Hemophilia B
Conditions
Keywords
gene therapy, Hemophilia B
Brief summary
A Phase 1/2, open-label, dose-finding safety study of single ascending doses of DTX101 in adult males with moderate/severe to severe hemophilia B.
Detailed description
Hemophilia B is an X-linked recessive genetic bleeding disorder caused by mutations in the factor IX (FIX) gene. FIX is produced in the liver and is critical for fibrin clot formation. Hemophilia B is characterized by frequent, spontaneous internal bleeding that can lead to chronic arthropathy (joint damage), intracranial hemorrhage, and even death. In patients with moderate/severe to severe hemophilia B, the majority of bleeding episodes occur in the joints and, if not treated, lead to debilitating damage and a decreased quality of life. This study will evaluate the safety and efficacy of the adeno-associated virus (AAV) to deliver human factor IX (hFIX) gene, the healthy gene necessary to make FIX, to the liver where FIX is normally produced. This study will determine if AAVrh10 can produce clinically meaningful FIX levels in patients with moderately/severe or severe hemophilia B. This study was previously posted by Dimension Therapeutics, which has been acquired by Ultragenyx in November 2017.
Interventions
GENETICDTX101
solution for IV infusion
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male ≥ 18 years of age. 2. Moderate/severe or severe hemophilia B (baseline FIX activity ≤ 2% of normal or documented history of FIX activity ≤2%). 3. At least 3 bleeding episodes per year that require on-demand treatment with FIX OR are treated with a prophylactic regimen of FIX. 4. At least 100 days exposure history to FIX. 5. No documented history of inhibitors (neutralizing antibodies) to exogenous FIX. 6. No known allergic reaction to exogenous FIX or any component of DTX101. 7. Willing to stop prophylactic treatment with recombinant FIX at specified time points during the study.
Exclusion criteria
1. History of significant liver disease (ie, portal hypertension). 2. Significant hepatic inflammation or cirrhosis. 3. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 4. History of human immunodeficiency virus (HIV) infection AND any of the following: CD4+ cell count \< 350 cells/mm\^3, change in antiretroviral therapy regimen within 6 months prior to Day 0, or plasma viral load \> 200 copies/mL, on 2 separate occasions, as measured by polymerase chain reaction. 5. Anti-AAVrh10 neutralizing antibody titer \> 1:5. 6. Participation (current or previous) in another gene therapy study. 7. Participation in another investigational medicine study within 3 months before screening. NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs) | up to 52 weeks after dosing (Cohort 1) or 44 weeks after dosing (Cohort 2) | An AE was defined as any untoward medical occurrence in a participant enrolled into this study (from the time the participant signed the informed consent form until his or her exit from the study), regardless of its causal relationship to study treatment. A TEAE was defined as any event not present before exposure to study product or any event already present that worsened in severity or increased in frequency after exposure to study product. |
| Change From Baseline in FIX Activity at Week 6 | Baseline, Week 6 | Peak plasma level of FIX after IV administration as determined by the activated partial thromboplastin time (aPTT) clot-based assay. Change from baseline: postbaseline value - baseline value. For the change from baseline, only participants with a value at both baseline visit and the specific postbaseline visit were included. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized FIX Replacement Therapy | Week 0 to Week 52 | The use of on-demand FIX replacement therapy was recorded by dose (IU/kg) administered, and the annualized use of FIX replacement therapy was calculated. Participants were not required to stop prophylactic treatment with recombinant FIX until after Week 4 and may have been restarted on their prophylactic recombinant FIX treatment after Week 14. |
| Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Day 0 (predose), Weeks 6, 8, 16, 32, 40, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal | The development of neutralizing antibodies to FIX (FIX inhibitors), as determined by a Bethesda assay. A value of \< 0.3 inhibitor units was considered to be no neutralizing antibodies. |
