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Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector For Gene Transfer in Hemophilia B

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00979238
Recruitment Status : Active, not recruiting
First Posted : September 17, 2009
Last Update Posted : May 15, 2023
National Heart, Lung, and Blood Institute (NHLBI)
Hemophilia of Georgia, Inc.
Children's Hospital of Philadelphia
University College, London
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief Summary:
The purpose of this study is to determine the safety of giving a normal factor IX gene to treat individuals who have an abnormal or no factor IX gene. Recruitment will be limited to adults (≥ 18 years) with a confirmed diagnosis of hemophilia B (HB), resulting from a missense mutation in the coagulation factor IX (FIX) gene or a nonsense mutation that has not been associated with an inhibitor. Only subjects who have no evidence of active hepatitis or anti-hFIX antibodies, and who have been treated/exposed to Factor IX concentrates for at least ten years and have had an average of 3 bleeding episodes per year requiring FIX administration will be enrolled. Patients will be recruited within the United States for treatment at St. Jude Children's Research Hospital, and patients will be recruited in England and other countries for treatment in London by our British collaborators.

Condition or disease Intervention/treatment Phase
Hemophilia B Genetic: Gene Transfer Drug: scAAV2/8-LP1-hFIXco Phase 1

Detailed Description:
Hemophilia B is caused by an absence or abnormality in the gene that produces the factor IX protein. Affected individuals cannot make a blood clot effectively and suffer from severe bleeding episodes. Repeated bleeding episodes, specifically into joints, can cause chronic joint disease and lead to disability. This research study will test the safety of giving an affected individual a normal factor IX gene which can produce factor IX protein in his body. We will give the normal gene for factor IX by using an inactivated (not able to function) virus called "the vector." The vector used in this study was developed from an adeno-associated virus that has been changed so that it is unable to cause a viral infection in humans. This inactivated virus was further altered to carry the factor IX gene and to locate within liver cells where factor IX protein is normally made.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open Label Dose-Escalation Study Of A Self Complementary Adeno-Associated Viral Vector (scAAV 2/8-LP1-hFIXco) For Gene Transfer in Hemophilia B
Actual Study Start Date : February 22, 2010
Estimated Primary Completion Date : June 12, 2032
Estimated Study Completion Date : December 31, 2032

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Group 1

All participants who meet the eligibility requirements.

Intervention: Gene Transfer and drug (scAAV2/8-LP1-hFIXco).

Genetic: Gene Transfer
Peripheral vein infusion of scAAV2/8-LP1-hFIXco vector once per participant

Drug: scAAV2/8-LP1-hFIXco
Peripheral vein infusion of scAAV2/8-LP1-hFIXco vector once per participant.
Other Name: vector

Primary Outcome Measures :
  1. To assess the safety of systemic administration of a novel self-complementary AAV vector in adults with severe hemophilia B at up to four different dosage levels. [ Time Frame: 15 years ]
    Outcome measures are descriptive in nature but data collected in a longitudinal manner will also be analyzed (as and when appropriate) using longitudinal methods such as mixed effect model which takes into account the correlation among the observation taken at various time points within a participant.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males ≥ 18 years of age with established severe HB (FIX:C<1u/dl),
  • Treated/exposed to FIX products (e.g., concentrates or fresh frozen plasma) for at least 10 years or 50 exposure days.
  • A minimum of an average of 3 bleeding episodes per year requiring FIX infusions or prophylactic FIX infusions because of frequent prior bleeding episodes
  • Able to give informed consent and comply with requirements of the trial
  • Currently free of inhibitor and have no history of inhibitors to FIX protein
  • A negative family history for the development of an inhibitor,
  • Willing to practice a reliable barrier method of contraception until 3 sequential samples are negative for vector genomes using our PCR assay.

Exclusion Criteria:

  • Evidence of active infection with Hepatitis B or C virus as reflected by HBsAg or NCV RNA positivity, respectively. To be considered negative for active infection, two negative assays at a minimum of a six month interval are required.
  • Exposure to Hepatitis B or C who are currently on antiviral therapy.
  • Serological evidence of HTLV or active HIV infection. Individuals who are effectively being treated with antiretroviral therapy are eligible. Specific criteria for effectiveness of treatment include the following:

    • Documented CD4+ T-cell count of > 350 cells/mm^3.
    • HIV-1 RNA viral load < 400 copy/ml for at least the past 12 months, including at least 2 viral load test results of < 400 copy/ml during the immediate 12 month interval prior to screening.
    • Screening HIV-RNA viral load < 400 copies/ml.
    • Stable HAART regimen (drugs of at least 2 different classes) for at least 12 months prior to study entry. Treatment regimen changes for dosing convenience and in response to toxicity are permitted.
    • Documented and confirmed (repeated) viral loads of ≥ 400 copies/ml during the 12 month time interval prior to screening are bases for exclusion although a single, unconfirmed, "glimpse" of ≥ 400 copies/ml are permitted.
  • Significant liver dysfunction as defined by an abnormal ALT (alanine transaminase), bilirubin, alkaline phosphatase or INR. Potential participants who have had a liver biopsy in the past 3 years will be excluded if they have significant fibrosis of 3 or 4 as rated on a scale of 0-4.
  • Coronary artery disease as a co-morbid condition
  • Platelet count of <50 x 10^9/l
  • Creatinine ≥ 1.5 mg/dl
  • Hypertension with systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg
  • History of active tuberculosis, fungal disease or other chronic infection
  • History of chronic disease that would adversely affect performance other than hemophilic arthropathy
  • Detectable antibodies reactive with AAV8
  • Subjects who are unwilling to provide the required semen samples
  • Poor performance status (WHO performance status score >1) or
  • Received an AAV vector or any other gene transfer agent in the previous 6 months
  • Presence of lung nodule(s) suspicious of malignancy on screening chest tomography
  • Presence of liver abnormalities suspicious of malignancy on screening liver ultrasound

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00979238

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United States, California
Stanford Medical School
Stanford, California, United States, 94305
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Hemophilia Center of Western Pennsylvania
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38119
United States, Texas
University of Texas Southwestern
Dallas, Texas, United States, 75390-9063
Scott and White Memorial Hospital
Temple, Texas, United States, 76508
United Kingdom
Katharine Dormandy Haemophilia Centre and Haemostasis Unit, University College of London
London, United Kingdom
Sponsors and Collaborators
St. Jude Children's Research Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Hemophilia of Georgia, Inc.
Children's Hospital of Philadelphia
University College, London
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Principal Investigator: Ulrike Reiss, MD St. Jude Children's Research Hospital
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: St. Jude Children's Research Hospital Identifier: NCT00979238    
Other Study ID Numbers: AGT4HB
5R01HL094396 ( U.S. NIH Grant/Contract )
First Posted: September 17, 2009    Key Record Dates
Last Update Posted: May 15, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by St. Jude Children's Research Hospital:
Hemophilia B
Factor IX Gene
Factor IX Protein
Additional relevant MeSH terms:
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Hemophilia A
Hemophilia B
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked