Hemophilia A, Congenital Clinical Trial
Official title:
A Multicenter Phase 2 Open-Label, Single-Arm, Prospective, Interventional Study of Plasma-Derived Factor VIII/VWF (Alphanate®) in Immune Tolerance Induction Therapy in Subjects With Congenital Hemophilia A
Verified date | October 2021 |
Source | Grifols Therapeutics LLC |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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: - An ITI Treatment Phase in which all eligible participants will receive ITI treatment with alphanate for a period of up to 33 months. Upon confirmation of complete immune tolerization, participants will then enter a 12-month Prophylactic Phase. If, after 33 months of ITI, a participants has achieved partial immune tolerance, the participants will enter a 12-month Prophylactic Phase. - A 12-month Prophylactic Phase for all participants who meet the criteria for complete or partial success to continue on a prophylactic dosing regimen of alphanate. Due to limited enrollment, this study was early terminated.
Status | Terminated |
Enrollment | 2 |
Est. completion date | September 18, 2020 |
Est. primary completion date | September 18, 2020 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | N/A to 12 Years |
Eligibility | Inclusion Criteria: - The subject has a documented diagnosis of severe congenital hemophilia A with FVIII:C <1% of normal. - The subject is a male <12 years (and at least 2 years of age if in India) at the Baseline Visit. - The subject's documented historical peak inhibitor titer is =5 BU and =200 BU. - The subject has an inhibitor titer >0.6 BU and <10 BU at Screening. - The subject has had a delay =24 months from the date of diagnosis of the inhibitor to the start of the subject's ITI treatment. Exclusion Criteria: - The subject has acquired factor VIII (FVIII) deficiency. - The subject has previously received ITI treatment. - The subject has a recent (within 1 month) history of central line infection at the time of Screening. - The subject has a high risk of cardiovascular, cerebrovascular, or thromboembolic event as judged by the investigator. - The subject is currently undergoing treatment with immunosuppressive drugs (eg, systemic corticosteroids), azathioprine, cyclophosphamide, high dose immunoglobulin, interferon, or the use of a protein A column or plasmapheresis and is unwilling to discontinue these treatments starting at the screening visit. - The subject has a known infection with human immunodeficiency virus (HIV) or has clinical signs and symptoms consistent with current HIV infection. - The subject has a known previous infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) or has clinical signs and symptoms consistent with current HBV or HCV infection. - The subject has significant proteinuria, has a history of acute renal failure or severe renal impairment (blood urea nitrogen or creatinine >2 times the upper limit of normal), or is receiving dialysis at Screening. - The subject has a value of aspartate transaminase or alanine aminotransferase >2 times the upper limit of normal at Screening. - The subject has clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the trial or place the subject at undue medical risk. - The subject has a history of anaphylaxis or severe systemic reaction to any plasma derived or other blood products. |
Country | Name | City | State |
---|---|---|---|
Canada | McMaster Children's Hospital | Hamilton | Ontario |
India | Lokmanya Tilak Municipal Medical College & General Hospital | Mumbai | Maharashtra |
India | B. J. Govt. Medical College & Sassoon Hospital | Pune | |
Italy | Azienda Ospedaliera Universitaria Careggi | Firenze | |
Italy | A.O.U. Santa Maria della Misericordia Perugia | Perugia | Umbria |
Italy | Universita degli Studi di Roma La Sapienza | Roma | |
Russian Federation | Kemerovo Regional Clinical Hospital | Kemerovo | |
Russian Federation | FGUs Hospital - Kirov Scientific Research Institute | Kirov | |
Russian Federation | Center for Hemophilia Treatment St.-Petersburg | Saint Petersburg | |
Spain | Hospital Universitario La Paz | Madrid | |
Spain | Hospital Universitario Virgen del Rocio | Sevilla | |
Spain | Hospital Universitari i Politecnic La Fe | Valencia | Autonomous Community Of Valencia |
United States | Emory University | Atlanta | Georgia |
United States | University of North Carolina at Chapel Hill, Hemophilia and Thrombosis Center | Chapel Hill | North Carolina |
United States | The Childrens Mercy Hospital | Kansas City | Missouri |
United States | University of Kentucky | Lexington | Kentucky |
United States | Childrens Hospital and Clinics of Minnesota | Minneapolis | Minnesota |
United States | Robert Wood Johnson Medical Group | New Brunswick | New Jersey |
United States | Newark Beth Israel Medical Center & Children's Hospital of New Jersey | Newark | New Jersey |
United States | Seattle Children's Hospital, Seattle Children's Research Institute | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Grifols Therapeutics LLC | Grifols Biologicals, LLC |
United States, Canada, India, Italy, Russian Federation, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Treatment-emergent Adverse Events | Incidence of treatment-emergent adverse events during the ITI Treatment Phase and Prophylactic Phase | Up to 32.5 months | |
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. | Up to 32.5 months | |
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. | 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. | 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 | Up to 32.5 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
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