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. 2022 Jan 13;10:1049. Originally published 2021 Oct 15. [Version 3] doi: 10.12688/f1000research.73884.3

Table 1.

Characteristics of the included studies.

Author, year Study location Clinical trial number Study design Total patients included for prophylactic treatment (F) Age * Definition of target joint
Mullins et al., 2017 9 Multicenter (11 countries) NCT02210091 Phase 3, open-label, non-randomized, uncontrolled clinical trial 66 (1) 6.0 ± 2.7 A joint (ankles, knees, hips or elbows) with ≥ 3 spontaneous bleeding episodes in any consecutive 6-month period
Chowdary et al., 2020 7 Multicenter (23 countries) NCT01945593 (CONTINUATION study) Phase 3b, open-label, non-randomized, uncontrolled clinical trial 216 (1) 22.8 ± 15.7 A joint with ≥ 3 spontaneous bleeding episodes in any consecutive 6-month period
Konkle et al., 2015 5 Multicenter (20 countries) NCT01736475 (PROLONG-ATE study) Phase 2/3, open-label, non-randomized, uncontrolled clinical trial 120 (0) 28.7 ± 9.0 A joint with ≥ 3 spontaneous bleeding episodes in any consecutive 6-month period
Klamroth et al., 2020 15 Multicenter (22 countries) NCT02585960 (PROPEL study) Phase 3, open-label, randomized, uncontrolled clinical trial 57 (0) 31.0 ± 13.6 A joint with ≥ 4 spontaneous bleeding episodes in any consecutive 6-month period
58 (0) 31.6 ± 12.9
Author, year Regimen type Patient characteristics Total patients in PPAS or analyzed for ABR based on regimen Type & TJ Total ABR Spontaneous ABR Injury ABR Joint ABR
Mean (95% CI) SD Mean (95% CI) SD Mean (95% CI) SD Mean (95% CI) SD
Mullins et al., 2017 9 Twice-weekly prophylaxis With TJs 14 3.54 (1.89–6.64) 4.11 1.20 (0.92–1.56) 2.22 2.09 (1.49–2.93) 2.93 1.10 (0.64–1.91) 2.58
Without TJs 52 2.92 (2.02–4.24) 3.99
Chowdary et al., 2020 7 Twice-weekly prophylaxis With and without TJs 186 2.23 (1.85–2.69) 3.06 1.20 (0.92–1.56) 2.33 N/A N/A 1.23 (0.96–1.58) 2.26
PK-guided prophylaxis With and without TJs 25 2.64 (1.70–4.08) 1.87 0.96 (0.54–1.71) 0.92 1.40 (0.91–2.17) 0.99
Konkle et al., 2015 5 Twice-weekly prophylaxis With TJs 32 3 4.9 2.2 3.7 N/A N/A 2.2 3.2
Without TJs 69 3.7 4.4 1.9 2.9 1.2 2.4
Klamroth et al., 2020 15 PK-guided prophylaxis (1–3%) With and without TJs 52 2.8 3 1.7 2.5 1.1 1.9 1.8 2.2
PK-guided prophylaxis (8–12%) With and without TJs 43 1.2 2.4 0.6 1.5 0.7 1.7 0.8 2.3
Author, year Patients with zero-bleeding during treatment Hemostatic efficacy Adverse events Number of deaths
Rating Events Total number of bleedings Number of patients with any AEs (non-SAEs and SAEs) Total non-SAEs Non-SAEs considered related to treatment Number of patients with SAEs Total SAEs SAEs considered related to treatment
Mullins et al., 2017 9 25 Excellent
Good
Fair
None
Not reported		 34
29
4
0
3		 70 43 152 0 3 4 0 0
Chowdary et al., 2020 7 51 Excellent
Good
Fair
None
Not reported 		438
368
48
4
52 		910 174 786 20 33 52 0 1 (considered unrelated to treatment)
Konkle et al., 2015 5 40 Excellent/Good
Fair/ None/Not reported		 498
20		 518 73 166 7 5 5 0 0
Klamroth et al., 2020 15 24 N/A N/A N/A 34 97 2 3 4 0 0
36 36 98 1 4 5 1 0
Author, year Development of FVIII inhibitory antibodies Development of binding antibodies to FVIII / PEG-FVIII/PEG during study
Mullins et al., 2017 9 No subjects developed inhibitory antibodies
  • •
    16 developed binding antibodies to FVIII, PEG-FVIII, or PEG prior to exposure, but turned negative while on treatment
  • •
    5 developed antibodies to PEG-VIII during treatment (2 were transient; 2 were only at study completion; and 1 was with decreasing titre)
  • •
    No development of persistent binding antibodies that affected efficacy or safety
Chowdary et al., 2020 7 No subjects developed inhibitory antibodies
  • •
    5 developed binding antibodies to FVIII
  • •
    8 developed binding antibodies to PEG-FVIII
  • •
    Only one persisted to the study end without any notable safety or efficacy findings
Konkle et al., 2015 5 No subjects developed inhibitory antibodies
  • •
    7 developed transient binding antibodies to PEG-FVIII or FVIII
  • •
    No subjects developed persistent binding antibodies to FVIII, PEG-FVIII, or PEG
  • •
    Binding antibodies that were detected could not be correlated to impaired treatment efficacy or related AEs
Klamroth et al., 2020 15 No subjects developed inhibitory antibodies
  • •
    3 had single positive binding antibodies to PEG-FVIII and PEG at baseline only
  • •
    Binding antibodies that were detected could not be correlated to impaired treatment efficacy or related AEs
1 subject (resolved at the study end)
  • •
    8 developed transient binding antibodies to PEG-FVIII or FVIII.
  • •
    Binding antibodies that were detected could not be correlated to impaired treatment efficacy or related AEs
*

Data are presented in mean ± SD.

ABR, annualized bleeding rate; CI, confidence interval; F, female; FVIII, factor VIII; N/A, not available or not applicable; Non-SAEs, non-serious adverse events; PEG, pegylated; PK, pharmacokinetic; PPAS, per-protocol analysis set; SAEs, serious adverse events; SD, standard deviation; TJ(s), target joint(s).