A Phase I Study of the Safety and Pharmacokinetics of Recombinant CD4 Immunoglobulin G (rCD4-IgG) in Infants and Children With Documented HIV-1 Infection

To determine the safety profile, assess pharmacokinetic properties (blood levels), and obtain preliminary indication of the antiviral and immunologic effects of recombinant CD4 immunoglobulin G (CD4-IgG).

CD4-IgG may be effective in blocking HIV transmission and spread, that is, CD4-IgG has antiviral effects. Studies done in adult patients with AIDS and AIDS related complex (ARC) have shown that rCD4 can be safely administered by intravenous bolus, intramuscular or subcutaneous injection. No serious or dose-limiting, drug-related toxicities have been observed to date.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: CD4-IgG

Detailed Description

CD4-IgG may be effective in blocking HIV transmission and spread, that is, CD4-IgG has antiviral effects. Studies done in adult patients with AIDS and AIDS related complex (ARC) have shown that rCD4 can be safely administered by intravenous bolus, intramuscular or subcutaneous injection. No serious or dose-limiting, drug-related toxicities have been observed to date.

Patients receive one intravenous injection the first week, followed by a 6 day washout period and then intravenous injections on a twice weekly basis from week 2 to week 12. The dose per injection may vary. The study evaluates 2 groups: (1) Children 3 months to 5 years of age; (2) Infants 0-3 months of age.

• Study Type: Interventional
• Enrollment: 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92103
      • UCSD Treatment Ctr
  • Florida
    • Miami, Florida, United States, 33136
      • Univ of Miami School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Univ Med School
  • New York
    • Great Neck, New York, United States, 11021
      • North Shore Univ Hosp
    • New York, New York, United States, 10032
      • Columbia Univ Babies' Hosp
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hosp / Baylor Univ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients must have the following:

• HIV-1 infection, or if less than 15 months old, born to mother with HIV-1 infection.
• Legally qualified guardian with the ability to sign a written, informed consent form.
• Willingness to abstain from all other experimental therapy for HIV-1 infection during the first 12 weeks of the study period.
• Anticipated life expectancy of at least 3 months.

Prior Medication:

Allowed:

• Prophylactic anti-Pneumocystis carinii pneumonia (PCP) or antifungal therapy.
• Gamma globulin as prophylaxis for measles and varicella.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Past or present history of neurological abnormalities including withdrawal syndrome or seizures.
• Past or present history of any serious active opportunistic infection including Pneumocystis carinii pneumonia (PCP).
• Echocardiogram values > 2 standard deviations from normal.
• Hematologic, renal, or hepatic insufficiency.

Concurrent Medication:

Excluded:

• Zidovudine (AZT).
• Intravenous gamma globulin (IVIG) except as prophylaxis for measles and varicella.
• Cancer chemotherapy.
• Corticosteroids.
• Other known immunomodulatory agents.
• Other experimental therapy not specifically allowed.

Patients with the following are excluded:

• Hematologic, renal, or hepatic insufficiency.
• Past or present history of any serious active opportunistic infection.

Prior Medication:

Excluded for a minimum of 3 weeks prior to study entry:

• Zidovudine (AZT).
• Intravenous gamma globulin (IVIG).
• Cancer chemotherapy.
• Immunomodulatory agents.
• Acyclovir and other experimental therapy.

Risk Behavior:

Excluded:

• Patients born to substance abusing mothers (including alcohol) during the pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Genentech, Inc.
• Investigators: Study Chair: W Shearer; Study Chair: R Yogev

Publications and helpful links

General Publications

• Weintrub P, Yogev R, Conner E, Wilfert K, Mordenti J, Ammann AJ. Safety and pharmacokinetics of recombinant CD4 in children with HIV infection. Int Conf AIDS. 1990 Jun 20-23;6(2):95 (abstract no FB23)
• Shearer WT, Israel RJ, Starr S, Fletcher CV, Wara D, Rathore M, Church J, DeVille J, Fenton T, Graham B, Samson P, Staprans S, McNamara J, Moye J, Maddon PJ, Olson WC. Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: phase 1/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team. J Infect Dis. 2000 Dec;182(6):1774-9. doi: 10.1086/317622. Epub 2000 Oct 27.

Study record dates

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: October 1, 1996

More Information

Terms related to this study

• Keywords: Acquired Immunodeficiency Syndrome; Drug Evaluation; Recombinant Proteins; IgG; Injections, Intravenous; Antigens, CD4; Carrier Proteins
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Physiological Effects of Drugs; Immunologic Factors; CD4 Immunoadhesins
• Other Study ID Numbers: ACTG 139; D0172g