Table 2.
Summary of studies of hemophilia patients switching between factor IX 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 | ||||||
| Alamelu49 |
(1) Alphanine (2) Benefix |
50 | 9 |
15‐73 (41.2) [42] |
7 | Compare PK and pharmacodynamics properties of rFIX and pdFIX |
| Aznar50 |
(1) Immunine/Octanine (2) FIX Grifols |
65‐75 | 25 |
12‐38 (23.1) |
7 | Compare pharmacokinetic profile of FIX Grifols to available Immunine or Octanine |
| Ewenstein51 |
(1) Benefix (2) Mononine |
50 | 43 |
7‐75 [18.5] |
7 | Assess PK properties of the 2 products and address how variables affect in vivo recovery and half‐life |
| Goudemand52 |
(1) FIX‐SD‐15 (2) FIX‐SD |
60 | 11 | ‐ | 10 | Compare PK and coagulation activation markers of FIX‐SD‐15 and FIX‐SD |
| Liebman53 |
(1) Alphanine (2) Mononine |
40 | 12 | ‐ | 7 | Evaluate kinetics of FIX activity and protein |
| Lissitchkov54 |
(1) Benefix (2) Alphanine |
65‐75 | 22 |
15‐45 (27) |
7 | Compare PK between Benefix and Alphanine |
| Martinowitz55 |
(1) Benefix (2) IB1001 |
75 ± 5 | 32 | 15‐64 | 5 | Compare PK of IB1001 with those of Benefix and assess consistency of PK parameters |
| Thomas56 |
(1) Conventional FIX (2) High‐purity FIX |
75 | 19 | ‐ | 7 | Compare PK of high‐purity FIX to conventional FIX |
| Windyga57 |
(1) Benefix (2) BAX326 |
75 ± 5 | 86 | 12‐65 | 5 | Characterize PK profile of BAX326 and determine PK equivalence with Benefix |
| Biosimilarity or comparative PK and inhibitor development studies | ||||||
| Collins58 |
(1) Benefix (2) IB1001 |
75 ± 5 | 32 |
14.8‐64.5 (32.7) [29.9] |
5 | Establish PK noninferiority of IB1001 to Benefix, safety, and efficacy |
| Kenet59 |
(1) Prior FIX product (2) rFIX‐FP |
50 | 27 |
1‐11 (5.9) |
‐ | Evaluate PK, efficacy, and safety of rFIX‐FP |
| Inhibitor development studies | ||||||
| Negrier60 |
(1) Prior FIX product (2) N9‐GP |
‐ 25/50/100 |
20 |
21‐55 [30] |
7 | Determine safety by evaluating adverse events, antibody formation against FIX and N9‐GP, physical examination, and clinical laboratory assessments |
| Powell61 |
(1) Benefix (2) rFIXFc |
50 | 22 | ‐ | 5 | Determine annualized bleeding rate and development of inhibitors |
| Solano Trujillo62 |
(1) Immunine (2) BAX326 |
20‐40 75 ± 5 |
44 | 1‐55 | ‐ | Document exposure to Immunine and monitor for inhibitor development |
‐, not specified; FIX, factor IX; FVIII, factor VIII; pdFX, plasma‐derived factor X; PK, pharmacokinetics; rFIX, recombinant factor X.