Hemophilia BPhase 2NCT03489291

Dose Confirmation Trial of AAV5-hFIXco-Padua

A Phase 2 study testing AAV5-hFIXco-Padua (AMT-061) in people with Hemophilia B, run by CSL Behring at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Hemophilia B
What is being tested?: AAV5-hFIXco-Padua (AMT-061)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: 4 sitesUnited States
Study dates: 24 Jul 2018to 21 Sep 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

University of Michigan
Ann Arbor, Michigan, 48109
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
University of California, Davis
Sacramento, California, 95817
University of California, San Diego
San Diego, California, 92122

Other trials in United States

About this study

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

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.

Conditions: Hemophilia B
Being tested: AAV5-hFIXco-Padua (AMT-061)
Keywords: Hemophilia,, Gene Therapy, Bleeding, Factor IX, FIX, viral vector, Padua
Medical subject headings: Hemophilia B, Hemophilia A, Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03489291
Study group	Role	What they receive
Single infusion of AMT-061	Experimental	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). Receives: Genetic: AAV5-hFIXco-Padua (AMT-061)

What is being measured

The primary outcome is the main question the study is designed to answer.

Factor IX Activity Levels
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.
Measured: 6 weeks post-dose

Secondary outcomes (15)

Annualized Exogenous Factor IX Usage
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.
Measured: 52 weeks post-dose
Annualized Bleeding Rate (ABR)
ABR was calculated as the ratio of the number of bleeds to the number of days in the time interval multiplied by 365.25.
Measured: 5 years post-dose
Factor IX Activity Levels
Measured by the one-stage (aPTT-based) assay.
Measured: 52 weeks post-dose
Number of Participants Remaining Free of Continuous Prophylaxis
Participants with no usage of continuous factor IX prophylaxis after AMT-061 (CSL222) treatment were considered free from continuous factor IX prophylaxis use.
Measured: 1 year post-dose
Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis
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.
Measured: Up to 5 years post-dose
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
Measured: Up to 5 years post-dose
Number of Participants With Clinically Meaningful Findings in Hematology and Serum Chemistry Parameters
Clinically meaningful findings were defined as values which were outside the standard normal reference ranges for hematology and serum chemistry parameters.
Measured: Up to 5 years post-dose
Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Changes in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels
Post-baseline newly occurring or worsening potentially clinically significant ALT and AST levels were defined as values greater than twice the baseline value.
Measured: From baseline and up to 5 years post-dose
Number of Participants Receiving Corticosteroids for AST and ALT Elevations
Measured: Up to 5 years post-dose
Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum
Measured: Baseline and at 5 years post-dose
Number of Participants With AAV5 Capsid-specific T Cell Response
Measured: Up to Week 52
Number of Participants With Inflammatory Marker Levels Outside Normal Ranges
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.
Measured: 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
Time to First Negative Results for Vector Deoxyribonucleic Acid (DNA) From Semen and Blood
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.
Measured: Up to 5 years post-dose
Number of Participants With Abnormal Values in Alpha-fetoprotein (AFP) Levels
Participants who were outside the normal limit range were to be reported.
Measured: Up to 5 years post-dose
Number of Participants With Abnormal Results in Abdominal Ultrasound
Ultrasounds were evaluated by qualified personnel and abnormalities were assessed by the Investigator.
Measured: At Months 36, 42, 48, 54, and 60 post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Jul 201821 Sep 2023

First posted5 Apr 2018
Study start24 Jul 2018
Primary completion30 Oct 2018
Study completion21 Sep 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Hemophilia BStudies of the same condition, open and under way.
More trials run by CSL BehringThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: open-label, single-dose, single-arm, multi-center trial
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03489291
Sponsor's protocol ID: CSL222_2001 (CT-AMT-061-01)
Status last verified: Jun 2024
First submitted: 19 Mar 2018
Last updated: 28 Jun 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Publications

von Drygalski A, Gomez E, Giermasz A, Castaman G, Key NS, Lattimore SU, Leebeek FWG, Miesbach WA, Recht M, Monahan PE, Le Quellec S, Pipe SW. Completion of phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years. Blood Adv. 2025 Jul 22;9(14):3543-3552. doi: 10.1182/bloodadvances.2024015291.
PubMed 40188458
O'Connell N, van der Valk P, Le Quellec S, Gomez E, Monahan PE, Crary SE, Coppens M, Lemons R, Castaman G, Klamroth R, Symington E, Quon DV, Kampmann P. Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B. J Thromb Haemost. 2025 Jan;23(1):73-84. doi: 10.1016/j.jtha.2024.08.027. Epub 2024 Sep 26.
PubMed 39341368
von Drygalski A, Gomez E, Giermasz A, Castaman G, Key NS, Lattimore SU, Leebeek FWG, Miesbach WA, Recht M, Gut R, Dolmetsch R, Monahan PE, Le Quellec S, Pipe SW. Stable and durable factor IX levels in patients with hemophilia B over 3 years after etranacogene dezaparvovec gene therapy. Blood Adv. 2023 Oct 10;7(19):5671-5679. doi: 10.1182/bloodadvances.2022008886.
PubMed 36490302
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.
PubMed 31698454

