• ClinicalTrials.gov Identifier: NCT04728841¹
• Prospective Phase 1 pilot study to evaluate the safety and efficacy of GS001²
• Open- label, non- randomized study

• Recruiting
• Last Update Posted: 2025-08-01

• Male subjects and ≥ 18 years of age
• Have hemophilia A with ≤1 IU/dL (≤1%) endogenous FVIII activity levels at the time of screening. If the screening result is >1% due to previous treatment with FVIII product, then it may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating ≤1% FVIII activity levels 
• Have no measurable FVII inhibitor as assessed by laboratory two times that were at least one week apart; or documented no prior history of FVIII inhibitor after 150 EDs and no clinical signs or symptoms of decreased response to FVIII infusion 

• Have participated in a previous gene therapy research trial within the last 52 weeks or in a clinical study with an investigational drug within the past 30 days
• Known inherited or acquired thrombophilia, including conditions associated with increased risk of thromboembolism, such as atrial fibrillation
• Hypersensitivity to the study vector

AAV8 capsid / HEK 293 cells²

The same FVIII-V3 variant described in Reference #3, referred to as FVIII-BDD-V3, was used in GS001

• It contains a 17-amino-acid peptide with six N-linked glycosylation motifs derived from the human FVIII B-domain

The FVIII expression cassette components described in the supplementary methods of Reference #2 include: 

• A chimeric promoter configuration that consists predominantly of two elements:
  • a sequence derived from dog SERPINA1 gene with sequence optimization
  • and a sequence from zebrafish ALBUMIN gene
• A polyadenylation signal from the common vole polyomavirus KS13 strain

Systemic

   Dose-cohorts for the 12 enrolled participants were reported in Reference #2 were as follows: 

• GS001 2 x 10¹² vg/kg group: 6 participants
• GS001 4 x 10¹² vg/kg group: 6 participants

At the time of data analysis reported in Reference #2, the median follow-up period were as follows:

• 2×10¹² vg/kg cohort: 156.0 weeks (range, 144.0-208.0 weeks)
• 4×10¹² vg/kg cohort: 110.5 weeks (range, 104.0-130.0 weeks)

As reported in Reference #2, FVIII:C was assessed using both a one-stage clotting assay (OS) and a chromogenic assay (CH)

FVIII activity data after GS001 infusion were reported in Reference #2 and are summarized below

• FVIII values were reported primarily using the one-stage clotting assay (OS)
• Reported OS FVIII levels were approximately 1.3-fold higher than those measured using the chromogenic assay (CH)

Additional participant-level FVIII data were reported in Reference #2 as follows:

• GS001 2 × 10¹² vg/kg cohort at week 144:
  • 8.1 and 10.5 IU/dL, consistent with mild haemophilia
  • 52.4 IU/dL, consistent with normal FVIII activity
  • 1.0 and 3.1 IU/dL, consistent with moderate haemophilia
• GS001 4 × 10¹² vg/kg cohort at week 104:
  • 29.4, 33.5, and 34.1 IU/dL, consistent with high mild haemophilia
  • 42.3 and 43.0 IU/dL, consistent with non-haemophilia status
  • 98.8 IU/dL, within the normal range

In the low-dose (2 × 10¹² vg/kg) cohort, an exploratory analysis showed the following:

• Participants 1–3 received prophylactic prednisone alone
• Participants 4–6 received prophylactic prednisone combined with tacrolimus
• Participants 4–6 had a more rapid FVIII increase and higher FVIII levels seven days after vector infusion in comparison to Participants 1–3
• Over the 144-week follow-up period, mean FVIII levels were consistently higher in Participants 4–6

Peak FVIII levels and time to peak FVIII response were extracted from Reference #2 and are summarized as follows:

ABR data from week 3.0 after GS001 infusion to the cut-off date were reported in Reference #2 and are summarized below:

Additional bleeding-related outcomes were reported in Reference #2 as follows:

• In both cohorts, all participants who had received prophylactic FVIII treatment discontinued FVIII use after gene therapy
• Two participants received low-dose FVIII prophylactic treatment due to joint arthroplasty.
• In the high-dose cohort, one participant maintained FVIII:C of 109.0 IU/dL at 53.0 weeks post-vector infusion and
  • subsequently underwent right knee, right hip
  • and left knee arthroplasty without FVIII replacement therapy during the procedures
• The median number of target joints decreased to 0 (range, 0–0) from post-infusion to the cut-off date in both cohorts

Annualized FVIII consumption data from week 3.0 after GS001 infusion to the cut-off date were reported in Reference #2 and are summarized below:

Additional FVIII infusion-related outcomes were reported in Reference #2 as follows:

• In both cohorts, all participants who had received prophylactic FVIII treatment discontinued FVIII use after gene therapy
• Two participants received low-dose FVIII prophylactic treatment due to joint arthroplasty
• In the GS001 4 × 10¹² vg/kg cohort, one participant maintained FVIII:C of 109.0 IU/dL at 53.0 weeks post-vector infusion and subsequently underwent right knee, right hip, and left knee arthroplasty without FVIII replacement therapy during the procedures
• None of the participants in the GS001 4 × 10¹² vg/kg cohort experienced bleeding events requiring exogenous FVIII treatment after GS001 infusion

No specific infusion-related reactions were reported in Reference #2

GS001-related treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) were reported in Table 2 and the results section of Reference #2 and are summarized below:

