Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00000870
Status:
COMPLETED
Last Update Posted:
2012-05-21
First Post:
1999-11-02
Brief Title:
A Phase II Study of Intermittent Recombinant Human Interleukin-2 rhIL-2 by Intravenous or Subcutaneous Administration in Subjects With HIV Infection on Highly Active Antiretroviral Therapy HAART Compared to HAART Alone
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
A Phase II Study of Intermittent Recombinant Human Interleukin-2 rhIL-2 by Intravenous or Subcutaneous Administration in Subjects With HIV Infection on Highly Active Antiretroviral Therapy HAART Compared to HAART Alone
Status:
COMPLETED
Status Verified Date:
2012-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To compare two different routes of intermittently administered rhIL-2 with a highly active antiretroviral regimen HAART to HAART alone The comparison is based on the following proportion of patients achieving at least 50-percent increase in CD4 counts above prerandomization baseline values after 1 year of rhIL-2 and the rate of change in CD4 counts To compare the safety and tolerance of these regimens and their effect on quality of life To assess the effects of rhIL-2 when combined with HAART on changes in immune cell phenotypes and function and on HIV viral load and the rate of antiviral drug resistance development
The poor responsiveness of late stage HIV-infected patients to rhIL-2 is thought to occur because of low T cell regenerative capacity and high viral burden If means were available to effectively suppress virus replication the indigenous immune restorative responses of the host may be further stimulated and enhanced by rhIL-2 The use of protease inhibitors with nucleoside-analogue combination regimens appears to be most effective in controlling virus replication High-dose intermittent rhIL-2 administered either intravenously or subcutaneously has been shown to be effective in inducing CD4 responses in a number of studies
The poor responsiveness of late stage HIV-infected patients to rhIL-2 is thought to occur because of low T cell regenerative capacity and high viral burden If means were available to effectively suppress virus replication the indigenous immune restorative responses of the host may be further stimulated and enhanced by rhIL-2 The use of protease inhibitors with nucleoside-analogue combination regimens appears to be most effective in controlling virus replication High-dose intermittent rhIL-2 administered either intravenously or subcutaneously has been shown to be effective in inducing CD4 responses in a number of studies
Detailed Description:
The poor responsiveness of late stage HIV-infected patients to rhIL-2 is thought to occur because of low T cell regenerative capacity and high viral burden If means were available to effectively suppress virus replication the indigenous immune restorative responses of the host may be further stimulated and enhanced by rhIL-2 The use of protease inhibitors with nucleoside-analogue combination regimens appears to be most effective in controlling virus replication High-dose intermittent rhIL-2 administered either intravenously or subcutaneously has been shown to be effective in inducing CD4 responses in a number of studies
All patients receive HAART consisting of two nucleoside analogues at least one of which is new to the patient and the protease inhibitor indinavir for 12 weeks At Week 10 an HIV RNA is done Patients with more than 5000 copiesml are taken off the study Patients with 5000 copiesml or less continue on the study and are stratified by their antiretroviral combination and randomized to one of three treatment arms Patients on Arm I continue HAART alone for an additional 72 weeks Patients on Arm II continue HAART plus intermittent rhIL-2 by continuous intravenous CIV administration for an additional 72 weeks 9 courses Patients who achieve both at least a 25-percent increase and at least a 100-cell increase in CD4 count above prerandomization baseline switch to subcutaneously administered rhIL-2 after 3 courses 24 weeks or 6 courses 48 weeks of CIV therapy for the remainder of their treatment course Patients on Arm III continue HAART plus subcutaneous rhIL-2 for an additional 72 weeks 9 courses AS PER AMENDMENT 103197 When protocol ACTG 928 is activated patients randomized on ACTG 328 are stratified based on whether or not they have registered on ACTG 928 AS PER AMENDMENT 103098 For the 4 weeks immediately prior to randomization patients must receive continuous HAART therapy Exceptions may be made by the protocol chair for short ie less than 48 hours interruptions of antiretroviral therapy during this period Also per this amendment two substudies have been added A5033s and A5046s Patients who choose to enroll in substudy A5046s must do so at Week 60 of ACTG 328 However if the patient is already beyond Week 60 but not beyond Week 84 of ACTG 328 when A5046s becomes available heshe is still encouraged to participate in A5046s For such patients ACTG 328 treatment is extended beyond Week 84 until the patient completes 24 weeks of A5046s AS PER AMENDMENT 42399 Patients who choose to enroll in substudy A5046s must do so at or after Week 64 of ACTG 328 and no later than Week 104 AS PER AMENDMENT 91699 Patients choosing to enroll in A5046s must do so at or after Week 64 and no later than Week 128 AS PER AMENDMENT 12299 A 16-week treatment extension is provided for patients who have reached Week 84 of ACTG 328 and intend to enroll in either A5051 or A5046s which are currently not available AS PER AMENDMENT 42399 Therapy is extended for 24 weeks beyond the original 