and to explore the correlation between these NNA and clinical/biological parameters.
- Conditions
- Hemophilia A
- Being tested
- blood test
- Keywords
- non neutralizing antibody, Epitopic profile, Clinical relevance
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood testBiological
One blood test entering in the usual follow-up of the patient
| Study group | Role | What they receive |
|---|---|---|
| severe, moderate and mild HA patients | one Arm: biological collection of 300 severe, moderate and mild HA patients Receives: Biological: blood test |
What is being measured
The primary outcome is the main question the study is designed to answer.
NNA prevalence
The primary outcome is the study of the development of ANN anti-FVIII at the severe, moderate or mild HA patients to establish prevalency of ACs targeted against the heavy chain, the light chain and the domains of the FVIII (6 months after the inclusion.
The investigators will evaluate the NNA prevalence by the x-MAP technology.
Measured: 18 months
Secondary outcomes (1)
Relationship between clinical and biological parameters and NNA presence
The secondary outcomes assess the evolution in time of these Acs of isotypes IgG and the relationship between clinical and biological parameters (FVIII%, recovery,..) and NNA presence.
The investigators will evaluate the secondary outcomes by the x-MAP technology.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2012 (estimated)
- Study startFeb 2012
- Primary completionFeb 2013
- Study completionAug 2013
Why it stopped: Promoter's change
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 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Collaborators
- Hôpital de la Timone, University Hospital, Clermont-Ferrand, Centre Hospitalier Universitaire de Saint Etienne, University Hospital, Toulouse, Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Nīmes
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01541527
- Sponsor's protocol ID
- UF 8844
- Status last verified
- Feb 2012
- First submitted
- 17 Feb 2012
- Last updated
- 31 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Lavigne-Lissalde G, Rothschild C, Pouplard C, Lapalud P, Gruel Y, Schved JF, Granier C. Characteristics, mechanisms of action, and epitope mapping of anti-factor VIII antibodies. Clin Rev Allergy Immunol. 2009 Oct;37(2):67-79. doi: 10.1007/s12016-009-8119-0.
PubMed 19172415Lavigne-Lissalde G, Tarrade C, Lapalud P, Chtourou S, Schved JF, Granier C, Villard-Saussine S. Simultaneous detection and epitope mapping of anti-factor VIII antibodies. Thromb Haemost. 2008 Jun;99(6):1090-6. doi: 10.1160/TH07-08-0497.
PubMed 18521513Lavigne-Lissalde G, Lacroix-Desmazes S, Wootla B, Tarrade C, Schved JF, Kaveri SV, Granier C, Villard-Saussine S. Molecular characterization of human B domain-specific anti-factor VIII monoclonal antibodies generated in transgenic mice. Thromb Haemost. 2007 Jul;98(1):138-47.
PubMed 17598006
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevalence and Epitope Specificity of Non-neutralizing Antibodies in Haemophilia A Patients Without Inhibitors, Immunogenicity of B Domain: A Prospective Study
- ClinicalTrials.gov ID
- NCT01541527
- Acronym / sponsor ID
- UF 8844
- Conditions
- Hemophilia A
- Keywords
- non neutralizing antibody, Epitopic profile, Clinical relevance
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Promoter's change
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Collaborators
- Hôpital de la Timone, University Hospital, Clermont-Ferrand, Centre Hospitalier Universitaire de Saint Etienne, University Hospital, Toulouse, Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Nīmes
- Study start
- Feb 2012
- Primary completion
- Feb 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 1 Mar 2012 (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.
Antibodies (Abs) directed against factorVIII (FVIII) remain the main iatrogenic complication in haemophilia A (HA) patients. Anti-FVIII Abs inhibiting pro-coagulant properties of the molecule are named inhibitors whereas Abs directed towards non-functional epitopes are named non-neutralizing antibodies (NNA). These NNA are poorly studied and their prevalence is ill-defined.
In a recent retrospective study the investigators evaluated, in a cohort of 210 patients without inhibitor, the NNA prevalence and the NNA epitope specificity against the heavy chain (HC)or the light chain(LC). For the first time, the investigators used two x-MAP based assays: the first to determine the specificity of anti-FVIII Abs against the HC or the LC, the second to display Abs directed towards the B domain. NNA were found in 38 out of 210 patients (18).
