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Study terminated as enrolled patients rolled over into a large international study in the same indication
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Wilate or Nuwiq prospective cohort | Evaluable haemophilia A patients with an inhibitor against FVIII enrolled prospectively |
| |
| Wilate or Nuwiq retrospective cohort | Evaluable haemophilia A patients with an inhibitor against FVIII enrolled retrospectively |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Wilate or Nuwiq | Drug | Wilate or Nuwiq administered via intravenous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From ITI start until termination of study, a maximum of 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
For patients in the prospective cohort:
For patients in the retrospective cohort:
Exclusion Criteria:
Patients who meet any of the following criteria are not eligible for the study:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Sri Adapa | Octapharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stollery children's hospital, University of Alberta | Edmonton | Alberta | Canada | |||
| Children's Hospital of Eastern Ontario |
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| ID | Title | Description |
|---|---|---|
| FG000 | Wilate® Retrospective Cohort | The retrospective cohort was made up of 8 patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment. All patients had evaluable hemophilia A with an inhibitor against FVIII. The treatment regimen, doses, dosing intervals and dose adjustments were determined at the discretion of the treating physician. A usual dose for long-term prophylaxis against bleeding in patients with severe hemophilia A is 20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days. All enrolled patients were treated with Wilate. No patient discontinued the study before the study was terminated. |
| FG001 | Wilate® Prospective Cohort | The prospective cohort was made up of 6 patients who were currently receiving Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate. All patients had evaluable hemophilia A with an inhibitor against FVIII. The treatment regimen, doses, dosing intervals and dose adjustments were determined at the discretion of the treating physician. A usual dose for long-term prophylaxis against bleeding in patients with severe hemophilia A is 20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days. All enrolled patients were treated with Wilate. No patient discontinued the study before the study was terminated. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Wilate® Retrospective Cohort | The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment. |
| BG001 | Wilate® Prospective Cohort |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Due to study termination, efficacy data was not collected for enrolled patients in the prospective cohort | Posted | Count of Participants | Participants | From ITI start until termination of study, a maximum of 2 years |
Adverse drug reactions were monitored throughout the study from first treatment through to study termination, a maximum of 2 years
There were no treatment-related ADRs during the study
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Wilate® Retrospective Cohort | The population consists of all patients who had received Wilate immune tolerance induction (ITI) therapy within 3 years of enrolment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Device-related infection | Infections and infestations | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | Infections and infestations | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Sigurd Knaub, Senior VP CR&D Haematology | Octapharma AG | 01554512141 | Sigurd.Knaub@octapharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 8, 2021 | Jun 6, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D014841 | von Willebrand Factor |
| D005169 | Factor VIII |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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|
| 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 | 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. | 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. | 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. | 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. | 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. | 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. | 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. | A maximum period of 5 years from ITI start |
| Ottawa |
| Ontario |
| Canada |
| Hamilton Health Science center | Toronto | Ontario | Canada |
The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Blood type | Count of Participants | Participants |
|
| Severity of hemophilia A | Moderate Hemophilia was defined as the patient having a FVIII activity level of between 1-5%. Severe Hemophilia was defined as the patient having a FVIII activity level below 1%. | Count of Participants | Participants |
|
| FVIII mutation | Count of Participants | Participants |
|
| Previous inhibitor treatment | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Wilate® Respective Cohort | This cohort was made up of patients who had received Wilate immune tolerance induction (ITI) therapy within three years of enrolment |
| OG001 | Wilate® Prospective Cohort | This cohort consisted of patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate |
|
|
| Secondary | 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. | Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome | Posted | A maximum period of 5 years from ITI start |
|
|
| Secondary | In Case of Complete or Partial ITI Success, Duration of Immune Tolerance | Time from start of ITI success to end of study period | Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome | Posted | A maximum period of 5 years from ITI start |
|
|
| Secondary | 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. | Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome | Posted | A maximum period of 5 years from ITI start |
|
|
| Secondary | 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. | Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome | Posted | A maximum period of 5 years from ITI start |
|
|
| Secondary | 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. | Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome | Posted | 12 months before the start of ITI with Wilate or Nuwiq to a maximum of 5 years from starting ITI with Wilate or Nuwiq |
|
|
| Secondary | 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. | Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome | Posted | A maximum period of 5 years from ITI start |
|
|
| Secondary | 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. | Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome | Posted | A maximum period of 5 years from ITI start |
|
|
| Secondary | 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. | Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome | Posted | A maximum period of 5 years from ITI start |
|
|
| Secondary | 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. | Due to study termination, data was not collected for enrolled patients in either cohort. Therefore, 0 participants were analysed for this outcome | Posted | A maximum period of 5 years from ITI start |
|
|
| 0 |
| 8 |
| 1 |
| 8 |
| 0 |
| 8 |
| EG001 | Wilate® Prospective Cohort | The population consists of all patients who were currently on Wilate ITI, had just initiated ITI, or were planned to initiate ITI treatment with Wilate. | 0 | 6 | 1 | 6 | 1 | 6 |
| Gastroenteritis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Bronchial hyperreactivity | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
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| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D001685 |
| Biological Factors |
| D011498 | Protein Precursors |