Table 1.
Summary of studies of hemophilia patients switching between factor VIII concentrates
| Author | Products | Dose (IU/kg) | No. of subjects screened for PK |
Age range (mean) [median] |
Minimum washout period (d) | Primary objective |
|---|---|---|---|---|---|---|
| Biosimilarity or comparative PK studies | ||||||
| Di Paola17 |
(1) Advate (2) ReFacto |
50 ± 5 | 21 |
19‐72 (35.8) [30] |
3 | Compare PK of ReFacto and Advate to establish bioequivalence |
| Dmoszynska31 |
(1) Prior FVIII product (2) Optivate |
50 | 15 | 12‐65 | 3 | Investigate the PK of Optivate against other FVIII products |
| Fijnvandraat32 |
(1) rFVIII SQ (2) Octonativ M |
50 | 12 |
17‐64 (34) |
4 | Compare PK of rFVIII SQ and Octonativ M |
| Kessler18 |
(1) ReFacto (2 formulations) (2) Hemofil M |
50 | 19 |
18‐44 (26.3) |
5 | Compare PK of the 2 formulations of ReFacto with Hemofil M to establish bioequivalence |
| Klamroth23 |
(1) Advate (2) rFVIII single‐chain |
50 | 27 |
19‐60 (35.4) |
4 | Compare PK parameters of rFVIII single‐chain with full‐length rFVIII |
| Martinowitz22 |
(1) Advate (2) N8 |
50 | 25 |
13‐54 (24) |
4 | Compare PK profiles of N8 and Advate to establish bioequivalence |
| Morfini33 |
(1) pdFVIII (2) rFVIII |
25‐56 25‐45 |
17 |
15‐51 (27.7) [24.9] |
7 | Compare PK profiles of 2 different classes of FVIII concentrates |
| Morfini34 |
(1) Recombinate (2) Hemofil M |
50 | 47 |
6‐62 (26.4) |
7 | Compare PK profiles of Recombinate and Hemofil M |
| Morfini35 |
(1) Hemofil M (2) Monoclate HT (3) Monoclate P |
25 | 10 | ‐ | 7 | Compare in vivo behavior among the 3 products |
| Recht36 |
(1) Advate (2) Xyntha |
50 | 24 |
12‐60 [24] |
3 | Demonstrate PK equivalence of Advate |
| Shah19 |
(1) Advate (2) Kovaltry |
50 | 18 |
19‐64 (37.3) [36] |
3 | Compare PK profile of Advate and Kovaltry |
| Shirahata37 |
(1) BAY14‐2222 (2) Kogenate |
50 | 5 |
15‐43 (32) [35] |
5 | Compare PK profile of BAY14‐2222 and Kogenate |
| Biosimilarity or comparative PK and inhibitor development studies | ||||||
| Abshire38 |
(1) Kogenate (2) rFVIII‐FS |
50 | 35 | ‐ | 4 | Compare PK and safety of Kogenate and rFVIII‐FS |
| Coyle39 |
(1) rFVIII‐FS (2) BAY 94‐9027 |
25/50 25/60 |
14 |
21‐58 (36.1) |
3 | Assess PK and safety of BAY 94‐9027 |
| Kulkarni40 |
(1) Prior FVIII product (2) Turoctocog alfa |
‐ 25‐60 |
69 |
1‐11 (6.1) |
3 | Investigate safety, efficacy, and PK properties of turoctocog alfa |
| Mahlangu29 |
(1) Advate (2) rFVIIIFc |
50 | 30 |
12‐65 [29] |
‐ | Evaluate safety, efficacy, and PK of rFVIIIFc |
| Meunier41 |
(1) Prior FVIII product (2) N8‐GP |
‐ 60 |
24 |
0‐11 (6.0) |
‐ | Assess safety, efficacy, and PK of N8‐GP |
| Mullins42 |
(1) Advate (2) BAX855 |
60 ± 5 | 31 |
1‐11 (6) [6] |
‐ | Determine immunogenicity, PK, efficacy, safety, and quality of life using BAX855 |
| Powell43 |
(1) Kogenate (2) Kogenate with pegylated liposome carrier (13 or 22 mg/kg) |
35 | 26 | 12‐60 | 2 | Investigate the safety, tolerability, bioavailability, pharmacokinetics, and pharmacodynamics of Kogenate with pegylated liposome barrier compared with standard Kogenate |
| Schwartz44 |
(1) Koate‐HS (2) Recombinant FVIII |
50 20‐40 |
17 | ‐ | 7 | Compare PK of plasma‐derived and recombinant FVIII, assess efficacy of recombinant FVIII for home therapy, and assess efficacy for major surgical procedures and hemorrhage |
| Skotnicki45 |
(1) Vocento (2) Biostate‐RP |
50 | 17 |
18‐57 (36.5) [37] |
4 | Evaluate efficacy, safety, and PK of Voncento |
| Tiede46 |
(1) Prior FVIII product (2) N8‐GP |
‐ 25/50/75 |
26 |
20‐60 [36.5] |
4 | Evaluate safety and PK of N8‐GP in comparison with previous FVIII products |
| Young30 |
(1) Prior FVIII product (2) rFVIIIFc |
50 | 60 |
1‐11 [5] |
3 | Evaluate safety, efficacy, and PK of rFVIIIFc |
| Inhibitor development studies | ||||||
| Hsu47 |
(1) Kogenate (2) Koate‐HS |
50 ‐ |
12 |
23‐53 (37.8) |
7 | Evaluate safety and efficacy of Kogenate |
| Powell48 |
(1) Advate (2) rFVIIIFc |
25/65 25/65 |
19 |
23‐61 (34.6) |
3 | Evaluate safety and treatment‐emergent adverse events, development of antibodies, and laboratory monitoring |
‐, not specified; FVIII, factor VIII; pdFVIII, plasma‐derived factor VIII; PK, pharmacokinetics; rFVIII, recombinant factor VIII; SQ, subcutaneous.