RICH: Rituximab to Treat Severe Hemophilia A
Study Details
Study Description
Brief Summary
Hemophilia A is a serious blood clotting disorder caused by a lack of factor VIII, a specialized protein needed for normal blood clotting to occur. Individuals with this disease may experience spontaneous bleeding, pain and swelling in their joints due to excess bleeding, and bruising. A common treatment for severe hemophilia A is to intravenously replace the deficient blood clotting factor; however, some individuals may develop antibodies to this replacement factor. This study will evaluate the effectiveness of rituximab at reducing the antibodies that develop in response to the replacement factor in individuals with severe hemophilia A.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
Hemophilia A is a hereditary blood clotting disorder. It is caused by a deficiency or abnormality of the blood clotting protein factor VIII. Individuals with hemophilia A are unable to form blood clots to stop bleeding and are at risk for experiencing serious and life-threatening bleeding episodes. The most common treatment for this disease is intravenous replacement of factor VIII. However, between 30 to 40% of individuals eventually develop inhibitors, or antibodies, to the replacement factor. In these individuals, the immune system recognizes the replacement factor as foreign and attacks it, thereby countering any potential benefits of the treatment. Some individuals with severe hemophilia A may undergo immune tolerance therapy (ITT), in which they receive replacement factor on a regular basis as a way for the body to adjust to the factor and stop inhibitor production. This treatment, however, is not always effective for everyone. Preliminary research has shown that rituximab, a medication used to treat non-Hodgkin's lymphoma, may be successful in suppressing or eliminating the inhibitors that develop. The purpose of this study is to evaluate the effectiveness of rituximab at lowering the levels of factor VIII inhibitors in individuals with severe hemophilia A.
This study will enroll individuals with severe hemophilia A. At study entry, participants will receive one intravenous dose of factor VIII. Inhibitor levels will be measured with a blood test 5 to 7 days following this procedure. If peak inhibitor level is above 5 Bethesda units (BU)/mL, 5 to 9 days later participants will begin receiving rituximab intravenously once a week for 4 weeks. Blood will be collected at each visit for laboratory testing. Two weeks following the last rituximab treatment, participants will have blood drawn for inhibitor testing; this testing will occur every 4 weeks through Week 22. If the participant's inhibitor level falls below 5 BU/mL, participants will receive a repeat dose of factor VIII, and blood will be drawn 5 to 7 days later for inhibitor testing. Follow-up visits will occur at Weeks 36, 52, and 100, and will include a physical examination, blood collection, and monitoring of bleeding events and infections. Telephone interviews will be conduced at Weeks 64, 76, and 88 to monitor bleeding events and infections.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Rituximab Rituximab administered at a dose of 375 mg/m2 by slow intravenous infusion once per week for 4 weeks |
Drug: Rituximab
Rituximab by slow intravenous infusion; for participants greater than or equal to 10 kg, 375 mg per m^2 BSA weekly for 4 weeks; for participants less than 10 kg, 12.5 mg/kg weekly for 4 weeks
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of Subjects With Major Response, i.e. Inhibitor Level Falls to Less Than 5 BU/mL Between Weeks 6 to 22 and Remains Below 5 BU/mL at 5-7 Days Following Re-challenge With FVIII [Measured within approximately 22 weeks]
Presence or absence of a major response in each participant. Major response is defined as occurring when inhibitor level falls to less than 5 BU/mL between Weeks 6 to 22 and remains below 5 BU/mL at 5-7 days following re-challenge with FVIII
Secondary Outcome Measures
- Proportion of Subjects With at Least Minor Response, i.e. Inhibitor Level Falls to <5 BU/mL Between Weeks 6-22 and Either Remains <5 BU/mL 5-7 Days Following FVIII Rechallenge or Titer Following FVIII Rechallenge is 5-10 BU/mL & <50% of Original Peak [Measured within approximately 22 weeks]
Presence or absence of at least a minor response in each participant
- Percent Change in Inhibitor Titer on Challenge With Factor VIII From Baseline Challenge to Post-treatment Challenge [Measured within approximately 22 weeks]
percent change=100%*(A-B)/B where A=inhibitor titer measured within 5-7 days following FVIII rechallenge and B=inhibitor titer measured within 5-14 days following baseline FVIII challenge. A FVIII rechallenge was performed within 10-18 days of the first monthly study visit in which an inhibitor titer result <5 BU/mL was obtained beginning 2 weeks and continuing through 18 weeks following the last rituximab infusion.