| Number of Participants With Cell-Mediated Immune Response to FIX | Day 0 (predose), Weeks 6, 8, 12, 16, 32, 40, 48, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal | The development of a cell-mediated immune response to FIX, as determined by enzyme-linked immunospot assay (ELISPOT). |
| Annualized Bleeding Rate | Week 0 to Week 52 | The number of bleeding episodes per participant was recorded, and the annualized number of bleeding episodes was calculated. |
| Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52) | The Haemophilia-Specific Quality of Life questionnaire asks subjects about their perceptions of their health and treatment. The questionnaire is divided into the following 10 dimensions: physical health, feelings, view of themselves, sports & leisure, work & school, dealing with hemophilia, treatment, future, family planning, and partnership & sexuality. Questions are based on a 5-point Likert-scale (1=never, 2=rarely, 3=sometimes, 4=often, 5=all the time). If the question does not apply to the subject, the not applicable response is allowed in 3 of the domains (sport & leisure, work & school, family planning). Positively worded items need to be re-coded and domains will be transformed ranging from 0 to 100; higher domain and total scores indicating a higher impairment of health-related quality of life. |
| Average Weekly Use of FIX Replacement Therapy | Baseline (Screening), Week 0 through Week 52 | The use of on-demand FIX replacement therapy was recorded by dose (IU/kg) administered and the average weekly use of FIX replacement therapy was calculated. Participants were not required to stop prophylactic treatment with recombinant FIX until after Week 4 and may have been restarted on their prophylactic recombinant FIX treatment after Week 14. |
| Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52) | EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3). |
| Change From Baseline in FIX Activity Over Time | Baseline, Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal | Peak plasma level of FIX after IV administration as determined by the aPTT clot-based assay. Change from baseline: postbaseline value - baseline value. For the change from baseline, only participants with a value at both baseline visit and the specific postbaseline visit were included. Participants were not required to stop prophylactic treatment with recombinant FIX until after Week 4 and may have been restarted on their prophylactic recombinant FIX treatment after Week 14. |
Countries
Bulgaria, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DTX101, Cohort 1 a single peripheral IV infusion of 1.6 x 10\^12 GC/kg DTX101 | 3 |
| DTX101, Cohort 2 a single peripheral IV infusion of 5.0 x 10\^12 GC/kg DTX101 | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | DTX101, Cohort 1 | DTX101, Cohort 2 | Total |
|---|---|---|---|
| Age, Customized 18-49 years | 0 participants | 3 participants | 3 participants |
| Age, Customized 50-84 years | 3 participants | 0 participants | 3 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Factor IX (FIX) Activity | 1.67 IU/dL STANDARD_DEVIATION 0.577 | 0.87 IU/dL STANDARD_DEVIATION 0.709 | 1.27 IU/dL STANDARD_DEVIATION 0.566 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 |
Outcome results
Primary
Change From Baseline in FIX Activity at Week 6
Peak plasma level of FIX after IV administration as determined by the activated partial thromboplastin time (aPTT) clot-based assay. Change from baseline: postbaseline value - baseline value. For the change from baseline, only participants with a value at both baseline visit and the specific postbaseline visit were included.
Time frame: Baseline, Week 6
Population: As Treated Set: all participants who received any amount of DTX101.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DTX101, Cohort 1 | Change From Baseline in FIX Activity at Week 6 | 5.00 IU/dL | Standard Deviation 1.732 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity at Week 6 | 9.80 IU/dL | Standard Deviation 4.687 |
Primary
Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs)
An AE was defined as any untoward medical occurrence in a participant enrolled into this study (from the time the participant signed the informed consent form until his or her exit from the study), regardless of its causal relationship to study treatment. A TEAE was defined as any event not present before exposure to study product or any event already present that worsened in severity or increased in frequency after exposure to study product.
