Efficacy and safety of Privigen(®) in patients with chronic inflammatory demyelinating polyneuropathy: results of a prospective, single-arm, open-label Phase III study (the PRIMA study)

Abstract

This prospective, multicenter, single-arm, open-label Phase III study aimed to evaluate the efficacy and safety of Privigen(®) (10% liquid human intravenous immunoglobulin [IVIG], stabilized with L-proline) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients received one induction dose of Privigen (2 g/kg body weight [bw]) and up to seven maintenance doses (1 g/kg bw) at 3-week intervals. The primary efficacy endpoint was the responder rate at completion, defined as improvement of ≥1 point on the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale. The preset success criterion was the responder rate being ≥35%. Of the 31 screened patients, 28 patients were enrolled including 13 (46.4%) IVIG-pretreated patients. The overall responder rate at completion was 60.7% (95% confidence interval [CI]: 42.41%-76.43%). IVIG-pretreated patients demonstrated a higher responder rate than IVIG-naïve patients (76.9% vs. 46.7%). The median (25%-75% quantile) INCAT score improved from 3.5 (3.0-4.5) points at baseline to 2.5 (1.0-3.0) points at completion, as did the mean (standard deviation [SD]) maximum grip strength (66.7 [37.24] kPa vs. 80.9 [31.06] kPa) and the median Medical Research Council sum score (67.0 [61.5-72.0] points vs. 75.5 [71.5-79.5] points). Of 108 adverse events (AEs; 0.417 AEs per infusion), 95 AEs (88.0%) were mild or moderate in intensity and resolved by the end of study. Two serious AEs of hemolysis were reported that resolved after discontinuation of treatment. Thus, Privigen provided efficacious and well-tolerated induction and maintenance treatment in patients with CIDP.

Figure 1

Patient disposition. Of 31 screened patients, 28 were enrolled into the study and received the induction Privigen® dose. A total of three patients discontinued during the induction and maintenance phases, leaving 25 patients who completed the study.

Figure 2

Secondary efficacy outputs have improved from baseline to completion (ITT). The median INCAT score, the mean maximum grip strength and the median MRC sum score are shown for all patients in the ITT analysis. Error bars represent either SD (maximum grip strength) or 25% and 75% quantile (adjusted INCAT score and MRC sum score).

Figure 3

Mean adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) score over time by intravenous immunoglobulin (IVIG)-pretreatment (ITT). The mean adjusted INCAT scores are shown for IVIG-pretreated (dashed gray line) and IVIG-naïve (solid black line) patients in the ITT analysis. Last observation carried forward was used to replace missing values. Error bars represent the standard error of the mean.

Figure 4

Response to treatment based on adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) score by intravenous immunoglobulin (IVIG)-pretreatment (ITT). Kaplan–Meier analysis of the proportion of responders based on the adjusted INCAT score is shown for all patients (blue), IVIG-naïve (red), and IVIG-pretreated (green) patients in the ITT analysis. The number of patients, who have achieved a response at least once by the time point (n), followed by the number of patients who have not yet responded (N) is indicated as ‘n/N’ below the graph. Please note that this analysis included 1 patient who had a response at Week 19 and Week 22 but not at completion (Week 25), resulting in 18 responders, 17 of which were responders at completion (shown in brackets).

Figure 5

Mean maximum grip strength and mean MRC sum score over time (ITT). The mean maximum grip strength of dominant hand and mean MRC sum score is shown for all patients in the ITT analysis. Error bars represent the standard error of the mean.