Rituximab to Treat Severe Hemophilia A

NCT00331006 | Completed Phase 2 Results DMC

• 11 other identifiers: 374U01HL072268U01HL072274U01HL072290U01HL072033U01HL072291U01HL072248U01HL072355U01HL072283U01HL072346U01HL072331
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 13

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.

Conditions

Hemophilia A

Keywords

Blood Coagulation Factor Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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 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

  Measured within approximately 22 weeks

• Percent Change in Inhibitor Titer on Challenge With Factor VIII From Baseline Challenge to Post-treatment Challenge

  Measured within approximately 22 weeks

• 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 Not Meeting the Criteria of a Serious Adverse Event

  Measured through Week 100

• Median Number of Serious Adverse Events Per Subject Other Than Bleeding Events

  Measured through Week 100

Study Arms (1)

Rituximab

EXPERIMENTAL

Rituximab administered at a dose of 375 mg/m2 by slow intravenous infusion once per week for 4 weeks

Drug: Rituximab

Interventions

Rituximab DRUG

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

Also known as: Rituxan

Rituximab

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Carelon Research: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Genentech, Inc.: collaborator

Study Sites (13)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

UNC at Chapel Hill Hospital

Chapel Hill, North Carolina, 27514, United States

Location

University Hospital of Cleveland

Cleveland, Ohio, 44106, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Comprehensive Center for Bleeding Disorders

Milwaukee, Wisconsin, 53201, United States

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was terminated before reaching its target sample size of 50 subjects due to low enrollment rates. Therefore, confidence intervals for proportions are wide.

Results Point of Contact

• Title: Susan F. Assmann, PhD
• Organization: New England Research Institutes, Inc.

sassmann@neriscience.com

617-972-3048

Study Officials

• Susan F. Assmann, PhD

  NERI

  PRINCIPAL INVESTIGATOR

• Cindy Leissinger, MD

  Tulane University Health Sciences Center

  PRINCIPAL INVESTIGATOR

• Joan Gill, MD

  Versiti Blood Health

  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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2006
• First Posted: May 29, 2006
• Study Start: June 1, 2006
• Primary Completion: November 1, 2010
• Study Completion: January 1, 2012
• Last Updated: June 11, 2013
• Results First Posted: June 11, 2013

Record last verified: 2013-06

Locations

US (13)