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

NCT00979238 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: AGT4HB5R01HL094396
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 4

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.

Conditions

Hemophilia B

Keywords

Hemophilia B; Factor IX Gene; Factor IX Protein; Vector

Outcome Measures

Primary Outcomes (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.

  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.

  15 years

Study Arms (1)

Group 1

OTHER

All participants who meet the eligibility requirements. Intervention: Gene Transfer and drug (scAAV2/8-LP1-hFIXco).

Genetic: Gene Transfer; Drug: scAAV2/8-LP1-hFIXco

Interventions

Gene Transfer GENETIC

Peripheral vein infusion of scAAV2/8-LP1-hFIXco vector once per participant

Group 1

scAAV2/8-LP1-hFIXco DRUG

Peripheral vein infusion of scAAV2/8-LP1-hFIXco vector once per participant.

Also known as: vector

Group 1

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Hemophilia of Georgia, Inc.: collaborator
• Children's Hospital of Philadelphia: collaborator
• University College, London: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

Stanford Medical School

Stanford, California, 94305, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38119, United States

Location

Scott and White Memorial Hospital

Temple, Texas, 76508, United States

Location

Katharine Dormandy Haemophilia Centre and Haemostasis Unit, University College of London

London, United Kingdom

Location

Related Publications (3)

• Reiss UM, Davidoff AM, Tuddenham EGD, Chowdary P, McIntosh J, Muczynski V, Journou M, Simini G, Ireland L, Mohamed S, Riddell A, Pie AJ, Hall A, Quaglia A, Mangles S, Mahlangu J, Haley K, Recht M, Shen YM, Halka KG, Fortner G, Morton CL, Gu Z, Hayden RT, Neufeld EJ, Okhomina VI, Kang G, Nathwani AC. Sustained Clinical Benefit of AAV Gene Therapy in Severe Hemophilia B. N Engl J Med. 2025 Jun 12;392(22):2226-2234. doi: 10.1056/NEJMoa2414783.

  PMID: 40499172 DERIVED

• Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, Della Peruta M, Lheriteau E, Patel N, Raj D, Riddell A, Pie J, Rangarajan S, Bevan D, Recht M, Shen YM, Halka KG, Basner-Tschakarjan E, Mingozzi F, High KA, Allay J, Kay MA, Ng CY, Zhou J, Cancio M, Morton CL, Gray JT, Srivastava D, Nienhuis AW, Davidoff AM. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014 Nov 20;371(21):1994-2004. doi: 10.1056/NEJMoa1407309.

  PMID: 25409372 DERIVED

• Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C, O'Beirne J, Smith K, Pasi J, Glader B, Rustagi P, Ng CY, Kay MA, Zhou J, Spence Y, Morton CL, Allay J, Coleman J, Sleep S, Cunningham JM, Srivastava D, Basner-Tschakarjan E, Mingozzi F, High KA, Gray JT, Reiss UM, Nienhuis AW, Davidoff AM. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 2011 Dec 22;365(25):2357-65. doi: 10.1056/NEJMoa1108046. Epub 2011 Dec 10.

  PMID: 22149959 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Hemophilia B

Interventions

Genetic Engineering; Disease Vectors

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; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Genetic Techniques; Investigative Techniques; Disease Transmission, Infectious; Public Health; Environment and Public Health; Chain of Infection; Epidemiologic Methods

Study Officials

• Ulrike Reiss, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2009
• First Posted: September 17, 2009
• Study Start: February 22, 2010
• Primary Completion: March 26, 2026
• Study Completion: March 26, 2026
• Last Updated: April 2, 2026

Record last verified: 2026-04

Locations

US (3); GB (1)