Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001083
Status:
COMPLETED
Last Update Posted:
2021-11-04
First Post:
1999-11-02
Brief Title:
Comparison of New Anti-HIV Drug Combinations in HIV-Infected Children Who Have Taken Anti-HIV Drugs
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 Rolling Arm Master Protocol PRAM of Novel Antiretroviral Therapy in Stable Experienced HIV- Infected Children PRAM-1 ZDV3TC vs d4TRitonavir vs ZDV3TCRitonavir PRAM-1 Step 2 d4TNevirapineRitonavir PRAM-1 Step 3 d4TIndinavir vs ZDV3TCIndinavir
Status:
COMPLETED
Status Verified Date:
2021-10
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:
For PRAM-1 To evaluate zidovudine ZDV lamivudine 3TC vs stavudine d4T ritonavir vs ZDV 3TC ritonavir with respect to the change in plasma HIV-1 RNA copy number from baseline to 48 weeks AS PER AMENDMENT 1598 72 weeks AS PER AMENDMENT 71798 48 weeks in stable HIV-infected children with 16 weeks of prior continuous antiretroviral therapy To evaluate the safety and tolerance of ZDV 3TC vs d4T ritonavir vs ZDV 3TC ritonavir based upon laboratory and clinical toxicities
AS PER AMENDMENT 102097 For PRAM-1 Step 2 To evaluate d4T nevirapine ritonavir with respect to change in plasma HIV-1 RNA copy number from baseline to 48 weeks in children who have received at least 12 weeks of therapy on the PRAM-1 ZDV3TC arm and have over 10000 viral copies at weeks 12 24 or 36 To evaluate the safety and tolerance of d4T nevirapine ritonavir based upon laboratory and clinical toxicities AS PER AMENDMENT 102398 To evaluate safety and tolerance of a switch from d4T ritonavir vs ZDV 3TC ritonavir to d4T indinavir vs ZDV 3TC indinavir in stable HIV-infected children with RNA values 10000 copiesml For PRAM-1 Evidence supports combination therapy with 2 or more antiviral agents as beneficial in the long-term management of HIV The possibility exists that combination therapy may result in a synergistic or additive activity over a prolonged period of time Also hypothesized is that the development of resistance to individual agents will be developed if viral replication is significantly decreased
AS PER AMENDMENT 102097 For PRAM-1 Step 2 Interim analysis at 12 weeks on PRAM-1 indicates that the proportion of children reaching undetectable RNA levels on the ZDV 3TC arm is significantly less than the other two arms The protocol therefore has been modified Step 2 to permit children in the ZDV 3TC arm with RNA copy number 10000 the opportunity to change to a novel therapeutic regimen d4T nevirapine ritonavir
AS PER AMENDMENT 102097 For PRAM-1 Step 2 To evaluate d4T nevirapine ritonavir with respect to change in plasma HIV-1 RNA copy number from baseline to 48 weeks in children who have received at least 12 weeks of therapy on the PRAM-1 ZDV3TC arm and have over 10000 viral copies at weeks 12 24 or 36 To evaluate the safety and tolerance of d4T nevirapine ritonavir based upon laboratory and clinical toxicities AS PER AMENDMENT 102398 To evaluate safety and tolerance of a switch from d4T ritonavir vs ZDV 3TC ritonavir to d4T indinavir vs ZDV 3TC indinavir in stable HIV-infected children with RNA values 10000 copiesml For PRAM-1 Evidence supports combination therapy with 2 or more antiviral agents as beneficial in the long-term management of HIV The possibility exists that combination therapy may result in a synergistic or additive activity over a prolonged period of time Also hypothesized is that the development of resistance to individual agents will be developed if viral replication is significantly decreased
AS PER AMENDMENT 102097 For PRAM-1 Step 2 Interim analysis at 12 weeks on PRAM-1 indicates that the proportion of children reaching undetectable RNA levels on the ZDV 3TC arm is significantly less than the other two arms The protocol therefore has been modified Step 2 to permit children in the ZDV 3TC arm with RNA copy number 10000 the opportunity to change to a novel therapeutic regimen d4T nevirapine ritonavir
Detailed Description:
