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

Primary Purpose

Cytomegalovirus Retinitis, HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sevirumab
Foscarnet sodium
Ganciclovir
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cytomegalovirus Retinitis focused on measuring AIDS-Related Opportunistic Infections, Ganciclovir, Foscarnet, Acquired Immunodeficiency Syndrome, Antibodies, Monoclonal, Cytomegalovirus Retinitis

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.)

Sites / Locations

  • Alabama Therapeutics CRS
  • USC CRS
  • Santa Clara Valley Med. Ctr.
  • Stanford CRS
  • University of Colorado Hospital CRS
  • Univ. of Miami AIDS CRS
  • Queens Med. Ctr.
  • Univ. of Hawaii at Manoa, Leahi Hosp.
  • Cook County Hosp. CORE Ctr.
  • Rush Univ. Med. Ctr. ACTG CRS
  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
  • Massachusetts General Hospital ACTG CRS
  • Beth Israel Deaconess - East Campus A0102 CRS
  • Beth Israel Deaconess Med. Ctr., ACTG CRS
  • Washington U CRS
  • SUNY - Buffalo, Erie County Medical Ctr.
  • Univ. of Rochester ACTG CRS
  • Univ. of Cincinnati CRS
  • Case CRS
  • Hosp. of the Univ. of Pennsylvania CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Facet Biotech
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1. Study Identification

Unique Protocol Identification Number
NCT00001061
Brief Title
Comparison of Two Methods in the Treatment of Cytomegalovirus of the Eyes in Patients With AIDS
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 1998 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Facet Biotech

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Retinitis, HIV Infections
Keywords
AIDS-Related Opportunistic Infections, Ganciclovir, Foscarnet, Acquired Immunodeficiency Syndrome, Antibodies, Monoclonal, Cytomegalovirus Retinitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
167 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Sevirumab
Intervention Type
Drug
Intervention Name(s)
Foscarnet sodium
Intervention Type
Drug
Intervention Name(s)
Ganciclovir

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility 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.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pollard RB
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Borucki M
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Gnann J
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Hirsch MS
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Therapeutics CRS
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
USC CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
900331079
Country
United States
Facility Name
Santa Clara Valley Med. Ctr.
City
San Jose
State/Province
California
ZIP/Postal Code
951282699
Country
United States
Facility Name
Stanford CRS
City
Stanford
State/Province
California
ZIP/Postal Code
943055107
Country
United States
Facility Name
University of Colorado Hospital CRS
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Univ. of Miami AIDS CRS
City
Miami
State/Province
Florida
ZIP/Postal Code
331361013
Country
United States
Facility Name
Queens Med. Ctr.
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Univ. of Hawaii at Manoa, Leahi Hosp.
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Cook County Hosp. CORE Ctr.
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Rush Univ. Med. Ctr. ACTG CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
462025250
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess - East Campus A0102 CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Beth Israel Deaconess Med. Ctr., ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
SUNY - Buffalo, Erie County Medical Ctr.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Univ. of Cincinnati CRS
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
452670405
Country
United States
Facility Name
Case CRS
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Hosp. of the Univ. of Pennsylvania CRS
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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)
Results Reference
background
PubMed Identifier
11363844
Citation
CMV retinitis study aborted. GMHC Treat Issues. 1996 Sep;10(9):8.
Results Reference
background
PubMed Identifier
15498605
Citation
Borucki MJ, Spritzler J, Asmuth DM, Gnann J, Hirsch MS, Nokta M, Aweeka F, Nadler PI, Sattler F, Alston B, Nevin TT, Owens S, Waterman K, Hubbard L, Caliendo A, Pollard RB; AACTG 266 Team. A phase II, double-masked, randomized, placebo-controlled evaluation of a human monoclonal anti-Cytomegalovirus antibody (MSL-109) in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with Cytomegalovirus retinitis. Antiviral Res. 2004 Nov;64(2):103-11. doi: 10.1016/j.antiviral.2004.06.012.
Results Reference
result

Learn more about this trial

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

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