Time frame: up to 52 weeks after dosing (Cohort 1) or 44 weeks after dosing (Cohort 2)
Population: Safety Set: all participants who received DTX101 including participants who received a partial dose or failed infusion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTX101, Cohort 1 | Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs) | All Serious TEAEs | 1 Participants |
| DTX101, Cohort 1 | Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs) | All TEAEs | 3 Participants |
| DTX101, Cohort 2 | Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs) | All TEAEs | 3 Participants |
| DTX101, Cohort 2 | Number of Participants With Adverse Events (AEs), Treatment-Related Adverse Events (TEAEs), and Serious AEs (SAEs) | All Serious TEAEs | 0 Participants |
Secondary
Annualized Bleeding Rate
The number of bleeding episodes per participant was recorded, and the annualized number of bleeding episodes was calculated.
Time frame: Week 0 to Week 52
Population: As Treated Set: all participants who received any amount of DTX101.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DTX101, Cohort 1 | Annualized Bleeding Rate | 8.7 bleeding episodes/year | Standard Deviation 5.53 |
| DTX101, Cohort 2 | Annualized Bleeding Rate | 5.0 bleeding episodes/year | Standard Deviation 1 |
Secondary
Annualized FIX Replacement Therapy
The use of on-demand FIX replacement therapy was recorded by dose (IU/kg) administered, and the annualized use of FIX replacement therapy was calculated. Participants were not required to stop prophylactic treatment with recombinant FIX until after Week 4 and may have been restarted on their prophylactic recombinant FIX treatment after Week 14.
Time frame: Week 0 to Week 52
Population: As Treated Set: all participants who received any amount of DTX101.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DTX101, Cohort 1 | Annualized FIX Replacement Therapy | 350115.2 IU/kg | Standard Deviation 522106.19 |
| DTX101, Cohort 2 | Annualized FIX Replacement Therapy | 64246.5 IU/kg | Standard Deviation 805.34 |
Secondary
Average Weekly Use of FIX Replacement Therapy
The use of on-demand FIX replacement therapy was recorded by dose (IU/kg) administered and the average weekly use of FIX replacement therapy was calculated. Participants were not required to stop prophylactic treatment with recombinant FIX until after Week 4 and may have been restarted on their prophylactic recombinant FIX treatment after Week 14.
Time frame: Baseline (Screening), Week 0 through Week 52
Population: As Treated Set: all participants who received any amount of DTX101, with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 51 to 52 | 20000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 3 to 4 | 24000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 5 to 6 | 9068.5 IU/kg | Standard Deviation 10611.55 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 27 to 28 | 8120.0 IU/kg | Standard Deviation 5487.15 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 9 to 10 | 32000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 11 to 12 | 8076.7 IU/kg | Standard Deviation 10325.91 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 13 to 14 | 12000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 15 to 16 | 16000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 17 to 18 | 8000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 19 to 20 | 12000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 21 to 22 | 7832.8 IU/kg | Standard Deviation 3057.68 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 23 to 24 | 8782.5 IU/kg | Standard Deviation 10207.09 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 25 to 26 | 8902.5 IU/kg | Standard Deviation 4380.53 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 29 to 30 | 12120.0 IU/kg | Standard Deviation 11144 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 31 to 32 | 28000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 33 to 34 | 12000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 35 to 36 | 12000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 37 to 38 | 4795.0 IU/kg | Standard Deviation 4532.55 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 39 to 40 | 26795.0 IU/kg | Standard Deviation 35645.25 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 43 to 44 | 20000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 47 to 48 | 20000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 41 to 42 | 24000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 45 to 46 | 20000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 49 to 50 | 24000.0 IU/kg | — |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Baseline | 9659.1 IU/kg | Standard Deviation 12502.19 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 0 to 2 | 12120.0 IU/kg | Standard Deviation 11144 |