For PRAM-1 Evidence supports combination therapy with 2 or more antiviral agents as beneficial in the long-term management of HIV The possibility exists that combination therapy may result in a synergistic or additive activity over a prolonged period of time Also hypothesized is that the development of resistance to individual agents will be developed if viral replication is significantly decreased
AS PER AMENDMENT 102097 For PRAM-1 Step 2 Interim analysis at 12 weeks on PRAM-1 indicates that the proportion of children reaching undetectable RNA levels on the ZDV 3TC arm is significantly less than the other two arms The protocol therefore has been modified Step 2 to permit children in the ZDV 3TC arm with RNA copy number 10000 the opportunity to change to a novel therapeutic regimen d4T nevirapine ritonavir
The Master PRAM is a Phase II multicenter randomized open-label trial of a standard therapeutic regimen in current use versus experimental therapies administered over 48 weeks It is designed to allow new therapeutic arms to be studied as rolling screens through multiple generations of PRAM Each PRAM generation compares 2 novel therapeutic arms with a linking arm that allows for an indirect comparison of included therapies Once accrual to PRAM-1 is complete a new treatment comparison opens for accrual PRAM-2 The linking arm to be used in PRAM-2 is decided by the Pediatric Primary Scientific Committee PRAM-2 will continue to accrue patients while PRAM-1 patients continue therapy
For PRAM-1 This study compares the following three treatment arms
Arm I ZDV plus 3TC Arm II d4T plus ritonavir Arm III ZDV plus 3TC plus ritonavir Prior to randomization to one of the three arms patients are stratified based on CD4 percents either less than 15 or greater than or equal to 15 The first 8 patients randomized to Arms II and III participate in a real-time Phase I pharmacokinetic study 16 patients total After the first 45 15 per arm patients entered are followed for 24 weeks an interim analysis is done Patients are treated for 48 weeks AS PER AMENDMENT 1598 72 weeks
AS PER AMENDMENT 102097
PRAM-1 Step 2
Patients initially assigned to Arm I ZDV plus 3TC who have RNA values greater than 10000 copies at week 12 24 or 36 are assigned to switch protocol treatment to d4T ritonavir nevirapine Patients may enroll in Step 2 no later than week 38 of PRAM-1 AS PER AMENDMENT 1598 Patients initially assigned to Arm 1 with viral load greater than 100000 copies may also switch to Step 2 or discontinue therapy Patients originally assigned to Arms I or II with viral load greater than 10000 may continue their current drugs or discontinue study therapy those with viral load greater than 100000 should discontinue study drugs AS PER AMENDMENT 71798 PRAM-1 has been extended to permit long-term follow-up of clinically stable HIV-infected children for a total of 120 weeks Patients still on initial treatment assignment for all three treatment arms are eligible for this extension as are children from PRAM-1 Step 2 Step 2 is now closed to enrollment Patients on 3TCZDV who reach virologic failure must discontinue study therapy
AS PER AMENDMENT 102398 PRAM-1 Step 3 This amendment substitutes indinavir IDV capsules for ritonavir capsules in PRAM-1 The regimens will switch from d4T plus ritonavir versus ZDV plus 3TC plus ritonavir to d4T plus IDV versus ZDV plus 3TC plus IDV All patients will be followed for 48 weeks Patients eligible for this change in regimens are those taking ritonavir capsules who have RNA values less than or equal to 10000 copiesml as demonstrated by the most recent viral load test after at least 72 weeks on PRAM-1 Step I Twelve patients with RNA values less than or equal to 400 copiesml will immediately join the study 6 will receive d4T plus IDV and 6 will receive ZDV plus 3TC plus IDV Additional patients may be added based on toxicity and viral load results A total sample size of 53 evaluable patients 37 with RNA values less than or equal to 400 copiesml and 16 with RNA values of greater than 400 to 10000 copiesml is anticipated PRAM-1 Step 2 patients are not eligible for Step 3 PRAM-1 Step 2 patients currently taking liquid ritonavir should continue their study drug those taking ritonavir capsules will switch to liquid ritonavir or go off study
