Introduction
Methods
Phase I Local Tolerability Study in Healthy Subjects
Subjects
Study Design
Tolerability Assessments
Phase III Efficacy and Safety Study in Patients With PID
Patients
Study Design
Efficacy and Safety Assessments
Statistical Methodology
Results
Phase I Local Tolerability Study in Healthy Subjects
Variable | IgPro16 (15 mL) | IgPro20 (15 mL) | IgPro20 (12 mL) | Vivaglobin (15 mL) |
---|---|---|---|---|
Subjects treateda
| 28 (100%) | 28 (100%) | 28 (100%) | 28 (100%) |
Maximum painb (mm), mean (SD) | 6.8 (12.52) | 7.6 (12.46) | 6.9 (12.13) | 9.3 (14.18) |
Mean painb (mm), mean (SD) | 2.36 (5.029) | 2.84 (3.612) | 2.24 (4.240) | 3.78 (7.244) |
Variable | Comparison | Differencec
| Two-sided 90% CI (p) | |
Maximum painb (mm) | IgPro16 (15 mL)–Vivaglobin | -2.54 | -4.82 to -0.26 (0.0679) | |
IgPro20 (15 mL)–Vivaglobin | -1.64 | -3.92 to 0.64 (0.2340) | ||
IgPro20 (12 mL)–Vivaglobin | -2.43 | -4.71 to -0.15 (0.0801) | ||
Mean painb (mm) | IgPro16 (15 mL)–Vivaglobin | -1.41 | -2.50 to -0.33 (0.0328) | |
IgPro20 (15 mL)–Vivaglobin | -0.94 | -2.02 to 0.15 (0.1545) | ||
IgPro20 (12 mL)–Vivaglobin | -1.54 | -2.62 to -0.46 (0.0205) |
IgPro16 (15 mL) | IgPro20 (15 mL) | IgPro20 (12 mL) | Vivaglobin (15 mL) | |
---|---|---|---|---|
Subjects treateda
| 28 (100) | 28 (100) | 28 (100) | 28 (100) |
Erythema
| 23 (82.1) | 26 (92.9) | 27 (96.4) | 28 (100) |
None | 5 (17.9) | 2 (7.1) | 1 (3.6) | – |
Very slight | 9 (32.1) | 9 (32.1) | 11 (39.3) | 4 (14.3) |
Well-defined | 12 (42.9) | 14 (50.0) | 16 (57.1) | 21 (75.0) |
Moderate to severe | 2 (7.1) | 2 (7.1) | – | 3 (10.7) |
Severe | – | 1 (3.6) | – | – |
Edema/Induration
| 28 (100) | 28 (100) | 28 (100) | 28 (100) |
None | – | – | – | – |
Very slight | – | – | – | – |
Slight | – | – | – | – |
Moderate | 1 (3.6) | – | – | – |
Severe | 27 (96.4) | 28 (100) | 28 (100) | 28 (100) |
Itching
| 10 (35.7) | 14 (50.0) | 11 (39.3) | 16 (57.1) |
None | 18 (64.3) | 14 (50.0) | 17 (60.7) | 12 (42.9) |
Mild | 10 (35.7) | 13 (46.4) | 10 (35.7) | 14 (50.0) |
Moderate | – | 1 (3.6) | 1 (3.6) | 2 (7.1) |
Severe | – | – | – | – |
Local heat
| 5 (17.9) | 1 (3.6) | 5 (17.9) | 4 (14.3) |
None | 23 (82.1) | 27 (96.4) | 23 (82.1) | 24 (85.7) |
Mild | 5 (17.9) | 1 (3.6) | 5 (17.9) | 4 (14.3) |
Moderate | – | – | – | – |
Severe | – | – | – | – |
Phase III Efficacy and Safety Study in Patients with PID
Patients
Characteristic | MITT population (N = 38) |
---|---|
Gender, n (%) | |
Female | 21 (55.3) |
Male | 17 (44.7) |
Age (years) | |
Mean (SD) | 36.3 (19.52) |
Median (range) | 36.5 (5–72) |
Age group, n (%) | |
5–11 years | 3 (7.9) |
12–15 years | 3 (7.9) |
16–64 years | 28 (73.7) |
65–72 years | 4 (10.5) |
Race or ethnic group, n (%) | |
White | 37 (97.4) |
Black or African American | 1 (2.6) |
Hispanic or Latinoa
| 2 (5.3) |
Weight (kg) | |
Mean (SD) | 70.0 (21.34) |
Median (range) | 70.0 (21–104) |
Primary disease | |
CVID, n (%) | 36 (95) |
XLA, n (%) | 2 (5) |
Median serum IgG trough levelb, g/L | |
Mean (SD) | 10.1 (2.57) |
Study Drug Administration
Efficacy
Efficacy end point | Number (%) of patients | Number (annual rate) of events/days [CI] |
---|---|---|
Total no. of patients/study days | N = 38 | N = 12,697a |
SBIs [upper 99% CI] | 0 (0) | 0 (0) |
[0.132] | ||
