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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AAV5-hFIXco-Padua (AMT-061) | Genetic | Single intravenous infusion of AAV5-hFIXco-Padua (AMT-061) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 weeks post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 52 weeks post-dose |
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Inclusion Criteria:
Exclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Steven Pipe, MD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Childrens Hospital | Phoenix | Arizona | 85016 | United States | ||
| University of California, Davis |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40188458 | Derived | 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. | |
| 39341368 |
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| ID | Title | Description |
|---|---|---|
| FG000 | AMT-061 (CSL222) | Adeno-associated viral vector serotype 5 (AAV5)-hFIXco-Padua (AMT-061 [CSL222]): Single intravenous infusion of AMT-061 (CSL222). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | AMT-061 (CSL222) | AAV5-hFIXco-Padua (AMT-061 [CSL222]): Single intravenous infusion of AMT-061 (CSL222). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All subjects treated. | Posted | Mean | Standard Deviation | Factor IX activity (%) | 6 weeks post-dose |
|
|
5 years post-dose
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AMT-061 (CSL222) | AAV5-hFIXco-Padua (AMT-061 [CSL222]): Single intravenous infusion of AMT-061 (CSL222). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | CSL Behring | +1 610-878-4000 | clinicaltrials@cslbehring.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 8, 2022 | May 17, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 7, 2021 | May 17, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D002836 | Hemophilia B |
| D006467 | Hemophilia A |
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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open-label, single-dose, single-arm, multi-center trial
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| 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. | 5 years post-dose |
| Factor IX Activity Levels | Measured by the one-stage (aPTT-based) assay. | 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. | 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. | 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 | 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. | 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. | From baseline and up to 5 years post-dose |
| Number of Participants Receiving Corticosteroids for AST and ALT Elevations | Up to 5 years post-dose |
| Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum | Baseline and at 5 years post-dose |
| Number of Participants With AAV5 Capsid-specific T Cell Response | 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. | 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. | 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. | 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. | At Months 36, 42, 48, 54, and 60 post-dose |
| Sacramento |
| California |
| 95817 |
| United States |
| University of California, San Diego | San Diego | California | 92122 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| 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. |
| 36490302 | Derived | 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. |
| 31698454 | Derived | 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. |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| Secondary | 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. | All subjects treated. | Posted | Mean | Standard Deviation | International units (IU)/kg/year | 52 weeks post-dose |
|
|
|
| Secondary | 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. | All subjects treated. | Posted | Number | bleeds/year/subject | 5 years post-dose |
|
|
|
| Secondary | Factor IX Activity Levels | Measured by the one-stage (aPTT-based) assay. | All subjects treated. | Posted | Mean | Standard Deviation | Factor IX activity (%) | 52 weeks post-dose |
|
|
|
| Secondary | 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. | All subjects treated. | Posted | Count of Participants | Participants | 1 year post-dose |
|
|
|
| Secondary | 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. | All subjects treated. | Posted | Mean | Standard Deviation | IU/year | Up to 5 years post-dose |
|
|
|
| Secondary | 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 | All subjects treated. | Posted | Count of Participants | Participants | Up to 5 years post-dose |
|
|
|
| Secondary | 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. | All subjects treated. | Posted | Count of Participants | Participants | Up to 5 years post-dose |
|
|
|
| Secondary | 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. | All subjects treated. | Posted | Count of Participants | Participants | From baseline and up to 5 years post-dose |
|
|
|
| Secondary | Number of Participants Receiving Corticosteroids for AST and ALT Elevations | All subjects treated. | Posted | Count of Participants | Participants | Up to 5 years post-dose |
|
|
|
| Secondary | Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum | All subjects treated. | Posted | Count of Participants | Participants | Baseline and at 5 years post-dose |
|
|
|
| Secondary | Number of Participants With AAV5 Capsid-specific T Cell Response | All subjects treated. | Posted | Count of Participants | Participants | Up to Week 52 |
|
|
|
| Secondary | 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. | All subjects treated. | Posted | Count of Participants | Participants | 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 |
|
|
|
| Secondary | 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. | All subjects treated. Here, the "Number Analyzed (n)" included participants who were evaluable at specific parameters. | Posted | Median | Full Range | Weeks | Up to 5 years post-dose |
|
|
|
| Secondary | Number of Participants With Abnormal Values in Alpha-fetoprotein (AFP) Levels | Participants who were outside the normal limit range were to be reported. | All subjects treated. | Posted | Count of Participants | Participants | Up to 5 years post-dose |
|
|
|
| Secondary | Number of Participants With Abnormal Results in Abdominal Ultrasound | Ultrasounds were evaluated by qualified personnel and abnormalities were assessed by the Investigator. | All subjects treated. Here, the "Number Analyzed (n)" included participants who were evaluable at specific timepoints. | Posted | Count of Participants | Participants | At Months 36, 42, 48, 54, and 60 post-dose |
|
|
|
| Post-Hoc | 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 5 years after dosing measured by the one-stage (activated partial thromboplastin [aPTT]-based) assay. | All subjects treated. | Posted | Mean | Standard Deviation | Factor IX activity (%) | 5 years post dose |
|
|
|
| Post-Hoc | 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. | All subjects treated. | Posted | Count of Participants | Participants | 5 years post dose |
|
|
|
| 0 |
| 3 |
| 1 |
| 3 |
| 3 |
| 3 |
| COVID 19 | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
|
| Coccidioidomycosis | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
|
| Joint range of motion decreased | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
|
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (26.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (26.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (26.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (26.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (26.1) | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA (26.1) | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA (26.1) | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA (26.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (26.1) | Systematic Assessment |
|
| Tongue disorder | Gastrointestinal disorders | MedDRA (26.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (26.1) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (26.1) | Systematic Assessment |
|
| Chronic fatigue syndrome | General disorders | MedDRA (26.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (26.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (26.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (26.1) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (26.1) | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA (26.1) | Systematic Assessment |
|
| C reactive protein increased | Investigations | MedDRA (26.1) | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA (26.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (26.1) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (26.1) | Systematic Assessment |
|
| Amblyopia | Eye disorders | MedDRA (26.1) | Systematic Assessment |
|
| Cataract nuclear | Eye disorders | MedDRA (26.1) | Systematic Assessment |
|
| Pinguecula | Eye disorders | MedDRA (26.1) | Systematic Assessment |
|
| Pseudophakia | Eye disorders | MedDRA (26.1) | Systematic Assessment |
|
| Refraction disorder | Eye disorders | MedDRA (26.1) | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA (26.1) | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (26.1) | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (26.1) | Systematic Assessment |
|
| Libido decreased | Psychiatric disorders | MedDRA (26.1) | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA (26.1) | Systematic Assessment |
|
| Aphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (26.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (26.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (26.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (26.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (26.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (26.1) | Systematic Assessment |
|
| Peripheral coldness | Vascular disorders | MedDRA (26.1) | Systematic Assessment |
|
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| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
|
| Joint bleeds |
|
|
| Participant with severe TEAEs |
|
| Participants with TEAEs related to study treatment |
|
| Participants with TEAEs unrelated to study treatment |
|
| Participants with serious TEAEs |
|
|
| At 5 years post dose for FIX |
|
| Title | Measurements |
|---|---|
|
| Week 40: IL-6 |
|
|
|
| Month 48 |
|
|
| Month 54 |
|
|
| Month 60 |
|
|