| DTX101, Cohort 1 | Average Weekly Use of FIX Replacement Therapy | Week 7 to 8 | 5120.0 IU/kg | Standard Deviation 1244.51 |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 27 to 28 | 4725.0 IU/kg | Standard Deviation 1025.3 |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 39 to 40 | 2375.0 IU/kg | Standard Deviation 883.88 |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 0 to 2 | 5000.0 IU/kg | — |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 41 to 42 | 1500.0 IU/kg | — |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 43 to 44 | 1750.0 IU/kg | — |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 25 to 26 | 5445.0 IU/kg | Standard Deviation 3952.73 |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 45 to 46 | 5000.0 IU/kg | — |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 47 to 48 | 7500.0 IU/kg | — |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 33 to 34 | 2816.7 IU/kg | Standard Deviation 1877.72 |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 17 to 18 | 3375.0 IU/kg | Standard Deviation 883.88 |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Baseline | 5037.2 IU/kg | Standard Deviation 3502.95 |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 29 to 30 | 2250.0 IU/kg | Standard Deviation 353.55 |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 3 to 4 | 7000.0 IU/kg | — |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 5 to 6 | 3000.0 IU/kg | — |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 19 to 20 | 8000.0 IU/kg | — |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 37 to 38 | 3500.0 IU/kg | Standard Deviation 2828.43 |
| DTX101, Cohort 2 | Average Weekly Use of FIX Replacement Therapy | Week 31 to 32 | 2750.0 IU/kg | Standard Deviation 1767.77 |
Secondary
Change From Baseline in FIX Activity Over Time
Peak plasma level of FIX after IV administration as determined by the aPTT clot-based assay. Change from baseline: postbaseline value - baseline value. For the change from baseline, only participants with a value at both baseline visit and the specific postbaseline visit were included. Participants were not required to stop prophylactic treatment with recombinant FIX until after Week 4 and may have been restarted on their prophylactic recombinant FIX treatment after Week 14.
Time frame: Baseline, Weeks 2, 4, 6, 8, 12, 16, 24, 32, 40, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal
Population: As Treated Set: all participants who received any amount of DTX101.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | Week 16 | 7.67 IU/dL | Standard Deviation 3.215 |
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | Week 40 | 15.33 IU/dL | Standard Deviation 23.965 |
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | Week 6 | 5.00 IU/dL | Standard Deviation 1.732 |
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | Week 8 | 14.67 IU/dL | Standard Deviation 17.786 |
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | Week 12 | 11.33 IU/dL | Standard Deviation 4.933 |
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | Week 4 | 8.67 IU/dL | Standard Deviation 7.234 |
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | Week 24 | 2.33 IU/dL | Standard Deviation 1.528 |
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | Week 32 | 9.33 IU/dL | Standard Deviation 11.846 |
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | End of Study/Early Withdrawal | 1.67 IU/dL | Standard Deviation 0.577 |
| DTX101, Cohort 1 | Change From Baseline in FIX Activity Over Time | Week 2 | 16.33 IU/dL | Standard Deviation 14.503 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | End of Study/Early Withdrawal | 22.47 IU/dL | Standard Deviation 1.38 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | Week 2 | 10.13 IU/dL | Standard Deviation 7.988 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | Week 4 | 14.47 IU/dL | Standard Deviation 10.835 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | Week 6 | 9.80 IU/dL | Standard Deviation 4.687 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | Week 8 | 11.80 IU/dL | Standard Deviation 6.646 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | Week 12 | 5.80 IU/dL | Standard Deviation 2.207 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | Week 24 | 2.47 IU/dL | Standard Deviation 2.214 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | Week 32 | 10.13 IU/dL | Standard Deviation 2.702 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | Week 16 | 5.47 IU/dL | Standard Deviation 3.066 |
| DTX101, Cohort 2 | Change From Baseline in FIX Activity Over Time | Week 40 | 12.80 IU/dL | Standard Deviation 16.008 |
Secondary
Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire
EQ-5D-5L is a standardized, subject-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has no problems (1), some problems (2), or severe problems (3).