- Median Number of Bleeding Events Per Subject Meeting the Criteria of a Serious Adverse Event [Measured through Week 100]
Median number of bleeding events per subject meeting the criteria of a serious adverse event
- Median Number of Bleeding Events Per Subject Not Meeting the Criteria of a Serious Adverse Event [Measured through Week 100]
Median Number of Bleeding Events Per Subject Not Meeting the Criteria of a Serious Adverse Event
- Median Number of Serious Adverse Events Per Subject Other Than Bleeding Events [Measured through Week 100]
Median Number of Serious Adverse Events Per Subject Other Than Bleeding Events
- Median Number of Adverse Events Per Subject That Were Not Bleeding Events and Did Not Meet the Criteria of a Serious Adverse Event [Measured through Week 100]
Median Number of Adverse Events Per Subject That Were Not Bleeding Events and Did Not Meet the Criteria of a Serious Adverse Event
- Proportion of Rituximab Infusions in Which a Reaction to the Infusion Was Reported [Measured at Week 1 through Week 4]
Proportion of rituximab infusions in which a reaction to the infusion was reported
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Severe congenital hemophilia A
-
Documented historical inhibitor titer to factor VIII of at least 5 BU/mL
-
Inhibitor level greater than or equal to 5 BU/mL 5 to 14 days after initial factor VIII exposure during screening
Exclusion Criteria:
-
Known hypersensitivities or allergies to murine and/or humanized antibodies
-
Currently participating in investigational hemophilia studies
-
HIV infected
-
Any immunodeficiency disorder
-
Liver disease and serum ALT or AST is greater than three times the upper limit of normal, albumin is less than 2.5g/dl, and/or INR is greater than 1.7
-
Received interferon or other immunomodulatory drugs, such as steroids or cytotoxic therapy in the 30 days prior to study entry
-
History of cardiac arrhythmias, any active febrile illness, kidney insufficiency, or pulmonary infiltrates
-
Has previously received rituximab treatment
-
Currently undergoing immune tolerance therapy
-
Evidence of Hepatitis B (HBV) infection, defined as one of the following:
-
HBsAg positive
-
HBsAg negative, HBsAb negative, HBcAb positive, and HBV DNA positive
-
Participants with a high responding inhibitor (at least 5 BU/mL) first detected fewer than 12 months prior to study entry, unless the participant has failed immune tolerance therapy, defined as one of the following:
-
Failure to fulfill the criteria for full or partial success within 33 months, as defined by a factor VIII recovery greater than or equal to 66% of expected and half-life greater than or equal to 6 hours measured after a 72-hour treatment-free washout period
-
Failure to achieve greater than 20% reduction in inhibitor titer during each interim non-overlapping 6-month period of ITT in the absence of documented infection, with 9 months as the minimum treatment period and 33 months as the maximum possible duration of unsuccessful ITT
-
Withdrawal from ITT for any other reason
-
Routinely receive factor VIII concentrate for the treatment of both major and minor bleeding events
-
Has received factor VIII concentrate in the 7 days prior to study entry
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Children's Hospital of Orange County | Orange | California | United States | 92868 |
2 | Children's Healthcare of Atlanta | Atlanta | Georgia | United States | 30322 |
3 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
4 | Tulane University Health Sciences Center | New Orleans | Louisiana | United States | 70112 |
5 | Children's Hospital Boston | Boston | Massachusetts | United States | 02115 |
6 | UNC at Chapel Hill Hospital | Chapel Hill | North Carolina | United States | 27514 |
7 | University Hospital of Cleveland | Cleveland | Ohio | United States | 44106 |
8 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
9 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
10 | Hemophilia Center of Western Pennsylvania | Pittsburgh | Pennsylvania | United States | 15213 |
11 | University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
12 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
13 | Comprehensive Center for Bleeding Disorders | Milwaukee | Wisconsin | United States | 53201 |
Sponsors and Collaborators
- HealthCore-NERI
- National Heart, Lung, and Blood Institute (NHLBI)
- Genentech, Inc.