Among this NNA positive population, 74% and 13% of patients had anti-FVIII Abs against both chains. The proportion of NNA directed towards the B domain was 18%.
Considering an approximate inhibitor prevalence of 30% and a NNA prevalence of 19% in severe HA patients, approximately 50% of severe HA patients develop an immune response against infused FVIII. Due to their unclear relevance, the NNA detection does not yet belong to the routine clinical practice.
However, in 2006, Dimichele advancedf a hypothesis concerning the influence of NNA on the variations in the kinectics of FVIII observed in certain patients.
The mechanism explaining the role of these NNA in the FVIII in the FVIII kinectics has not still been demonstrated.
The investigators propose to perform a multicentre prospective study with the aim to confirm, in severe, moderate and mild HA treated patietns, the NNA prevalence observed in our retrospective study, to study the evolution over time of the epitopemapping of these NNA and to explore the correlation between these NNA and clinical/biological parameters.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| severe, moderate and mild HA patients | – | Biological: blood testone Arm: biological collection of 300 severe, moderate and mild HA patients |
Who may qualify
- Ages
- 6 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- severe, moderate and mild HA patients (sex: Male and age > 6 years)
Key inclusion criteria (4 listed)
- male with Age > 6 years
- Severe, moderate or mild treated HA patients with negative inhibitor titer (<0.6UB)
- An information form will be presented to the patient or his/her legal representative by the physician who includes the patient in the study protocol
- Patient with national insurance
Key exclusion criteria (3 listed)
- Patient without his agreement for this study
- Patient deprived of freedom
- Patient without national insurance
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 |
|---|---|---|
| blood testOne blood test entering in the usual follow-up of the patient | Biological | severe, moderate and mild HA patients |
Primary outcome
NNA prevalence
Time frame: 18 months
The primary outcome is the study of the development of ANN anti-FVIII at the severe, moderate or mild HA patients to establish prevalency of ACs targeted against the heavy chain, the light chain and the domains of the FVIII (6 months after the inclusion. The investigators will evaluate the NNA prevalence by the x-MAP technology.
1 secondary outcome
Relationship between clinical and biological parameters and NNA presence
Time frame: 18 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 31 Dec 2014.
- Results publication: PubMed 19172415Lavigne-Lissalde G, Rothschild C, Pouplard C, Lapalud P, Gruel Y, Schved JF, Granier C. Characteristics, mechanisms of action, and epitope mapping of anti-factor VIII antibodies. Clin Rev Allergy Immunol. 2009 Oct;37(2):67-79. doi: 10.1007/s12016-009-8119-0.
- Results publication: PubMed 18521513Lavigne-Lissalde G, Tarrade C, Lapalud P, Chtourou S, Schved JF, Granier C, Villard-Saussine S. Simultaneous detection and epitope mapping of anti-factor VIII antibodies. Thromb Haemost. 2008 Jun;99(6):1090-6. doi: 10.1160/TH07-08-0497.
- Results publication: PubMed 17598006Lavigne-Lissalde G, Lacroix-Desmazes S, Wootla B, Tarrade C, Schved JF, Kaveri SV, Granier C, Villard-Saussine S. Molecular characterization of human B domain-specific anti-factor VIII monoclonal antibodies generated in transgenic mice. Thromb Haemost. 2007 Jul;98(1):138-47.
Related trials for Hemophilia A
RecruitingPhase 1/2
A First-in Human Study of ARD001 in Healthy Volunteers and People With Hemophilia A
Hemophilia A, Healthy Adult Participants
RecruitingPhase 3
A Research Study Investigating Denecimig (Mim8) in Adults With Acquired Haemophilia A
Haemophilia A
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B
Hemophilia
Not yet recruitingObservational study
A Study to Describe Patient REal-world FitusiRan ExpeRience
Hemophilia A or B
RecruitingPhase 3
Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors
Hemophilia A, Hemophilia 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophilia A, run by University Hospital, Montpellier at 1 site in France.
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 4 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: withdrawn, as of the sponsor's last update on 31 Dec 2014. 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 France. 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 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?
NNA prevalence (time frame: 18 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 NCT01541527, 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 31 Dec 2014.