Trial of AAV5-hFIX in Severe or Moderately Severe Hemophilia B
Study Details
Study Description
Brief Summary
This study evaluates how safe gene therapy treatment with AAV5-hFIX is in adult patients with severe or moderately severe hemophilia B and severe bleeding type.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Cohort 1 AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion |
Genetic: AAV5-hFIX
AAV5hFIX gene therapy
Other Names:
|
Experimental: Cohort 2 AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion |
Genetic: AAV5-hFIX
AAV5hFIX gene therapy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events [From AMT-060 infusion through end of study (5 years post-dose)]
Secondary Outcome Measures
- FIX-replacement-therapy-free FIX Activity [From AMT-060 infusion through end of study (5 years post-dose)]
FIX activity measured any time from 72 hours after latest FIX replacement therapy administration and until next administration of FIX replacement therapy. Only assessments performed more than 10 days after most recent FIX-replacement therapy administration included.
- Total Annualized Bleeding Rate (ABR) [From AMT-060 infusion through end of study (5 years post-dose)]
Annualized: Sum of post-treatment bleeding episodes divided by subjects' average number of years (365.25 days) from treatment start to until the data cutoff date.
- Total Consumption of FIX Replacement Therapy [From AMT-060 infusion through end of study (5 years post dose).]
- Change From Baseline in Short Form-36 (SF-36) Quality of Life (QoL) Scores [From AMT-060 infusion through the end of study (5 years post dose)]
Scores range from 0 to 100, with a higher score defining a more favorable health state.
- Time to Vector DNA Stopped Shedding From Blood, Nasal Secretions, Saliva, Urine, Feces, and Semen [From AMT-060 infusion through end of study (5 years post dose).]
- Number of Subjects Developing Neutralizing Antibodies to AAV5 [From AMT-060 infusion through end of study (5 years post dose)]
- Total IgG and IgM Antibody Titers to AAV5 [AMT-060 infusion through end of study (5 years post dose)]
For subjects with a titer of 109350 and 50, the actual titer is >109350 and <50.
- Number of Subjects With a Positive AAV5 Capsid-specific T Cell Response [From AMT-060 infusion through 26 weeks post-dose]
Specific AAV5 response (results >17 SFC/million PBMCs) were regarded as positive.
- Number of Subjects With Antibodies to FIX [From AMT-060 infusion through the end of study (5 years post dose)]
- Number of Subjects With FIX Inhibitors [From AMT-060 infusion through the end of study (5 years post dose)]
- Number of Subjects With Clinically Significant Inflammatory Markers: IL-1β, IL-2, IL-6, INFγ, MCP-1 [From AMT-060 infusion through 18 weeks post dose]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male
-
Age ≥ 18 years
-
Patients with congenital hemophilia B classified as one of the following:
-
Known severe FIX deficiency with plasma FIX activity level < 1% and a severe bleeding phenotype defined by one of the following:
-
Currently on prophylactic FIX replacement therapy for a history of bleeding
-
Currently on on-demand therapy with a current or past history of frequent bleeding defined as four or more bleeding episodes in the last 12 months or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints
-
Known moderately severe FIX deficiency with plasma FIX activity level between ≥ 1% and ≤ 2% and a severe bleeding phenotype defined by one of the following:
-
Currently on prophylactic FIX replacement therapy for a history of bleeding
-
Currently on on-demand therapy with a current or past history of frequent bleeding defined as four or more bleeding episodes in the last 12 months or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints
-
More than 150 previous exposure days of treatment with FIX protein.
-
Acceptance to use a condom during sexual intercourse in the period from Investigational Medicinal Product (IMP) administration until AAV5 has been cleared from semen, as evidenced by the central laboratory from negative analysis results for at least 3 consecutively collected semen samples (this criterion is applicable also for subjects who are surgically sterilized)
-
Following receipt of verbal and written information about the trial, the subject has provided signed informed consent before any trial related activity is carried out.
