      Document 0171
 DOCN  DRG0171
 UNIQUE IDENTIFIER        DRG-0076
 NAME OF SUBSTANCE        CD4-IgG [Int Conf AIDS Jul 19-24;8(2):
                          abstract no. PoB 3028]
 STANDARD CHEMICAL NAME   Recombinant Human CD4 Immunoglobulin
                          (rCD4-IgG) [NIAID  ACTG 121]
 SYNONYMS                 Recombinant human CD4 immunoglobulin
                          (rCD4-IgG) [NIAID ACTG 121]
 PROTOCOL ID NUMBERS      NIAID ACTG 121
 PROTOCOL ID NUMBERS      NIAID ACTG 134
 PROTOCOL ID NUMBERS      NIAID ACTG 139
 PROTOCOL ID NUMBERS      NIAID 90 I-15
 PROTOCOL ID NUMBERS      NCI 89 C-CD4
 PROTOCOL ID NUMBERS      FDA 076A
 PROTOCOL ID NUMBERS      NIAID 90 I-114
 PROTOCOL ID NUMBERS      NIAID ACTG 146
 PROTOCOL ID NUMBERS      IRP 011
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: rCD4-IgG blocks the
                          cytopathic effect of HIV in T cell lines and
                          blocks the infection of H-9 or U937 cells. It
                          has been shown that CD4-IgG can mediate
                          antibody-dependent cytotoxicity directed
                          against HIV infected target cells. In vitro
                          studies in animals have demonstrated no
                          evidence of rCD4-IgG related toxicity.
                          rCD4-IgG crosses the human placenta to the
                          same extent IgG does. Following IV therapy in
                          a 12 week dose escalating study the mean peak
                          serum level was 8.28 mcg/ml with a serum
                          half-life of 32 h. [Intl Conf AIDS Jul
                          19-24;8(2)] [J Acquir Immune Defic Syndr Hum
                          Retrovirol 1995 Feb 1;8(2)] [NIAID ACTG 121]
 DISEASES STUDIED/TREATED Prevention of HIV infections in newborns when
                          administered during pregnancy [AmFAR Tx Dir
                          1992 Sept;6(1)] [AmFAR Tx Dir 1993 Jan;6(2)]
 DISEASES STUDIED/TREATED Treatment of immune thrombocytopenic purpura
                          [AmFAR Tx Dir 1992 Sept;6(1)] [AmFAR Tx Dir
                          1993 Jan;6(2)]
 CLASSIFICATION CODE      Immunomodulator [NIAID ACTG 121]
 CLASSIFICATION CODE      Antiretroviral [USP DI 1995]
 ADVERSE EFFECTS          So far rCD4-IgG is well tolerated, with no
                          important clinical or immunological
                          toxicities noted. In pregnant women neither
                          the mother or infants have shown evidence of
                          rCD4-IgG related toxicity. Seven of 41
                          patients had severe adverse reactions
                          following 300 to 1000 mcg/kg IV doses over 12
                          weeks. Reactions included nausea, fever,
                          abnormal liver function tests and
                          neutropenia. [Intl Conf AIDS Jul 19-24; 8(2):
                          (abstract no. PoB 3028)] [Antimicrob Agents
                          Chemother 1991 Dec;35(12)] [J Acquir Immune
                          Defic Syndr Hum Retrovirol 1995 Feb 1;8(2)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Recombinant hybrid molecule
                          that combines the CD4 binding sites for gp120
                          with the heavy chain of human immunoglobulin
                          of the IgG 1 class [Nature, 1989; 337]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Lyophilized powder
                          [NIAID ACTG 121]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Vials of 5.0 mg rCD4-IgG.
                          Reconstitute with 1.2 ml sterile water for
                          injection. This results in a concentration of
                          5.0 mg/ml. [NIAID ACTG 121]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous; intramuscular.
                          [Int Conf AIDS 1992 Jul 19-24;8(2): (abstract
                          no. PoB 3028)]
 SUBSTANCE DELIVERY DATA  STORAGE: Stored refrigerated at 2-8 C. [NIAID
                          ACTG 121]
 MANUFACTURERS            Genentech
 REFERENCES               Meng TC, Fischl MA, Cheeseman SH, Spector SA,
                          Resnick L, Boota A, Petrakis T, Wright B,
                          Richman DD. Combination therapy with
                          recombinant human soluble CD4-immunoglobulin
                          G and zidovudine in patients with HIV
                          infection: a phase I study. J Acquir Immune
                          Defic Syndr Hum Retrovirol. 1995 Feb
                          1;8(2):152-60.
 REFERENCES               Spear GT, Ghassemi M, Takefman DM. HIV-1
                          strain dependence of complement-mediated
                          virolysis induced by recombinant CD4-IgG
                          [letter]. J Acquir Immune Defic Syndr. 1994
                          Jan;7(1):100-1.
 REFERENCES               Clerici M, Yarchoan R, Blatt S, Hendrix CW,
                          Amman AJ, Broder S, Shearer GM. Effect of a
                          recombinant CD4-IgG on in vitro T helper cell
                          function: data from a phase I/II study of
                          patients with AIDS. J Infect Dis. 1993
                          Oct;168(4):1012-6.
 REFERENCES               Mulligan M, Duliege A. Nail C, Petrakis T,
                          Shaw G, Saag M. HIV-1 therapy with high dose
                          CD4-IgG. Int Conf AIDS 1993 Jun 6-11;9(1):470
                          (abstract no. PO-B26-2007).
 REFERENCES               Duliege AM, Shearer WT, Hammill H, Kline MW,
                          Minkoff HL, Izu A, Ammann A. Transplacental
                          transfer of rCD4-IgG given one week and
                          immediately prior to birth: safety and
                          pharmacokinetics in HIV-1 seropositive
                          pregnant women and their newborn infants. Int
                          Conf AIDS. 1992 Jul 19-24;8(2):B91 (abstract
                          no. PoB 3028).
 REFERENCES               Hodges TL, Kahn JO, Kaplan LD, Groopman JE,
                          Volberding PA, Amman AJ, Arri CJ, Bouvier LM,
                          Mordenti J, Izu AE, et al. Phase 1 study of
                          recombinant human CD4-immunoglobulin G
                          therapy of patients with AIDS and
                          AIDS-related complex. Antimicrob Agents
                          Chemother. 1991 Dec;35(12):2580-6.
 REFERENCES               Kahn J, Hassner A, Arri C, Coleman R, Kaplan
                          L, Volberding P, Ammann A, Abrams D. A phase
                          1 study of recombinant human CD4
                          immunoglobulin G (rCD4-IgG) in patients with
                          HIV-associated immune thrombocytopenic
                          purpura. Int Conf AIDS. 1991 Jun
                          16-21;7(2):221 (abstract no. W.B.2156).
 REFERENCES               Davey RT Jr, Davey V, Metcalf J, Zurlo J,
                          Polis M, Fallon J, Kovacs J, Zunich K, Ammann
                          A, Masur H, et al. Recombinant human
                          CD4-immunoglobulin (rCD4-IGG) in patients
                          with HIV-1 infection. Int Conf AIDS. 1991 Jun
                          16-21;7(2):212 (abstract no. W.B.2123).
 ENTRY MONTH              8910
 LAST REVISION DATE       960310
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
