Clinical trial NCT00000663: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Recombinant Proteins
Injections, Intravenous
IgG
Drug Evaluation
Acquired Immunodeficiency Syndrome
Antigens, CD4
Carrier Proteins
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Genentech, Inc.
First posted: 2001-08-31
Enrollment: 18
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Treatment Ctr
state: California
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Chicago
country: United States
facility: Cook County Hosp
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ Med School
state: Louisiana
city: Great Neck
country: United States
facility: North Shore Univ Hosp
state: New York
city: New York
country: United States
facility: Columbia Univ Babies' Hosp
state: New York
city: Houston
country: United States
facility: Texas Children's Hosp / Baylor Univ
state: Texas
Study officials:
name: R Yogev
role: STUDY_CHAIR
name: W Shearer
role: STUDY_CHAIR
References:
citation: 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)
citation: 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.