Exclusion Criteria:
-
History of FIX inhibitors measured to be ≥ 0.6 Bethesda Units (BU)/mL
-
FIX inhibitors ≥ 0.6 BU/mL at Visit 1 (measured by the local laboratory)
-
Neutralizing antibodies against AAV5 at Visit 1 (measured by the central laboratory)
-
Visit 1 laboratory values (measured by the central laboratory):
-
alanine aminotransferase > 2 times upper normal limit
-
aspartate aminotransferase > 2 times upper normal limit
-
total bilirubin > 2 times upper normal limit
-
alkaline phosphatase > 2 times upper normal limit
-
creatinine > 1.5 times upper normal limit
-
Positive HIV serological test at Visit 1, not controlled with anti-viral therapy as shown by cluster of differentiation 4+ counts ≤ 200 per μL or by a viral load of >200 copies per mL (measured by the central laboratory)
-
Active infection with Hepatitis B or C virus as reflected by Hepatitis B Surface Antigen (HBsAg), Hepatitis B extracellular Antigen (HBeAg), Hepatitis B Virus DeoxyriboNucleic Acid (HBV DNA) or Hepatitis C Virus RiboNucleic Acid (HCV RNA) positivity, respectively, at Visit 1 (measured by the central laboratory).
-
History of Hepatitis B or C exposure, currently controlled by antiviral therapy
-
Any coagulation disorder other than hemophilia B
-
Thrombocytopenia, defined as a platelet count below 50 × 10E9 / L, at Visit 1 (measured by the central laboratory)
-
Body mass index < 16 or ≥ 35 kg/m2
-
Planned surgery for the initial 6 months after IMP administration in this trial
-
Previous arterial or venous thrombotic event (e.g. acute myocardial infarction, cerebrovascular disease and venous thrombosis)
-
Active severe infection or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease, alcoholism, drug dependency or any other psychological disorder evaluated by the investigator to interfere with adherence to the protocol procedures or with the degree of tolerance to the IMP
-
Known significant medical condition including disseminated intravascular coagulation, fibrinolysis and liver fibrosis which, in the opinion of the investigator, may confound, contraindicate or limit the interpretation of either safety or efficacy data
-
Known history of an allergic reaction or anaphylaxis to FIX products
-
Known uncontrolled allergic conditions or allergy/hypersensitivity to any component of the IMP excipients
-
Previous gene therapy treatment and/or previous participation in a gene therapy clinical trial
-
Receipt of an experimental agent within 60 days prior to Visit 1
-
Current participation or anticipated participation within one year after IMP administration in this trial in any other interventional clinical trial involving drugs or devices.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | uniQure Investigative Site | Copenhagen | Denmark | ||
2 | uniQure Investigative Site | Berlin | Germany | ||
3 | uniQure Investigative Site | Frankfurt | Germany | ||
4 | uniQure Investigative Site | Amsterdam | Netherlands | ||
5 | uniQure Investigative Site | Groningen | Netherlands | ||
6 | uniQure Investigative Site | Rotterdam | Netherlands | ||
7 | uniQure Investigative Site | Utrecht | Netherlands |
Sponsors and Collaborators
- CSL Behring
Investigators
- Study Director: uniQure Clinical Trials, UniQure Biopharma B.V.
