Clinical Trial Results:
A Phase 3 Open-Label, Single-Arm Study To Evaluate The Efficacy and Safety of BMN 270, an Adeno-Associated Virus Vector–Mediated Gene Transfer of Human Factor VIII in Hemophilia A Patients with Residual FVIII Levels <= 1 IU/dL Receiving Prophylactic FVIII Infusions
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Summary
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EudraCT number |
2017-003215-19 |
Trial protocol |
GB DE ES FR BE IT |
Global end of trial date |
20 Nov 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Dec 2025
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First version publication date |
20 Dec 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
270-301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03370913 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
BioMarin Pharmaceutical Inc
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Sponsor organisation address |
105 Digital Drive, Novato, CA, United States, 94949
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Public contact |
Clinical Trials Information, BioMarin Pharmaceutical Inc., medinfo@bmrn.com
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Scientific contact |
Clinical Trials Information, BioMarin Pharmaceutical Inc., medinfo@bmrn.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Nov 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Nov 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Nov 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Assess the efficacy of BMN 270 (compared to no treatment) defined as FVIII activity, as measured by chromogenic substrate assay, at Week 260 following intravenous infusion of BMN 270
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Protection of trial subjects |
This study was conducted in accordance with the following:
• European Clinical Trial Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC, for studies conducted within any European country
• US Code of Federal Regulations (CFR) sections that address clinical research studies, and/or other national and local regulations, as applicable
• ICH Harmonised Tripartite Guideline: Guideline for Good Clinical Practice E6 (ICH E6)
The study was conducted under a protocol reviewed and approved by an IRB/IEC and is conducted by scientifically and medically qualified persons. The benefits of the study were in proportion to the risks. The rights and welfare of the participants were respected, and the investigators conducting the study did not find the hazards to outweigh the potential benefits.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Dec 2017
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Safety | ||
Long term follow-up duration |
5 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 4
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Country: Number of subjects enrolled |
United Kingdom: 23
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Country: Number of subjects enrolled |
Belgium: 5
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Country: Number of subjects enrolled |
France: 3
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Country: Number of subjects enrolled |
Germany: 3
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
United States: 30
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Country: Number of subjects enrolled |
South Africa: 16
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Country: Number of subjects enrolled |
Korea, Republic of: 1
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Country: Number of subjects enrolled |
Israel: 5
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Country: Number of subjects enrolled |
Taiwan: 10
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Country: Number of subjects enrolled |
Brazil: 19
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Country: Number of subjects enrolled |
Australia: 14
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Worldwide total number of subjects |
134
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EEA total number of subjects |
16
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
133
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was conducted at 48 sites worldwide (United States, Australia, Belgium, Brazil, France, Germany, Israel, Italy, South Korea, South Africa, Spain, Taiwan, and United Kingdom). | ||||||||||||||
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Pre-assignment
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Screening details |
Of the 181 participants screened, 37 failed screening. Of the remaining 144 participants in 270-301, 134 were treated with 6E13 vg/kg BMN 270. Ten participants enrolled but were not dosed (5 each from the directly enrolling and from the rollover pools of potential participants). | ||||||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Double blind [1] | ||||||||||||||
Roles blinded |
Monitor, Data analyst, Assessor | ||||||||||||||
Blinding implementation details |
This was an open-label study. However, the Sponsor implemented role-based access control for certain study data.
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Arms
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Arm title
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BMN 270 (Valoctocogene Roxaparvovec) | ||||||||||||||
Arm description |
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
BMN 270
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Investigational medicinal product code |
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Other name |
AAV5-hFVIII-SQ/BMN 270
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
BMN 270 was infused through the catheter or butterfly needle using an appropriate infusion pump at an initial rate of 1 mL/min, which was increased every 30 minutes by 1mL/min up to a maximum of 4 mL/min, provided that the participant’s clinical condition permitted such an increase. Of note, the IP has been shown to be stable at room temperature for 7.5 hours following completion of product thaw. Vital signs (pulse, blood pressure, respiration rate and temperature) were monitored at 15-minute (± 5 minutes) intervals throughout the time period of the infusion.
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| Notes [1] - The roles blinded appear to be inconsistent with a double blind trial. Justification: This was an open-label study. However, the Sponsor implemented role-based access control for certain study data. |
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
6E13 vector genomes (vg) per kilogram of body weight, given as a single intravenous dose IV). valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Severe Hemophilia A | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BMN 270 (Valoctocogene Roxaparvovec)
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Reporting group description |
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects | ||
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End point title |
Mean change from Baseline in FVIII Activity as Measured by Chromogenic Substrate Assay at Week 52 Post-BMN 270 Infusion [1] | ||||||||
End point description |
The change from baseline (assuming no treatment for severe hemophilia A) in FVIII activity, as measured by chromogenic substrate assay, Weeks 49-52 post-BMN 270 infusion.