AS PER AMENDMENT 102097 For PRAM-1 Step 2 Interim analysis at 12 weeks on PRAM-1 indicates that the proportion of children reaching undetectable RNA levels on the ZDV 3TC arm is significantly less than the other two arms The protocol therefore has been modified Step 2 to permit children in the ZDV 3TC arm with RNA copy number 10000 the opportunity to change to a novel therapeutic regimen d4T nevirapine ritonavir
The Master PRAM is a Phase II multicenter randomized open-label trial of a standard therapeutic regimen in current use versus experimental therapies administered over 48 weeks It is designed to allow new therapeutic arms to be studied as rolling screens through multiple generations of PRAM Each PRAM generation compares 2 novel therapeutic arms with a linking arm that allows for an indirect comparison of included therapies Once accrual to PRAM-1 is complete a new treatment comparison opens for accrual PRAM-2 The linking arm to be used in PRAM-2 is decided by the Pediatric Primary Scientific Committee PRAM-2 will continue to accrue patients while PRAM-1 patients continue therapy
For PRAM-1 This study compares the following three treatment arms
Arm I ZDV plus 3TC Arm II d4T plus ritonavir Arm III ZDV plus 3TC plus ritonavir Prior to randomization to one of the three arms patients are stratified based on CD4 percents either less than 15 or greater than or equal to 15 The first 8 patients randomized to Arms II and III participate in a real-time Phase I pharmacokinetic study 16 patients total After the first 45 15 per arm patients entered are followed for 24 weeks an interim analysis is done Patients are treated for 48 weeks AS PER AMENDMENT 1598 72 weeks
AS PER AMENDMENT 102097
PRAM-1 Step 2
Patients initially assigned to Arm I ZDV plus 3TC who have RNA values greater than 10000 copies at week 12 24 or 36 are assigned to switch protocol treatment to d4T ritonavir nevirapine Patients may enroll in Step 2 no later than week 38 of PRAM-1 AS PER AMENDMENT 1598 Patients initially assigned to Arm 1 with viral load greater than 100000 copies may also switch to Step 2 or discontinue therapy Patients originally assigned to Arms I or II with viral load greater than 10000 may continue their current drugs or discontinue study therapy those with viral load greater than 100000 should discontinue study drugs AS PER AMENDMENT 71798 PRAM-1 has been extended to permit long-term follow-up of clinically stable HIV-infected children for a total of 120 weeks Patients still on initial treatment assignment for all three treatment arms are eligible for this extension as are children from PRAM-1 Step 2 Step 2 is now closed to enrollment Patients on 3TCZDV who reach virologic failure must discontinue study therapy
AS PER AMENDMENT 102398 PRAM-1 Step 3 This amendment substitutes indinavir IDV capsules for ritonavir capsules in PRAM-1 The regimens will switch from d4T plus ritonavir versus ZDV plus 3TC plus ritonavir to d4T plus IDV versus ZDV plus 3TC plus IDV All patients will be followed for 48 weeks Patients eligible for this change in regimens are those taking ritonavir capsules who have RNA values less than or equal to 10000 copiesml as demonstrated by the most recent viral load test after at least 72 weeks on PRAM-1 Step I Twelve patients with RNA values less than or equal to 400 copiesml will immediately join the study 6 will receive d4T plus IDV and 6 will receive ZDV plus 3TC plus IDV Additional patients may be added based on toxicity and viral load results A total sample size of 53 evaluable patients 37 with RNA values less than or equal to 400 copiesml and 16 with RNA values of greater than 400 to 10000 copiesml is anticipated PRAM-1 Step 2 patients are not eligible for Step 3 PRAM-1 Step 2 patients currently taking liquid ritonavir should continue their study drug those taking ritonavir capsules will switch to liquid ritonavir or go off study
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 |
|---|---|---|---|
| 11309 | REGISTRY | DAIDS ES | None |