Investigators
- Principal Investigator: Susan F. Assmann, PhD, NERI
- Principal Investigator: Cindy Leissinger, MD, Tulane University Health Sciences Center
- Principal Investigator: Joan Gill, MD, Versiti
- Principal Investigator: Keith McCrae, MD, University Hospital of Cleveland
- Principal Investigator: Ellis Neufeld, MD, Boston Children's Hospital
- Principal Investigator: Cassandra Josephson, MD, Children's Healthcare of Atlanta
- Principal Investigator: Nigel Key, MD, University of North Carolina
- Principal Investigator: Charles Sexauer, MD, University of Oklahoma
- Principal Investigator: Janna Journeycake, MD, University of Texas Southwestern Medical Center
- Principal Investigator: Leslie Raffini, MD, Children's Hospital of Philadelphia
- Principal Investigator: Margaret Ragni, MD, Hemophilia Center of Western Pennsylvania
- Principal Investigator: Leonard Valentino, MD, Rush University Medical Center
- Principal Investigator: Diane Nugent, MD, Children's Hospital of Orange County
- Principal Investigator: Marcella Torres, MD, Cook Children's Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 374
- U01HL072268
- U01HL072274
- U01HL072290
- U01HL072033
- U01HL072291
- U01HL072248
- U01HL072355
- U01HL072283
- U01HL072346
- U01HL072331
Study Results
Participant Flow
Recruitment Details | Subjects were recruited at clinical sites and Hemophilia Treatment Centers participating in the study. The recruitment period began in August 2006 and continued through November 2011. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Period Title: Screening Phase | |
STARTED | 23 |
COMPLETED | 16 |
NOT COMPLETED | 7 |
Period Title: Screening Phase | |
STARTED | 16 |
COMPLETED | 15 |
NOT COMPLETED | 1 |
Period Title: Screening Phase | |
STARTED | 15 |
COMPLETED | 14 |
NOT COMPLETED | 1 |
Period Title: Screening Phase | |
STARTED | 14 |
COMPLETED | 11 |
NOT COMPLETED | 3 |
Baseline Characteristics
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Overall Participants | 23 |
Age (Count of Participants) | |
<=18 years |
19
82.6%
|
Between 18 and 65 years |
4
17.4%
|
>=65 years |
0
0%
|
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
15.85
(12.02)
|
Sex: Female, Male (Count of Participants) | |
Female |
0
0%
|
Male |
23
100%
|
Region of Enrollment (participants) [Number] | |
United States |
23
100%
|
Outcome Measures
Title | Proportion of Subjects With Major Response, i.e. Inhibitor Level Falls to Less Than 5 BU/mL Between Weeks 6 to 22 and Remains Below 5 BU/mL at 5-7 Days Following Re-challenge With FVIII |
---|---|
Description | Presence or absence of a major response in each participant. Major response is defined as occurring when inhibitor level falls to less than 5 BU/mL between Weeks 6 to 22 and remains below 5 BU/mL at 5-7 days following re-challenge with FVIII |
Time Frame | Measured within approximately 22 weeks |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received at least one dose of rituximab |
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Measure Participants | 16 |
Number (95% Confidence Interval) [proportion of participants] |
.1875
0.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Rituximab |
---|---|---|
Comments | The null hypothesis is that the proportion of participants in which the inhibitor level falls to less than 5 BU/mL between weeks 6 to 22 and remains below 5 BU/mL at 5-7 days following re-challenge with factor VIII is no more than 0.05 | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.043 |
Comments | the a priori p-value was 0.05 for statistical significance | |
Method | Exact Binomial | |
Comments | ||
Method of Estimation | Estimation Parameter | Proportion |
Estimated Value | .1875 | |
Confidence Interval |
