Hemophilia APREVAILNCT03344003

Immune Tolerance Induction in Haemophilia A Patients Using Wilate or Nuwiq

An observational study of Hemophilia A, run by Octapharma at 3 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial summary

Uncontrolled, multi-centre, non-interventional study with a prospective and a retrospective cohort, to evaluate the efficacy of Wilate or Nuwiq in achieving complete or partial immune tolerance induction (ITI) success in severe and moderate haemophilia A patients with inhibitors Read more about this study

Who is it for?: Any age, men only
Conditions the study is for: Hemophilia A
What is being tested?: Wilate or Nuwiq
Type of treatment: Injection or infusion
How many people: 14 participants
Where: 3 sitesCanada
Study dates: 28 Jun 2018to 20 Nov 2020
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Study population: A total of at least 80 patients were planned, at least 40 in the prospective cohort and 40 in the retrospective cohort. Due to study termination, only 14 patients were enrolled.

Who may be able to join

Male patients of any age with moderate or severe haemophilia A.
Patients with a first occurrence of inhibitors, inhibitors refractory to previous ITI attempt(s), or relapsed inhibitors to FVIII, with an inhibitor titre of ≥0.6 BU measured on 2 separate occasions at least 2 weeks apart.
Informed written consent from the patient and/or the patient's parent(s) or legal guardian(s)
For patients in the prospective cohort:
Patients who are currently on Wilate or Nuwiq ITI, have just initiated ITI, or are planned to initiate ITI treatment with Wilate or Nuwiq.
For patients in the retrospective cohort:

Show all 12Show fewer

Patients having received Wilate or Nuwiq ITI before entry into this study. Retrospective data will be collected for a maximum of 3 years before enrolment into the study. To be eligible, the following information is needed:
Wilate or Nuwiq treatment details (start date, dose, treatment frequency, and dose change).
Reliably documented bleeding frequency.
FVIII inhibitor titres.
FVIII half-life.
FVIII IVR.

Who cannot join

Patients who meet any of the following criteria are not eligible for the study:
Congenital or acquired bleeding disorders other than haemophilia A.
A history of hypersensitivity to blood products and/or plasma-derived FVIII concentrates.
Inability to speak/read English or French well enough to provide consent and adhere to the study.
People who are receiving other non-factor therapies, e.g. concizumab

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

Stollery children's hospital, University of Alberta
Edmonton, Alberta
Children's Hospital of Eastern Ontario
Ottawa, Ontario
Hamilton Health Science center
Toronto, Ontario

Other trials in Canada

About this study

Official title: Immune Tolerance Induction in Haemophilia A Patients Using Wilate or Nuwiq - A Canadian Study

Conditions: Hemophilia A
Being tested: Wilate or Nuwiq
Medical subject headings: Hemophilia A

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Wilate or NuwiqDrug
Also called Wilate: Human von Willebrand factor / human coagulation factor VIII. Nuwiq: recombinant factor VIII (rhFVIII)
Wilate or Nuwiq administered via intravenous injection

Study groups in NCT03344003
Study group	Role	What they receive
Wilate or Nuwiq prospective cohort		Evaluable haemophilia A patients with an inhibitor against FVIII enrolled prospectively Receives: Drug: Wilate or Nuwiq
Wilate or Nuwiq retrospective cohort		Evaluable haemophilia A patients with an inhibitor against FVIII enrolled retrospectively Receives: Drug: Wilate or Nuwiq

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Moderate and Severe Haemophilia A Patients With Inhibitors Achieving Complete or Partial Immune Tolerance Induction (ITI) Success
ITI success will be determined using predefined success criteria to analyze the proportion of patients achieving complete or partial ITI success. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre <0.6BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental in vivo recovery (IVR) of FVIII in the normal range (≥66% of normal); 3) FVIII half-life ≥6 hours Wilate infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to <5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.
Measured: From ITI start until termination of study, a maximum of 2 years

Secondary outcomes (9)

