Clinical trial NCT03489291: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilia B
Keywords: Hemophilia,
Gene Therapy
Bleeding
Factor IX
FIX
viral vector
Padua
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2018-04-05
Enrollment: 3
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open-label, single-dose, single-arm, multi-center trial
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Factor IX Activity Levels
timeFrame: 6 weeks post-dose
Secondary outcomes:
measure: Annualized Exogenous Factor IX Usage
timeFrame: 52 weeks post-dose
measure: Annualized Bleeding Rate (ABR)
timeFrame: 5 years post-dose
measure: Factor IX Activity Levels
timeFrame: 52 weeks post-dose
measure: Number of Participants Remaining Free of Continuous Prophylaxis
timeFrame: 1 year post-dose
measure: Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis
timeFrame: Up to 5 years post-dose
measure: 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
timeFrame: Up to 5 years post-dose
measure: Number of Participants With Clinically Meaningful Findings in Hematology and Serum Chemistry Parameters
timeFrame: Up to 5 years post-dose
measure: Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Changes in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels
timeFrame: From baseline and up to 5 years post-dose
measure: Number of Participants Receiving Corticosteroids for AST and ALT Elevations
timeFrame: Up to 5 years post-dose
measure: Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum
timeFrame: Baseline and at 5 years post-dose
measure: Number of Participants With AAV5 Capsid-specific T Cell Response
timeFrame: Up to Week 52
measure: Number of Participants With Inflammatory Marker Levels Outside Normal Ranges
timeFrame: 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
measure: Time to First Negative Results for Vector Deoxyribonucleic Acid (DNA) From Semen and Blood
timeFrame: Up to 5 years post-dose
measure: Number of Participants With Abnormal Values in Alpha-fetoprotein (AFP) Levels
timeFrame: Up to 5 years post-dose
measure: Number of Participants With Abnormal Results in Abdominal Ultrasound
timeFrame: At Months 36, 42, 48, 54, and 60 post-dose
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Steven Pipe, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.