Study 2: a multi-center, open-label, cross-over, uncontrolled, randomized study in adolescent and adult (age ≥12 years to <65 years) PTPs (≥150 EDs) eva luated the superiority of prophylaxis over on-demand treatment with KOVALTRY over a one-year treatment period (see TABLE 7). The primary efficacy variable was ABR. The prophylactic regimen was 20 to 30 IU/kg two times per week or 30 to 40 IU/kg three times per week and the treatment group was assigned by randomization.
Study 3: a multi-center, open-label, uncontrolled study in pediatric (age ≤12 years) PTPs (≥50 EDs) eva luated the pharmacokinetics, efficacy and safety of routine prophylaxis, and perioperative management of bleeding of KOVALTRY (see TABLE 8). The primary efficacy variable was annualized number of total bleeds during routine prophylaxis that occurred within 48 hours following previous prophylaxis infusion. ABR during prophylaxis, independent of time of infusion, was also analyzed. The prophylactic regimen was 25 to 50 IU/kg at frequencies of either 2 times per week, 3 times per week or every other day and could be adapted to individual subject’s need by the investigator.
In all studies, treatments of breakthrough bleeds and perioperative management were at the investigator’s discretion based on standard of care.
A total of 204 subjects were enrolled in the completed clinical trials, 153 subjects ≥12 years of age and 51 subjects <12 years of age. One hundred-forty (140) subjects were treated for at least 12 months, and 43 of these subjects were treated for 24 months.
Table 7: Overview of Study 1 (Prophylaxis Treatment Phase) and Study 2
Study 1
(N=62) Study 2
(N=80)
Age: mean ± SD
31.5 ± 12.7 years
29.6 ± 11.0 years
Previous treatment: %
Prophylaxis: 80.6%
On-demand: 100%
Number of Target joints at baseline:
mean ± SD
1.4 ± 1.3
3.0 ± 2.1
Joint hemorrhage history
(during 12 months prior to study):
mean ± SD of joint bleeds
8.0 ± 11.9
32.1 ± 23.8
Table 8: Overview of Study 3
Study 3
PTPs 0 to <6 yrs
(N=25) PTPs 6 to 12 yrs
(N=26)
Age: mean ± SD (range)
3.8 ± 1.3 years (1-5)
8.8 ± 1.8 years (6-11)
Previous treatment: %
Prophylaxis: 92.0%
Prophylaxis: 65.4%
Number of Target joints at baseline: mean ± SD
0.2 ± 0.4
0.7 ± 1.1
14.1 On-demand Treatment and Control of Bleeding Episodes
Adolescents and Adults
A total of 1892 bleeding episodes in 110 subjects were treated with KOVALTRY in Study 1 and Study 2 (see TABLE 9). The majority of the bleeding episodes were spontaneous, localized in joints, and mild to moderate in severity.
In Study 1 and Study 2, the treatment responses in a total of 1859 treated bleeds were assessed by the subjects compared to their previous treatment experience.
Table 9: On-demand Treatment and Control of Bleeding Episodes in Adolescents and Adults Treated with KOVALTRY
* Total number excluding uncharacterized bleeds † The % is calculated from number of treated bleeds assessed for response
Characteristics of Bleeding Episodes
Study 1
Study 2
Prophylaxis
Main Study
N=62
Prophylaxis
Extension
N=55
Prophylaxis
N=59
On-demand
N=21
Total number of bleeds
241
154
293
1204
Sp