Time Necessary to Achieve Complete or Partial ITI Success
Time to achieve complete or partial ITI success will be determined using predefined success criteria. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre <0.6 BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental IVR of FVIII in the normal range (≥66% of normal) ; 3) FVIII half-life ≥6 hours. Wilate infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to <5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.
0 participants analysed for this outcome due to termination of study.
Measured: A maximum period of 5 years from ITI start
In Case of Complete or Partial ITI Success, Duration of Immune Tolerance
Time from start of ITI success to end of study period
Measured: A maximum period of 5 years from ITI start
Bleeding Frequency While on Wilate or Nuwiq ITI Treatment
Bleeding episodes occurring during the study period will be documented by the patient or their parents in a patient study diary.
Measured: A maximum period of 5 years from ITI start
Association of Inhibitor Titres With the Probability of ITI Success
Inhibitor titre will be assessed at the start of and throughout ITI treatment, including peak inhibitor titres, with the probability of ITI success.
ITI success will be determined using predefined success criteria. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre <0.6 BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental IVR of FVIII in the normal range (≥66% of normal) ; 3) FVIII half-life ≥6 hours. Wilate or Nuwiq infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to <5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.
Measured: A maximum period of 5 years from ITI start
Use of Bypassing Agents Before and During ITI Treatment With Wilate or Nuwiq
Use of bypassing agents is at the discretion of the Investigator, either to treat bleeding or to provide prophylactic therapy. As long as the patient's inhibitor level is ≥0.6 Bethesda units (BU), treatment of BEs may, in addition to FVIII treatment, require the administration of activated prothrombin complex concentrates (aPCC) or recombinant FVIIa.
Measured: 12 months before the start of ITI with Wilate or Nuwiq to a maximum of 5 years from starting ITI with Wilate or Nuwiq
Use of Emicizumab (Hemlibra) During ITI Treatment With Wilate or Nuwiq
The dosing and frequency of emicizumab (Hemlibra) used is at the discretion of the Investigator. As a general guidance, the recommended dose is 3mg/kg once weekly for the first 4 weeks, followed by 1.5mg/kg once weekly, administered as a subcutaneous injection, as per the product monograph.
Measured: A maximum period of 5 years from ITI start
Relapse Rate Following Complete or Partial Successful ITI Using Wilate or Nuwiq
Reoccurrence of >0.6 BU in at least 2 consecutive blood samples after having reached the prophylactic treatment phase; a further ITI initiation (re-start) with Wilate or Nuwiq is at the discretion of the Investigator.
Measured: A maximum period of 5 years from ITI start
Time to Relapse Following Complete or Partial Successful ITI Using Wilate or Nuwiq
Time to reoccurrence of >0.6 BU in at least 2 consecutive blood samples after having reached the prophylactic treatment phase; a further ITI initiation (re-start) with Wilate or Nuwiq is at the discretion of the Investigator.
Measured: A maximum period of 5 years from ITI start
Adherence With the ITI Regimen
During ITI, any injections of Wilate or Nuwiq will be recorded in the patient study diary. The treating physician will review and verify the information provided by the patient.
Measured: A maximum period of 5 years from ITI start

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jun 201820 Nov 2020

First posted17 Nov 2017
Study start28 Jun 2018
Primary completion20 Nov 2020
Study completion20 Nov 2020

Why it stopped: Study terminated as enrolled patients rolled over into a large international study in the same indication

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hemophilia AStudies of the same condition, open and under way.
More trials run by OctapharmaThe 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: Other
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03344003
Sponsor's protocol ID: WIL-26
Acronym: PREVAIL
Status last verified: Mar 2024
First submitted: 8 Nov 2017
Last updated: 9 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B

All Hemophilia A trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Immune Tolerance Induction in Haemophilia A Patients Using Wilate or Nuwiq - A Canadian Study
ClinicalTrials.gov ID: NCT03344003
Acronym / sponsor ID: PREVAIL / WIL-26
Conditions: Hemophilia A
Study type: Observational
Recruitment status: TerminatedReason stopped: Study terminated as enrolled patients rolled over into a large international study in the same indication
Enrolment: 14 participants (actual)
Lead sponsor: OctapharmaIndustry (pharma, biotech, devices)
Study start: 28 Jun 2018 (actual)
Primary completion: 20 Nov 2020 (actual)
Study completion: 20 Nov 2020 (actual)
First posted: 17 Nov 2017 (actual)
Results: Posted 9 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Observational model: Cohort
Time perspective: Other
Number of arms: 2

Arm	Type	Receives
Wilate or Nuwiq prospective cohort	–	Drug: Wilate or NuwiqEvaluable haemophilia A patients with an inhibitor against FVIII enrolled prospectively
Wilate or Nuwiq retrospective cohort	–	Drug: Wilate or NuwiqEvaluable haemophilia A patients with an inhibitor against FVIII enrolled retrospectively

Who may qualify

Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
Study population: A total of at least 80 patients were planned, at least 40 in the prospective cohort and 40 in the retrospective cohort. Due to study termination, only 14 patients were enrolled.