Modified Intent-to-Treat (mITT) Population (n=132): All HIV-negative subjects at study screening who were dosed in 270-301.
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End point type |
Primary
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End point timeframe |
Baseline to Week 52
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was analyzed for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Median change from Baseline in FVIII Activity as Measured by Chromogenic Substrate Assay at Week 52 Post-BMN 270 Infusion [2] | ||||||||
End point description |
Values for FVIII activity were excluded from analysis if obtained within 72 hours (or 3 calendar days if time is not available) since the last infusion of exogenous FVIII replacement therapy.
FVIII activity levels below the LLOQ (Lower limit of quantification) were imputed with 0 IU/dL.
Modified Intent-to-Treat (mITT) Population (n=132).
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End point type |
Primary
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End point timeframe |
Baseline to Week 52
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was analyzed for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants with Treatment-related Adverse Events | ||||||||||||||||||||||||
End point description |
A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
Participants with more than one AE of the same category were counted only once for that category.
Serious adverse event (SAE)
Intent-to-Treat (ITT) Population (n=134) – all participants dosed in 270-301
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End point type |
Secondary
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End point timeframe |
Up to 5 years after dosing
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Mean Change From Baseline in Annualized FVIII Utilization in EEP | ||||||||
End point description |
The change from baseline in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the Post FVIII Prophylaxis to Last Visit in the EEP.
The annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy is defined as Sum of FVIII use (IU/kg) during calculation period/Total number of days during the calculation period ×365.25
Rollover Population (n=112) – all participants dosed in 270-301 who previously participated in 270-902 (all participants were HIV-negative)
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End point type |
Secondary
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End point timeframe |
Baseline to EEP
Efficacy evaluation period (EEP): Week 5 to Last Visit.
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| No statistical analyses for this end point | |||||||||
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End point title |
Median Change From Baseline in the Annualized FVIII Utilization in EEP | ||||||||
End point description |
The change from baseline in the annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy in the Post FVIII Prophylaxis to Last Visit in the EEP.
The annualized utilization (IU/kg/year) of exogenous FVIII replacement therapy is defined as Sum of FVIII use (IU/kg) during calculation period/Total number of days during the calculation period ×365.25
Rollover Population (n=112)
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End point type |
Secondary
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End point timeframe |
Baseline to EEP
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change from baseline in annualized FVIII infusion rate at EEP | ||||||||
End point description |
Annualized FVIII infusion rate (count/yr) = (sum(Number of FVIII replacement infusions during calculation period)/sum(follow-up days of the period)) x 365.25.
Rollover Population (n=112)
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End point type |
Secondary
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End point timeframe |
Baseline to EEP
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| No statistical analyses for this end point | |||||||||
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End point title |
Median Change from baseline in annualized FVIII infusion rate at EEP | ||||||||
End point description |
Annualized FVIII infusion rate (count/yr) = (sum(Number of FVIII replacement infusions during calculation period)/sum(follow-up days of the period)) x 365.25.
Rollover Population (n=112)
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End point type |
Secondary
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End point timeframe |
Baseline to EEP
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Therapy (ABR for Treated Bleeds) in the EEP | ||||||||
End point description |
ABR for treated bleeds=Number of bleeding episodes for treated bleeds during the calculation period/total number of days during the calculation period * 365.25
Rollover Population (n=112)
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End point type |
Secondary
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End point timeframe |
Baseline to EEP
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| No statistical analyses for this end point | |||||||||
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End point title |
Median Change From Baseline in the Annualized Number of Bleeding Episodes Requiring Exogenous FVIII Replacement Therapy (ABR for Treated Bleeds) in the EEP | ||||||||
End point description |
ABR for treated bleeds=Number of bleeding episodes for treated bleeds during the calculation period/total number of
days during the calculation period * 365.25
Rollover Population (n=112)
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End point type |
Secondary
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End point timeframe |
Baseline to EEP
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| No statistical analyses for this end point | |||||||||
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End point title |
Mean Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 260 | ||||||||
End point description |
The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-QoL-A Total score, at Week 260 post -BMN 270 infusion.
