Hemophilia ASPIRITNCT07539402
Searching Patterns In the Robustness of Immunological FVIII Tolerance
An observational study of Hemophilia A and Hemophilia A, Congenital, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Children with hemophilia A lack clotting factor VIII (FVIII) due to a genetic mutation. It is well known that administration of FVIII concentrate leads to immunological tolerance for the FVIII protein in the majority of children. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Hemophilia A, Hemophilia A, Congenital
- How many people
- 500 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 May 2026to Mar 2029
- How long will I take part?
- 5 Years
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Children with hemophilia A, who are treated with non-factor therapy as prophylaxis, and who are aged <18 years. The subjects will be recruited from Hemophilia Treatment Centres (HTCs) in the Netherlanss and internationally.
Who may be able to join
- Congenital hemophilia A of all severities
- Using NFT for prophylaxis
- Aged under 18 years
- Written informed consent
Who cannot join
- Acquired hemophilia A
- Any other bleeding disorder
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Lilianne E van Stam contact
Netherlands1 site
Amsterdam UMC, locatie AMC
Amsterdam, North Holland, 1105AZ
Samantha C Gouw, MD, PhD, +31(0)2056629111, s.c.gouw@amsterdamumc.nl
Lilianne E van Stam, MSc, PhD Candidate
About this study
Official title: Searching Patterns In the Robustness of Immunological FVIII Tolerance (SPIRIT)
Children with hemophilia A lack clotting factor VIII (FVIII) due to a genetic mutation. It is well known that administration of FVIII concentrate leads to immunological tolerance for the FVIII protein in the majority of children. In 30% of these children tolerance is not achieved leading to the development of anti-FVIII antibodies (i.e. inhibitors). Our knowledge on the underlying immunological mechanisms leading to tolerance is limited. Recently, Non-Factor Therapy (NFT) has become available for prevention of bleeding in patients with hemophilia, i.e. prophylaxis. Currently, many children with severe hemophilia A use NFT as the subcutaneous administration of NFT is very convenient. In children on NFT prophylaxis, intravenous FVIII concentrate is exclusively used on-demand for treatment of bleeding. As NFT is very effective in the prevention of bleeds, patients may not be exposed to the deficient FVIII protein for periods up to a year or longer. It is currently not known how robust immunological tolerance is in the absence of exposure to a deficient antigen. The infrequent exposure to FVIII, enabled by NFT, provides an opportunity to study the immunological tolerance mechanisms for FVIII in children with hemophilia A.
The aim of SPIRIT is to investigate the mechanisms of the immunological tolerance to FVIII in patients with hemophilia A aged younger than 18 years using NFT for prophylaxis.
Read more
In this observational cohort study, children (aged <18 years) with congenital hemophilia A, who are treated with non-factor therapy as prophylaxis, will be longitudinally followed. Participants will have blood drawn anually, during the regular clinic visits, and additionally following FVIII exposure. Feces samples will be collected and analyzed in children aged <12 years, following the same scheme as blood sampling.
The main study endpoint are the immunological mechanisms underlying tolerance to FVIII, including presence, titers, subtypes and affinities of FVIII-specific (non-)neutralizing antibodies, FVIII-specific T and B cell responses and the role of gut microbiota.
- Conditions
- Hemophilia A, Hemophilia A, Congenital
- Keywords
- Hemophilia A, Factor VIII, Tolerance
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Children with congenital Hemophilia A on NFT | Pediatric patients (aged younger than 18 years), with congenital hemophilia A of all severities, using non-factor therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
FVIII-specific non-neutralizing antibody development
Patients will be longitudinally monitored for the development of FVIII-specific non-neutralizing antibodies (NNAs). The development of FVIII-specific NNAs will be assessed with a direct enzyme-linked immunosorbent assay (ELISA)(Optical Density (OD)), by reporting the presence of FVIII-specific NNAs (Yes/No). Incidence will be calculated as the proportion of patients who develop newly detectable FVIII-specific NNAs during the study period.
Measured: From enrollment up to 5 years
Characterization of FVIII-specific antibodies (Immunoglobulin isotypes)
FVIII-specific antibodies will be characterized by measuring immunoglobulin isotypes (IgA, IgM, and IgG) over time using ELISA.
