Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R34HL105870-01A1 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
study was non-feasible per DSMB
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this pilot R34 trial is to determine the feasibility of a large single dose Phase III study of hemophilia adult prophylaxis comparing once weekly with thrice-weekly recombinant factor VIII. Efficacy will measured by bleeding frequency, factor usage, joint range of motion, cost, quality-of-life, F.VIII level, and inter-dose hypocoagulability by thrombin generation. Safety will be measured by inhibitor formation and bleeding events unresponsive to up to two rescue doses.
The purpose of this 52-week pilot R34 randomized, open-label, non-inferiority, cross-over study is to determine the feasibility of a large single dose Phase III study of hemophilia adult prophylaxis. The primary efficacy endpoint will be bleeding frequency. Secondary endpoints will include factor usage, joint range of motion, cost, quality-of-life, and inter-dose hypocoagulability by thrombin generation time and F.VIII activity will also be determined. Safety will be measured by the frequency of bleeding unresponsive to up to two rescue treatments. Inhibitor formation by anti-F.VIII Bethesda assay, and clinical frequency of thrombosis and allergic reactions will also be assessed. Subject acceptance and adherence to the treatment interventions will be determined; and web-based data entry of case report forms, digital range-of-motion images, and quality-of-life instrument will be implemented. The relation of bleeding frequency to relative inter-dose hypocoagulability, will be assessed by inter-dose thrombin generation time (TGT), endogenous thrombin potential (ETP), and factor VIII levels. Optimal blood sample collection and shipping methods will be determined. For all tests, we will estimate and determine completeness and congruency, in order to determine adjustments or revisions required before initiating a large phase III Randomized clinical trial. All testing will be exploratory, so that we may determine if the test, approach are realistic, and to estimate standard deviations for future power analyses.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | The intervention for Arm A is 40 IU/kg recombinant factor VIII (rFVIII) by once-weekly intravenous injection for 26 weeks. Cross-over will occur at 26 weeks after a 72 hour washout period, after which 40 IU/kg recombinant factor VIII (rFVIII) will be given thrice-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds. |
|
| Arm B | Experimental | The intervention for Arm B is 40 IU/kg recombinant factor VIII (rFVIII) by thrice-weekly intravenous injection for 26 weeks. Cross-over will occur at 26 weeks after a 72 hour washout period, after which 40 IU/kg recombinant factor VIII (rFVIII) will be given once-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rF.VIII | Drug | 40 IU/kg recombinant factor VIII will be given once-weekly or thrice-weekly by intravenous injection for 26 weeks. At 26 weeks after a 72 hour washout period, 40 IU/kg recombinant factor VIII will be given thrice-weekly or once-weekly, respectively, by intravenous injection until week 52, with up to two rescue doses per week for bleeds |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Bleeds | The primary outcome was bleed frequency. The data were total number of events for each Arm, and not per-participant. | Weeks 26 (first intervention) and 52 (second intervention) |
| Measure | Description | Time Frame |
|---|---|---|
| Inter-dose Hypocoagulability by Thrombin Generation | Thrombin generation was performed at week 8 and week 34, i.e. 8 weeks after initiation of factor dosing in Weeks 1-26, and 8 weeks after initiation of factor dosing in Weeks 27-52. | The time frame is 52 weeks per subject. |
| F.VIII Activity |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Margaret V. Ragni, MD, MPH | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Georgetown University | Washington D.C. | District of Columbia | 20057-1168 | United States | ||
| Hospital of the University of Pennsylvania |
The data from this trial will be available, pending NIH approval, through BioLINCC https://biolincc.nhlbi.nih.gov.
