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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-005524-26 | EudraCT Number |
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Terminated due to limited enrollment (non-safety related decision)
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| Name | Class |
|---|---|
| Grifols Biologicals, LLC | INDUSTRY |
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This is a multicenter, multinational, prospective, single-arm, nonrandomized, open-label study, planned in of approximately 25 male participants with congenital hemophilia A who will receive their first (primary) immune tolerance induction (ITI) treatment with alphanate.
The study consists of 2 phases:
Male participants <12 years of age with an inhibitor titer >0.6 to <10 Bethesda Units (BU) will be screened before the planned start of ITI treatment. Participants continuing to meet the entrance criteria will enter the ITI Treatment Phase and receive daily doses of alphanate 100 IU/kg/day for up to 33 months, with a one-time option to increase to a dosing regimen of 200 IU/kg/day at any time after 90 days of ITI treatment.
Participants will continue to receive their daily alphanate dose for up to 33 months until the titer is negative (<0.6 BU) on 2 consecutive assessments and treatment success is confirmed by FVIII:C pharmacokinetic assessments, at which time they will enter the 12-month Prophylactic Phase.
In addition, participants who have achieved partial immune tolerance at the completion of 33 months of ITI treatment will enter the 12-month Prophylactic Phase. Participants who do not achieve partial immune tolerance at the completion of 33 months of ITI treatment will be discontinued as treatment failures.
The Prophylactic Phase begins with an 8-week taper period for participants tolerized with 100 IU/kg/day or with a 12-week taper period for participants tolerized with 200 IU/kg/day to bring the dose down in a step-wise manner to a prophylactic dose of alphanate 50 IU/kg every other day or 3 times per week, at the investigator's discretion. During the Prophylactic Phase, participants will be monitored monthly for the first 4 months and then every 2 months for the remaining 8 months to assess sustainability of immune tolerance. Due to limited enrollment, this study was early terminated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alphanate | Experimental | Participants were to receive alphanate 100 International Units (IU/kg/day) for up to 33 months in Immune tolerance induction (ITI) Treatment Phase. The dose could be increased up to 200 IU/kg/day based on Investigator's discretion. Following ITI Treatment Phase, participants were to enter the Prophylactic Phase where alphanate dose was to be tapered down in a step wise manner to reach a final prophylactic dose of 50 IU/kg every other day or 3 times per week, at the investigator's discretion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alphanate | Biological | Bolus IV injection. |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieved Complete Immune Tolerance Within 33 Months of Initiation of Immune Tolerance Induction (ITI) Treatment Phase | Complete immune tolerance was defined as the participants achieving 2 consecutive undetectable inhibitor titers (<0.6 BU) performed within 2 weeks of each other, Factor VIII activity (FVIII:C) in vivo plasma recovery ≥66% of the predicted normal value and FVIII:C half-life ≥6 hours after a 72-hour FVIII treatment-free period. | Up to 32.5 months |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Who Achieved Either Complete or Partial Immune Tolerance Within 33 Months of Initiation of ITI Treatment Phase | Complete immune tolerance was defined as the participants achieving 2 consecutive undetectable inhibitor titers (<0.6 BU) performed within 2 weeks of each other, Factor VIII activity (FVIII:C) in vivo plasma recovery ≥66% of the predicted normal value and FVIII:C half-life ≥6 hours after a 72-hour FVIII treatment-free period. Partial immune tolerance was defined as participants achieving reduction of inhibitor titer to <5 BU confirmed at 2 consecutive assessments within 2 weeks of each other, FVIII:C in vivo plasma recovery of <66% of the predicted normal value or FVIII:C half-life of <6 hours after a 72-hour FVIII treatment-free period and clinical response to FVIII therapy. |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment-emergent Adverse Events | Incidence of treatment-emergent adverse events during the ITI Treatment Phase and Prophylactic Phase | Up to 32.5 months |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30322 | United States | ||
| University of Kentucky |
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Male participants with diagnosis of Congenital Hemophilia A were enrolled in a single arm to receive alphanate. The study was to be conducted in 2 phases: Immune Tolerance Induction Phase followed by Prophylactic Phase. However, due to the limited enrollment, the study was terminated prior to the start of Prophylactic Phase.
Participants took part in the study at two sites in India from 03 January 2018 (first participant enrolled to receive the study drug) to 18 September 2020 (last participant completed).
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| ID | Title | Description |
|---|---|---|
| FG000 | Alphanate | Participants entered the immune tolerance induction (ITI) phase and received alphanate IV at a starting dose of 100 IU/kg/day. Dose could be uptitrated to 200 IU/kg/day based on investigator's discretion. The maximum duration of treatment was 32 months and 2 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Alphanate | Participants entered the immune tolerance induction (ITI) phase and received alphanate IV at a starting dose of 100 IU/kg/day. Dose could be uptitrated to 200 IU/kg/day based on investigator's discretion. The maximum duration of treatment was 32 months and 2 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Percentage of Participants Who Achieved Complete Immune Tolerance Within 33 Months of Initiation of Immune Tolerance Induction (ITI) Treatment Phase | Complete immune tolerance was defined as the participants achieving 2 consecutive undetectable inhibitor titers (<0.6 BU) performed within 2 weeks of each other, Factor VIII activity (FVIII:C) in vivo plasma recovery ≥66% of the predicted normal value and FVIII:C half-life ≥6 hours after a 72-hour FVIII treatment-free period. | Data for this outcome measure was not collected and analysed, as the study was early terminated by the sponsor due to limited enrollment (non-safety related decision). | Posted | Up to 32.5 months |
|
From first dose up to 32.5 months
Safety population included all participants who received any amount of alphanate.
