Dose Confirmation Trial of AAV5-hFIXco-Padua
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|ClinicalTrials.gov Identifier: NCT03489291|
Recruitment Status : Active, not recruiting
First Posted : April 5, 2018
Results First Posted : June 16, 2022
Last Update Posted : April 6, 2023
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This is an open-label, single-dose, single-arm, multi-center trial, with a screening, a treatment + post-treatment follow-up phase, and a long-term follow-up phase.
The IMP AMT-061 is a recombinant adeno-associated viral vector of serotype 5 (AAV5) containing the Padua variant of a codon-optimized human FIX complementary deoxyribonucleic acid (cDNA) under the control of a liver-specific promoter. The IMP is identified as AAV5-hFIXco-Padua (AMT- 061). The pharmaceutical form of AMT-061 is a solution for intravenous infusion.
The administered dose of AMT-061 will be 2 x 10^13 gc/kg.
|Condition or disease||Intervention/treatment||Phase|
|Hemophilia B||Genetic: AAV5-hFIXco-Padua (AMT-061)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||open-label, single-dose, single-arm, multi-center trial|
|Masking:||None (Open Label)|
|Official Title:||Phase IIb, Open-label, Single-dose, Single-arm, Multi-center Trial to Confirm the Factor IX Activity Level of the Serotype 5 Adeno-associated Viral Vector Containing the Padua Variant of a Codon-optimized Human Factor IX Gene (AAV5-hFIXco-Padua, AMT-061) Administered to Adult Subjects With Severe or Moderately Severe Hemophilia B|
|Actual Study Start Date :||July 24, 2018|
|Actual Primary Completion Date :||October 30, 2018|
|Estimated Study Completion Date :||September 20, 2023|
Experimental: Single infusion of AMT-061
Subjects will receive a single infusion of AAV5-hFIXco-Padua (AMT- 061) at baseline. After IMP administration (post IMP), subjects will be monitored for tolerance to the IMP and detection of potential immediate AEs at the clinical trial site for 24 hours (overnight stay).
Genetic: AAV5-hFIXco-Padua (AMT-061)
Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)
- FIX Activity Levels [ Time Frame: 6 weeks post-dose ]To confirm that a single dose of 2x10^13 gc/kg AMT-061 will result in FIX activity levels of ≥5% at 6 weeks after dosing measured by the one-stage (aPTT-based) assay.
- Annualized Exogenous Factor IX Usage [ Time Frame: 30 months post-dose ]Annualized use was calculated as the normalized amount of therapy administered per baseline weight, extrapolated where necessary from any time period less or greater than 1 year. Therapy administered included the total dosage of FIX given as prophylaxis and on-demand. Use for invasive procedures was not included.
- Annualized Bleeding Rate (ABR) [ Time Frame: 30 months post-dose ]ABR was calculated as the ratio of the number of bleeds to the number of days in the time interval multiplied by 365.25.
- FIX Activity Levels [ Time Frame: 52 weeks post-dose ]Measured by the one-stage (aPTT-based) assay.
- Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis [ Time Frame: 30 months post-dose ]The Post-Continuous-Prophylaxis period began on the day after the end of continuous (routine) prophylaxis.
- Safety Endpoints [ Time Frame: 5 years post-dose ]
- Hematology and serum chemistry parameters
- ALT/AST levels and corticosteroid use for ALT/AST elevations
- Parameters on antibody formation to AAV5 and human factor IX
- AAV5 capsid-specific T cell response
- Inflammatory markers
- Vector DNA in semen and blood
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Male|
|Gender Based Eligibility:||Yes|
|Gender Eligibility Description:||Hemophilia B is an X-linked, recessive condition, since it occurs almost exclusively in males. Females typically are asymptomatic carriers. Therefore eligibility is restricted to male participants.|
|Accepts Healthy Volunteers:||No|
- Age ≥18 years
- Subjects with congenital hemophilia B classified as severe or moderately severe
- >20 previous exposure days of treatment with FIX protein
- History of FIX inhibitors
- Positive FIX inhibitor test at screening
- Select screening laboratory values > 2 times upper normal limit:
- Positive human immunodeficiency virus (HIV) at screening, not controlled with anti-viral therapy
- Active infection with Hepatitis B or C virus at screening
- History of Hepatitis B or C exposure, currently controlled by antiviral therapy
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 ClinicalTrials.gov identifier (NCT number): NCT03489291
|United States, Arizona|
|Phoenix Childrens Hospital|
|Phoenix, Arizona, United States, 85016|
|United States, California|
|University of California, Davis|
|Sacramento, California, United States, 95817|
|University of California, San Diego|
|San Diego, California, United States, 92122|
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Steven Pipe, MD||University of Michigan|
Documents provided by CSL Behring:
|Responsible Party:||CSL Behring|
|Other Study ID Numbers:||
|First Posted:||April 5, 2018 Key Record Dates|
|Results First Posted:||June 16, 2022|
|Last Update Posted:||April 6, 2023|
|Last Verified:||April 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Undecided|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Coagulation Protein Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked