OCTAGAM 10% Rx

Treatment of Chronic Immune Thrombocytopenic Purpura 

A prospective, open-label, single-arm, multicenter study assessed the efficacy, safety, and tolerability of Octagam 10% in 116 patients with tentative newly diagnosed or chronic ITP and a platelet count of 20x109 /L or less. Patients ranged in age from 17 to 88; 64% were female and 36% were male. 

Patients received a 2 g/kg dose of Octagam 10% administered as two daily 1 g/kg intravenous doses, given on 2 consecutive days. Pre-medication to alleviate potential adverse drug reactions was allowed but only given to 1 (0.9%) of 116 patients. In the initial study phase, the infusion rate allowed for Octagam 10% administration was up to 6 mg/kg/min [0.06 mL/kg/min], which was achieved in 24 of 26 patients (92%). Subsequently, the maximum infusion rate allowed was 12 mg/kg/min [0.12mL/kg/min], which was achieved in 54 of 90 patients (60%). Platelet counts were measured on Days 1 to 7, 14, 21, and 63. 

The study was designed to determine the response rate defined as the percentage of patients with an increase in platelet count to at least 50x10⁹ /L within 7 days after the first infusion (responders). Additionally, maximum platelet count, the time to reach a platelet count of at least 50x10⁹ /L within the first 7 days, the duration of that response (ie, the number of days the platelet count remained in excess of 50x10⁹ /L), and the regression of hemorrhages in patients who had bleeding at baseline were observed. 

Of the 66 patients with chronic ITP in the efficacy analysis, 54 (82%) responded to Octagam 10% with a rise in platelet counts to at least 50x10⁹ /L within 7 days after the first infusion. The lower bound of the overall 95% confidence interval for the response rate (73%) is above the predefined response rate of 70%. The mean maximum platelet count achieved in the 66 patients with chronic ITP was 227x10⁹ /L.

The median time to reach a platelet response of at least 50x10⁹ /L was 2 days after the first infusion. The duration of platelet response was analyzed for the 54 subjects with chronic ITP who achieved a response within 7 days after the first infusion: the median duration of platelet response in these subjects was 12 days (range: 1 to 79 days). 

In 35 of the 45 subjects with chronic ITP (78%) who had bleeding at baseline, the hemorrhages had completely resolved by Day 7. A decrease in the severity of hemorrhage from baseline to Day 7 was observed in 38 of 45 subjects (84%) with chronic ITP.

Treatment of Dermatomyositis 

In a prospective, double-blind, randomized, placebo-controlled, multicenter study, 95 adults with dermatomyositis were enrolled and randomized. Forty-seven patients received Octagam and 48 patients received placebo in an initial 16week, double-blind First Period, followed by a 6-month, open-label Extension Period, during which all patients who were eligible to continue, received Octagam 10% every 4 weeks. Forty-five patients in the initial Octagam group and 46 patients in the placebo group entered the Extension Period.

Efficacy in this study was based on the proportion of responders at week 16. A responder was defined as a patient with a minimal improvement of ≥20 points on the Total Improvement Score (TIS). TIS is based on six Core Set Measures (CSM) which include: Manual Muscle Testing MMT-8, Physician Global Disease Activity (GDA) as part of Myositis Disease Activity Assessment Tool (MDAAT) assessed by the Investigator on a Visual Analog Scale (VAS), Extramuscular Activity as part of MDAAT assessed by the Investigator on a VAS, Patient GDA assessed by the Patient on a VAS, Health Assessment Questionnaire (HAQ) assessed by the Patient, and Muscle Enzymes: aldolase, creatine kinase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH).

At week 16, results showed that patients with a minimal improvement of ≥20 points on the TIS in the Octagam 10% group was 37 (78.7%) compared to 21 (43.8%) in the placebo group; difference in responder proportion was 35% [95% CI: 16.7%, 53.2%], P= 0.0008.

The median time to response was 35 days in the Octagam 10% group. In addition, there was a greater proportion of patients in the Octagam 10% group compared to placebo with at least moderate improvement defined as ≥40 points on the TIS and major improvement defined as ≥60 points on the TIS (see full labeling for data).

Efficacy was further supported by an improvement in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score, with a mean decrease of 9.4 (SD: 10.5) points from baseline to week 16 in the Octagam 10% group versus 1.2 (SD: 7.0) point in the placebo group. 

The Octagam 10% group maintained their improvement in TIS (32/45, 71.1%) during the 6-month Extension Period. Among the 46 patients who switched from placebo to Octagam 10% in the Extension Period, 69.6% (32/46) were classified as responders at the end of the 6-month Extension Period.