Study Documents (Full-Text)
More Information
Publications
None provided.- CT-AMT-060-01
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Patients with congenital haemophilia B. Known severe FIX deficiency with plasma FIX activity level < 1% and a severe bleeding phenotype. Known moderately severe FIX deficiency with plasma FIX activity level between ≥ 1% and ≤ 2% and a severe bleeding phenotype. More than 150 previous exposure days of treatment with FIX protein |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Period Title: Overall Study | ||
STARTED | 5 | 5 |
COMPLETED | 5 | 5 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) | Total |
---|---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | Total of all reporting groups |
Overall Participants | 5 | 5 | 10 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
2
40%
|
5
100%
|
7
70%
|
>=65 years |
3
60%
|
0
0%
|
3
30%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
60.2
(15.9)
|
38.2
(5.9)
|
49.2
(16.2)
|
Sex: Female, Male (Count of Participants) | |||
Female |
0
0%
|
0
0%
|
0
0%
|
Male |
5
100%
|
5
100%
|
10
100%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
Not Hispanic or Latino |
5
100%
|
5
100%
|
10
100%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
1
20%
|
1
10%
|
White |
5
100%
|
4
80%
|
9
90%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | |||
Netherlands |
3
60%
|
3
60%
|
6
60%
|
Denmark |
1
20%
|
0
0%
|
1
10%
|
Germany |
1
20%
|
2
40%
|
3
30%
|
Outcome Measures
Title | Number of Participants With Adverse Events |
---|---|
Description | |
Time Frame | From AMT-060 infusion through end of study (5 years post-dose) |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set (FAS) which was comprised of all dosed subjects |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
Number [participants] |
5
100%
|
5
100%
|
Title | FIX-replacement-therapy-free FIX Activity |
---|---|
Description | FIX activity measured any time from 72 hours after latest FIX replacement therapy administration and until next administration of FIX replacement therapy. Only assessments performed more than 10 days after most recent FIX-replacement therapy administration included. |
Time Frame | From AMT-060 infusion through end of study (5 years post-dose) |
Outcome Measure Data
Analysis Population Description |
---|
FAS. Only assessments performed more than 10 days after most recent FIX-replacement therapy administration included. |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 4 | 5 |
one-stage aPTT assay |
7.43
(1.28)
|
6.60
(1.96)
|
amidolytic/chromogenic assay |
4.58
(2.88)
|
4.74
(1.43)
|
Title | Total Annualized Bleeding Rate (ABR) |
---|---|
Description | Annualized: Sum of post-treatment bleeding episodes divided by subjects' average number of years (365.25 days) from treatment start to until the data cutoff date. |
Time Frame | From AMT-060 infusion through end of study (5 years post-dose) |
Outcome Measure Data
Analysis Population Description |
---|
FAS. One subject in Cohort 2 did not report any bleeding information for the period 1 year prior to screening. Post-tapering period = from discontinuation of FIX prophylaxis until data cutoff. |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
One Year Prior to Screening |
14.40
(5.73)
|
4.00
(3.16)
|
Post-tapering Period |
5.39
(5.94)
|
0.71
(0.58)
|
Title | Total Consumption of FIX Replacement Therapy |
---|---|
Description | |
Time Frame | From AMT-060 infusion through end of study (5 years post dose). |
Outcome Measure Data
Analysis Population Description |
---|
FAS. Post-tapering period = from discontinuation of FIX prophylaxis until data cutoff. |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
One year prior to screening |
326532
(234900)
|
233778
(156873)
|
Post-tapering period |
252950
(222790)
|
85800
(84482)
|
Title | Change From Baseline in Short Form-36 (SF-36) Quality of Life (QoL) Scores |
---|---|
Description | Scores range from 0 to 100, with a higher score defining a more favorable health state. |
Time Frame | From AMT-060 infusion through the end of study (5 years post dose) |
Outcome Measure Data
Analysis Population Description |
---|
FAS |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
Physical Functioning |
0.00
(10.00)
|
-7.00
(9.75)
|
Role-Physical |
-15.00
(8.39)
|
-10.00
(22.79)
|
Bodily Pain |
-9.00
(9.00)
|
1.20
(14.81)
|
General Health |
-0.80
(20.22)
|
-2.40
(8.99)
|
Vitality |
-11.25
(19.96)
|
-6.25
(12.50)
|
Social Functioning |
-20.00
(25.92)
|
-5.00
(14.25)
|
Role-Emotional |
-13.33
(27.39)
|
-10.00
(13.69)
|
Mental Health |
-13.00
(22.80)
|
-9.00
(12.94)
|
Title | Time to Vector DNA Stopped Shedding From Blood, Nasal Secretions, Saliva, Urine, Feces, and Semen |
---|---|
Description | |
Time Frame | From AMT-060 infusion through end of study (5 years post dose). |
Outcome Measure Data
Analysis Population Description |
---|
FAS. Subject in Cohort 1 was unable to produce semen due to a historical medical condition. |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
Blood |
508.8
(261.7)
|
705.4
