Severe Hemophilia ANAVIGATENCT05802836
Dynamics of the Anti-factor VIII Antibody Signature During Treatment With Emicizumab
An observational study of Severe Hemophilia A and Severe Hemophilia A With Inhibitor, run by Christoph Königs at 1 site in Germany.
Trial summary
The goal of this observational study is to learn about the changes of antibodies and inhibitors against the coagulation factor VIII in patients with severe hemophilia A receiving emicizumab therapy. No additional visits or procedures are planned. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Severe Hemophilia A, Severe Hemophilia A With Inhibitor, Severe Hemophilia A Without Inhibitor
- How many people
- 100 participants
- Where
- 1 siteGermany
- Study dates
- 26 Apr 2023to Dec 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study aims to recruit 100 patients with severe hemophilia A from 15 study sites in germany.
Who may be able to join
- Severe congenital hemophilia A (CHA)
- Treatment with emicizumab irrespective of any other treatment
- Informed consent
Who cannot join
- No therapy with emicizumab
- Immunosuppressive therapy
- HIV-infection with CD4 (cluster of differentiation 4) cells <200/µl
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Frankfurt, Goethe University
Frankfurt am Main, Hesse, 60590
Stephan Schultze-Strasser, Dr., 00496963016998, stephan.schultze-strasser@kgu.de
Christoph Koenigs, PD Dr. Dr., 004969630183030, christoph.koenigs@kgu.de
About this study
The goal of this observational study is to learn about the changes of antibodies and inhibitors against the coagulation factor VIII in patients with severe hemophilia A receiving emicizumab therapy. No additional visits or procedures are planned. Patients in this study will continue to receive their routine care and analysis will be done from left over samples from routine visits.
- Conditions
- Severe Hemophilia A, Severe Hemophilia A With Inhibitor, Severe Hemophilia A Without Inhibitor
- Being tested
- no interventions
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no interventionsOther
no intervention, only 3 different patients groups
| Study group | Role | What they receive |
|---|---|---|
| Inhibitor negative, FVIII on demand or regularly | Patients with severe hemophilia A receiving emicizumab therapy which are negative for factor VIII Inhibitor (including patients post ITI) and are receiving factor VIII therapy either on demand or regularly, Receives: Other: no interventions | |
| Inhibitor positive, FVIII therapy regularly (ITI) | Patients with severe hemophilia A receiving emicizumab therapy which are positive for factor VIII Inhibitor and are receiving regularly factor VIII therapy (ITI) Receives: Other: no interventions | |
| Inhibitor positive, no FVIII therapy | Patients with severe hemophilia A receiving emicizumab therapy which are positive for factor VIII Inhibitor and are receiving no factor VIII therapy Receives: Other: no interventions |
What is being measured
The primary outcome is the main question the study is designed to answer.
FVIII inhibitor development in inhibitor negative subjects
Rate of FVIII inhibitor development during three years of emicizumab prophylaxis in inhibitor negative subjects. Assessed with Bethesda Assay (BU/ml). Number of patients who develop an FVIII inhibitor within the study period, but were FVIII inhibitor negative at start of the study.
Measured: 3 years
FVIII antibody development in inhibitor negative subjects
Rate of FVIII antibody development during three years of emicizumab prophylaxis in inhibitor negative subjects. FVIII anti drug antibody (ADA) is assessed by FVIII specific ELISA (OD=Optical Density). Number of patients who develop an FVIII antibody (ADA) within the study period, but were FVIII inhibitor negative at start of the study.
Measured: 3 years
FVIII inhibitor disappearance in inhibitor positive subjects
Rate of FVIII inhibitor disappearance during three years of emicizumab prophylaxis in inhibitor positive subjects. Assessed with Bethesda Assay (BU/ml). Number of patients who loose an FVIII inhibitor within the study period, but were FVIII inhibitor positive at start of the study.
Measured: 3 years
FVIII antibody disappearance in inhibitor positive subjects
Rate of FVIII antibody disappearance during three years of emicizumab prophylaxis in inhibitor positive subjects. FVIII anti drug antibody (ADA) is assessed by FVIII specific ELISA (OD=Optical Density). Number of patients who develop an FVIII antibody within the study period, but were FVIII inhibitor positive at start of the study.
Measured: 3 years
Secondary outcomes (7)
Anti-FVIII inhibitor development
Anti-FVIII inhibitor development (median BU/ml) over time. Assessed with Bethesda Assay (BU/ml). Description of inhibitor development in the different patient groups within the study period. Cut off is 0,6 BU/ml.
Measured: 3 years
Anti-FVIII antibody development
Anti-FVIII antibody development (median arbitrary units, OD) over time. Description of antibody development in the different patient groups within the study period.
Measured: 3 years
Time to negative inhibitor titers
Time to negative inhibitor titers. Assessed with Bethesda Assay (BU/ml). Description of the Time (days) observed for FVIII inhibitor disappearance within the study period in the patient groups. Cut off for inhibitor titer is 0,6 BU/ml.
Measured: 3 years
Treatment of bleeds
Description of the use of FVIII and/or Bypassing agents treatment in addition to Emicizumab treatment in case of bleeds.
Measured: 3 years
Response to treatment
Classification of bleeds as Effective, Partially Effective, Ineffective. Defined as: Effective: Bleeding episode responded to the usual number of injections or dose of FVIII as expected by the treating physician; Partially Effective: The bleeding episode responded with a higher number of injections and/or dose as expected by the treating physician; Ineffective: Routine failure to control hemostasis or hemostatic control required additional agents
Measured: 3 years
Quality of the antibody response (FVIII epitopes)
Description of the location of FVIII epitopes over time, assessed by epitope mapping technique (ELISA)
Measured: 3 years
Quality of the antibody response (IgG subclasses)
Description of a potential immune response over time, assessed by IgG subclass determination (ELISA).
