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Efficacy, Safety, Tolerability, and Pharmacokinetics of Human Immune Globulin Subcutaneous, 20% (IGSC 20%): Final Analysis of a Phase 2/3 Study in Patients with Primary Immunodeficiency Disease (PIDD) in North America
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Daniel Suez, MD, FAAAAI, Isaac Melamed, MD, Iftikhar Hussain, MD, FAAAAI, Mark R. Stein, MD FAAAAI, Sudhir Gupta, MD, PhD, FAAAAI, Kenneth Paris, MD MPH, Sandor Fritsch, PhD, Christelle Bourgeois, PhD, Heinz Leibl, PhD, Barbara McCoy, PhD, Leman Yel, MD, FAAAAI
Rationale:

We report final results from a study of IGSC 20% in patients aged ≥2 years with PIDD in North America.

Methods:

Epoch 1 (13 weeks): immunoglobulin G 10% was administered intravenously (IGIV) at prestudy doses every 3-4 weeks (Q3W/Q4W). Epochs 2-4: IGSC 20% administered weekly (Epoch 2 [~12-16 weeks], 145% of the weekly equivalent Epoch 1 dose; Epoch 3 [12 weeks], dose adjusted per AUC assessments in Epochs 1-2; Epoch 4 [40 weeks], dose adapted individually per Epoch 3 IgG trough levels). Primary endpoint=validated acute serious bacterial infection (VASBI) rate.

Results:

Seventy-four patients aged 3-83 years received IGSC 20% and 67 completed; no patient discontinued IGSC 20% due to a serious adverse event (SAE) or adverse reaction (AR). During IGSC 20% treatment (n=74), 1 VASBI (rate=0.012/year; P<0.0001) was reported; the all-infection rate/patient-year was 2.41. Local ARs occurred in 23/74 patients (rate=0.022/infusion); all were mild (92.5%) and moderate (7.5%). In 4327 IGSC 20% infusions, median infusion rate was 60 mL/hr/site, resulting in a <1h-median infusion time. A 30-59-mL volume/site was used in 67.4% of infusions, and 7.4% infusions employed a ≥60mL/site volume without tolerability issues. Overall, 84.9% of infusions were administered using ≤2 infusion sites; 99.8% were completed without slowing the rate or interrupting/stopping administration. Ratio of geometric means of AUC/week for IgG with individualized IGSC 20% treatment over IGIV 10% Q3W/Q4W was 109% (90% CI=1.0394-1.1336).

Conclusions:

In patients treated with IGSC 20%, VASBI and infection rates were low, and infusions—most administered using ≤2 sites—were well-tolerated at relatively high infusion rates.