(1-Sided) 95% .053 to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Proportion of Subjects With at Least Minor Response, i.e. Inhibitor Level Falls to <5 BU/mL Between Weeks 6-22 and Either Remains <5 BU/mL 5-7 Days Following FVIII Rechallenge or Titer Following FVIII Rechallenge is 5-10 BU/mL & <50% of Original Peak |
---|---|
Description | Presence or absence of at least a minor response in each participant |
Time Frame | Measured within approximately 22 weeks |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received at least one dose of rituximab |
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Measure Participants | 16 |
Number (95% Confidence Interval) [proportion of participants] |
0.25
1.1%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Rituximab |
---|---|---|
Comments | No hypothesis about the value of this proportion was specified in the study design | |
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Proportion |
Estimated Value | .25 | |
Confidence Interval |
(2-Sided) 95% 0.073 to 0.524 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Percent Change in Inhibitor Titer on Challenge With Factor VIII From Baseline Challenge to Post-treatment Challenge |
---|---|
Description | percent change=100%*(A-B)/B where A=inhibitor titer measured within 5-7 days following FVIII rechallenge and B=inhibitor titer measured within 5-14 days following baseline FVIII challenge. A FVIII rechallenge was performed within 10-18 days of the first monthly study visit in which an inhibitor titer result <5 BU/mL was obtained beginning 2 weeks and continuing through 18 weeks following the last rituximab infusion. |
Time Frame | Measured within approximately 22 weeks |
Outcome Measure Data
Analysis Population Description |
---|
All subjects who received a post-treatment rechallenge and had at least a minor response. |
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Measure Participants | 4 |
Median (Inter-Quartile Range) [percentage change] |
-64.31
|
Title | Median Number of Bleeding Events Per Subject Meeting the Criteria of a Serious Adverse Event |
---|---|
Description | Median number of bleeding events per subject meeting the criteria of a serious adverse event |
Time Frame | Measured through Week 100 |
Outcome Measure Data
Analysis Population Description |
---|
Data on bleeding events were collected at every study visit for all study participants. Data for this outcome was collected through the particpants end of study or Week 100, whichever came first, and is restricted to the 16 subjects who received at least one dose of rituximab. |
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Measure Participants | 16 |
Median (Inter-Quartile Range) [participants] |
0
0%
|
Title | Median Number of Bleeding Events Per Subject Not Meeting the Criteria of a Serious Adverse Event |
---|---|
Description | Median Number of Bleeding Events Per Subject Not Meeting the Criteria of a Serious Adverse Event |
Time Frame | Measured through Week 100 |
Outcome Measure Data
Analysis Population Description |
---|
Data on bleeding events were collected at every study visit for all study participants. Data for this outcome was collected through the particpants end of study or Week 100, whichever came first, and is restricted to the 16 subjects who received at least one dose of rituximab. |
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Measure Participants | 16 |
Median (Inter-Quartile Range) [participants] |
19.5
84.8%
|
Title | Median Number of Serious Adverse Events Per Subject Other Than Bleeding Events |
---|---|
Description | Median Number of Serious Adverse Events Per Subject Other Than Bleeding Events |
Time Frame | Measured through Week 100 |
Outcome Measure Data
Analysis Population Description |
---|
Data on bleeding events were collected at every study visit for all study participants. Data for this outcome was collected through the particpants end of study or Week 100, whichever came first, and is restricted to the 16 subjects who received at least one dose of rituximab. |