Measured: From enrollment up to 5 years
Characterization of FVIII-specific antibodies (IgG subclasses)
FVIII-specific antibodies will be characterized by measuring IgG subclasses (IgG1, IgG2, IgG3, and IgG4) over time using ELISA.
Measured: From enrollment up to 5 years
Characterization of FVIII-specific antibodies (affinity)
FVIII-specific antibodies will be characterized by measuring the affinity (KA [M-1]) over time using ELISA.
Measured: From enrollment up to 5 years
Characterization of FVIII-specific antibodies (titer)
FVIII-specific antibodies will be characterized by measuring inhibitor titers (Bethesda Units (BU)/mL) over time using the Nijmegen-modified Bethesda assay.
Measured: From enrollment up to 5 years
FVIII inhibitor development (neutralizing antibodies)
Participants will be longitudinally monitored for the development of FVIII-specific neutralizing antibodies using the Nijmegen-modified Bethesda assay (BU/mL). Inhibitor development will be defined as a titer ≥ 0.6 BU/mL confirmed on at least two consecutive measurements. Incidence will be calculated as the proportion of patients who develop confirmed FVIII inhibitors during the study period.
Measured: From enrollment up to 5 years
Secondary outcomes (3)
FVIII-specific T and B cell responses
FVIII-specific T- and B-cell responses will be characterized by assessing differential gene expression profiles and immune activation signatures over time using RNA sequencing. FVIII-specific T- and B-cell responses will be compared between patients with FVIII-specific NNAs and/or inhibitors and patients without FVIII-specific NNAs and/or inhibitors.
Measured: From enrollment up to 5 years
Immunomodulatory microbial metabolites (in children <12 years)
In participants younger than 12 years of age, concentrations of immunomodulatory microbial metabolites (i.e. short chain fatty acids, including butyrate and/or tryptophan catabolites (umol/g)) in fecal samples will be assessed over time using high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Concentrations of immunomodulatory microbial metabolites in fecal samples will be compared between patients with FVIII-specific NNAs and/or inhibitors and patients without FVIII-specific NNAs and/or inhibitors.
Measured: From enrollment up to 5 years
Gut microbiota composition (in children <12 years)
In participants younger than 12 years of age, microbial composition, including diversity indices and diversity indices, in fecal samples will be assessed over time using 16S rRNA gene sequencing. Gut microbiota composition in fecal samples will be compared between patients with FVIII-specific NNAs and/or inhibitors and patients without FVIII-specific NNAs and/or inhibitors.
Measured: From enrollment up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2026
- Study start1 May 2026 (estimated)
- Primary completionMar 2029 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam UMC, location AMC
- Responsible party
- Principal investigator, Karin Fijnvandraat, Amsterdam UMC, location AMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07539402
- Sponsor's protocol ID
- NL83658.018.23
- Acronym
- SPIRIT
- Status last verified
- Apr 2026
- First submitted
- 28 Apr 2025
- Last updated
- 20 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Searching Patterns In the Robustness of Immunological FVIII Tolerance (SPIRIT)
- ClinicalTrials.gov ID
- NCT07539402
- Acronym / sponsor ID
- SPIRIT / NL83658.018.23
- Conditions
- Hemophilia A, Hemophilia A, Congenital
- Keywords
- Hemophilia A, Factor VIII, Tolerance
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Amsterdam UMC, location AMC
- Study start
- 1 May 2026 (estimated)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 20 Apr 2026 (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.
Children with hemophilia A lack clotting factor VIII (FVIII) due to a genetic mutation. It is well known that administration of FVIII concentrate leads to immunological tolerance for the FVIII protein in the majority of children. In 30% of these children tolerance is not achieved leading to the development of anti-FVIII antibodies (i.e. inhibitors). Our knowledge on the underlying immunological mechanisms leading to tolerance is limited. Recently, Non-Factor Therapy (NFT) has become available for prevention of bleeding in patients with hemophilia, i.e. prophylaxis. Currently, many children with severe hemophilia A use NFT as the subcutaneous administration of NFT is very convenient. In children on NFT prophylaxis, intravenous FVIII concentrate is exclusively used on-demand for treatment of bleeding. As NFT is very effective in the prevention of bleeds, patients may not be exposed to the deficient FVIII protein for periods up to a year or longer. It is currently not known how robust immunological tolerance is in the absence of exposure to a deficient antigen. The infrequent exposure to FVIII, enabled by NFT, provides an opportunity to study the immunological tolerance mechanisms for FVIII in children with hemophilia A.
