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A5288/MULTI-OCTAVE: Management Using Latest Technologies to Optimize Combination Therapy After Viral Failure (MULTI-OCTAVE)

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ClinicalTrials.gov Identifier: NCT01641367
Recruitment Status : Active, not recruiting
First Posted : July 16, 2012
Results First Posted : February 20, 2018
Last Update Posted : February 20, 2018
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
AbbVie
Gilead Sciences
Janssen Pharmaceuticals
Merck Sharp & Dohme Corp.
Dimagi Inc.
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: HIV-1 Infection
Interventions: Drug: Darunavir
Drug: Etravirine
Drug: Emtricitabine/tenofovir disoproxil fumarate
Drug: Raltegravir
Drug: Second line ART regimens - based on a boosted protease inhibitor (bPI) plus two nucleoside analogues (NRTIs)
Drug: Study provided drugs according to patient resistance profile (DRV, ETR, RTV, FTC/TDF) + any in country available drug as applicable & available
Other: SOC adherence versus SOC+CPI adherence

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled between 22FEB2013 and 21DEC2015 at non-US based clinical research sites. Participants were followed until 48 weeks after the last participant enrolled to Step 1.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Experimental: Cohort A

Under Protocol version 1.0:

No resistance to NRTIs, PIs, or NNRTI

• Continue current second-line regimen; NRTIs could be modified

Changed under LOA#2 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue second-line regimen which may include LPV/RTV; NRTIs could be modified

Changed under LOA#3 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.

Experimental: Sub-cohort B1

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • Best available NRTIs, RAL, & DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• Best available NRTIs, RAL, & DRV/RTV

Experimental: Sub-cohort B2

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• ETR, RAL, and DRV/RTV

Experimental: Sub-cohort B3

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening)

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Experimental: Cohort C

Under Protocol version 1.0:

Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) • Best available NRTIs, RAL, and DRV/RTV

Changed under LOA#2:

Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure

• Best available NRTIs, RAL, and DRV/RTV

Experimental: Cohort D

Under Protocol version 1.0:

Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure:

• Best available regimen, including study-provided and any locally available drugs

Changed under LOA#2:

Not eligible for Cohort A, B, or C:

• Best available regimen, including study-provided and any locally available drugs

Updated under protocol v2.0:

• Best available ART regimen, including study-provided and any locally available non-experimental drugs


Participant Flow:   Overall Study
    Experimental: Cohort A   Experimental: Sub-cohort B1   Experimental: Sub-cohort B2   Experimental: Sub-cohort B3   Experimental: Cohort C   Experimental: Cohort D
STARTED   287   74   72   8   70   34 
COMPLETED [1]   253   73   68   8   67   33 
NOT COMPLETED   34   1   4   0   3   1 
Death                18                1                2                0                1                1 
Lost to Follow-up                16                0                2                0                2                0 
[1] Completed the study = participant must have had the last step 1/2 visit between 22NOV2016-13FEB2017



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled participants.

Reporting Groups
  Description
Experimental: Cohort A

Under Protocol version 1.0:

No resistance to NRTIs, PIs, or NNRTI

• Continue current second-line regimen; NRTIs could be modified

Changed under LOA#2 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure • Continue second-line regimen which may include LPV/RTV; NRTIs could be modified

Changed under LOA#3 to:

No LPV/RTV resistance and susceptible to at least one NRTI, regardless of NNRTI resistance or prior RAL exposure

• Continue PI backbone; NRTIs could be modified. If on a RAL-containing regimen, RAL must be discontinued.

Experimental: Sub-cohort B1

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • Best available NRTIs, RAL, & DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• Best available NRTIs, RAL, & DRV/RTV

Experimental: Sub-cohort B2

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and without active hepatitis B infection at screening • ETR, RAL, and DRV/RTV

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (and without active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (and without active hepatitis B infection at screening)

• ETR, RAL, and DRV/RTV

Experimental: Sub-cohort B3

Under Protocol version 1.0:

Susceptible to DRV/RTV and ETR with or without resistance to NRTIs (and may have resistance to other PIs) and with active hepatitis B infection at screening • RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Changed under LOA#2 to:

Resistance to LPV/RTV but susceptible to DRV/RTV and ETR and with no prior RAL exposure and regardless of NRTI resistance (with active hepatitis B infection at screening) OR Resistance to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and ETR and with no prior RAL exposure (with active hepatitis B infection at screening)

• RAL, DRV/RTV, and FTC/TDF or TDF+3TC

Experimental: Cohort C

Under Protocol version 1.0:

Resistance to NRTIs and ETR or resistance to ETR alone (and may have resistance to PIs other than DRV) • Best available NRTIs, RAL, and DRV/RTV

Changed under LOA#2:

Resistance to LPV/RTV and ETR but susceptible to DRV/RTV and with no prior RAL exposure and regardless of NRTI resistance OR Resistance to ETR and to all NRTIs (i.e. susceptible to none) but susceptible to DRV/RTV and with no prior RAL exposure

• Best available NRTIs, RAL, and DRV/RTV

Experimental: Cohort D

Under Protocol version 1.0:

Multiple NRTI resistance and/or DRV/RTV resistance or prior RAL exposure:

• Best available regimen, including study-provided and any locally available drugs