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Measure Participants | 16 |
Median (Inter-Quartile Range) [participants] |
1
4.3%
|
Title | Median Number of Adverse Events Per Subject That Were Not Bleeding Events and Did Not Meet the Criteria of a Serious Adverse Event |
---|---|
Description | Median Number of Adverse Events Per Subject That Were Not Bleeding Events and Did Not Meet the Criteria of a Serious Adverse Event |
Time Frame | Measured through Week 100 |
Outcome Measure Data
Analysis Population Description |
---|
Data on bleeding events were collected at every study visit for all study participants. Data for this outcome was collected through the particpants end of study or Week 100, whichever came first, and is restricted to the 16 subjects who received at least one dose of rituximab. |
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Measure Participants | 16 |
Median (Inter-Quartile Range) [participants] |
1.5
6.5%
|
Title | Proportion of Rituximab Infusions in Which a Reaction to the Infusion Was Reported |
---|---|
Description | Proportion of rituximab infusions in which a reaction to the infusion was reported |
Time Frame | Measured at Week 1 through Week 4 |
Outcome Measure Data
Analysis Population Description |
---|
All rituximab infusions given to study participants |
Arm/Group Title | Rituximab |
---|---|
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks |
Measure Participants | 16 |
Measure rituximab infusions | 61 |
Number (95% Confidence Interval) [proportion of rituximab infusions] |
0.11
|
Adverse Events
Time Frame | Through week 100 | |
---|---|---|
Adverse Event Reporting Description | Restricted to the 16 subjects who received at least one dose of rituximab. | |
Arm/Group Title | Rituximab | |
Arm/Group Description | Rituximab administered at a dose of 375 mg/m^2 by slow intravenous infusion once per week for 4 weeks | |
All Cause Mortality |
||
Rituximab | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Rituximab | ||
Affected / at Risk (%) | # Events | |
Total | 11/16 (68.8%) | |
Gastrointestinal disorders | ||
Diarrhea | 1/16 (6.3%) | 1 |
Mallory-Weiss tear | 1/16 (6.3%) | 1 |
General disorders | ||
Allergic reaction/hypersensitivity | 1/16 (6.3%) | 1 |
Fever | 1/16 (6.3%) | 1 |
Infections and infestations | ||
Central line infection | 1/16 (6.3%) | 1 |
Pulmonary/upper respiratory infection | 1/16 (6.3%) | 1 |
Sepsis | 1/16 (6.3%) | 1 |
Viral meningitis | 1/16 (6.3%) | 1 |
Zoster infection | 1/16 (6.3%) | 1 |
Injury, poisoning and procedural complications | ||
Bleeding and/or hematoma due to injury | 1/16 (6.3%) | 1 |
Bleeding and/or hematoma due to procedure complication | 1/16 (6.3%) | 1 |
Hematoma due to injury | 1/16 (6.3%) | 2 |
Hematoma due to procedure complication | 1/16 (6.3%) | 1 |
Joint and other bleeding due to injury | 1/16 (6.3%) | 2 |
Joint bleeding due to injury | 3/16 (18.8%) | 6 |
Joint bleeding due to procedure complication | 1/16 (6.3%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Bleeding and/or hematoma - spontaneous | 1/16 (6.3%) | 1 |
Bone fracture | 1/16 (6.3%) | 1 |
Joint and other bleeding - spontaneous | 1/16 (6.3%) | 1 |
Joint bleeding - spontaneous | 4/16 (25%) | 11 |
Nervous system disorders | ||
Headache | 1/16 (6.3%) | 1 |
Subdural hemorrhage | 1/16 (6.3%) | 2 |
Respiratory, thoracic and mediastinal disorders | ||
Shortness of breath | 1/16 (6.3%) | 1 |
Surgical and medical procedures | ||
Port placement | 1/16 (6.3%) | 1 |
Port removal and replacement | 1/16 (6.3%) | 1 |
Synovectomy | 2/16 (12.5%) | 2 |
Vascular disorders | ||
Hypotension | 1/16 (6.3%) | 1 |
Splenic hematoma | 1/16 (6.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Rituximab | ||
Affected / at Risk (%) | # Events | |
Total | 15/16 (93.8%) | |
Blood and lymphatic system disorders | ||
Anemia | 1/16 (6.3%) | 3 |
