Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B

NCT ID: NCT01687608

Last Updated: 2025-02-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-11
• Study Completion Date: 2030-01-17

Brief Summary

The purpose of this study is to evaluate the safety of single ascending IV doses of a Factor IX (FIX) Gene Therapy in up to 16 Adults with Hemophilia B.

Detailed Description

Hemophilia B is a genetic X-linked bleeding disorder caused by a deficiency in blood-clotting Factor IX (FIX) activity. FIX is synthesized in the liver and circulates in the blood as a proenzyme. Current treatment for hemophilia B is based on replacement of the deficient FIX with IV injections of recombinant FIX protein prophylactically or as needed to treat bleeding episodes. This clinical program will test a gene transfer approach involving the use of a gene delivery vector carrying a FIX gene. This first-in-humans study is intended to evaluate the safety, kinetics, and if possible, the dose of AskBio009 required to achieve stable plasma FIX activity between 10% and 40% of normal activity.

Conditions

Hemophilia B

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AskBio009 Dose Escalation

Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy

Group Type: EXPERIMENTAL

AskBio009

Intervention Type: BIOLOGICAL

Single dose IV injection

Interventions

AskBio009

Single dose IV injection

Intervention Type: BIOLOGICAL

Other Intervention Names

BAX 335

Eligibility Criteria

Inclusion Criteria

• Males age 18-75 years, inclusive
• Established hemophilia B with ≥3 hemorrhages per year requiring treatment with exogenous FIX OR use of FIX prophylaxis because of history of frequent bleeding episodes
• Plasma FIX activity ≤2% (<1% for first cohort; then per protocol)
• Negative for active Hepatitis C virus (HCV), defined as Hepatitis C virus antibody negative and negative (undetectable) PCR test for plasma Hepatitis C virus ribonucleic acid (RNA) OR if Hepatitis C virus antibody positive must have ≥2 consecutive negative (undetectable) PCR tests for plasma HCV RNA at least 3 months apart, and negative at screening

Exclusion Criteria

• Family history of inhibitor to FIX protein or personal laboratory evidence of having developed inhibitors to FIX protein at any time (>0.6 Bethesda Units on any single test)
• Documented prior allergic reaction to any FIX product
• Detectable AAV8 neutralizing antibodies
• Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or more of the following:

• Platelet count <175,000/μL
• Albumin ≤3.5 g/dL
• Total bilirubin >1.5 x ULN and direct bilirubin ≥0.5 mg/dL
• Alkaline phosphatase >2.0 x ULN
• ALT or AST >2.0 x ULN (except for subjects who are HIV infected)
• Liver biopsy in the past indicating moderate or severe fibrosis (Metavir staging of 2 or greater)
• History of ascites, varices, variceal hemorrhage or hepatic encephalopathy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Shire

Locations

Orthopaedic Hemophilia Treatment Center

Los Angeles, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

University of California Davis Medical Center

Sacramento, California, United States

University of California at San Diego Medical Center

San Diego, California, United States

U of Colorado School of Medicine, Hemophilia & Thrombosis Treatment Center

Aurora, Colorado, United States

Emory University

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Children's Hospital of Boston

Boston, Massachusetts, United States

University of Minnesota, Masonic Clinical Research Unit, Clinical and Translational Science Institute

Minneapolis, Minnesota, United States

Mount Sinai Medical Center

New York, New York, United States

The Hemophilia Center, Oregon Health and Science University

Portland, Oregon, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Gulf States Hemophilia and Thrombosis Center

Houston, Texas, United States

Bloodworks Northwest

Seattle, Washington, United States

BloodCenter of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Konkle BA, Walsh CE, Escobar MA, Josephson NC, Young G, von Drygalski A, McPhee SWJ, Samulski RJ, Bilic I, de la Rosa M, Reipert BM, Rottensteiner H, Scheiflinger F, Chapin JC, Ewenstein B, Monahan PE. BAX 335 hemophilia B gene therapy clinical trial results: potential impact of CpG sequences on gene expression. Blood. 2021 Feb 11;137(6):763-774. doi: 10.1182/blood.2019004625.

Reference Type: DERIVED

PMID: 33067633 (View on PubMed)

Weber A, Engelmaier A, Voelkel D, Pachlinger R, Scheiflinger F, Monahan PE, Rottensteiner H. Development of Methods for the Selective Measurement of the Single Amino Acid Exchange Variant Coagulation Factor IX Padua. Mol Ther Methods Clin Dev. 2018 Jun 28;10:29-37. doi: 10.1016/j.omtm.2018.05.004. eCollection 2018 Sep 21.

Reference Type: DERIVED

PMID: 30003118 (View on PubMed)

Related Links

https://clinicaltrials.takeda.com/find-a-trial?idFilter=%5B%22AskBio009-101%22%5D

To obtain more information on the study, click here/on this link

Other Identifiers

231401

Identifier Type: OTHER

Identifier Source: secondary_id

AskBio009-101

Identifier Type: -

Identifier Source: org_study_id