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Completed

NCT Number: NCT03489291

Dose Confirmation Trial of AAV5-hFIXco-Padua

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.

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Key information

Conditions

Hemophilia B Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Hematologic Diseases Hemic and Lymphatic Diseases Hemophilia A Hemorrhage Hemorrhagic Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Phoenix Childrens Hospital, Phoenix, Arizona, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male
  • Age ≥18 years
  • Subjects with congenital hemophilia B classified as severe or moderately severe
  • >20 previous exposure days of treatment with FIX protein

Exclusion criteria

  • 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

Treatment and study plan

AAV5-hFIXco-Padua (AMT-061)

Genetic

Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)

Primary outcomes

  1. Factor IX Activity Levels

    Time frame: 6 weeks post-dose

    To confirm that a single dose of 2x10^13 gc/kg AMT-061 (CSL222) resulted in factor IX activity levels of ≥5% at 6 weeks after dosing measured by the one-stage (activated partial thromboplastin [aPTT]-based) assay.

Secondary outcomes

  1. Annualized Exogenous Factor IX Usage

    Time frame: 52 weeks 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.

  2. Annualized Bleeding Rate (ABR)

    Time frame: 5 years 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.

  3. Factor IX Activity Levels

    Time frame: 52 weeks post-dose

    Measured by the one-stage (aPTT-based) assay.

  4. Number of Participants Remaining Free of Continuous Prophylaxis

    Time frame: 1 year post-dose

    Participants with no usage of continuous factor IX prophylaxis after AMT-061 (CSL222) treatment were considered free from continuous factor IX prophylaxis use.

  5. Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis

    Time frame: Up to 5 years post-dose

    The post-continuous-prophylaxis period began on the day after the end of continuous (routine) prophylaxis.Therapy administered included the total dosage of FIX given as prophylaxis and on-demand. Use for invasive procedures was not included.

  6. Number of Participants With Treatment Emergent (TE): Adverse Events (AE), Mild, Moderate, and Severe AEs, AEs Related and Unrelated to the Study Treatment, and Serious AEs

    Time frame: Up to 5 years post-dose

  7. Number of Participants With Clinically Meaningful Findings in Hematology and Serum Chemistry Parameters

    Time frame: Up to 5 years post-dose

    Clinically meaningful findings were defined as values which were outside the standard normal reference ranges for hematology and serum chemistry parameters.

  8. Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Changes in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels

    Time frame: From baseline and up to 5 years post-dose

    Post-baseline newly occurring or worsening potentially clinically significant ALT and AST levels were defined as values greater than twice the baseline value.

  9. Number of Participants Receiving Corticosteroids for AST and ALT Elevations

    Time frame: Up to 5 years post-dose

  10. Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum

    Time frame: Baseline and at 5 years post-dose

  11. Number of Participants With AAV5 Capsid-specific T Cell Response

    Time frame: Up to Week 52

  12. Number of Participants With Inflammatory Marker Levels Outside Normal Ranges

    Time frame: Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, 24, 26, 31, 36, 40, 44, 48 and 52

    Inflammatory markers included interleukin (IL)-1β, IL-2, IL-6, interferon gamma (IFNγ), and monocyte chemotactic protein-1 (MCP-1). Only those biomarkers for which the data were higher than the normal range at the specified timepoints have been presented.

  13. Time to First Negative Results for Vector Deoxyribonucleic Acid (DNA) From Semen and Blood

    Time frame: Up to 5 years post-dose

    Time in weeks until the first negative result confirmed by negative result in 3 consecutive timepoints. A participant was considered to no longer be shedding vector DNA if they had a negative laboratory result for 3 or more consecutive timepoints.

  14. Number of Participants With Abnormal Values in Alpha-fetoprotein (AFP) Levels

    Time frame: Up to 5 years post-dose

    Participants who were outside the normal limit range were to be reported.

  15. Number of Participants With Abnormal Results in Abdominal Ultrasound

    Time frame: At Months 36, 42, 48, 54, and 60 post-dose

    Ultrasounds were evaluated by qualified personnel and abnormalities were assessed by the Investigator.

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2018
Study completion
2023
First posted
Apr 5, 2018
Registry last updated
Jun 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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