Summary Information For: AAV-Spark100, FIX-Padua, Fidanacogene elaparvovec, NCT02484092 *ˑ ⁹ˑ ¹⁰
AAV-Spark100, FIX-Padua, Fidanacogene elaparvovec, NCT02484092 *ˑ ⁹ˑ ¹⁰
Haemophilia B
Pfizer *
General Study Information
  • Identifier: NCT02484092
  • A Phase 1/2, Open-Label, Non-Randomized, Dose-Escalation 
  • Study of SPK-9001 in Subjects with Hemophilia B
  • Completed*, Last Update Posted: June 16, 2020*
  • Follow up continuing on P1/2a study. P3 trial ongoing
  • Last Update Posted: June 16, 2020
  • Male and ≥18 years of age have
  • Hemophilia B with ≤2 IU/dL (≤2%) endogenous FIX activity levels as
  • Had ≥50 prior EDs to any FIX protein products    
  • Have anti-AAV-Spark100 neutralizing antibody titers ≥1:5 
  • Participation in a previous gene therapy research trial within the last 52 weeks

Bioengineered capsid AAV-Spark100 9/ HEK293 cells

Codon-opimized FIX-Padua 9

The FIX expression cassette includes:

  • APOE gene hepatic-control region (APOE-HCR) enhancer and the
  • Liver-specific human α1 -antitrypsin (hAAT) promoter 9

Systemic 28

Infusion of single vector dose as follows:

  • 5e11 (10) reported here 9 and subsequently 
  • 5e11 (15) reported here 1087 and here NCT02484092
  • 28 to 78 weeks reported here 9
  • ≥ 52 weeks reported here 1087

Further statements regarding the follow-up were collected from here 87 and summarized as follows:

  • All 15 pts. completed the phase 1/2a study for 52 weeks and were eligible to enroll in a long-term follow-up (LTFU) of ≤5 years
  • As of August 2022, 8 pts, were continuing, 4 completed, and 2 discontinued the LTFU (3–6 years post vector infusion)

OS 9-10

Efficacy details

Sustained steady-state factor IX–R338L expression was reached within 14 weeks after vector infusion and reported by 2 publications as follows:

  • Among all pts. mean (± SD) steady-state vector-based FIX coagulant activity was 33.7 ± 18.5% of the normal value 9
  • The mean (± SD) post-infusion steady-state FIX:C was 22.9% ± 9.9% at 1-year post vector infusion 10 

Peak and steady-state vector-derived circulating FIX activity levels were determined in a time frame from W12 up to W52 as reported here NCT02484092

  • Mean (SD) peak FIX activity: 29.1 (11.63)
  • steady-state level of 22.9 (9.89) % of normal

For all pts., FIX activity generally remained in the mild to normal range post infusion for up to 6 years 87


Peaks not reported, possibly W28 based on Fig. 1 9

  • The ABR mean was reduced from 11.1 events per year [range, 0 to 48] before vector administration to a mean rate of 0.4 events per year [range, 0 to 4] after vector administration 9
  • That corresponds to 96% reduction of the mean bleeding rate per year

    ABRs for the time period of six years and data concerning further characteristics of bleeding events were reported here 87 as follows:

ABR follow-up for the time period up to 6 years


Bleeds over the period of 52 weeks a








affected pts.

Year 1



6 spontaneous

7 b



Year 2








Year 3




Bleeds during the long-term follow-up (LTFU) of ≤5 years

Year 3







affected pts.

Year 4




17 spontaneous

13 c, d, e



Year 5




7 traumatic

4 f



Year 6








    a At enrollment in the phase 1/2a study, the majority of patients had target joints and/or joint arthropathy at baseline
    b All target joints or with known arthropathy
    c Occurred in joints in 2 patients who also had bleeds in the 1/2a study
    d In 1 pt., 6 of 10 bleeds were in target joints or joints with known arthropathy and 3 bleeds were in a wrist with known carpel tunnel syndrome
    e In the other pt., 3 bleeds occurred over 1.7 years in the same joint that was not a target joint and did not have known arthropathy
    f 4 were in joints; only 1 was not in a target joint or joint with known arthropathy


The mean use of FIX concentrate in the 52 weeks before screening and after vector infusion was reduced from 2908 IU/kg [range, 0 to 8090] to 49.3 IU/kg [range, 0 to 376] 9

Safety Details

No SAEs occurred during or after vector infusion 9

AEs likely related to the study vector were taken from here 9 and summarized as follows:

  • 1/10 pts. (P9) experienced transient grade 1 elevation of ALT level (to >2.5 X the ULN range) that was the only AE that was deemed to be likely related to the study vector
  • P7 had an increase in liver-enzyme levels above baseline within the range of normal values that did not meet the criteria regarding toxic effects

No AEs related to glucocorticoid in the 2/10 pts. that took prednisone observed 9

  • 2/10 pts. with peak levels of approx. 70-140 U/L at W5 and W9 according to Fig. 2 9
  • 3/15 pts. were treated with corticoids for elevations in hepatic transaminases but peak level and timing not reported 10
  • 2/10 pts. with peak levels of approx. 50-80 U/L at W5 and W8 according to Fig. 2 9
  • 3/15 pts. with hepatic enzyme elevations, but peak levels and timings were not reported 10
  • 2/10 pts. that experienced ALT elevation had also peak values of 330 SFU/1e6 PBMCs at W6 and of 1200 SFU/1e6 PBMCs at W5 9
  • In the 3/15 pts. with hepatic enzyme elevation, 2 pts. were positive for capsid reactive T cells by interferon-γ ELISpot but peak values and timings were not reported (n=15) 10

Yes, P7 and P9 received prednisone for a total of 130 and 119 days as reported in in the supplementary appendix here 9

Yes, in 1/2 pts. with ALT/AST elevations + T-cell response FIX coagulant activity declined from 48% to 30% on day 56 and to 18% on day 62 9

Not reported


9.    George, L.A., et al., Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant. N Engl J Med, 2017. 377(23): p. 2215-2227.
       Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant | NEJM
10.  George, L.A., et al., Efficacy and Safety in 15 Hemophilia B Patients Treated with the AAV Gene Therapy Vector Fidanacogene Elaparvovec and
        Followed for at Least 1 Year. Blood, 2019. 134(Suppl. 1): p. 3347. 
        Efficacy and Safety in 15 Hemophilia B Patients Treated with the AAV Gene Therapy Vector Fidanacogene Elaparvovec and Followed for at
        Least 1 Year | Blood | American Society of Hematology (

28. Nathwani, A.C., Gene therapy for hemophilia. Hematology Am Soc Hematol Educ Program, 2019. 2019(1): p. 1-8. Gene therapy for hemophilia - PMC (       
       POSTER ABSTRACTS - Mulders - 2023 - Haemophilia - Wiley Online Library

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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