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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 | Alphanate | Participants entered the ITI phase and received alphanate IV at a starting dose of 100 IU/kg/day. Dose could be uptitrated to 200 IU/kg/day based on investigator's discretion. The maximum duration of treatment was 32 months and 2 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lower respiratory tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombophlebitis | Vascular disorders | MedDRA 17.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rhonda Griffin | Grifols Therapeutics LLC | 919-316-6693 | rhonda.griffin@grifols.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 | Mar 21, 2019 | Oct 13, 2021 | Prot_SAP_001.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 |
|---|---|
| C509423 | factor VIII, von Willebrand factor drug combination |
| D014841 | von Willebrand Factor |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Up to 32.5 months |
| Percentage of Participants Who Achieved Complete or Partial Immune Tolerance Without Relapse During the Prophylactic Phase | Relapse during the prophylactic phase for participants who have achieved complete immune tolerance was defined as a return of FVIII inhibitor titer to detectable levels (≥0.6 BU) or FVIII:C recovery <66% of the predicted normal value or FVIII:C half-life <6 hours, confirmed by repeat assessment within approximately 2 weeks. Relapse for participants who have achieved partial immune tolerance was defined as an increase of FVIII inhibitor titer to ≥5 BU, confirmed by repeat assessment within approximately 2 weeks. | 12 months during prophylactic phase |
| Number of Bleeding Events During ITI Treatment Phase and Prophylactic Phase | Annualized frequencies of bleeding events during the ITI Treatment Phase and the Prophylactic Phase | Up to 32.5 months |
| Lexington |
| Kentucky |
| 40536 |
| United States |
| Childrens Hospital and Clinics of Minnesota | Minneapolis | Minnesota | 55404 | United States |
| The Childrens Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Robert Wood Johnson Medical Group | New Brunswick | New Jersey | 08901 | United States |
| Newark Beth Israel Medical Center & Children's Hospital of New Jersey | Newark | New Jersey | 07112 | United States |
| University of North Carolina at Chapel Hill, Hemophilia and Thrombosis Center | Chapel Hill | North Carolina | 27517 | United States |
| Seattle Children's Hospital, Seattle Children's Research Institute | Seattle | Washington | 98101 | United States |
| McMaster Children's Hospital | Hamilton | Ontario | L8N-3Z5 | Canada |
| Lokmanya Tilak Municipal Medical College & General Hospital | Mumbai | Maharashtra | 400022 | India |
| B. J. Govt. Medical College & Sassoon Hospital | Pune | 411001 | India |
| A.O.U. Santa Maria della Misericordia Perugia | Perugia | Umbria | 6132 | Italy |
| Azienda Ospedaliera Universitaria Careggi | Florence | 50134 | Italy |
| Universita degli Studi di Roma La Sapienza | Roma | 00161 | Italy |
| Kemerovo Regional Clinical Hospital | Kemerovo | 650061 | Russia |
| FGUs Hospital - Kirov Scientific Research Institute | Kirov | 610027 | Russia |
| Center for Hemophilia Treatment St.-Petersburg | Saint Petersburg | 191186 | Russia |
| Hospital Universitari i Politecnic La Fe | Valencia | Autonomous Community of Valencia | 46026 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
| Secondary | Percentage of Participants Who Achieved Either Complete or Partial Immune Tolerance Within 33 Months of Initiation of ITI Treatment Phase | Complete immune tolerance was defined as the participants achieving 2 consecutive undetectable inhibitor titers (<0.6 BU) performed within 2 weeks of each other, Factor VIII activity (FVIII:C) in vivo plasma recovery ≥66% of the predicted normal value and FVIII:C half-life ≥6 hours after a 72-hour FVIII treatment-free period. Partial immune tolerance was defined as participants achieving reduction of inhibitor titer to <5 BU confirmed at 2 consecutive assessments within 2 weeks of each other, FVIII:C in vivo plasma recovery of <66% of the predicted normal value or FVIII:C half-life of <6 hours after a 72-hour FVIII treatment-free period and clinical response to FVIII therapy. | Data for this outcome measure was not collected and analysed, as the study was early terminated by the sponsor due to limited enrollment (non-safety related decision). | Posted | Up to 32.5 months |
|
|
| Secondary | Percentage of Participants Who Achieved Complete or Partial Immune Tolerance Without Relapse During the Prophylactic Phase | Relapse during the prophylactic phase for participants who have achieved complete immune tolerance was defined as a return of FVIII inhibitor titer to detectable levels (≥0.6 BU) or FVIII:C recovery <66% of the predicted normal value or FVIII:C half-life <6 hours, confirmed by repeat assessment within approximately 2 weeks. Relapse for participants who have achieved partial immune tolerance was defined as an increase of FVIII inhibitor titer to ≥5 BU, confirmed by repeat assessment within approximately 2 weeks. | Data for this outcome measure was not collected and analysed, as the study was early terminated by the sponsor due to limited enrollment (non-safety related decision). | Posted | 12 months during prophylactic phase |
|
|
| Secondary | Number of Bleeding Events During ITI Treatment Phase and Prophylactic Phase | Annualized frequencies of bleeding events during the ITI Treatment Phase and the Prophylactic Phase | This study was terminated, and the data is not reported for this outcome measure to maintain participant's confidentiality. | Posted | Up to 32.5 months |
|
|
| Other Pre-specified | Treatment-emergent Adverse Events | Incidence of treatment-emergent adverse events during the ITI Treatment Phase and Prophylactic Phase | Not Posted | Up to 32.5 months | Participants |
| 0 |
| 2 |
| 2 |
| 2 |
| 2 |
| 2 |
| Subdural hemorrhage | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Hepatitis C Antibody positive | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 17.1 | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA 17.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
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| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
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| Varicella | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsors' request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsors' request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor Inventions.
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D001685 |
| Biological Factors |