Trial of AAV5-hFIX in Severe or Moderately Severe Hemophilia B

• Sponsor: CSL Behring (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02396342
• Collaborator: (none)
• Enrollment: 10
• Locations: 7
• Arms: 2
• Actual Duration (Months): 70.2
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

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
Hemophilia B	Genetic: AAV5-hFIX	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II, Open-label, Uncontrolled, Single-dose, Dose-ascending, Multi-centre Trial Investigating an Adeno-associated Viral Vector Containing a Codon-optimized Human Factor IX Gene (AAV5-hFIX) Administered to Adult Patients With Severe or Moderately Severe Hemophilia B
• Actual Study Start Date: Jun 10, 2015
• Actual Primary Completion Date: Apr 15, 2021
• Actual Study Completion Date: Apr 15, 2021

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: AAV5 containing a codon-optimized human factor IX gene
Experimental: Cohort 2 AAV5-hFIX 2 × 10E13 gc/kg intravenous single infusion	Genetic: AAV5-hFIX; AAV5hFIX gene therapy; Other Names: AAV5 containing a codon-optimized human factor IX gene

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [From AMT-060 infusion through end of study (5 years post-dose)]

Secondary Outcome Measures

1. 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.

2. 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.

3. Total Consumption of FIX Replacement Therapy [From AMT-060 infusion through end of study (5 years post dose).]

4. 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.

5. 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).]

6. Number of Subjects Developing Neutralizing Antibodies to AAV5 [From AMT-060 infusion through end of study (5 years post dose)]

7. 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.

8. 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.

9. Number of Subjects With Antibodies to FIX [From AMT-060 infusion through the end of study (5 years post dose)]

10. Number of Subjects With FIX Inhibitors [From AMT-060 infusion through the end of study (5 years post dose)]

11. 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

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male

2. Age ≥ 18 years

3. 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

1. More than 150 previous exposure days of treatment with FIX protein.

2. 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)

3. 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:

1. History of FIX inhibitors measured to be ≥ 0.6 Bethesda Units (BU)/mL

2. FIX inhibitors ≥ 0.6 BU/mL at Visit 1 (measured by the local laboratory)

3. Neutralizing antibodies against AAV5 at Visit 1 (measured by the central laboratory)

4. 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

1. 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)

2. 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).

3. History of Hepatitis B or C exposure, currently controlled by antiviral therapy

4. Any coagulation disorder other than hemophilia B

5. Thrombocytopenia, defined as a platelet count below 50 × 10E9 / L, at Visit 1 (measured by the central laboratory)

6. Body mass index < 16 or ≥ 35 kg/m2

7. Planned surgery for the initial 6 months after IMP administration in this trial

8. Previous arterial or venous thrombotic event (e.g. acute myocardial infarction, cerebrovascular disease and venous thrombosis)

9. 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

10. 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

11. Known history of an allergic reaction or anaphylaxis to FIX products

12. Known uncontrolled allergic conditions or allergy/hypersensitivity to any component of the IMP excipients

13. Previous gene therapy treatment and/or previous participation in a gene therapy clinical trial

14. Receipt of an experimental agent within 60 days prior to Visit 1

15. 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)

• Study Protocol - Apr 20, 2021
• Statistical Analysis Plan - May 27, 2021

More Information

Publications

None provided.

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT02396342
• Other Study ID Numbers: CT-AMT-060-01
• First Posted: Mar 24, 2015
• Last Update Posted: Jun 27, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by CSL Behring: Hemophilia B, gene therapy
• Additional relevant MeSH terms: Hemophilia A; Hemophilia B

Study Results

Participant Flow

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

1. Primary Outcome

Title	Number of Participants With Adverse Events
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%

2. Secondary Outcome

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)

3. Secondary Outcome

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)

4. Secondary Outcome

Title	Total Consumption of FIX Replacement Therapy
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)

5. Secondary Outcome

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)

6. Secondary Outcome

Title	Time to Vector DNA Stopped Shedding From Blood, Nasal Secretions, Saliva, Urine, Feces, and Semen
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)

7. Secondary Outcome

Title	Number of Subjects Developing Neutralizing Antibodies to AAV5
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%

8. Secondary Outcome

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

9. Secondary Outcome

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%

10. Secondary Outcome

Title	Number of Subjects With Antibodies to FIX
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%

11. Secondary Outcome

Title	Number of Subjects With FIX Inhibitors
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%

12. Secondary Outcome

Title	Number of Subjects With Clinically Significant Inflammatory Markers: IL-1β, IL-2, IL-6, INFγ, MCP-1
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
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

[Not Specified]

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.