84 weeks Study treatment for patients awaiting co-enrollment into A5046s continues for up to 20 weeks until co-enrollment and then until completion of A5046s 24 weeks Study treatment continues for 24 weeks beyond Week 84 for patients who are awaiting enrollment in A5051 or who have chosen not to participate in A5046s AS PER AMENDMENT 6399 A 24-week treatment extension has been added for patients who have reached Week 100 and intend to enroll in A5046s AS PER AMENDMENT 91699 A treatment extension has been added for up to 44 weeks beyond Week 84 and through completion of A5046s 24 weeks for on-studyon-study treatment patients who intend to co-enroll in A5046s Patients who intend to enroll in A5051 or A5046s and remain on ACTG 328 study treatment are eligible for the treatment extension from Week 84 to Week 108 Patients who intend to co-enroll in A5046s and remain on ACTG 328 study treatment are eligible for the treatment extension from Week 108 to Week 128 All patients who are awaiting co-enrollment in A5046s must continue to receive their assigned ACTG 328 treatment regimen Study treatment for ACTG 328 patients awaiting co-enrollment into A5046s will continue for up to 44 weeks and until completion of A5046s 24 weeks Each patient is followed every 8 weeks for the duration of the treatment extension period to monitor for safety and to collect cells and plasma for storage No substudy evaluations are performed during the 24-week extension
All patients receive HAART consisting of two nucleoside analogues at least one of which is new to the patient and the protease inhibitor indinavir for 12 weeks At Week 10 an HIV RNA is done Patients with more than 5000 copiesml are taken off the study Patients with 5000 copiesml or less continue on the study and are stratified by their antiretroviral combination and randomized to one of three treatment arms Patients on Arm I continue HAART alone for an additional 72 weeks Patients on Arm II continue HAART plus intermittent rhIL-2 by continuous intravenous CIV administration for an additional 72 weeks 9 courses Patients who achieve both at least a 25-percent increase and at least a 100-cell increase in CD4 count above prerandomization baseline switch to subcutaneously administered rhIL-2 after 3 courses 24 weeks or 6 courses 48 weeks of CIV therapy for the remainder of their treatment course Patients on Arm III continue HAART plus subcutaneous rhIL-2 for an additional 72 weeks 9 courses AS PER AMENDMENT 103197 When protocol ACTG 928 is activated patients randomized on ACTG 328 are stratified based on whether or not they have registered on ACTG 928 AS PER AMENDMENT 103098 For the 4 weeks immediately prior to randomization patients must receive continuous HAART therapy Exceptions may be made by the protocol chair for short ie less than 48 hours interruptions of antiretroviral therapy during this period Also per this amendment two substudies have been added A5033s and A5046s Patients who choose to enroll in substudy A5046s must do so at Week 60 of ACTG 328 However if the patient is already beyond Week 60 but not beyond Week 84 of ACTG 328 when A5046s becomes available heshe is still encouraged to participate in A5046s For such patients ACTG 328 treatment is extended beyond Week 84 until the patient completes 24 weeks of A5046s AS PER AMENDMENT 42399 Patients who choose to enroll in substudy A5046s must do so at or after Week 64 of ACTG 328 and no later than Week 104 AS PER AMENDMENT 91699 Patients choosing to enroll in A5046s must do so at or after Week 64 and no later than Week 128 AS PER AMENDMENT 12299 A 16-week treatment extension is provided for patients who have reached Week 84 of ACTG 328 and intend to enroll in either A5051 or A5046s which are currently not available AS PER AMENDMENT 42399 Therapy is extended for 24 weeks beyond the original 84 weeks Study treatment for patients awaiting co-enrollment into A5046s continues for up to 20 weeks until co-enrollment and then until completion of A5046s 24 weeks Study treatment continues for 24 weeks beyond Week 84 for patients who are awaiting enrollment in A5051 or who have chosen not to participate in A5046s AS PER AMENDMENT 6399 A 24-week treatment extension has been added for patients who have reached Week 100 and intend to enroll in A5046s AS PER AMENDMENT 91699 A treatment extension has been added for up to 44 weeks beyond Week 84 and through completion of A5046s 24 weeks for on-studyon-study treatment patients who intend to co-enroll in A5046s Patients who intend to enroll in A5051 or A5046s and remain on ACTG 328 study treatment are eligible for the treatment extension from Week 84 to Week 108 Patients who intend to co-enroll in A5046s and remain on ACTG 328 study treatment are eligible for the treatment extension from Week 108 to Week 128 All patients who are awaiting co-enrollment in A5046s must continue to receive their assigned ACTG 328 treatment regimen Study treatment for ACTG 328 patients awaiting co-enrollment into A5046s will continue for up to 44 weeks and until completion of A5046s 24 weeks Each patient is followed every 8 weeks for the duration of the treatment extension period to monitor for safety and to collect cells and plasma for storage No substudy evaluations are performed during the 24-week extension
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| Substudy ACTG A5094s | Registry Identifier | DAIDS ES Registry Number | None |
| 10689 | REGISTRY | None | None |
| Substudy ACTG 872 | None | None | None |
| Substudy ACTG 873 | None | None | None |
| Substudy ACTG 874 | None | None | None |
| Substudy ACTG A5033s | None | None | None |