Dose Confirmation Trial of AAV5-hFIXco-Padua

• ClinicalTrials.gov Identifier: NCT03489291
• Recruitment Status: Active, not recruiting
• First Posted: April 5, 2018
• Results First Posted: June 16, 2022
• Last Update Posted: June 16, 2022
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

Tracking Information

• First Submitted Date: March 19, 2018
• First Posted Date: April 5, 2018
• Results First Submitted Date: May 17, 2022
• Results First Posted Date: June 16, 2022
• Last Update Posted Date: June 16, 2022
• Actual Study Start Date: July 24, 2018
• Actual Primary Completion Date: October 30, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 17, 2022)

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.

Original Primary Outcome Measures (submitted: April 3, 2018)

FIX activity levels [ Time Frame: 6 weeks ]

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.

Current Secondary Outcome Measures (submitted: May 17, 2022)

• 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 ]
  • AEs
  • 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
  • AFP

Original Secondary Outcome Measures (submitted: April 3, 2018)

• Usage of FIX replacement therapy [ Time Frame: 52 weeks post-dose ]
  Patients will record all use of prophylactic and on-demand FIX replacement therapy in an e-diary, including reason for FIX use, date and time of infusion and total dose.
• Annualized Bleeding Rate [ Time Frame: 52 weeks post-dose ]
• Adverse Events [ Time Frame: 5 years post dose ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Confirmation Trial of AAV5-hFIXco-Padua
• 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

open-label, single-dose, single-arm, multi-center trial

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Hemophilia B

Intervention

Genetic: AAV5-hFIXco-Padua (AMT-061)

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

Study Arms

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).

Intervention: Genetic: AAV5-hFIXco-Padua (AMT-061)

• Publications *: Von Drygalski A, Giermasz A, Castaman G, Key NS, Lattimore S, Leebeek FWG, Miesbach W, Recht M, Long A, Gut R, Sawyer EK, Pipe SW. Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Adv. 2019 Nov 12;3(21):3241-3247. doi: 10.1182/bloodadvances.2019000811. Erratum In: Blood Adv. 2020 Aug 11;4(15):3668.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 3, 2018): 3
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 20, 2023
• Actual Primary Completion Date: October 30, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male
2. Age ≥18 years
3. Subjects with congenital hemophilia B classified as severe or moderately severe
4. >20 previous exposure days of treatment with FIX protein

Exclusion Criteria:

1. History of FIX inhibitors
2. Positive FIX inhibitor test at screening
3. Select screening laboratory values > 2 times upper normal limit:
4. Positive human immunodeficiency virus (HIV) at screening, not controlled with anti-viral therapy
5. Active infection with Hepatitis B or C virus at screening
6. History of Hepatitis B or C exposure, currently controlled by antiviral therapy

Sex/Gender

• 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.

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03489291
• Other Study ID Numbers: CSL222_2001 (CT-AMT-061-01)
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: CSL Behring
• Original Responsible Party: UniQure Biopharma B.V.
• Current Study Sponsor: CSL Behring
• Original Study Sponsor: UniQure Biopharma B.V.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Steven Pipe, MD; University of Michigan

• PRS Account: CSL Behring
• Verification Date: May 2022