The Haemo-QoL-A questionnaire is a validated hemophilia-specific Health-related quality of life (HRQoL) questionnaire for adults consisting of 41 questions covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns), plus a Total Score. Items are answered on a 6-point Likert-type scale, ranging from 0 (None of the time) to 5 (All of the time), with a 1-month recall. Higher scores mean better HRQoL or less impairment (for a subscale).
mITT Population: (n=132)
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End point type |
Secondary
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End point timeframe |
Baseline to Week 260
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| No statistical analyses for this end point | |||||||||
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End point title |
Median Change From Baseline in Haemo-QoL-A Quality of Life: Total Score at Week 260 | ||||||||
End point description |
The change from baseline (assuming no treatment for severe hemophilia A) in Haemo-QoL-A Total score, at Week 260 post -BMN 270 infusion.
The Haemo-QoL-A questionnaire is a validated hemophilia-specific Health-related quality of life (HRQoL) questionnaire for adults consisting of 41 questions covering six domains (Physical Functioning, Role Functioning, Worry, Consequences of Bleeding, Emotional Impact and Treatment Concerns), plus a Total Score. Items are answered on a 6-point Likert-type scale, ranging from 0 (None of the time) to 5 (All of the time), with a 1-month recall. Higher scores mean better HRQoL or less impairment (for a subscale)
mITT Population (n=132)
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End point type |
Secondary
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End point timeframe |
Baseline to Week 260
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 5 years after dosing.
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Adverse event reporting additional description |
AEs with onset or worsening after the investigational product were included.
Intent-to-Treat (ITT) Population: All subjects dosed in 270-301 study
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
BMN 270 (Valoctocogene Roxaparvovec)
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Reporting group description |
Single administration of valoctocogene roxaparvovec at a dose of 6E13 vg/kg valoctocogene roxaparvovec: Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Hemophilia A subjects | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Jan 2018 |
Amendment 1:
• Sample size changed to70
• Timing of interim analysis(IA)changed to occur after20 treated participants(prtps)completed Wk26.IA changed to perform hypothesis testing for primary endpoint.Method for adjusting multiplicity changed accordingly
• Language(lang)in prot have suggested doses of BMN270>6E13vg/kg may potentially be eval as part of study clarified
• Study Saf Eval Crit lang revised to make it clear that enrol will be temp halted if stopping crit listed are met
• Lang around Expedited Saf Rept Req amended to clarify which SAEs are subj to expedited rept reqs
• Twice weekly eval of LTs added during times when prtp’s ALT is>=3xULN
• Guidance added for mgmt of prtps who have FVIII activity levels<5IU/dL(after showing initial response toBMN270)foll BMN270 infusion(inf)
• Assessment(assmt)of dermatologic & musculoskeletal systems added to brief PE
• Testing of expl samples for Direct Thrombin Activity Test&TGA Assay clarified as optional
• Specific testing of TNF-α & IL10a single nucleotide polymorphisms removed from biomarker testing
• Fasting lipid panel(bld trigly,total chol,HDL chol&LDL chol)added on day of BMN270 inf
• Initial von Willebrand Factor antigen(VWF:Ag)assmt moved from SCR to Baseline
• Freq of liver function & FVIII testing increased during Yrs2-5 FUP period.Testing performed every4wks(+2wks/as sched to align with other sched study visits)during Yr2,& every6wks(±2wks)during Yrs3-5
• Clarified post-CS testing for HepB/C reactivation should be performed only in prtps who have previous hist of +ve HepB/C tests
• PROBE questionnaire added as qual of life assmt
• In event of +ve Bethesda assay result during Yrs3-5,addnl sample added to be collected within4wks of visit where+ve result obtained
• Emicizumab,fitusiran,&concizumab were added as prohibited meds starting30days before SCR & through EOS
• Prtps were advised to abstain blood/sperm donation afterBMN270 inf until there is no evidence of vector shedding |
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28 Jun 2018 |
Amendment 2:
• The sample size of the study was changed to 130, and the number of potential sites was increased to 60
• Details of the sample size calculation, missing data handling, and sensitivity analyses were added
• Language concerning the occurrence and management of infusion-associated events was added
• Language in the inclusion criterion related to a participant’s history of FVIII inhibitors was clarified
• Language regarding the HIV inclusion criterion was modified.
• Language was added to permit use of mobile nursing (MN) services, provided that the site is able to implement them and the participant consents, for non every 3 month visits after Week 52
• Language was added to include ABO blood antigen testing.
• Clarified that, on the day of infusion, participants are not required to be admitted to a hospital to receive the infusion (ie, the infusion may be conducted in any facility that has the requisite capabilities to prepare and perform the infusion, as well as monitor participants for at least 8 hours).