(245.1)
|
Nasal secretions |
83.4
(41.7)
|
108.4
(66.0)
|
Saliva |
75.8
(38.4)
|
129.2
(48.9)
|
Urine |
46.4
(20.9)
|
82.0
(41.1)
|
Feces |
74.0
(25.7)
|
165.0
(68.9)
|
Semen |
227.8
(147.7)
|
157.2
(78.4)
|
Title | Number of Subjects Developing Neutralizing Antibodies to AAV5 |
---|---|
Description | |
Time Frame | From AMT-060 infusion through end of study (5 years post dose) |
Outcome Measure Data
Analysis Population Description |
---|
FAS |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
Number [participants] |
5
100%
|
5
100%
|
Title | Total IgG and IgM Antibody Titers to AAV5 |
---|---|
Description | For subjects with a titer of 109350 and 50, the actual titer is >109350 and <50. |
Time Frame | AMT-060 infusion through end of study (5 years post dose) |
Outcome Measure Data
Analysis Population Description |
---|
FAS |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
IgG (subject 1) |
79499
|
109350
|
IgG (subject 2) |
109350
|
109350
|
IgG (subject 3) |
109350
|
109350
|
IgG (subject 4) |
109350
|
107344
|
IgG (subject 5) |
109350
|
109350
|
IgM (subject 1) |
56
|
30071
|
IgM (subject 2) |
1321
|
20000
|
IgM (subject 3) |
557
|
6649
|
IgM (subject 4) |
11568
|
50
|
IgM (subject 5) |
809
|
50
|
Title | Number of Subjects With a Positive AAV5 Capsid-specific T Cell Response |
---|---|
Description | Specific AAV5 response (results >17 SFC/million PBMCs) were regarded as positive. |
Time Frame | From AMT-060 infusion through 26 weeks post-dose |
Outcome Measure Data
Analysis Population Description |
---|
FAS |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
Number [participants] |
1
20%
|
0
0%
|
Title | Number of Subjects With Antibodies to FIX |
---|---|
Description | |
Time Frame | From AMT-060 infusion through the end of study (5 years post dose) |
Outcome Measure Data
Analysis Population Description |
---|
FAS |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
Number [participants] |
1
20%
|
0
0%
|
Title | Number of Subjects With FIX Inhibitors |
---|---|
Description | |
Time Frame | From AMT-060 infusion through the end of study (5 years post dose) |
Outcome Measure Data
Analysis Population Description |
---|
FAS |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
Number [participants] |
0
0%
|
0
0%
|
Title | Number of Subjects With Clinically Significant Inflammatory Markers: IL-1β, IL-2, IL-6, INFγ, MCP-1 |
---|---|
Description | |
Time Frame | From AMT-060 infusion through 18 weeks post dose |
Outcome Measure Data
Analysis Population Description |
---|
FAS |
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) |
---|---|---|
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy |
Measure Participants | 5 | 5 |
Number [participants] |
0
0%
|
0
0%
|
Adverse Events
Time Frame | 5 years post-dose | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) | ||
Arm/Group Description | AAV5-hFIX 5 × 10E12 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion AAV5-hFIX: AAV5hFIX gene therapy | ||
All Cause Mortality |
||||
AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/5 (0%) | 0/5 (0%) | ||
Serious Adverse Events |
||||
AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/5 (60%) | 2/5 (40%) | ||
General disorders | ||||
Pyrexia | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Investigations | ||||
Hepatic Enzyme Increased | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Alanine Aminotransferase Increased | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Nervous system disorders | ||||
Myelopathy | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Renal and urinary disorders | ||||
Renal Colic | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Calculus Ureteric | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
AAV5-hFIX Low Dose (Cohort 1) | AAV5-hFIX High Dose (Cohort 2) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/5 (100%) | 5/5 (100%) | ||
Blood and lymphatic system disorders | ||||
Splenomegaly | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Cardiac disorders | ||||
Tachycardia | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Palpitations | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Ear and labyrinth disorders | ||||
Vertigo positional | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Cerumen impaction | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Eye disorders | ||||
Blepharitis | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Cataract | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Gastrointestinal disorders | ||||
Dyspepsia | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Constipation | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Diarrhoea | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Food poisoning | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Abdominal pain lower | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Toothache | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Large intestine polyp | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Irritable bowel syndrome | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Abdominal pain | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Gastrointestinal sounds abnormal | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Abdominal pain upper | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Abdominal discomfort | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Gastrointestinal disorder | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
