Hemophilia APhase 2RICHNCT00331006
Rituximab to Treat Severe Hemophilia A
A Phase 2 study testing Rituximab in people with Hemophilia A, run by Carelon Research at 13 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 months and older
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 13 sitesUnited States
- Study dates
- Jun 2006to Jan 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital Boston
Boston, Massachusetts, 02115
UNC at Chapel Hill Hospital
Chapel Hill, North Carolina, 27514
Rush University Medical Center
Chicago, Illinois, 60612
University Hospital of Cleveland
Cleveland, Ohio, 44106
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Cook Children's Medical Center
Fort Worth, Texas, 76104
Comprehensive Center for Bleeding Disorders
Milwaukee, Wisconsin, 53201
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Rituximab for the Treatment of Inhibitors in Congenital Hemophilia A (A TMH CTN Study)
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.
Read the 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.
- Conditions
- Hemophilia A
- Being tested
- Rituximab
- Keywords
- Blood Coagulation Factor Inhibitors
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
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
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Rituximab administered at a dose of 375 mg/m2 by slow intravenous infusion once per week for 4 weeks Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Measured: Measured within approximately 22 weeks
Secondary outcomes (7)
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
Presence or absence of at least a minor response in each participant
Measured: Measured within approximately 22 weeks
Percent Change in Inhibitor Titer on Challenge With Factor VIII From Baseline Challenge to Post-treatment Challenge
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.
Measured: Measured within approximately 22 weeks
Median Number of Bleeding Events Per Subject Meeting the Criteria of a Serious Adverse Event
Median number of bleeding events per subject meeting the criteria of a serious adverse event
Measured: Measured through Week 100
Median Number of Bleeding Events Per Subject Not 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: Measured through Week 100
Median Number of Serious Adverse Events Per Subject Other Than Bleeding Events
Median Number of Serious Adverse Events Per Subject Other Than Bleeding Events
Measured: 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
Median Number of Adverse Events Per Subject That Were Not Bleeding Events and Did Not Meet the Criteria of a Serious Adverse Event
Measured: Measured through Week 100
Proportion of Rituximab Infusions in Which a Reaction to the Infusion Was Reported
Proportion of rituximab infusions in which a reaction to the infusion was reported
Measured: Measured at Week 1 through Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2006 (estimated)
- Study startJun 2006
- Primary completionNov 2010
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carelon Research
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susan F. Assmann, PhD, Principal investigator, NERICindy Leissinger, MD, Principal investigator, Tulane University Health Sciences CenterJoan Gill, MD, Principal investigator, Versiti Blood HealthKeith McCrae, MD, Principal investigator, University Hospital of ClevelandEllis Neufeld, MD, Principal investigator, Boston Children's HospitalCassandra Josephson, MD, Principal investigator, Children's Healthcare of AtlantaNigel Key, MD, Principal investigator, University of North CarolinaCharles Sexauer, MD, Principal investigator, University of Oklahoma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00331006
- Sponsor's protocol ID
- 374
- Other IDs
- U01HL072268, U01HL072274, U01HL072290, U01HL072033, U01HL072291, U01HL072248, U01HL072355, U01HL072283
- Acronym
- RICH
- Status last verified
- Jun 2013
- First submitted
- 26 May 2006
- Last updated
- 11 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rituximab for the Treatment of Inhibitors in Congenital Hemophilia A (A TMH CTN Study)
- ClinicalTrials.gov ID
- NCT00331006
- Acronym / sponsor ID
- RICH / 374
- Conditions
- Hemophilia A
- Keywords
- Blood Coagulation Factor Inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Carelon ResearchUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Genentech, Inc.
- Study start
- Jun 2006
- Primary completion
- Nov 2010 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 29 May 2006 (estimated)
- Results
- Posted 11 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabRituximab administered at a dose of 375 mg/m2 by slow intravenous infusion once per week for 4 weeks |
Who may qualify
- Ages
- 18 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: RituxanRituximab 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 | Drug | Rituximab |
Primary outcome
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
Time frame: 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
7 secondary outcomes
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
Time frame: Measured within approximately 22 weeks
Percent Change in Inhibitor Titer on Challenge With Factor VIII From Baseline Challenge to Post-treatment Challenge
Time frame: Measured within approximately 22 weeks
Median Number of Bleeding Events Per Subject Meeting the Criteria of a Serious Adverse Event
Time frame: Measured through Week 100
Median Number of Bleeding Events Per Subject Not Meeting the Criteria of a Serious Adverse Event
Time frame: Measured through Week 100
Median Number of Serious Adverse Events Per Subject Other Than Bleeding Events
Time frame: 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
Time frame: Measured through Week 100
Proportion of Rituximab Infusions in Which a Reaction to the Infusion Was Reported
Time frame: Measured at Week 1 through Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
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A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
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Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan F. Assmann, PhD principal investigator
NERI
Cindy Leissinger, MD principal investigator
Tulane University Health Sciences Center
Joan Gill, MD principal investigator
Versiti Blood Health
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Hemophilia A, run by Carelon Research at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Measured within approximately 22 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2013.