J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website http://www.thejh.org

Original Article

Volume 7, Number 3, September 2018, pages 87-95

Efficacy and Safety of IQYMUNE®, a Ten Percent Intravenous Immunoglobulin in Adult Patients With Chronic, Primary Immune Thrombocytopenia

Figure 1. Platelet count over time. Blood samples for platelet determination were drawn on Day 1 pre-infusion (hospital), Day 2 post-infusion (hospital), Days 3, 4, 5, 6, 7, 9, 11 (outpatient/visiting nurse), Day 14 ± 1 (hospital), Day 21 ± 1 (outpatient/visiting nurse) and Day 30 ± 1 (hospital). Means and standard deviations are presented. EOS/ET: end of study/early termination.

**Table 1.** Demographics and Baseline Characteristics of Patients (N = 38 Patients)
Parameter	Results
*Defined as a drop in platelet count to ≤ 50 × 10⁹. ITP: immune thrombocytopenia.
Demographics
Sex (n (%))
Male	14 (36.8)
Female	24 (63.2%)
Age (years)
Mean ± SD	37.2 ± 11.8
Median (range)	35.0 (18, 60)
Weight (kg)
Mean ± SD	67.5 ± 17.0
Median (range)	68.5 (43.0, 115.0)
Body mass index (kg/m²)
Mean ± SD	23.8 ± 4.2
Median (range)	23.8 (17.0, 34.9)
Medical condition/history reported by ≥ 3 patients (n (%))
Hypertension	6 (15.8)
Anemia	6 (15.8)
Tonsillectomy	5 (13.2)
Gastritis	5 (13.2)
Appendectomy	4 (10.5)
History of ITP
Time from diagnosis (years)
Mean ± SD	7.55 ± 8.63
Median (range)	3.65 (1.0, 40.7)
Platelet count at diagnosis (10⁹/L)
Mean ± SD	24.4 ± 24.7
Median (range)	17.0 (0.7, 101.0)
Frequency of acute* episodes per month (n)
Mean ± SD	0.74 ± 2.03
Median (range)	0.30 (0.0, 12.0)
Time from previous acute* episode (months)
Mean ± SD	16.67 ± 36.36
Median (range)	3.00 (0.0, 157.0)
Platelet count at baseline (10⁹/L)
Mean ± SD	16.7 ± 8.00
Median (range)	18.1 (1, 29)
Patients with a platelet count ≤ 20 × 10⁹/L at baseline (n (%))	23 (60.5)
Refractory ITP and splenectomy (n (%))	6 (15.8)
Bleeding (n (%))
Bleeding history	30 (78.9)
Life-threatening bleeding history	3 (7.9)
Bleeding history reported in ≥ 3 patients
Cutaneous	27 (71.1)
Mucosal	17 (56.7)
Genitourinary tract	7 (23.3)
Bleeding at baseline	29 (76.3)
Prior ITP medication in ≥ 3 patients (n (%))	35 (92.1)
Corticosteroids, systemic	32 (84.2)
Immunoglobulins	11 (28.9)
Azathioprine	3 (7.9)
Eltrombopag	2 (5.3)
Rituximab	2 (5.3)
Other blood products	2 (5.3)

Table 1. Demographics and Baseline Characteristics of Patients (N = 38 Patients)

Parameter

Results

*Defined as a drop in platelet count to ≤ 50 × 10⁹. ITP: immune thrombocytopenia.

Demographics

Sex (n (%))

Male

14 (36.8)

Female

24 (63.2%)

Age (years)

Mean ± SD

37.2 ± 11.8

Median (range)

35.0 (18, 60)

Weight (kg)

Mean ± SD

67.5 ± 17.0

Median (range)

68.5 (43.0, 115.0)

Body mass index (kg/m²)

Mean ± SD

23.8 ± 4.2

Median (range)

23.8 (17.0, 34.9)

Medical condition/history reported by ≥ 3 patients (n (%))

Hypertension

6 (15.8)

Anemia

6 (15.8)

Tonsillectomy

5 (13.2)

Gastritis

5 (13.2)