General disorders | ||||
Pyrexia | 1/5 (20%) | 1 | 2/5 (40%) | 2 |
Influenza like illness | 3/5 (60%) | 3 | 0/5 (0%) | 0 |
Fatigue | 1/5 (20%) | 1 | 1/5 (20%) | 1 |
Peripheral swelling | 0/5 (0%) | 0 | 1/5 (20%) | 2 |
Malaise | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Pain | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Drug ineffective | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Immune system disorders | ||||
Hypersensitivity | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Infections and infestations | ||||
Nasopharyngitis | 1/5 (20%) | 2 | 3/5 (60%) | 8 |
Influenza | 2/5 (40%) | 2 | 0/5 (0%) | 0 |
Eye infection | 0/5 (0%) | 0 | 1/5 (20%) | 2 |
Cellulitis | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Upper respiratory tract infection | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Sinusitis | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Bronchitis | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Rhinitis | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Cystitis | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Pulpitis dental | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Oral herpes | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Laryngitis | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Herpes zoster | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Respiratory tract infection | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Fungal skin infection | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Ear infection | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Injury, poisoning and procedural complications | ||||
Fall | 1/5 (20%) | 5 | 1/5 (20%) | 1 |
Upper limb fracture | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Ulna fracture | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Tooth fracture | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Joint injury | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Hand fracture | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Bone contusion | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Injury | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Muscle strain | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Arthropod bite | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Investigations | ||||
Hepatic enzyme increased | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Haemoglobin decreased | 1/5 (20%) | 2 | 0/5 (0%) | 0 |
Transaminases increased | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Platelet count decreased | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Blood urine present | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||
Joint swelling | 2/5 (40%) | 3 | 2/5 (40%) | 2 |
Arthralgia | 3/5 (60%) | 10 | 0/5 (0%) | 0 |
Back pain | 1/5 (20%) | 2 | 1/5 (20%) | 3 |
Musculoskeletal pain | 2/5 (40%) | 4 | 0/5 (0%) | 0 |
Pain in extremity | 1/5 (20%) | 1 | 1/5 (20%) | 1 |
Groin pain | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Tenosynovitis | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Synovial cyst | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Neck pain | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Musculoskeletal stiffness | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Intervertebral disc protrusion | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Nervous system disorders | ||||
Headache | 1/5 (20%) | 1 | 1/5 (20%) | 1 |
Dizziness | 2/5 (40%) | 2 | 0/5 (0%) | 0 |
Nervous system disorder | 0/5 (0%) | 0 | 1/5 (20%) | 2 |
Paraesthesia | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Hypoaesthesia | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Psychiatric disorders | ||||
Sleep disorder | 1/5 (20%) | 2 | 1/5 (20%) | 1 |
Anxiety | 1/5 (20%) | 1 | 1/5 (20%) | 1 |
Renal and urinary disorders | ||||
Renal colic | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Nephrolithiasis | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Dysuria | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Reproductive system and breast disorders | ||||
Prostatitis | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||
Chronic obstructive pulmonary disease | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||
Dermatitis atopic | 0/5 (0%) | 0 | 1/5 (20%) | 2 |
Actinic keratosis | 1/5 (20%) | 2 | 0/5 (0%) | 0 |
Rash | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Eczema | 1/5 (20%) | 1 | 0/5 (0%) | 0 |
Vascular disorders | ||||
Haematoma | 0/5 (0%) | 0 | 1/5 (20%) | 2 |
Lymphoedema | 0/5 (0%) | 0 | 1/5 (20%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | CSL Behring |
Phone | 610-878-4000 |
clinicaltrials@cslbehring.com |
- CT-AMT-060-01