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Recombinant Soluble CD4 Therapy in Patients with the Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related Complex
A Phase I-II Escalating Dosage Trial
- Robert T. Schooley, MD;
- Thomas C. Merigan, MD;
- Paula Gaut, MD;
- Martin S. Hirsch, MD;
- Mark Holodniy, MD;
- Theresa Flynn, RN;
- Susan Liu, BS;
- Roy E. Byington, BS;
- Stuart Henochowicz, MD;
- Ed Gubish, PhD;
- David Spriggs, MD;
- Donald Kufe, MD;
- John Schindler, PhD;
- Adrian Dawson, MBchB;
- David Thomas, PhD;
- Donald G. Hanson, PhD;
- Bruce Letwin, PhD;
- Theresa Liu, PhD;
- Jack Gulinello;
- Sally Kennedy, BA;
- Richard Fisher, PhD; and
- David D. Ho, MD
Abstract
Study Objective: To study the safety and pharmacokinetics and to derive preliminary evidence on surrogate indicators of efficacy of recombinant soluble CD4 (rsCD4) in patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex.
Design: Open label, escalating dosage, phase I-II tolerance trial.
Setting: Massachusetts General Hospital, Cedars-Sinai Medical Center, and Stanford University Medical School, three tertiary care institutions and members of the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.
Instructions: Cohorts of 3 to 11 patients received rsCD4 by intravenous infusion or intramuscular injection in dosages of up to 30 mg per day for 28 days.
Measurements and Main Results: Recombinant soluble CD4 was tolerated by these patients with no significant clinical or immunologic toxicities. Serum levels of rsCD4 in patients receiving doses of 9 or 30 mg per day administered intramuscularly were in the range of rsCD4 concentrations required to inhibit replication of human immunodeficiency virus 1 (HIV-1) in vitro. A decline in serum HIV-1 p24 antigen was seen in patients receiving 30 mg of rsCD4 daily, but no such changes were noted at lower dosages.
Conclusions: Recombinant soluble CD4 is well tolerated by patients with AIDS or advanced AIDS-related complex. Our study has also provided preliminary evidence of antiviral activity of rsCD4 in vivo. Our data suggest that further trials of receptor-based therapies against HIV-1 are warranted.
Article and Author Information
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From Massachusetts General Hospital and Dana Farber Cancer Institute, Boston, Massachusetts; Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, California; Stanford University School of Medicine, Palo Alto, California; National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; and Biogen Inc., Cambridge, Massachusetts. For current author addresses, see end of text.
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Grant Support: In part by a NIAID National Collaborative Drug Discovery Group Cooperative Agreement AI25662, the NIAID AIDS Clinical Trials Group AI27659, AI2766004, AI27666, and Biogen, Inc.
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Requests for Reprints: Robert T. Schooley, MD, Infectious Disease Unit, Massachusetts General Hospital, Boston, MA 02114.
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Current Author Addresses: Drs. Schooley and Hirsch, Ms. Flynn and Mr. Byington: Infectious Disease Unit, Massachusetts General Hospital, Boston, MA 02114.
Drs. Merigan and Holodniy: Infectious Disease Division, Stanford University School of Medicine, Palo Alto, CA 94305.
Drs. Ho and Gaut and Ms. Liu: Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Infectious Disease Division, Los Angeles, CA 90048. Dr. Henochowicz: 3301 New Mexico Avenue, NW, Suite 302, Washington, D.C. 20016.
Dr. Gubish: Division of AIDS, NIAID, 6003 Executive Boulevard, Bethesda, MD 20892.
Drs. Spriggs and Kufe: Dana Farber Cancer Institute, 44 Binney Street, Room 1730, Dana Building, Boston, MA 02115.
Drs. Schindler, Dawson, Thomas, Hanson, Letwin, Liu, and Fisher and Mr. Gulinello and Ms. Kennedy: Biogen Incorporated, 14 Cambridge Center, Cambridge, MA 02142.
- ©1990 American College of Physicians
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