• Clarified that the requirement for contraception use can end as early as Week 12, in the case that a participant has had 3 consecutive negative semen vector shedding assessments prior to that time point.
• Clarified that assessment of concomitant medications and adverse events should be performed at the every 4-week visits during Year 2, and at the every 6 week visits during Years 3-5.
• Clarified that vector shedding assessments, if required, could be performed at the every 6 week visits during Years 3-5
• Added language that participants will fast for at least 8 hours prior to collection of pre infusion laboratory samples on the day of infusion. |
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24 Aug 2018 |
Amendment 3:
• HIV-positive patients were excluded from the study
• Efavirenz and lamivudine were added to the list of prohibited concomitant medications
•The exclusion criterion concerning liver test levels at Screening was changed to require all assessed liver tests (ie, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, and total bilirubin) to be no higher than the 1.25 times the ULN for eligibility purposes
• An additional fasting serum sample was added on Day 1, in case it is needed for future exploratory assessments
• The timing of assessment visits during Years 2-5 was modified
• An abbreviated visit schedule was made available during Years 2 5 for participants who are considered to have not responded to BMN 270 therapy
• Additional details were included concerning information to be collected as part of the medical history assessment at Screening
• The statistical analysis population definitions and language surrounding the primary endpoint were updated
• Language concerning when to consider restarting FVIII prophylaxis following BMN 270 infusion was modified
• An additional criterion to initiate reactive oral CS for elevated ALT levels, following consultation with the medical monitor, of ALT > ULN and > 2x baseline value was added. |
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09 Nov 2018 |
Amendment 4:
• Some visits during Year 1 of the study were designated as optional mobile nursing or lab draw-only visits for participants enrolling in 270-301 following participation in 270 902.
• Development of anti-FVIII inhibitory antibodies (inhibitors) was added as an Event of Special Interest for safety reporting purposes.
• Assessment of the Direct Thrombin Activity test was removed |
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10 May 2019 |
Amendment 5:
Global Amendment 5 was never submitted to health authorities or sites. The primary change in Amendment 5 was a revision of the interim analysis language to allow for the possibility of a second interim analysis. After the first interim analysis was performed, it was determined that the second interim analysis would not be needed and, as such, the protocol amendment would no longer be needed. |
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03 Apr 2020 |
Amendment 6:
• Lang concerning interim analysis was modified
• PBMC collection was removed from Wk30 visit
• Prohibition on use of non-corticosteroid systemic immunosuppressive agents following BMN 270 dosing was removed
• Vector shedding & contraception use language was updated to change determination of a “clear” result from negative to below the limit of detection
• Clarifying language was provided for circumstances where a +ve vector shedding sample occurs after 3 consecutive tests below the limit of detection have already been obtained
• Requirements around use of MN services to conduct unscheduled visits for assessment of FVIII levels or LTs were clarified
• At sites where use of MN services has been approved, at visits not specifically designated for MN eligibility(ie,visits where participant is intended to return to site for assessment)MN services may be used if participant is unable to attend site to complete study visit during acceptable window for that visit, upon prior approval by medical monitor & discussion between medical monitor & investigator
• In event that neither an MN visit nor a lab-only visit is possible at a post-infusion visit timepoint, site should telephone participant to collect AE, concomitant medication, & diary(bleeding events & FVIII usage)information
• Guidance for monitoring & management of elevated hepatic transaminases was modified
• An optional liver biopsy substudy was added to protocol
• Occurrence of events of Hy’s law was added as an EOSI for purposes of expedited safety reporting, & additional safety monitoring in event of a case potentially meeting Hy’s law criteria was added
• An optional monthly phone check-in was added during Yrs2-5 for participants who are returning to site only every 12wks due to poor FVIII response following BMN 270 infusion
• Option to assess an AE as related/not related to CS or AIS was added
• Guidance for tapering CS was updated
• Lamivudine was removed as a prohibited medication |
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15 Jul 2021 |
Amendment 7:
• Changes were made to enhance screening for potential malignancies (including hepatic cancers) after dosing with BMN 270
• Malignancy (except non-melanoma skin cancer) was added as an Event of Special Interest (EOSI)
• Language around the statistical analysis of secondary endpoints and objective was amended
• Language was added concerning the use of the SARS-CoV-2 vaccines
• The reactive CS regimen for ALT elevation was updated
• Thrombin generation assay (TGA) assessment was removed
• The definition of treatment failure was changed
• Frequency of several laboratory assessments during Years 2-5 was decreased |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