Additional GS001-related AE details were reported in Reference #2 as follows:

• In the GS001 2 × 10¹² vg/kg cohort:
  • The most common GS001-related TEAEs were increased ALT and increased lactate dehydrogenase (LDH), each reported in 3 of 6 participants (50%).
  • All GS001-related TEAEs were grade 1 or grade 2 in severity.
  • One participant experienced an SAE of increased AST at week 16:
    • AST: 102.5 U/L
    • Normal range: 0–50.0 U/L
    • Severity: grade 1
    • ALT at the same visit: 27.7 U/L
    • AST returned to normal after three days of methylprednisolone pulse therapy
  • One additional SAE of increased transaminases at week 93 was considered not related to GS001 treatment.
• In the GS001 4 × 10¹² vg/kg cohort:
  • The most common GS001-related TEAE was increased FVIII:C >150.0 IU/dL, reported in 6 of 6 participants (100%)
  • Most increased FVIII:C events occurred within the first three weeks after GS001 treatment
  • Increased ALT was reported in 5 of 6 participants (83.3%)
  • Increased AST was reported in 3 of 6 participants (50.0%)
  • Participants 7 and 8 experienced SAEs of increased FVIII:C:
    • Participant 7: FVIII:C 201 IU/dL, starting on day 14 after GS001 infusion, grade 1
    • Participant 8: FVIII:C 170.9 IU/dL, starting on day 21 after GS001 infusion, grade 1
  • In Participant 7, ALT increased to 3.3 × ULN and was classified as a grade 2 TEAE
  • ALT increases in the other participants were grade 1 in severity
  • No thromboembolic events were reported
• In both dose cohorts:
  • No deaths were reported
  • No GS001-related TEAEs led to withdrawal from the study

Glucocorticoid-related treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) were reported in Table 2 and the results section of Reference #2 and are summarized below:

Additional glucocorticoid-related AE details were reported in Reference #2 as follows:

• All 12 participants received prophylactic glucocorticoids
• Glucocorticoid-related AEs were reported in 11 of 12 participants (91.7%)
• The most common glucocorticoid-related AEs were:
  • increased white blood cell count
  • acne
  • hypokalemia
  • insomnia
  • weight gain
• Infection AEs attributed to glucocorticoids and/or tacrolimus included:
  • Skin infection, reported in one participant
  • Anal infection, reported in one participant
  • Epstein-Barr virus infection, reported in one participant
• All infection AEs except two anal infection events were grade 1 in severity and resolved without intervention
• No participants experienced SAEs attributed to glucocorticoids

ALT elevation data were reported in the results section of Reference #2 and are summarized below:

AST elevation data were reported in the results section of Reference #2 and are summarized below:

Capsid-directed T cell response data based on IFN-γ ELISpot analysis of PBMC samples from Participants 4–12 are summarized below, as reported in Reference #2:

Summary of key findings:

• IFN-γ ELISpot assays were performed using PBMC samples from Participants 4–12
• Immune responses were evaluated at Day 0 and Day 7 post-infusion
• No significant differences in IFN-γ-secreting T cell frequencies were observed between the 2 × 10¹² and 4 × 10¹² vg/kg dose cohorts
• Participant 12 in the 4 × 10¹² vg/kg cohort demonstrated capsid-specific T cell activation
• The capsid-specific T cell response in Participant 12 was temporally associated with:
  • Elevations in ALT
  • Decline in FVIII expression
• Specific peak SFU/1 × 10⁶ PBMC values were not reported
• Exact timing of peak capsid-directed T cell activation was not reported

Additional immune-response findings:

• A higher FVIII decline rate (defined as ≥80% reduction from peak FVIII to week 52) was associated with higher T cell counts on the day of infusion, although this association was not statistically significant
• By Day 7, participants with a high FVIII decline rate had significantly higher specific T cell counts
• No significant differences in AAV binding or neutralizing antibody levels were observed between participants with high and low FVIII decline rates

1. Gene Therapy for Chinese Hemophilia A (HA).  Available at: Study Details | NCT04728841 | Gene Therapy for Chinese Hemophilia A | ClinicalTrials.gov

2. Liu W, Pei X, Yu T, Xu B, Dai X, Xue F, Chen L, Wang X, Wang Y, Chen Y, Liu X, Fu R, Wang W, Chi Y, Li HY, Yang R, Zhang L. Phase 1 pilot study for hemophilia-A: AAV8 vector with prophylactic tacrolimus-glucocorticoid achieves therapeutic FVIII activity. Signal Transduct Target Ther. 2026 Mar 11;11(1):88. doi: 10.1038/s41392-026-02599-3. PMID: 41813646; PMCID: PMC12979573. Phase 1 pilot study for hemophilia-A: AAV8 vector with prophylactic tacrolimus-glucocorticoid achieves therapeutic FVIII activity - PubMed

3. McIntosh J, Lenting PJ, Rosales C, Lee D, Rabbanian S, Raj D, Patel N, Tuddenham EG, Christophe OD, McVey JH, Waddington S, Nienhuis AW, Gray JT, Fagone P, Mingozzi F, Zhou SZ, High KA, Cancio M, Ng CY, Zhou J, Morton CL, Davidoff AM, Nathwani AC. Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant. Blood. 2013 Apr 25;121(17):3335-44. doi: 10.1182/blood-2012-10-462200. Epub 2013 Feb 20. PMID: 23426947; PMCID: PMC3637010. Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant - PubMed