Total no. of patients/study days | N = 38 | N = 12,697a |
Infection episodes (nonserious) [95% CIs] | 31 (81.6) | 96 (2.76) |
[2.235–3.370] | ||
Total no. of patients/study days | N = 38 | N = 12,605b |
Days missed from work/school | 12 (31.6) | 71 (2.06) |
NA | ||
Total no. of patients/study days | N = 38 | N = 12,605b |
Days hospitalized due to infection | 1 (2.6) | 7 (0.2) |
NA | ||
Total no. of patients/study days | N = 38 | N = 12,697a |
Days with antibiotics for infection prophylaxis or treatment | 27 (71.1) | 1,688 (48.5) |
NA |
Safety and Tolerability
AE | Mild | Moderate | Severe | Total |
---|---|---|---|---|
Local reactions, n (rate)b
| 1,251 (0.553) | 85 (0.038) | 4 (0.002) | 1,340 (0.592) |
Injection site reaction, n (rate) | 1,227 (0.542) | 83 (0.037) | 4 (0.002) | 1,314 (0.580) |
Injection site bruising, n (rate) | 19 (0.008) | 0 | 0 | 19 (0.008) |
Injection site cyst, n (rate) | 2 (<0.001) | 0 | 0 | 2 (<0.001) |
AE | All events | Temporally associated (72 h) | ||
---|---|---|---|---|
No. (%) of patients (n = 49) | No. (rate) of events (n = 2,264) | No. (%) of patients (n = 49) | No. (rate) of events (n = 2,264) | |
Any AE | 49 (100) | 1,749 (0.773) | 49 (100) | 1,566 (0.692) |
Injection site reaction | 49 (100) | 1,314 (0.580) | 49 (100) | 1,298 (0.573) |
Sinusitis | 14 (28.6) | 20 (0.009) | 7 (14.3) | 10 (0.004) |
Headache | 13 (26.5) | 40 (0.018) | 12 (24.5) | 32 (0.014) |
Nasopharyngitis | 11 (22.4) | 15 (0.007) | 8 (16.3) | 8 (0.004) |
Cough | 8 (16.3) | 9 (0.004) | 5 (10.2) | 6 (0.003) |
Diarrhea | 7 (14.3) | 8 (0.004) | 5 (10.2) | 6 (0.003) |
Bronchitis | 6 (12.2) | 9 (0.004) | 5 (10.2) | 6 (0.003) |
Fatigue | 6 (12.2) | 6 (0.003) | 4 (8.2) | 4 (0.002) |
Injection site bruising | 5 (10.2) | 19 (0.008) | 5 (10.2) | 18 (0.008) |
Back pain | 5 (10.2) | 11 (0.005) | 4 (8.2) | 5 (0.002) |
Acute sinusitis | 5 (10.2) | 7 (0.003) | 4 (8.2) | 5 (0.002) |
Nausea | 5 (10.2) | 5 (0.002) | 4 (8.2) | 4 (0.002) |
Abdominal pain upper | 5 (10.2) | 5 (0.002) | 3 (6.1) | 3 (0.001) |
Upper respiratory tract infection | 5 (10.2) | 6 (0.003) | 3 (6.1) | 3 (0.001) |
Rash | 5 (10.2) | 7 (0.003) | 2 (4.1) | 3 (0.001) |
Infusion-related | Infusion-related and temporally associated (72 h) | |||
---|---|---|---|---|
AE | No. (%) of patients (n = 49) | No. (rate) of events (n = 2,264) | No. (%) of patients (n = 49) | No. (rate) of events (n = 2,264) |
Any AE | 49 (100) | 1,436 (0.634) | 49 (100) | 1,397 (0.617) |
Injection site reaction | 49 (100) | 1,313 (0.580) | 49 (100) | 1,297 (0.573) |
Headache | 12 (24.5) | 36 (0.016) | 11 (22.4) | 31 (0.014) |
Injection site bruising | 5 (10.2) | 19 (0.008) | 5 (10.2) | 18 (0.008) |
Vomiting | 3 (6.1) | 3 (0.001) | 3 (6.1) | 3 (0.001) |
Pain | 3 (6.1) | 4 (0.002) | 2 (4.1) | 3 (0.001) |
Fatigue | 3 (6.1) | 3 (0.001) | 2 (4.1) | 2 (<0.001) |
Contusion | 2 (4.1) | 3 (0.001) | 2 (4.1) | 3 (0.001) |
Back pain | 2 (4.1) | 3 (0.001) | 2 (4.1) | 2 (<0.001) |
Diarrhea | 2 (4.1) | 2 (<0.001) | 2 (4.1) | 2 (<0.001) |
Abdominal pain upper | 2 (4.1) | 2 (<0.001) | 2 (4.1) | 2 (<0.001) |
Nausea | 2 (4.1) | 2 (<0.001) | 2 (4.1) | 2 (<0.001) |
Migraine | 2 (4.1) | 3 (0.001) | 1 (2.0) | 2 (<0.001) |
Rash | 2 (4.1) | 2 (<0.001) | 1 (2.0) | 1 (<0.001) |
Arthralgia | 2 (4.1) | 2 (<0.001) | 1 (2.0) | 1 (<0.001) |