Comparison of Two Methods in the Treatment of Cytomegalovirus of the Eyes in Patients With AIDS

This study has been completed.
Sponsor:
Collaborator:
Facet Biotech
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001061
First received: November 2, 1999
Last updated: May 8, 2012
Last verified: May 2012
  Purpose

To evaluate the effect of MSL 109, human monoclonal anti-cytomegalovirus (CMV) antibody, on time to progression of CMV retinitis. To determine the safety and pharmacokinetic profile of MS 109. To evaluate the relationship between pharmacokinetic measurements of MSL 109 and efficacy and virologic markers.

Therapeutic agents currently available for CMV retinitis are limited by their inherent toxicities and short half-lives which require frequent intravenous dosing. Alternatively, MSL 109 has demonstrated safety and effectiveness in neutralizing CMV isolates at concentrations easily maintained in AIDS patients.


Condition Intervention Phase
Cytomegalovirus Retinitis
HIV Infections
Drug: Sevirumab
Drug: Foscarnet sodium
Drug: Ganciclovir
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase II, Double-Masked, Randomized, Placebo-Controlled Evaluation of Standard Therapy vs. Standard Therapy Combined With Human Monoclonal Anti-Cytomegalovirus Antibody (MSL 109) in the Therapy of AIDS Patients With Cytomegalovirus (CMV) Retinitis

Resource links provided by NLM:


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

Estimated Enrollment: 167
Study Completion Date: March 1998
Detailed Description:

Therapeutic agents currently available for CMV retinitis are limited by their inherent toxicities and short half-lives which require frequent intravenous dosing. Alternatively, MSL 109 has demonstrated safety and effectiveness in neutralizing CMV isolates at concentrations easily maintained in AIDS patients.

Patients receive induction therapy with intravenous ganciclovir or foscarnet daily for 14 days, then are placed on standard maintenance therapy with the induction drug for at least 11 months or until progression. Patients are randomized to receive 1 of 2 doses of MLS 109 or placebo every 2 weeks during induction and maintenance. They are followed at weeks 2 and 4 and every 4 weeks thereafter for 40 weeks. Patients who have not progressed by week 40 continue study drug with follow-up every 2 months until CMV progression occurs. AS PER AMENDMENT 11/29/96: Enrollment onto the current study has been discontinued. To study the enhancement of humoral immunity, a high-dose cohort has been added. Patients are now randomized to MSL 109 given at a higher dose or placebo administered at the same intervals as before. Randomization is weighted 2:1 in favor of high-dose MSL 109. Interim analyses will be performed to provide for early discontinuation, as indicated. Patients randomized under earlier versions may continue on their original study assignment if a study endpoint has not been reached.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • G-CSF and GM-CSF.
  • Antiretroviral therapy.

Patients must have:

  • HIV infection.
  • First episode of CMV retinitis.
  • No prior end-organ CMV disease - PER AMENDMENT 4/25/96: No prior end organ CMV disease within the past 6 months. Subjects who have been prophylaxed with oral ganciclovir and develop an episode of CMV retinitis are eligible.
  • No active AIDS-defining opportunistic infection or malignancy that requires nephrotoxic or myelosuppressive therapy.
  • Life expectancy of at least 6 months.
  • Consent of parent or guardian if less than 18 years of age.

NOTE:

  • This protocol is approved for prisoner participation.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • PER AMENDMENT 4/25/96: Retinal detachment not scheduled for surgical repair, in all eyes meeting other eligibility criteria. (Was written as - No current retinal detachment (although old retinal detachments unrelated to HIV infection which have been repaired are permitted).
  • Corneal, lens, or vitreous opacification that precludes funduscopic exam.
  • Clinically significant pulmonary or neurologic impairment, such as intubation or coma. (Patients with a CNS mass or history of seizure disorder may enroll.)
  • Tuberculous, diabetic, or hypertensive retinopathy, or other retinal lesions that would interfere with measurements of response or progression.
  • Known hypersensitivity to the study drugs.

PER AMENDMENT 4/25/96:

  • Presence of CMV retinal lesions that are only in areas of the retina which cannot be photographed.

Concurrent Medication:

Excluded:

  • Immunomodulators, biologic response modifiers, interferon, or investigational agents that may influence course of CMV infection.
  • Systemic acyclovir or any nephrotoxic agent, specifically aminoglycosides, amphotericin B, and parenteral pentamidines.
  • Any concomitant therapy that would preclude use of cidofovir, foscarnet or ganciclovir.

Prior Medication:

Excluded: PER AMENDMENT 4/25/96:

  • Use of IV ganciclovir, foscarnet or cidofovir within 6 months prior to study enrollment. (Was written - Ganciclovir or foscarnet for non-CMV herpes infections within 6 months prior to study entry.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001061

Locations
United States, Alabama
Alabama Therapeutics CRS
Birmingham, Alabama, United States, 35294
United States, California
USC CRS
Los Angeles, California, United States, 900331079
Santa Clara Valley Med. Ctr.
San Jose, California, United States, 951282699
Stanford CRS
Stanford, California, United States, 943055107
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 331361013
United States, Hawaii
Queens Med. Ctr.
Honolulu, Hawaii, United States, 96816
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Illinois
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 462025250
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 452670405
Case CRS
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Facet Biotech
Investigators
Study Chair: Pollard RB
Study Chair: Borucki M
Study Chair: Gnann J
Study Chair: Hirsch MS
  More Information

Additional Information:
Publications:
Borucki M, Spritzler J, Gnann J, Hirsch M, Nokta M, Aweeka F, Pollard R. A phase II double masked, placebo-controlled evaluation of standard therapy vs standard therapy combined with human monoclonal anti-cytomegalovirus antibody (MSL-109) in the therapy of AIDS patients with newly diagnosed cytomegalovirus (CMV) retinitis in ACTG 266. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:154 (abstract no 460)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001061     History of Changes
Other Study ID Numbers: ACTG 266, 11242
Study First Received: November 2, 1999
Last Updated: May 8, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Ganciclovir
Foscarnet
Acquired Immunodeficiency Syndrome
Antibodies, Monoclonal
Cytomegalovirus Retinitis

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Retinitis
Cytomegalovirus Retinitis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Retinal Diseases
Eye Diseases
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Eye Infections, Viral
Eye Infections
Foscarnet
Phosphonoacetic Acid
Ganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014