A Phase I, Dose-Escalating Safety and Tolerance Study of sCD4-PE40 in HIV-Infected Persons - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators:	Upjohn Glaxo Wellcome
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000743

Purpose

To determine the safety and tolerance of alvircept sudotox (sCD4-PE40) given at various dosing intervals and concentrations. To determine whether frequent dosing alters immunogenicity or toxicity. To obtain preliminary data to ascertain whether sCD4-PE40 has activity against HIV in human subjects. To determine whether there is any additive toxicity with combined use of sCD4-PE40 and zidovudine (AZT).

There is some evidence that AZT and sCD4-PE40, an experimental drug with anti-HIV activity previously demonstrated in vitro, may produce increased benefit when used in combination in HIV-infected patients.

Condition	Intervention	Phase
HIV Infections	Drug: Alvircept sudotox Drug: Zidovudine	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label, Safety Study
Official Title:	A Phase I, Dose-Escalating Safety and Tolerance Study of sCD4-PE40 in HIV-Infected Persons

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Zidovudine Alvircept sudotox

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

64

Detailed Description:

There is some evidence that AZT and sCD4-PE40, an experimental drug with anti-HIV activity previously demonstrated in vitro, may produce increased benefit when used in combination in HIV-infected patients.

Cohorts of six patients each receive escalating doses of sCD4-PE40 in a single IV weekly dose for 8 weeks. All six patients at a given dose must complete 2 weeks of therapy without dose-limiting toxicity before dose escalation in subsequent patient cohorts may occur. The MTD is defined as the dose of sCD4-PE40 immediately below that at which two or more of six patients experience grade 3 or higher toxicity or one or more of six patients experience grade 4 toxicity. After the MTD for the once-weekly schedule is reached, subsequent cohorts receive escalated doses of sCD4-PE40 on a 5x weekly schedule for approximately 4 weeks, in an attempt to establish the MTD for that schedule. When an MTD has been determined for the 5x weekly schedule, and if antiretroviral activity is observed, six additional patients receive this dose combined with AZT for 4 weeks.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

PCP prophylaxis with aerosolized pentamidine, trimethoprim / sulfamethoxazole, or dapsone.
Clotrimazole troches or nystatin oral suspension for oral candidiasis.
Acyclovir (up to 1000 mg/day for 10 days) for herpes lesions.
Erythropoietin.

Patients must have:

Documented HIV infection by ELISA confirmed by a second method. If a prior diagnosis of AIDS has not been established by CDC criteria, a confirmatory test is required.
CD4 count = or < 300 cells/mm3 within 4 weeks prior to study entry.
Positive p24 antigen.

Patients entering the AZT portion of the study only:

Must be AZT naive or have had less than 2 months of AZT therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

Hemophilia.
Acute medical problems (including active opportunistic infections such as active cryptococcosis, Pneumocystis carinii, herpes zoster, histoplasmosis, or CMV or nonopportunistic diseases including liver disease, renal disease, or orthostatic hypotension) at time of study entry.
Active pulmonary disease.
Chronic active hepatitis B surface antigenemia or unstable hepatitis C.
Current diagnosis of malignancy for which systemic therapy would be required during the study.
Inadequate intravenous access.

Concurrent Medication:

Excluded:

Hepatotoxic agents.
Other antiretroviral or immunomodulator agents (including but not limited to AZT, ddI, ddC, interferon, and steroids).
Other investigational drugs.
Systemic therapy for malignancy.
G-CSF and GM-CSF.

Prior Medication:

Excluded:

Other antiretroviral or immunomodulator agents (including but not limited to AZT, ddI, ddC, interferon, and steroids) within 4 weeks prior to study entry.
Ribavirin within 90 days prior to study entry.
Cytotoxic chemotherapy within one month prior to study entry.
Prior soluble CD4 or CD4-Ig.

Excluded in patients entering the AZT portion of the study:

More than 2 months of prior AZT therapy.

Current active alcoholism or active substance abuse.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000743

Locations

United States, California
UCLA CARE Ctr
Los Angeles, California, United States, 90095
United States, District of Columbia
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
United States, Louisiana
Tulane Univ Med School
New Orleans, Louisiana, United States, 701122699
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
State of MD Div of Corrections / Johns Hopkins Univ Hosp
Baltimore, Maryland, United States, 212052196
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Upjohn

Glaxo Wellcome

Investigators

Study Chair:

van der Horst C

More Information

Additional Information:

Click here for more information about Zidovudine This link exits the ClinicalTrials.gov site

Publications:

Alston B, Mitsuyasu R, Lertora J, Flexner C, Timpone J, van der Horst C. Phase I study of sCd4-PE40 in HIV infected persons: (ACTG 201). Int Conf AIDS. 1993 Jun 6-11;9(1):498 (abstract no PO-B29-2178)

Fiscus S, et al. Safety and efficacy of soluble CD4-pseudomonas exotoxin 40 in HIV infected individuals (ACTG 201). Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:70

Study ID Numbers:	ACTG 201
Study First Received:	November 2, 1999
Last Updated:	July 29, 2008
ClinicalTrials.gov Identifier:	NCT00000743 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Recombinant Proteins
Acquired Immunodeficiency Syndrome
Antigens, CD4
AIDS-Related Complex
Zidovudine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Zidovudine
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Immunologic Deficiency Syndromes
Reverse Transcriptase Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on November 27, 2009