Not provided
Not provided
Not provided
Not provided
Following enrollment, subjects initiated study drug according to the randomization to Arm A (once-weekly FVIII) or Arm B (thrice-weekly FVIII) for a 26 week period followed by a 72 hour washout period prior to crossover to the other arm for the second 26 week period.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Once-Weekly Then Thrice-Weekly FVIII | Subjects randomized to receive either once-weekly F.VIII at 40 IU/kg (Arm A) or thrice-weekly F.VIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm for the last 26 weeks, following a 72 hour washout period. Group 1, will receive Arm A for the first 26 weeks, and Arm B for the last 26 weeks. Group 2, will receive Arm B for the first 26 weeks and Arm A for the last 26 weeks. |
| FG001 | Thrice-Weekly Then Once-Weekly FVIII | Subjects randomized to receive either once-weekly F.VIII at 40 IU/kg (Arm A) or thrice-weekly F.VIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm for the last 26 weeks, following a 72 hour washout period. Group 1, will receive Arm A for the first 26 weeks, and Arm B for the last 26 weeks. Group 2, will receive Arm B for the first 26 weeks and Arm A for the last 26 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Severe Hemophilia A | Subjects will be randomized to receive either once-weekly F.VIII at 40 IU/kg (Arm A) or thrice-weekly F.VIII at 40 IU/kg (Arm B) for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm for the last 26 weeks, following a 72 hour washout period. |
| 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 | Number of Bleeds | The primary outcome was bleed frequency. The data were total number of events for each Arm, and not per-participant. | 3 completing study were analyzed | Posted | Number | bleeds per 26 weeks | Weeks 26 (first intervention) and 52 (second intervention) |
|
52 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A Once-weekly F.VIII at 40 IU/kg | Subjects in Arm A will be randomized to receive either once-weekly F.VIII at 40 IU/kg for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm (thrice-weekly) for the last 26 weeks, following a 72 hour washout period. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| sinus infection | Infections and infestations | Systematic Assessment | developed (his usual) mild inflammation of sinuses, manifested by nasal stuffiness |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Margaret V. Ragni, MD, MPH | University of Pittsburgh | 412-209-7288 | ragni@pitt.edu |
Not provided
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D005169 | Factor VIII |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
F.VIII Activity (IU/mL) performed at week 8 and week 34, i.e. 8 weeks after initiation of factor dosing in Weeks 1-26, and 8 weeks after initiation of factor dosing in Weeks 27-52. |
| The time frame is 52 weeks per subject. |
| Philadelphia |
| Pennsylvania |
| 19104-4206 |
| United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104-4318 | United States |
| Hemophilia Center of Western Pennsylvania | Pittsburgh | Pennsylvania | 15213-4306 | United States |
| Vanderbilt University | Nashville | Tennessee | 37235-7749 | United States |
| Puget Sound Blood Center | Seattle | Washington | 98104-1256 | United States |
| Participants |
|
| Age, Continuous | Median | Full Range | year |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Inter-dose Hypocoagulability by Thrombin Generation | Thrombin generation was performed at week 8 and week 34, i.e. 8 weeks after initiation of factor dosing in Weeks 1-26, and 8 weeks after initiation of factor dosing in Weeks 27-52. | Posted | Median | Full Range | nMs | The time frame is 52 weeks per subject. |
|
|
|
| Secondary | F.VIII Activity | F.VIII Activity (IU/mL) performed at week 8 and week 34, i.e. 8 weeks after initiation of factor dosing in Weeks 1-26, and 8 weeks after initiation of factor dosing in Weeks 27-52. | Posted | Median | Full Range | IU/mL | The time frame is 52 weeks per subject. |
|
|
|
| 0 |
| 4 |
| 1 |
| 4 |
| EG001 | Arm B Thrice-weekly F.VIII at 40 IU/kg | Subjects will be randomized to receive thrice-weekly F.VIII at 40 IU/kg for the first 26 weeks of study. Then, at 26 weeks, they will undergo "Cross-Over", that is, switch to the alternative Study Arm (once-weekly) for the last 26 weeks, following a 72 hour washout period. | 0 | 4 | 0 | 4 |
|
Not provided
Not provided
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D011498 |
| Protein Precursors |
| D001685 | Biological Factors |