Trial Outcomes & Findings for Dose Confirmation Trial of AAV5-hFIXco-Padua (NCT NCT03489291)
NCT ID: NCT03489291
Last Updated: 2024-06-28
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
3 participants
Primary outcome timeframe
6 weeks post-dose
Results posted on
2024-06-28
Participant Flow
Participant milestones
| Measure |
AMT-061 (CSL222)
Adeno-associated viral vector serotype 5 (AAV5)-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Overall Study
STARTED
|
3
|
|
Overall Study
COMPLETED
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dose Confirmation Trial of AAV5-hFIXco-Padua
Baseline characteristics by cohort
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
|
Age, Continuous
|
46.7 years
STANDARD_DEVIATION 3.5 • n=93 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 6 weeks post-dosePopulation: All subjects treated.
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.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Factor IX Activity Levels
|
30.6 Factor IX activity (%)
Standard Deviation 6.97
|
SECONDARY outcome
Timeframe: 52 weeks post-dosePopulation: All subjects treated.
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.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Annualized Exogenous Factor IX Usage
|
7.1 International units (IU)/kg/year
Standard Deviation 6.4
|
SECONDARY outcome
Timeframe: 5 years post-dosePopulation: All subjects treated.
ABR was calculated as the ratio of the number of bleeds to the number of days in the time interval multiplied by 365.25.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Annualized Bleeding Rate (ABR)
All bleeds (Spontaneous + Traumatic + Joint)
|
0.14 bleeds/year/subject
|
|
Annualized Bleeding Rate (ABR)
Spontaneous bleeds
|
0.07 bleeds/year/subject
|
|
Annualized Bleeding Rate (ABR)
Traumatic bleeds
|
0.07 bleeds/year/subject
|
|
Annualized Bleeding Rate (ABR)
Joint bleeds
|
0.00 bleeds/year/subject
|
SECONDARY outcome
Timeframe: 52 weeks post-dosePopulation: All subjects treated.
Measured by the one-stage (aPTT-based) assay.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Factor IX Activity Levels
|
40.8 Factor IX activity (%)
Standard Deviation 9.45
|
SECONDARY outcome
Timeframe: 1 year post-dosePopulation: All subjects treated.
Participants with no usage of continuous factor IX prophylaxis after AMT-061 (CSL222) treatment were considered free from continuous factor IX prophylaxis use.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants Remaining Free of Continuous Prophylaxis
|
3 Participants
|
SECONDARY outcome
Timeframe: Up to 5 years post-dosePopulation: All subjects treated.
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.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Annualized Exogenous Factor IX Usage Post-Continuous Prophylaxis
|
342.1 IU/year
Standard Deviation 592.5
|
SECONDARY outcome
Timeframe: Up to 5 years post-dosePopulation: All subjects treated.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
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
Participant with TEAEs
|
3 Participants
|
|
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
Participant with mild TEAEs
|
3 Participants
|
|
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
Participant with moderate TEAEs
|
2 Participants
|
|
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
Participant with severe TEAEs
|
2 Participants
|
|
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
Participants with TEAEs related to study treatment
|
1 Participants
|
|
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
Participants with TEAEs unrelated to study treatment
|
3 Participants
|
|
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
Participants with serious TEAEs
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 5 years post-dosePopulation: All subjects treated.
Clinically meaningful findings were defined as values which were outside the standard normal reference ranges for hematology and serum chemistry parameters.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants With Clinically Meaningful Findings in Hematology and Serum Chemistry Parameters
|
0 Participants
|
SECONDARY outcome
Timeframe: From baseline and up to 5 years post-dosePopulation: All subjects treated.
Post-baseline newly occurring or worsening potentially clinically significant ALT and AST levels were defined as values greater than twice the baseline value.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Changes in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels
AST
|
1 Participants
|
|
Number of Participants With Newly Occurring or Worsening Potentially Clinically Significant Changes in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels
ALT
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 5 years post-dosePopulation: All subjects treated.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants Receiving Corticosteroids for AST and ALT Elevations
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline and at 5 years post-dosePopulation: All subjects treated.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum
At Baseline for AAV5
|
3 Participants
|
|
Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum
At 5 years post dose for AAV5
|
3 Participants
|
|
Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum
At Baseline for FIX
|
0 Participants
|
|
Number of Participants Positive With AAV5 and Factor IX Neutralising Antibodies in Serum
At 5 years post dose for FIX
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 52Population: All subjects treated.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants With AAV5 Capsid-specific T Cell Response
|
1 Participants
|
SECONDARY outcome
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 52Population: All subjects treated.
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.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants With Inflammatory Marker Levels Outside Normal Ranges
Baseline: MCP-1
|
1 Participants
|
|
Number of Participants With Inflammatory Marker Levels Outside Normal Ranges
Week 1: MCP-1
|
1 Participants
|
|
Number of Participants With Inflammatory Marker Levels Outside Normal Ranges
Week 8: MCP-1
|
1 Participants
|
|
Number of Participants With Inflammatory Marker Levels Outside Normal Ranges
Week 40: IL-6
|
1 Participants
|
SECONDARY outcome
Timeframe: Up to 5 years post-dosePopulation: All subjects treated. Here, the "Number Analyzed (n)" included participants who were evaluable at specific parameters.