Key inclusion criteria (12 listed)

Male patients of any age with moderate or severe haemophilia A.
Patients with a first occurrence of inhibitors, inhibitors refractory to previous ITI attempt(s), or relapsed inhibitors to FVIII, with an inhibitor titre of ≥0.6 BU measured on 2 separate occasions at least 2 weeks apart.
Informed written consent from the patient and/or the patient's parent(s) or legal guardian(s)
Patients who are currently on Wilate or Nuwiq ITI, have just initiated ITI, or are planned to initiate ITI treatment with Wilate or Nuwiq.
Patients having received Wilate or Nuwiq ITI before entry into this study. Retrospective data will be collected for a maximum of 3 years before enrolment into the study. To be eligible, the following information is needed:

Key exclusion criteria (5 listed)

Congenital or acquired bleeding disorders other than haemophilia A.
A history of hypersensitivity to blood products and/or plasma-derived FVIII concentrates.
Inability to speak/read English or French well enough to provide consent and adhere to the study.
People who are receiving other non-factor therapies, e.g. concizumab

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
Wilate or NuwiqAlso: Wilate: Human von Willebrand factor / human coagulation factor VIII. Nuwiq: recombinant factor VIII (rhFVIII)Wilate or Nuwiq administered via intravenous injection	Drug	Wilate or Nuwiq prospective cohort, Wilate or Nuwiq retrospective cohort

Primary outcome

Number of Moderate and Severe Haemophilia A Patients With Inhibitors Achieving Complete or Partial Immune Tolerance Induction (ITI) Success
Time frame: From ITI start until termination of study, a maximum of 2 years
ITI success will be determined using predefined success criteria to analyze the proportion of patients achieving complete or partial ITI success. Complete success is defined by achieving all of the following variables: 1) Inhibitor titre <0.6BU (at least 2 separate blood samplings) assessed using the modified Bethesda assay; 2) Incremental in vivo recovery (IVR) of FVIII in the normal range (≥66% of normal); 3) FVIII half-life ≥6 hours Wilate infusion. Partial success is defined as two of the three criteria being met, whilst partial response is defined as one of the three criteria being met. Partial failure is defined as none of the three criteria are met, but the inhibitor titre has decreased to <5 BU; complete failure is defined as none of the three criteria are met, and the inhibitor titre is still ≥5 BU.

9 secondary outcomes

Time Necessary to Achieve Complete or Partial ITI Success
Time frame: A maximum period of 5 years from ITI start
In Case of Complete or Partial ITI Success, Duration of Immune Tolerance
Time frame: A maximum period of 5 years from ITI start
Bleeding Frequency While on Wilate or Nuwiq ITI Treatment
Time frame: A maximum period of 5 years from ITI start
Association of Inhibitor Titres With the Probability of ITI Success
Time frame: A maximum period of 5 years from ITI start
Use of Bypassing Agents Before and During ITI Treatment With Wilate or Nuwiq
Time frame: 12 months before the start of ITI with Wilate or Nuwiq to a maximum of 5 years from starting ITI with Wilate or Nuwiq
Use of Emicizumab (Hemlibra) During ITI Treatment With Wilate or Nuwiq
Time frame: A maximum period of 5 years from ITI start
Relapse Rate Following Complete or Partial Successful ITI Using Wilate or Nuwiq
Time frame: A maximum period of 5 years from ITI start
Time to Relapse Following Complete or Partial Successful ITI Using Wilate or Nuwiq
Time frame: A maximum period of 5 years from ITI start
Adherence With the ITI Regimen
Time frame: A maximum period of 5 years from ITI start

Results and safety

Results posted to the registry on 9 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Wilate® Retrospective Cohort	8	6
Wilate® Prospective Cohort	6	6

Primary outcome: Number of Moderate and Severe Haemophilia A Patients With Inhibitors Achieving Complete or Partial Immune Tolerance Induction (ITI) Success

Time frame: From ITI start until termination of study, a maximum of 2 years. Count of participants. Unit: Participants

Measure	Wilate® Respective Cohort n = 8	Wilate® Prospective Cohort n = 0
Complete success	7	0
Partial success	0	0
Partial failure	0	0
Complete failure	1	0

Population analysed: Due to study termination, efficacy data was not collected for enrolled patients in the prospective cohort

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse drug reactions were monitored throughout the study from first treatment through to study termination, a maximum of 2 years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Wilate® Retrospective Cohort	1 of 8 (12.5%)	0 of 8 (0%)	0 of 8
Wilate® Prospective Cohort	1 of 6 (16.7%)	1 of 6 (16.7%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Hemophilia A

RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
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Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia 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.

Sri Adapa study director

Octapharma

3 sites 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 Octapharma at 3 sites in Canada.

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 12 inclusion and 5 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: stopped early, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. 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?

Yes. Results are posted in the registry (first posted 9 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Moderate and Severe Haemophilia A Patients With Inhibitors Achieving Complete or Partial Immune Tolerance Induction (ITI) Success (time frame: From ITI start until termination of study, a maximum of 2 years). 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 NCT03344003.

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 9 Aug 2024.