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hemophilia B trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03489291
Acronym / sponsor ID: CSL222_2001 (CT-AMT-061-01)
Conditions: Hemophilia B
Keywords: Hemophilia,, Gene Therapy, Bleeding, Factor IX, FIX, viral vector, Padua
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 3 participants (actual)
Lead sponsor: CSL BehringIndustry (pharma, biotech, devices)
Study start: 24 Jul 2018 (actual)
Primary completion: 30 Oct 2018 (actual)
Study completion: 21 Sep 2023 (actual)
First posted: 5 Apr 2018 (actual)
Results: Posted 16 Jun 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 administered dose of AMT-061 will be 2 x 10^13 gc/kg.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: open-label, single-dose, single-arm, multi-center trial

Arm	Type	Receives
Single infusion of AMT-061	Experimental	Genetic: AAV5-hFIXco-Padua (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).

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AAV5-hFIXco-Padua (AMT-061)Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061)	Genetic	Single infusion of AMT-061

Primary outcome

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.

15 secondary outcomes

Annualized Exogenous Factor IX Usage
Time frame: 52 weeks post-dose
Annualized Bleeding Rate (ABR)
Time frame: 5 years post-dose
Factor IX Activity Levels
Time frame: 52 weeks post-dose
Number of Participants Remaining Free of Continuous Prophylaxis
Time frame: 1 year post-dose
Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis
Time frame: Up to 5 years post-dose
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
Number of Participants With Clinically Meaningful Findings in Hematology and Serum Chemistry Parameters
Time frame: Up to 5 years post-dose
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
Number of Participants Receiving Corticosteroids for AST and ALT Elevations
Time frame: Up to 5 years post-dose
Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum
Time frame: Baseline and at 5 years post-dose
Number of Participants With AAV5 Capsid-specific T Cell Response
Time frame: Up to Week 52
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
Time to First Negative Results for Vector Deoxyribonucleic Acid (DNA) From Semen and Blood
Time frame: Up to 5 years post-dose
Number of Participants With Abnormal Values in Alpha-fetoprotein (AFP) Levels
Time frame: Up to 5 years post-dose
Number of Participants With Abnormal Results in Abdominal Ultrasound
Time frame: At Months 36, 42, 48, 54, and 60 post-dose

Results and safety

Results posted to the registry on 16 Jun 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AMT-061 (CSL222)	3	3

Primary outcome: Factor IX Activity Levels

Time frame: 6 weeks post-dose. Mean (Standard Deviation). Unit: Factor IX activity (%)

Measure	AMT-061 (CSL222) n = 3
Value	30.6 (6.97)

Population analysed: All subjects treated.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: 5 years post-dose. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AMT-061 (CSL222)	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40188458von Drygalski A, Gomez E, Giermasz A, Castaman G, Key NS, Lattimore SU, Leebeek FWG, Miesbach WA, Recht M, Monahan PE, Le Quellec S, Pipe SW. Completion of phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years. Blood Adv. 2025 Jul 22;9(14):3543-3552. doi: 10.1182/bloodadvances.2024015291.
Derived from this study: PubMed 39341368O'Connell N, van der Valk P, Le Quellec S, Gomez E, Monahan PE, Crary SE, Coppens M, Lemons R, Castaman G, Klamroth R, Symington E, Quon DV, Kampmann P. Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B. J Thromb Haemost. 2025 Jan;23(1):73-84. doi: 10.1016/j.jtha.2024.08.027. Epub 2024 Sep 26.
Derived from this study: PubMed 36490302von Drygalski A, Gomez E, Giermasz A, Castaman G, Key NS, Lattimore SU, Leebeek FWG, Miesbach WA, Recht M, Gut R, Dolmetsch R, Monahan PE, Le Quellec S, Pipe SW. Stable and durable factor IX levels in patients with hemophilia B over 3 years after etranacogene dezaparvovec gene therapy. Blood Adv. 2023 Oct 10;7(19):5671-5679. doi: 10.1182/bloodadvances.2022008886.
Derived from this study: PubMed 31698454Von 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.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Steven Pipe, MD principal investigator

University of Michigan

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AAV5-hFIXco-Padua (AMT-061) in people with Hemophilia B, run by CSL Behring at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Factor IX Activity Levels (time frame: 6 weeks post-dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03489291, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2024; AzTrials last refreshed its copy on 6 Nov 2026.