Treatment of Chronic Immune Thrombocytopenic Purpura 

A prospective, open-label, single-arm, multicenter study assessed the efficacy, safety, and tolerability of Octagam 10% in 116 patients with tentative newly diagnosed or chronic ITP and a platelet count of 20x109 /L or less. Patients ranged in age from 17 to 88; 64% were female and 36% were male. 

Patients received a 2 g/kg dose of Octagam 10% administered as two daily 1 g/kg intravenous doses, given on 2 consecutive days. Pre-medication to alleviate potential adverse drug reactions was allowed but only given to 1 (0.9%) of 116 patients. In the initial study phase, the infusion rate allowed for Octagam 10% administration was up to 6 mg/kg/min [0.06 mL/kg/min], which was achieved in 24 of 26 patients (92%). Subsequently, the maximum infusion rate allowed was 12 mg/kg/min [0.12mL/kg/min], which was achieved in 54 of 90 patients (60%). Platelet counts were measured on Days 1 to 7, 14, 21, and 63. 

The study was designed to determine the response rate defined as the percentage of patients with an increase in platelet count to at least 50x10⁹ /L within 7 days after the first infusion (responders). Additionally, maximum platelet count, the time to reach a platelet count of at least 50x10⁹ /L within the first 7 days, the duration of that response (ie, the number of days the platelet count remained in excess of 50x10⁹ /L), and the regression of hemorrhages in patients who had bleeding at baseline were observed. 

Of the 66 patients with chronic ITP in the efficacy analysis, 54 (82%) responded to Octagam 10% with a rise in platelet counts to at least 50x10⁹ /L within 7 days after the first infusion. The lower bound of the overall 95% confidence interval for the response rate (73%) is above the predefined response rate of 70%. The mean maximum platelet count achieved in the 66 patients with chronic ITP was 227x10⁹ /L.

The median time to reach a platelet response of at least 50x10⁹ /L was 2 days after the first infusion. The duration of platelet response was analyzed for the 54 subjects with chronic ITP who achieved a response within 7 days after the first infusion: the median duration of platelet response in these subjects was 12 days (range: 1 to 79 days). 

In 35 of the 45 subjects with chronic ITP (78%) who had bleeding at baseline, the hemorrhages had completely resolved by Day 7. A decrease in the severity of hemorrhage from baseline to Day 7 was observed in 38 of 45 subjects (84%) with chronic ITP.

Treatment of Dermatomyositis 

In a prospective, double-blind, randomized, placebo-controlled, multicenter study, 95 adults with dermatomyositis were enrolled and randomized. Forty-seven patients received Octagam and 48 patients received placebo in an initial 16week, double-blind First Period, followed by a 6-month, open-label Extension Period, during which all patients who were eligible to continue, received Octagam 10% every 4 weeks. Forty-five patients in the initial Octagam group and 46 patients in the placebo group entered the Extension Period.

Efficacy in this study was based on the proportion of responders at week 16. A responder was defined as a patient with a minimal improvement of ≥20 points on the Total Improvement Score (TIS). TIS is based on six Core Set Measures (CSM) which include: Manual Muscle Testing MMT-8, Physician Global Disease Activity (GDA) as part of Myositis Disease Activity Assessment Tool (MDAAT) assessed by the Investigator on a Visual Analog Scale (VAS), Extramuscular Activity as part of MDAAT assessed by the Investigator on a VAS, Patient GDA assessed by the Patient on a VAS, Health Assessment Questionnaire (HAQ) assessed by the Patient, and Muscle Enzymes: aldolase, creatine kinase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH).

At week 16, results showed that patients with a minimal improvement of ≥20 points on the TIS in the Octagam 10% group was 37 (78.7%) compared to 21 (43.8%) in the placebo group; difference in responder proportion was 35% [95% CI: 16.7%, 53.2%], P= 0.0008.

The median time to response was 35 days in the Octagam 10% group. In addition, there was a greater proportion of patients in the Octagam 10% group compared to placebo with at least moderate improvement defined as ≥40 points on the TIS and major improvement defined as ≥60 points on the TIS (see full labeling for data).

Efficacy was further supported by an improvement in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) total activity score, with a mean decrease of 9.4 (SD: 10.5) points from baseline to week 16 in the Octagam 10% group versus 1.2 (SD: 7.0) point in the placebo group. 

The Octagam 10% group maintained their improvement in TIS (32/45, 71.1%) during the 6-month Extension Period. Among the 46 patients who switched from placebo to Octagam 10% in the Extension Period, 69.6% (32/46) were classified as responders at the end of the 6-month Extension Period.