Summary Information For: AAV2, FIX-WT, AAV-hF.IX, NCT00076557 ²⁹
AAV2, FIX-WT, AAV-hF.IX, NCT00076557 ²⁹
Haemophilia B
Avigen/CHOP ²⁸
General Study Information
  • Identifier:  NCT00076557
  • Phase I/II, open-label, phase 1/2 open-label study

Terminated *, Last Update Posted: April 4, 2007*, closed 28

  • 18 years or older Males with severe FIX deficiency
  • > 20 EDs of treatment with FIX protein

Presence of inflammatory muscle disease (e.g., myositis) 29

AAV2, HEK293 cells 29

FIX is assembled by exon 1, a portion of the human FIX intron I and exons 2-8 of the human F9 gene 29

Data regarding the vector regulatory elements of the utilized expreswsion cassette were taken from here 29 and summarized as follows:

  • Cytomegalovirus (CMV) enhancer/promoter fragment
  • Exon 1 and 1.4-kb portion of intron 1 of the human F9 gene
  • Exons 2-8 of the human FIX cDNA (FIX cDNA)
  • SV40 late polyadenylation sequence

Intramuscular injections 29

  • Co. 1: 2e11 (3) 
  • Co. 2: 6e11 (3)
  • Co. 3: 1.8e12 (2)

2 - 10 months

OS 29

Efficacy details

4/8 subjects with detectable FIX levels higher than the baseline in the range of 0.3%-1.2% (8 - 52 weeks) as follows: 

  • Subject A had a 1% level measured 52 weeks after vector injection
  • Subject B also showed measurable increases in FIX levels, from a baseline of less than 0.3%, up to 0.8%
  • Subject D had a level of 0.7% at 8 weeks, with a baseline of 0.2%
  • Subject G had a level of 0.8% at 4 weeks after treatment
  • All other FIX levels, measured at least 14 days after factor concentrate infusion, were less than 1% in the remaining subjects

Not reported

Circulating levels of FIX were too low for a therapeutic effect 29

Not reported

Safety Details
  • IM injection was well-tolerated in all subjects, with n osystemic symptoms
  • In one subject a 5-fold elevation in the creatine phosphokinase (CPK) returned to baseline 1 week after injection 29
  • 1 subject had a mild inflammatory reaction to the tattoo dye that was injected at a few sites, that resolved without treatment  
  • 5/8 pts. developed small hematomas or pain at one or more vector injection sites, which resolved uneventfully 
  • 4/8 pts. developed transient minor abnormalities (hematoma, induration, transient numbness) at the site of muscle biopsy 29    

Not reported

No abnormalities in serum chemistries 29

Not applicable

Not reported

Not applicable

Not applicable

Not reported


28. 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 (      
29. Manno, C.S., et al., AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood, 2003. 101(8): p. 2963-72.
       AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B | Blood | American Society of Hematology ( 

AAV, Adeno-associated virus; AEs, Adverse events; 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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