Appendectomy

4 (10.5)

History of ITP

Time from diagnosis (years)

Mean ± SD

7.55 ± 8.63

Median (range)

3.65 (1.0, 40.7)

Platelet count at diagnosis (10⁹/L)

Mean ± SD

24.4 ± 24.7

Median (range)

17.0 (0.7, 101.0)

Frequency of acute* episodes per month (n)

Mean ± SD

0.74 ± 2.03

Median (range)

0.30 (0.0, 12.0)

Time from previous acute* episode (months)

Mean ± SD

16.67 ± 36.36

Median (range)

3.00 (0.0, 157.0)

Platelet count at baseline (10⁹/L)

Mean ± SD

16.7 ± 8.00

Median (range)

18.1 (1, 29)

Patients with a platelet count ≤ 20 × 10⁹/L at baseline (n (%))

23 (60.5)

Refractory ITP and splenectomy (n (%))

6 (15.8)

Bleeding (n (%))

Bleeding history

30 (78.9)

Life-threatening bleeding history

3 (7.9)

Bleeding history reported in ≥ 3 patients

Cutaneous

27 (71.1)

Mucosal

17 (56.7)

Genitourinary tract

7 (23.3)

Bleeding at baseline

29 (76.3)

Prior ITP medication in ≥ 3 patients (n (%))

35 (92.1)

Corticosteroids, systemic

32 (84.2)

Immunoglobulins

11 (28.9)

Azathioprine

3 (7.9)

Eltrombopag

2 (5.3)

Rituximab

2 (5.3)

Other blood products

2 (5.3)

**Table 2.** Efficacy Endpoints (Full Analysis Set)
Efficacy variable	N = 38
Response was defined as a platelet count ≥ 30 × 10⁹/L and a 2-fold increase from baseline, no new bleeding events, and no intake of forbidden medications. Complete Response was defined as a platelet count ≥ 100 × 10⁹/L, no new bleeding events, and no intake of forbidden medications. *Determined in the full analysis set N = 38. †N = 37; exclusion of one patient who took a forbidden treatment on Day 1. CI: confidence interval.
Response, n (%); (Clopper-Pearson 95% CI)	24 (63.2); (46.0; 78.2)
Time to Response (days), median (range)	1 (1 - 6)
Duration of Response (days), estimate (Kaplan Meier 95% CI)	13.5 (10.0; 20.0)
Loss of Response, n (%); (Clopper-Pearson 95% CI)	17 (70.8); (48.9; 87.4)
No Response, n (%); (Clopper-Pearson 95% CI)	14 (36.8); (21.8; 54.0)
Complete Response, n (%); (Clopper-Pearson 95% CI)	11 (28.9); (15.4; 45.9)
Time to Complete Response (days), median (range)	2 (1 - 8)
Duration of Complete Response (days), estimate (Kaplan Meier 95% CI)	12 (10.0; 18.0)
Loss of Complete Response, n (%); (Clopper-Pearson 95% CI)	9 (81.8); (48.2; 97.7)
No Complete Response, n (%); (Clopper-Pearson 95% CI)	27 (71.1); (54.1; 84.6)
Maximum platelet count (× 10⁹)*, mean (Hodges-Lehmann 95% CI)	165 (113; 189)
Time to maximum platelet count (days)†, median (Kaplan Meier 95% CI)	4.0 (3.0; 6.0)

Table 2. Efficacy Endpoints (Full Analysis Set)

Efficacy variable

N = 38

Response was defined as a platelet count ≥ 30 × 10⁹/L and a 2-fold increase from baseline, no new bleeding events, and no intake of forbidden medications. Complete Response was defined as a platelet count ≥ 100 × 10⁹/L, no new bleeding events, and no intake of forbidden medications. *Determined in the full analysis set N = 38. †N = 37; exclusion of one patient who took a forbidden treatment on Day 1. CI: confidence interval.