Enlarged lymph nodes | 1/16 (6.3%) | 1 |
Increased blood lymphocytes | 1/16 (6.3%) | 1 |
Increased blood monocytes | 1/16 (6.3%) | 2 |
Neutropenia | 1/16 (6.3%) | 1 |
White blood cell decrease | 1/16 (6.3%) | 3 |
Endocrine disorders | ||
Sweating | 1/16 (6.3%) | 1 |
Eye disorders | ||
Pink eye | 1/16 (6.3%) | 1 |
Gastrointestinal disorders | ||
Abdominal pain | 2/16 (12.5%) | 3 |
Bleeding - spontaneous | 4/16 (25%) | 12 |
Diarrhea | 1/16 (6.3%) | 1 |
Heartburn | 1/16 (6.3%) | 1 |
Nausea | 1/16 (6.3%) | 3 |
Toothache | 1/16 (6.3%) | 1 |
Vomiting | 1/16 (6.3%) | 4 |
General disorders | ||
Bleed and/or hematoma | 1/16 (6.3%) | 1 |
Chills | 3/16 (18.8%) | 3 |
fatigue | 1/16 (6.3%) | 2 |
Fever | 2/16 (12.5%) | 4 |
Lethargy | 1/16 (6.3%) | 1 |
Hepatobiliary disorders | ||
Decreased ALT | 1/16 (6.3%) | 3 |
Elevated ALT | 1/16 (6.3%) | 7 |
Immune system disorders | ||
Allergy | 1/16 (6.3%) | 1 |
Infections and infestations | ||
Cold sore | 1/16 (6.3%) | 1 |
Group A strep | 1/16 (6.3%) | 2 |
Influenza | 2/16 (12.5%) | 2 |
Septic polyarthritis | 1/16 (6.3%) | 1 |
Sinusitis | 1/16 (6.3%) | 1 |
Injury, poisoning and procedural complications | ||
Bleed and/or hematoma due to injury | 4/16 (25%) | 12 |
Bleeding due to injury | 3/16 (18.8%) | 9 |
Bleeding due to procedure complication | 2/16 (12.5%) | 2 |
Head injury | 2/16 (12.5%) | 2 |
Joint bleeding due to injury | 11/16 (68.8%) | 31 |
Joint pain due to injury | 1/16 (6.3%) | 1 |
vaccination site reaction | 1/16 (6.3%) | 1 |
Hematoma due to injury | 6/16 (37.5%) | 14 |
Hematoma due to procedure complication | 4/16 (25%) | 5 |
Pain | 1/16 (6.3%) | 1 |
Metabolism and nutrition disorders | ||
Anorexia | 1/16 (6.3%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Joint bleeding, spontaneous | 15/16 (93.8%) | 262 |
Joint pain | 1/16 (6.3%) | 1 |
Joint pain, spontaneous | 1/16 (6.3%) | 2 |
Joint range of motion decreased | 2/16 (12.5%) | 2 |
Muscle pain, spontaneous | 1/16 (6.3%) | 2 |
Pain | 2/16 (12.5%) | 2 |
Bleed and/or hematoma - spontaneous | 10/16 (62.5%) | 26 |
Bleeding - spontaneous | 1/16 (6.3%) | 1 |
Hematoma - spontaneous | 3/16 (18.8%) | 3 |
Nervous system disorders | ||
Bells palsy | 1/16 (6.3%) | 1 |
Bleeding - spontaneous | 1/16 (6.3%) | 1 |
Headache | 2/16 (12.5%) | 2 |
Intolerance to light | 1/16 (6.3%) | 1 |
Renal and urinary disorders | ||
Bleeding - spontaneous | 1/16 (6.3%) | 2 |
Hematuria | 1/16 (6.3%) | 1 |
Reproductive system and breast disorders | ||
Cold | 2/16 (12.5%) | 2 |
Respiratory, thoracic and mediastinal disorders | ||
Asthma | 1/16 (6.3%) | 3 |
Bleeding - spontaneous | 1/16 (6.3%) | 1 |
Cough | 1/16 (6.3%) | 3 |
Elevated carbon dioxide in the blood | 1/16 (6.3%) | 1 |
Nasal congestion | 1/16 (6.3%) | 1 |
Runny nose | 2/16 (12.5%) | 3 |
Sore throat | 1/16 (6.3%) | 1 |
Wheezing | 1/16 (6.3%) | 2 |
Skin and subcutaneous tissue disorders | ||
Bleed and/or hematoma - spontaneous | 7/16 (43.8%) | 20 |
Hematoma - spontaneous | 9/16 (56.3%) | 24 |
Rash | 2/16 (12.5%) | 3 |
Sunburn | 1/16 (6.3%) | 1 |
Bleeding - spontaneous | 1/16 (6.3%) | 1 |
Vascular disorders | ||
High blood pressure | 1/16 (6.3%) | 1 |
Low blood pressure | 1/16 (6.3%) | 4 |
Pulmonary hypertension | 1/16 (6.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Baxter donated Factor VIII and Genentech donated rituximab for the study. Both Baxter and Genentech can review results communications prior to public release for a period of time less than or equal to 60 days from the time submitted to them for review. These companies cannot require changes to the communication.
Results Point of Contact
Name/Title | Susan F. Assmann, PhD |
---|---|
Organization | New England Research Institutes, Inc. |
Phone | 617-972-3048 |
sassmann@neriscience.com |
- 374
- U01HL072268
- U01HL072274
- U01HL072290
- U01HL072033
- U01HL072291
- U01HL072248
- U01HL072355
- U01HL072283
- U01HL072346
- U01HL072331