WINRHO SDF Solution for injection Ref.[50374] Active ingredients: Human normal immunoglobulin G

In a clinical study with Rh_o(D)-negative volunteers (nine males and one female), Rh_o(D)-positive RBCs were completely cleared from the circulation within 8 hours of intravenous administration of WinRho SDF. There was no indication of Rh isoimmunization of these subjects at six months after the clearance of the Rh_o(D)-positive RBCs.

IM versus IV Administration (Lyophilized Powder)

In a clinical study involving Rh_o(D)-negative volunteers, two subjects received 600 IU (120 mcg) WinRho SDF by intravenous (IV) administration and two subjects received this dose by intramuscular (IM) administration. Peak levels (36 to 48 ng/mL) were reached within two hours of IV administration and peak levels (18 to 19 ng/mL) were reached at five to 10 days after IM administration. Although no statistical comparisons were made, the calculated areas under the curve were comparable for both routes of administration. The t_½ for anti-Rh_o(D) was about 24 days following IV administration and about 30 days following IM administration.

Lyophilized Powder versus Liquid Formulation

In two comparative pharmacokinetics studies, 101 volunteers were administered the liquid or lyophilized formulation of WinRho SDF intravenously (n=41) or intramuscularly (n=60). The formulations were bioequivalent following IV administration based on area under the curve to 84 days and had comparable pharmacokinetics following IM administration. The average peak concentrations (C_max) of anti-Rh_o(D) for both formulations were comparable following IV or IM administration and occurred within 30 minutes or 2-4 days of administration, respectively. Both formulations also had similar elimination half-lives (t_½) following IV or IM administration.

14.1 Treatment of ITP

Efficacy was documented in four subgroups of patients with ITP:

Childhood Chronic ITP

In an open-label, single arm, multicenter study, 24 non-splenectomized, Rh_o(D)-positive children with ITP of greater than six-months duration were treated initially with 250 IU/kg (50 mcg/kg) WinRho SDF [125 IU/kg (25 mcg/kg) on days 1 and 2, with subsequent doses ranging from 125 to 275 IU/kg (25 to 55 mcg/kg)]. Response was defined as a platelet increase to at least 50,000/mm³ and a doubling of the baseline. Nineteen of 24 patients responded for an overall response rate of 79%, an overall mean peak platelet count of 229,400/mm³ (range 43,300 to 456,000), and a mean duration of response of 36.5 days (range 6 to 84).¹⁵

Childhood Acute ITP

A multicenter, randomized, controlled trial comparing WinRho SDF to high dose and low dose Immune Globulin Intravenous (Human) (IGIV) and prednisone was conducted in 146 non-splenectomized, Rh_o(D)-positive children with acute ITP and platelet counts less than 20,000/mm³. Of 38 patients receiving WinRho SDF [125 IU/kg (25 mcg/kg) on days 1 and 2], 32 patients (84%) responded (platelet count ≥ 50,000/mm³) with a mean peak platelet count of 319,500/mm³ (range 61,000 to 892,000), with no statistically significant differences compared to other treatment arms. The mean times to achieving ≥20,000/mm³ or ≥50,000/mm³ platelets for patients receiving WinRho SDF were 1.9 and 2.8 days respectively. When comparing the different therapies for time to platelet count ≥20,000/mm³ or ≥50,000/mm³, no statistically significant differences among treatment groups were detected, with a range of 1.3 to 1.9 days and 2.0 to 3.2 days, for IGIV and prednisone respectively.^16,17

Adult Chronic ITP

Twenty-four non-splenectomized Rh_o(D)-positive adults with ITP of greater than six-months duration and platelet counts <30,000/mm³ or requiring therapy were enrolled in a single-arm, open-label trial were treated with 100 to 375 IU/kg (20 to 75 mcg/kg) WinRho SDF [mean dose 231 IU/kg (46.2 mcg/kg)]. Twenty-one of 24 patients responded (increase ≥20,000/mm³) during the first two courses of therapy for an overall response rate of 88% with a mean peak platelet count of 92,300/mm³ (range 8,000 to 229,000).^18,19

ITP Secondary to HIV Infection

Eleven children and 52 adults, who were non-splenectomized and Rh_o(D)-positive, with all Walter Reed classes of HIV infection and ITP, with initial platelet counts of ≤ 30,000/mm³ or requiring therapy, were treated with 100 to 375 IU/kg (20 to 75 mcg/kg) WinRho SDF in an open label trial. WinRho SDF was administered for an average of 7.3 courses (range 1 to 57) over a mean period of 407 days (range 6 to 1,952). Fifty-seven of 63 patients responded (increase ≥20,000/mm³) during the first six courses of therapy for an overall response rate of 90%. The overall mean change in platelet count for six courses was 60,900/mm³ (range -2,000 to 565,000), and the mean peak platelet count was 81,700/mm³ (range 16,000 to 593,000).^18-20

14.2 Suppression of Rh Isoimmunization

A study was conducted in 1,186 non-sensitized, Rh_o(D)-negative pregnant women in cases in which the blood types of the fathers were Rh_o(D)-positive or unknown. WinRho SDF was administered according to one of three regimens: 1) 93 women received 600 IU (120 mcg) at 28 weeks; 2) 131 women received 1,200 IU (240 mcg) each at 28 and 34 weeks; 3) 962 women received 1,200 IU (240 mcg) at 28 weeks. All women received a postnatal administration of 600 IU (120 mcg) if the newborn was found to be Rh_o(D)-positive. Of 1,186 women who received antenatal WinRho SDF, 806 were given WinRho SDF postnatal following the delivery of a Rh_o(D)-positive infant, of which 325 women underwent testing at six months after delivery for evidence of Rh isoimmunization. Of these 325 women, 23 would have been expected to display signs of Rh isoimmunization, however, none was observed (p <0.001 in a Chi-square test of significance of difference between observed and expected isoimmunization in the absence of WinRho SDF).