Summary Information For: AAV2, FIX-WT, AAV-hF.IX, NCT00076557
AAV2, FIX-WT, AAV-hF.IX, NCT00076557
Haemophilia B
Avigen┬╣/CHOP ┬▓
General Study Information
  • Identifier:   NCT000765571
  • Phase I/II, open-label, phase 1/2 open-label study

Terminated, Last Update Posted: April 4, 20071 ,closed2

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

Presence of inflammatory muscle disease (e.g., myositis)3

AAV2, HEK293 cells3

FIX is assembled by exon 1, a portion of the human FIX intron I and exons 2-8 of the human F9 gene3

Data regarding the included expression cassette components were taken from here3 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 injections3

As reported here3, the trial included three dose cohorts as follows: 

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

2 - 10 months


Efficacy details

Detectable FIX levels higher than the baseline in the range of 0.3%-1.4% (8 - 52 weeks) were observed in 4/8 subjects, as reported in reference3 and summarized as follows: 

  • Subject A was first noted to have a F.IX level higher than baseline at 8 weeks after injection and was again noted to have a level higher than baseline (1.4%) at 12 weeks
  • 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 effect3

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 injection3

Adverse events were reported here3 and are summarized as follows:

  • 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

Not reported

No abnormalities in serum chemistries3

Not applicable

Not reported

Not applicable

Not applicable

Not reported

  1. Safety of a New Type of Treatment Called Gene Transfer for the Treatment of Severe Hemophilia B. Available at: Study Details | Safety of a New Type of Treatment Called Gene Transfer for the Treatment of Severe Hemophilia B |
  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 (
  3. 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; 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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