Trial reportBlood2020
Activity of transgene-produced B-domain-deleted factor VIII in human plasma following AAV5 gene therapy.
Trial report in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1/2, Dose-Escalation, Safety, Tolerability and Efficacy Study of Valoctocogene Roxaparvovec, an Adenovirus-Associated Virus Vector-Mediated Gene Transfer of Human Factor VIII in Patients With Severe Haemophilia A
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
Who cites it
47 citing papers in PubMed, 68 citations in OpenAlex.
- Durability of efficacy, safety, and quality of life 5 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A: final phase 3 GENEr8-1 trial results.Research and practice in thrombosis and haemostasis · 2026Trial
- Trial
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- Article
- Synonymous Gene Recoding Affects the Accuracy of Protein Quantification Measurements.The AAPS journal · 2026Article
- Laboratory Challenges in the Era of Novel Haemophilia Therapies.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2026Review
- Perioperative management of total hip arthroplasty in hemophilia A following gene therapy.Haematologica · 2026Article
- An analysis of attitudes toward gene therapy in people with severe hemophilia in Germany, a survey-based cross-sectional study.Therapeutic advances in hematology · 2026Article
- Mutations of six amino acid residues in a B domain-deleted blood coagulation factor VIII have a cumulative effect on increasing its secretion.Research and practice in thrombosis and haemostasis · 2026Article
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- Review
- In vivo applications and toxicities of AAV-based gene therapies in rare diseases.Orphanet journal of rare diseases · 2025Review
- Evaluation of One-Stage Assays for the Monitoring of Recombinant Human Factor IX Padua Activity After Etranacogene Dezaparvovec Gene Therapy.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Article
- Viral-based gene therapy clinical trials for immune deficiencies and blood disorders from 2013 until 2023 - an overview.Regenerative therapy · 2025Review
- Article
- Review
- Adeno-associated virus-based gene therapy for hemophilia-addressing the gaps.Research and practice in thrombosis and haemostasis · 2025Review
- Adeno-associated virus gene therapy for hemophilia: an update meta-analysis and systematic review.Frontiers in medicine · 2025Article
- Efficacy, safety, and quality of life 4 years after valoctocogene roxaparvovec gene transfer for severe hemophilia A in the phase 3 GENEr8-1 trial.Research and practice in thrombosis and haemostasis · 2024Article
- Roctavian gene therapy for hemophilia A.Blood advances · 2024Review
Corrections and comments
- Commented on by
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adeno-associated virus (AAV)-based gene therapies can restore endogenous factor VIII (FVIII) expression in hemophilia A (HA). AAV vectors typically use a B-domain-deleted FVIII transgene, such as human FVIII-SQ in valoctocogene roxaparvovec (AAV5-FVIII-SQ). Surprisingly, the activity of transgene-produced FVIII-SQ was between 1.3 and 2.0 times higher in one-stage clot (OS) assays than in chromogenic-substrate (CS) assays, whereas recombinant FVIII-SQ products had lower OS than CS activity. Transgene-produced and recombinant FVIII-SQ showed comparable specific activity (international units per milligram) in the CS assay, demonstrating that the diverging activities arise in the OS assay. Higher OS activity for transgene-produced FVIII-SQ was observed across various assay kits and clinical laboratories, suggesting that intrinsic molecular features are potential root causes. Further experiments in 2 participants showed that transgene-produced FVIII-SQ accelerated early factor Xa and thrombin formation, which may explain the higher OS activity based on a kinetic bias between OS and CS assay readout times. Despite the faster onset of coagulation, global thrombin levels were unaffected. A correlation with joint bleeds suggested that both OS and CS assay remained clinically meaningful to distinguish hemophilic from nonhemophilic FVIII activity levels. During clinical development, the CS activity was chosen as a surrogate end point to conservatively assess hemostatic efficacy and enable comparison with recombinant FVIII-SQ products. Relevant trials are registered on clinicaltrials.gov as #NCT02576795 and #NCT03370913 and, respectively, on EudraCT (European Union Drug Regulating Authorities Clinical Trials Database; https://eudract.ema.europa.eu) as #2014-003880-38 and #2017-003215-19.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.