Time frame: Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52)
Population: Safety Set: all participants who received DTX101 including participants who received a partial dose or failed infusion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTX101, Cohort 1 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | Week 36 | 3 Participants |
| DTX101, Cohort 1 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | Week 24 | 3 Participants |
| DTX101, Cohort 1 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | Week 48 | 2 Participants |
| DTX101, Cohort 1 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | End of Study/Early Withdrawal | 2 Participants |
| DTX101, Cohort 1 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | Day 0 | 3 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | Week 24 | 3 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | End of Study/Early Withdrawal | 0 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | Week 36 | 2 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | Day 0 | 3 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the EuroQoL-5D-5 Level (EQ-5D-5L) Questionnaire | Week 48 | 1 Participants |
Secondary
Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire
The Haemophilia-Specific Quality of Life questionnaire asks subjects about their perceptions of their health and treatment. The questionnaire is divided into the following 10 dimensions: physical health, feelings, view of themselves, sports & leisure, work & school, dealing with hemophilia, treatment, future, family planning, and partnership & sexuality. Questions are based on a 5-point Likert-scale (1=never, 2=rarely, 3=sometimes, 4=often, 5=all the time). If the question does not apply to the subject, the not applicable response is allowed in 3 of the domains (sport & leisure, work & school, family planning). Positively worded items need to be re-coded and domains will be transformed ranging from 0 to 100; higher domain and total scores indicating a higher impairment of health-related quality of life.
Time frame: Baseline (Day 0 predose), Weeks 24, 36, 48, End of Study/Early Withdrawal (up to Week 52)
Population: Safety Set: all participants who received DTX101 including participants who received a partial dose or failed infusion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTX101, Cohort 1 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | Day 0 | 3 Participants |
| DTX101, Cohort 1 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | Week 36 | 3 Participants |
| DTX101, Cohort 1 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | Week 48 | 2 Participants |
| DTX101, Cohort 1 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | End of Study/Early Withdrawal | 2 Participants |
| DTX101, Cohort 1 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | Week 24 | 3 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | End of Study/Early Withdrawal | 0 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | Week 24 | 3 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | Week 48 | 1 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | Day 0 | 3 Participants |
| DTX101, Cohort 2 | Number of Participants Responding to the Haemophilia-Specific Quality of Life Questionnaire | Week 36 | 2 Participants |
Secondary
Number of Participants With Cell-Mediated Immune Response to FIX
The development of a cell-mediated immune response to FIX, as determined by enzyme-linked immunospot assay (ELISPOT).
Time frame: Day 0 (predose), Weeks 6, 8, 12, 16, 32, 40, 48, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal
Population: Safety Set: all participants who received DTX101 including subjects who received a partial dose or failed infusion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTX101, Cohort 1 | Number of Participants With Cell-Mediated Immune Response to FIX | Day 0 (predose) | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 12 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 6 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 40 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 8 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 16 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Cell-Mediated Immune Response to FIX | End of Study/Early Withdrawal | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 48 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 32 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 48 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 12 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 16 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 32 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Cell-Mediated Immune Response to FIX | End of Study/Early Withdrawal | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Cell-Mediated Immune Response to FIX | Day 0 (predose) | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 6 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 40 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Cell-Mediated Immune Response to FIX | Week 8 | 0 Participants |
Secondary
Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors)
The development of neutralizing antibodies to FIX (FIX inhibitors), as determined by a Bethesda assay. A value of \< 0.3 inhibitor units was considered to be no neutralizing antibodies.
Time frame: Day 0 (predose), Weeks 6, 8, 16, 32, 40, End of Study (Week 52 for Cohort 1, Week 44 for Cohort 2)/Early Withdrawal
Population: As Treated Set: all participants who received any amount of DTX101.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DTX101, Cohort 1 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Day 0 (predose) | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 6 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 32 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 40 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | End of Study/Early Withdrawal | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 8 | 0 Participants |
| DTX101, Cohort 1 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 16 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | End of Study/Early Withdrawal | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Day 0 (predose) | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 6 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 16 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 32 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 8 | 0 Participants |
| DTX101, Cohort 2 | Number of Participants With Neutralizing Antibodies to FIX (FIX Inhibitors) | Week 40 | 0 Participants |