The aim of SPIRIT is to investigate the mechanisms of the immunological tolerance to FVIII in patients with hemophilia A aged younger than 18 years using NFT for prophylaxis.
In this observational cohort study, children (aged <18 years) with congenital hemophilia A, who are treated with non-factor therapy as prophylaxis, will be longitudinally followed. Participants will have blood drawn anually, during the regular clinic visits, and additionally following FVIII exposure. Feces samples will be collected and analyzed in children aged <12 years, following the same scheme as blood sampling.
The main study endpoint are the immunological mechanisms underlying tolerance to FVIII, including presence, titers, subtypes and affinities of FVIII-specific (non-)neutralizing antibodies, FVIII-specific T and B cell responses and the role of gut microbiota.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children with congenital Hemophilia A on NFT | – | –Pediatric patients (aged younger than 18 years), with congenital hemophilia A of all severities, using non-factor therapy |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Children with hemophilia A, who are treated with non-factor therapy as prophylaxis, and who are aged <18 years. The subjects will be recruited from Hemophilia Treatment Centres (HTCs) in the Netherlanss and internationally.
Key inclusion criteria (4 listed)
- Congenital hemophilia A of all severities
- Using NFT for prophylaxis
- Aged under 18 years
- Written informed consent
Key exclusion criteria (2 listed)
- Acquired hemophilia A
- Any other bleeding disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
FVIII-specific non-neutralizing antibody development
Time frame: From enrollment up to 5 years
Patients will be longitudinally monitored for the development of FVIII-specific non-neutralizing antibodies (NNAs). The development of FVIII-specific NNAs will be assessed with a direct enzyme-linked immunosorbent assay (ELISA)(Optical Density (OD)), by reporting the presence of FVIII-specific NNAs (Yes/No). Incidence will be calculated as the proportion of patients who develop newly detectable FVIII-specific NNAs during the study period.
Characterization of FVIII-specific antibodies (Immunoglobulin isotypes)
Time frame: From enrollment up to 5 years
FVIII-specific antibodies will be characterized by measuring immunoglobulin isotypes (IgA, IgM, and IgG) over time using ELISA.
Characterization of FVIII-specific antibodies (IgG subclasses)
Time frame: From enrollment up to 5 years
FVIII-specific antibodies will be characterized by measuring IgG subclasses (IgG1, IgG2, IgG3, and IgG4) over time using ELISA.
Characterization of FVIII-specific antibodies (affinity)
Time frame: From enrollment up to 5 years
FVIII-specific antibodies will be characterized by measuring the affinity (KA [M-1]) over time using ELISA.
Characterization of FVIII-specific antibodies (titer)
Time frame: From enrollment up to 5 years
FVIII-specific antibodies will be characterized by measuring inhibitor titers (Bethesda Units (BU)/mL) over time using the Nijmegen-modified Bethesda assay.
FVIII inhibitor development (neutralizing antibodies)
Time frame: From enrollment up to 5 years
Participants will be longitudinally monitored for the development of FVIII-specific neutralizing antibodies using the Nijmegen-modified Bethesda assay (BU/mL). Inhibitor development will be defined as a titer ≥ 0.6 BU/mL confirmed on at least two consecutive measurements. Incidence will be calculated as the proportion of patients who develop confirmed FVIII inhibitors during the study period.
3 secondary outcomes
FVIII-specific T and B cell responses
Time frame: From enrollment up to 5 years
Immunomodulatory microbial metabolites (in children <12 years)
Time frame: From enrollment up to 5 years
Gut microbiota composition (in children <12 years)
Time frame: From enrollment up to 5 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 20 Apr 2026.
- Individual participant dataSharing planned: Undecided
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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.
Lilianne E van Stam contact
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 and Hemophilia A, Congenital, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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 2 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: opening soon, as of the sponsor's last update on 20 Apr 2026. 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 Netherlands. 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 Samantha C Gouw, MD, PhD (+31(0)2056629111, s.c.gouw@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FVIII-specific non-neutralizing antibody development (time frame: From enrollment up to 5 years). The study lists 6 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 20 Apr 2026.