Response, n (%); (Clopper-Pearson 95% CI)

24 (63.2); (46.0; 78.2)

Time to Response (days), median (range)

1 (1 - 6)

Duration of Response (days), estimate (Kaplan Meier 95% CI)

13.5 (10.0; 20.0)

Loss of Response, n (%); (Clopper-Pearson 95% CI)

17 (70.8); (48.9; 87.4)

No Response, n (%); (Clopper-Pearson 95% CI)

14 (36.8); (21.8; 54.0)

Complete Response, n (%); (Clopper-Pearson 95% CI)

11 (28.9); (15.4; 45.9)

Time to Complete Response (days), median (range)

2 (1 - 8)

Duration of Complete Response (days), estimate (Kaplan Meier 95% CI)

12 (10.0; 18.0)

Loss of Complete Response, n (%); (Clopper-Pearson 95% CI)

9 (81.8); (48.2; 97.7)

No Complete Response, n (%); (Clopper-Pearson 95% CI)

27 (71.1); (54.1; 84.6)

Maximum platelet count (× 10⁹)*, mean (Hodges-Lehmann 95% CI)

165 (113; 189)

Time to maximum platelet count (days)†, median (Kaplan Meier 95% CI)

4.0 (3.0; 6.0)

**Table 3.** Safety Evaluation: Adverse Events and Serious Adverse Events (38 Patients, 73 Infusions)
	Patients (N (% patients))	Adverse event (N)
GFR: glomerular filtration rate.
Treatment emergent adverse events, total	31 (81.6)	89
Treatment emergent drug-related adverse events, total	25 (65.8)	66
Treatment emergent drug-related adverse events, in ≥ two patients
Headache	13 (34.2)	21
Pyrexia	6 (15.8)	6
Creatinine renal clearance decrease or GFR decrease	4 (10.5)	6
Systolic blood pressure increase	3 (7.9)	4
Vomiting	3 (7.9)	3
Body temperature increase	2 (5.3)	2
Influenza-like illness	2 (5.3)	2
Nausea	2 (5.3)	2
Arthralgia	2 (5.3)	2
Temporally associated adverse events, total	27 (71.1)	64
Discontinuation of study drug due to adverse event	2 (5.3)	4
Interruption of infusion due to adverse event	2 (5.3)	2
Flow rate decrease due to mild pyrexia	1 (2.6)	1
Serious adverse events, total	7 (18.4)	8
Study drug overdose	1 (2.6)	1
Study drug underdose	1 (2.6)	1
Decrease in glomerular filtration rate	1 (2.6)	1
Aseptic meningitis	1 (2.6)	1
Influenza-like illness	1 (2.6)	1
Pyrexia	1 (2.6)	1
Headache, recurrent	1 (2.6)	1
Positive human immunodeficiency virus test	1 (2.6)	1

Table 3. Safety Evaluation: Adverse Events and Serious Adverse Events (38 Patients, 73 Infusions)

Patients (N (% patients))

Adverse event (N)

GFR: glomerular filtration rate.

Treatment emergent adverse events, total

31 (81.6)

Treatment emergent drug-related adverse events, total

25 (65.8)

Treatment emergent drug-related adverse events, in ≥ two patients

Headache

13 (34.2)

Pyrexia

6 (15.8)

Creatinine renal clearance decrease or GFR decrease

4 (10.5)

Systolic blood pressure increase

3 (7.9)

Vomiting

3 (7.9)

Body temperature increase

2 (5.3)

Influenza-like illness

2 (5.3)

Nausea

2 (5.3)

Arthralgia

2 (5.3)

Temporally associated adverse events, total

27 (71.1)

Discontinuation of study drug due to adverse event

2 (5.3)

Interruption of infusion due to adverse event

2 (5.3)

Flow rate decrease due to mild pyrexia

1 (2.6)

Serious adverse events, total

7 (18.4)

Study drug overdose

1 (2.6)

Study drug underdose

1 (2.6)

Decrease in glomerular filtration rate

1 (2.6)

Aseptic meningitis

1 (2.6)

Influenza-like illness

1 (2.6)

Pyrexia

1 (2.6)

Headache, recurrent

1 (2.6)

Positive human immunodeficiency virus test

1 (2.6)