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2023
- Study start26 Apr 2023
- Primary completionDec 2028 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe 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
- Other
- Time perspective
- Other
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Christoph Königs
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG, Chugai Pharma Germany GmbH
- Responsible party
- Sponsor-investigator, Christoph Königs, Goethe University
- Investigators
- Christoph Koenigs, PD Dr. Dr, Principal investigator, Goethe University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05802836
- Sponsor's protocol ID
- ML44394
- Other IDs
- DRKS00031196
- Acronym
- NAVIGATE
- Status last verified
- Jul 2023
- First submitted
- 6 Mar 2023
- Last updated
- 10 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamics of the Anti-factor VIII Antibody Signature During Treatment With Emicizumab
- ClinicalTrials.gov ID
- NCT05802836
- Acronym / sponsor ID
- NAVIGATE / ML44394
- Conditions
- Severe Hemophilia A, Severe Hemophilia A With Inhibitor, Severe Hemophilia A Without Inhibitor
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Christoph KönigsUniversity, hospital or other
- Collaborators
- Roche Pharma AG, Chugai Pharma Germany GmbH
- Study start
- 26 Apr 2023 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 7 Apr 2023 (actual)
- 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 goal of this observational study is to learn about the changes of antibodies and inhibitors against the coagulation factor VIII in patients with severe hemophilia A receiving emicizumab therapy. No additional visits or procedures are planned. Patients in this study will continue to receive their routine care and analysis will be done from left over samples from routine visits.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Inhibitor negative, FVIII on demand or regularly | – | Other: no interventionsPatients with severe hemophilia A receiving emicizumab therapy which are negative for factor VIII Inhibitor (including patients post ITI) and are receiving factor VIII therapy either on demand or regularly, |
| Inhibitor positive, FVIII therapy regularly (ITI) | – | Other: no interventionsPatients with severe hemophilia A receiving emicizumab therapy which are positive for factor VIII Inhibitor and are receiving regularly factor VIII therapy (ITI) |
| Inhibitor positive, no FVIII therapy | – | Other: no interventionsPatients with severe hemophilia A receiving emicizumab therapy which are positive for factor VIII Inhibitor and are receiving no factor VIII therapy |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study aims to recruit 100 patients with severe hemophilia A from 15 study sites in germany.
Key inclusion criteria (3 listed)
- Severe congenital hemophilia A (CHA)
- Treatment with emicizumab irrespective of any other treatment
- Informed consent
Key exclusion criteria (3 listed)
- No therapy with emicizumab
- Immunosuppressive therapy
- HIV-infection with CD4 (cluster of differentiation 4) cells <200/µl
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 |
|---|---|---|
| no interventionsno intervention, only 3 different patients groups | Other | Inhibitor negative, FVIII on demand or regularly, Inhibitor positive, FVIII therapy regularly (ITI), Inhibitor positive, no FVIII therapy |
Primary outcome
FVIII inhibitor development in inhibitor negative subjects
Time frame: 3 years
Rate of FVIII inhibitor development during three years of emicizumab prophylaxis in inhibitor negative subjects. Assessed with Bethesda Assay (BU/ml). Number of patients who develop an FVIII inhibitor within the study period, but were FVIII inhibitor negative at start of the study.
FVIII antibody development in inhibitor negative subjects
Time frame: 3 years
Rate of FVIII antibody development during three years of emicizumab prophylaxis in inhibitor negative subjects. FVIII anti drug antibody (ADA) is assessed by FVIII specific ELISA (OD=Optical Density). Number of patients who develop an FVIII antibody (ADA) within the study period, but were FVIII inhibitor negative at start of the study.
FVIII inhibitor disappearance in inhibitor positive subjects
Time frame: 3 years
Rate of FVIII inhibitor disappearance during three years of emicizumab prophylaxis in inhibitor positive subjects. Assessed with Bethesda Assay (BU/ml). Number of patients who loose an FVIII inhibitor within the study period, but were FVIII inhibitor positive at start of the study.
FVIII antibody disappearance in inhibitor positive subjects
Time frame: 3 years
Rate of FVIII antibody disappearance during three years of emicizumab prophylaxis in inhibitor positive subjects. FVIII anti drug antibody (ADA) is assessed by FVIII specific ELISA (OD=Optical Density). Number of patients who develop an FVIII antibody within the study period, but were FVIII inhibitor positive at start of the study.
7 secondary outcomes
Anti-FVIII inhibitor development
Time frame: 3 years
Anti-FVIII antibody development
Time frame: 3 years
Time to negative inhibitor titers
Time frame: 3 years
Treatment of bleeds
Time frame: 3 years
Response to treatment
Time frame: 3 years
Quality of the antibody response (FVIII epitopes)
Time frame: 3 years
Quality of the antibody response (IgG subclasses)
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2023.
- Individual participant dataSharing planned: No
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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.
Christoph Koenigs, PD Dr. Dr principal investigator
Goethe University
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 Severe Hemophilia A and Severe Hemophilia A With Inhibitor, run by Christoph Königs at 1 site in Germany.
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 3 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: looking for participants now, as of the sponsor's last update on 10 Jul 2023. 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 Germany. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stephan Schultze-Strasser, Dr. (+496963016998, stephan.schultze-strasser@kgu.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FVIII inhibitor development in inhibitor negative subjects (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jul 2023.