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.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Time to First Negative Results for Vector Deoxyribonucleic Acid (DNA) From Semen and Blood
Semen
|
26.21 Weeks
Interval 26.1 to 26.3
|
|
Time to First Negative Results for Vector Deoxyribonucleic Acid (DNA) From Semen and Blood
Blood
|
78.29 Weeks
Interval 31.1 to 168.9
|
SECONDARY outcome
Timeframe: Up to 5 years post-dosePopulation: All subjects treated.
Participants who were outside the normal limit range were to be reported.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants With Abnormal Values in Alpha-fetoprotein (AFP) Levels
|
0 Participants
|
SECONDARY outcome
Timeframe: At Months 36, 42, 48, 54, and 60 post-dosePopulation: All subjects treated. Here, the "Number Analyzed (n)" included participants who were evaluable at specific timepoints.
Ultrasounds were evaluated by qualified personnel and abnormalities were assessed by the Investigator.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants With Abnormal Results in Abdominal Ultrasound
Month 36
|
3 Participants
|
|
Number of Participants With Abnormal Results in Abdominal Ultrasound
Month 42
|
2 Participants
|
|
Number of Participants With Abnormal Results in Abdominal Ultrasound
Month 48
|
3 Participants
|
|
Number of Participants With Abnormal Results in Abdominal Ultrasound
Month 54
|
2 Participants
|
|
Number of Participants With Abnormal Results in Abdominal Ultrasound
Month 60
|
3 Participants
|
POST_HOC outcome
Timeframe: 5 years post dosePopulation: All subjects treated.
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.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Factor IX Activity Levels
|
45.67 Factor IX activity (%)
Standard Deviation 6.18
|
POST_HOC outcome
Timeframe: 5 years post dosePopulation: All subjects treated.
Participants with no usage of continuous factor IX prophylaxis after AMT-061 (CSL222) treatment were considered free from continuous factor IX prophylaxis use.
Outcome measures
| Measure |
AMT-061 (CSL222)
n=3 Participants
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Number of Participants Remaining Free of Continuous Prophylaxis
|
3 Participants
|
Adverse Events
AMT-061 (CSL222)
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AMT-061 (CSL222)
n=3 participants at risk
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
Other adverse events
| Measure |
AMT-061 (CSL222)
n=3 participants at risk
AAV5-hFIXco-Padua (AMT-061 \[CSL222\]): Single intravenous infusion of AMT-061 (CSL222).
|
|---|---|
|
Infections and infestations
Bronchitis
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Infections and infestations
COVID 19
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Infections and infestations
Coccidioidomycosis
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Infections and infestations
Influenza
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Infections and infestations
Pneumonia
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Infections and infestations
Sinusitis
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Infections and infestations
Upper respiratory tract infection
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
100.0%
3/3 • Number of events 5 • 5 years post-dose
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
66.7%
2/3 • Number of events 2 • 5 years post-dose
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
66.7%
2/3 • Number of events 3 • 5 years post-dose
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Nervous system disorders
Headache
|
66.7%
2/3 • Number of events 5 • 5 years post-dose
|
|
Nervous system disorders
Dizziness
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Nervous system disorders
Hypoaesthesia
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Nervous system disorders
Paraesthesia
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Nervous system disorders
Sciatica
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Nervous system disorders
Sinus headache
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Gastrointestinal disorders
Dental caries
|
66.7%
2/3 • Number of events 3 • 5 years post-dose
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3 • Number of events 3 • 5 years post-dose
|
|
Gastrointestinal disorders
Tongue disorder
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
General disorders
Asthenia
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
General disorders
Chest pain
|
33.3%
1/3 • Number of events 3 • 5 years post-dose
|
|
General disorders
Chronic fatigue syndrome
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
General disorders
Pain
|
33.3%
1/3 • Number of events 6 • 5 years post-dose
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Investigations
Blood creatine phosphokinase increased
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Investigations
Blood potassium decreased
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Investigations
C reactive protein increased
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Investigations
Transaminases increased
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Cardiac disorders
Tachycardia
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Ear and labyrinth disorders
Vertigo
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Eye disorders
Amblyopia
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Eye disorders
Cataract nuclear
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Eye disorders
Pinguecula
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Eye disorders
Pseudophakia
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Eye disorders
Refraction disorder
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Immune system disorders
Hypersensitivity
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Injury, poisoning and procedural complications
Procedural pain
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Psychiatric disorders
Libido decreased
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Respiratory, thoracic and mediastinal disorders
Aphonia
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
|
Vascular disorders
Hypertension
|
33.3%
1/3 • Number of events 2 • 5 years post-dose
|
|
Vascular disorders
Peripheral coldness
|
33.3%
1/3 • Number of events 1 • 5 years post-dose
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place