Summary Information For: AAV2, FIX-WT, rAAV-hAAT-F.IX
Haemophilia B
Non-commercial, Avigen/CHOP
General Study Information

1/2 dose-escalation clinical study1

Non-commercial, Avigen/CHOP2  

  • Males ≥ 18 years old with pre-treatment AAV titers up to 1:17 and severe hemophilia B with Factor IX activity level < 1% of normal
  • > 20 EDs of treatment with Factor IX protein

Subjects who must remain on, or desire to remain on, a regimen of prophylactic infusion of FIX protein

AAV2/ HEK293 cells

FIX-WT is composed of the human F9 cDNA interrupted by a 1.4 kb fragment of intron 11

According to this reference1 the APOE-HCR/hAAT enhancer/promoter is composed of :

  • The human alpha1-antitrypsin (hAAT) promoter and            
  • The hepatic locus control region and a single copy of the APOE enhancer (APOE-HCR)

The human F9 cDNA is interrupted by a 1.4 kb fragment of intron 1

Trough hepatic artery 1

As reported here1,  the trial included three dose cohorts as follows:

  • Co. 1: 8e10 (2) 
  • Co. 2: 4e11 (3), 
  • Co. 3: 2e12 (2) a

a Lower doses in Co. 1 and Co. 2 did not result in a detectable increase in FIX activity

12 - 40 months

Not reported

Efficacy details

As reported in this reference1, therapeutic levels of F.IX were achieved at the highest dose tested and the duration of the expression at therapeutic levels was limited to a period of ~ 8 weeks.
The reported expression levels were taken from Table 21 and summarized as follows:  

  • All subjects in Co. 1 (8e10 vg/kg) and Co. 2 (4e11 vg/kg) exposed FIX activity levels < 1%  
  • Both subjects in Co. 3 exposed short-term expression levels with FIX activity peaks at 3% and 11%

Peak at week 2 and maintained for approximately 4 and 10 weeks

Not applicable, FIX expression persisted in one subject for 10 weeks1

Not reported

Safety Details
  • None of the subjects experienced adverse reactions like fever, chills, nausea or vomiting observed after vector infusion1
  • 3/7 subjects developed small hematomas at the site of catheter insertion in the groin1

No AEs possibly/likely related to Study Agent reported1

Not reported

Peak and and timing of ALT elevations were reported here1 and summarized as follows: 

  • Co. 1: 2/2 pts. within normal range
  • Co. 2: 1/3 pts. (105 IU/L / week 6) 
  • Co. 3: 1/2 pts. (532 IU/L /week 4-5 )

Peak and and timing of AST elevations were reported here1 and summarized as follows:  

  • Co. 1: 2/2 within normal range, 
  • Co. 2: 1/3, (67 IU/L, 6 weeks),
  • Co. 3: 1/2, (approx. 200 IU/L, 4-5 weeks)

Yes (only reported for 1 pt. in the 4e11 gc/kg group)

Not applicable

Yes, in Subject E from Co. 3 (1/2 pts.) with a low pretreatment NAb titer of 1:2 and elevated ALT levels, FIX activity declined as follows: 

FIX activities for Subject E are taken from Figure 11 







approx. FIX activity







Not reported

  1. Manno, C.S., et al., Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. , 2006. 12(3): p. 342-7. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response - PubMed (
  2. Nathwani, A.C., Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program, 2019. 2019(1): p. 1-8. Gene therapy for hemophilia | Hematology, ASH Education Program | American Society of Hematology (

AAV, Adeno-associated virus; ABR, Annualized bleeding rate; AEs: adverse events; AIR, Annualized FVIII/FIX infusion rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CH, Chromogenic Assay; Co., cohort; DOACs, Direct oral anticoagulants; D, days; EDs, exposure days; FIX, factor IX; FIX-Padua, gain of function FIX variant; FVIII, factor VIII; gc, genome copies; HEK cells, human embryonic kidney cells; IQR, interquartile range; IRR, Infusion-related reaction; NAbs, neutralizing antibodies; OS, One-stage clotting assay; Pop., population; pt., patient/participant; pts., patients/participants; P1, Participant 1; PI, phase I; PBGD, porphobilinogen deaminase; PBMC, peripheral blood mononuclear cells; SAEs, serious adverse events; SFU, spot-forming units; TAC, tacrolimus; ULN, upper limit of normal; VCN, vector copy number; vg, vector genomes; W, weeks; WT, wild type; Y, year

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