Changed under LOA#2:

Not eligible for Cohort A, B, or C:

• Best available regimen, including study-provided and any locally available drugs

Updated under protocol v2.0:

• Best available ART regimen, including study-provided and any locally available non-experimental drugs

Total Total of all reporting groups

Baseline Measures
   Experimental: Cohort A   Experimental: Sub-cohort B1   Experimental: Sub-cohort B2   Experimental: Sub-cohort B3   Experimental: Cohort C   Experimental: Cohort D   Total 
Overall Participants Analyzed 
[Units: Participants]
 287   74   72   8   70   34   545 
Age 
[Units: Years]
Mean (Standard Deviation)
 40  (11)   42  (10)   42  (9)   40  (10)   42  (10)   42  (10)   41  (10) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
             
Female      160  55.7%      29  39.2%      28  38.9%      4  50.0%      23  32.9%      14  41.2%      258  47.3% 
Male      127  44.3%      45  60.8%      44  61.1%      4  50.0%      47  67.1%      20  58.8%      287  52.7% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
             
Hispanic or Latino      38  13.2%      7   9.5%      9  12.5%      0   0.0%      1   1.4%      8  23.5%      63  11.6% 
Not Hispanic or Latino      241  84.0%      62  83.8%      59  81.9%      8 100.0%      60  85.7%      24  70.6%      454  83.3% 
Unknown or Not Reported      8   2.8%      5   6.8%      4   5.6%      0   0.0%      9  12.9%      2   5.9%      28   5.1% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
             
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Asian      62  21.6%      21  28.4%      17  23.6%      3  37.5%      35  50.0%      8  23.5%      146  26.8% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American      195  67.9%      49  66.2%      49  68.1%      5  62.5%      34  48.6%      21  61.8%      353  64.8% 
White      7   2.4%      1   1.4%      3   4.2%      0   0.0%      0   0.0%      3   8.8%      14   2.6% 
More than one race      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      1   2.9%      1   0.2% 
Unknown or Not Reported      23   8.0%      3   4.1%      3   4.2%      0   0.0%      1   1.4%      1   2.9%      31   5.7% 
Region of Enrollment 
[Units: Participants]
Count of Participants
             
Brazil   25   8   8   0   0   8   49 
Haiti   34   3   5   1   2   0   45 
India   55   18   16   2   32   5   128 
Kenya   32   9   8   1   7   2   59 
Malawi   18   6   2   0   9   2   37 
Peru   18   2   1   0   1   0   22 
South Africa   58   7   11   0   7   1   84 
Thailand   7   3   1   1   3   3   18 
Uganda   34   13   17   2   6   9   81 
Zimbabwe   6   5   3   1   3   4   22 
Plasma HIV-1 RNA, categorical [1] 
[Units: Participants]
Count of Participants
             
< 40 copies/mL      11   3.8%      1   1.4%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      12   2.2% 
40 - < 200 copies/mL      11   3.8%      2   2.7%      1   1.4%      1  12.5%      2   2.9%      1   2.9%      18   3.3% 
200 - < 1000 copies/mL      32  11.1%      5   6.8%      3   4.2%      1  12.5%      9  12.9%      2   5.9%      52   9.5% 
1000 - < 10,000 copies/mL      59  20.6%      17  23.0%      20  27.8%      3  37.5%      12  17.1%      10  29.4%      121  22.2% 
10,000 - < 100,000 copies/mL      106  36.9%      21  28.4%      18  25.0%      1  12.5%      20  28.6%      9  26.5%      175  32.1% 
100,000 - < 1,000,000 copies/mL      60  20.9%      27  36.5%      25  34.7%      2  25.0%      22  31.4%      10  29.4%      146  26.8% 
1,000,000 - < 10,000,000 copies/mL      8   2.8%      1   1.4%      4   5.6%      0   0.0%      5   7.1%      2   5.9%      20   3.7% 
>= 10,000,000 copies/mL      0   0.0%      0   0.0%      1   1.4%      0   0.0%      0   0.0%      0   0.0%      1   0.2% 
[1] Baseline Plasma HIV-1 RNA is defined as the last available result on or before the date of study entry
CD4+ T-Cell Count, categorical [1] 
[Units: Participants]
Count of Participants
             
< 50 cells/mm^3      50  17.4%      17  23.0%      11  15.3%      1  12.5%      9  12.9%      7  20.6%      95  17.4% 
50 - < 200 cells/mm^3      108  37.6%      27  36.5%      25  34.7%      1  12.5%      31  44.3%      10  29.4%      202  37.1% 
200 - < 350 cells/mm^3      79  27.5%      15  20.3%      23  31.9%      5  62.5%      19  27.1%      7  20.6%      148  27.2% 
350 - < 500 cells/mm^3      30  10.5%      12  16.2%      6   8.3%      1  12.5%      6   8.6%      8  23.5%      63  11.6% 
>= 500 cells/mm^3      20   7.0%      3   4.1%      7   9.7%      0   0.0%      5   7.1%      2   5.9%      37   6.8% 
[1] Baseline CD4+ T-cell count is defined as the last available result on or before the date of study entry
IV drug history, categorical 
[Units: Participants]
Count of Participants
             
Never      286  99.7%      74 100.0%      72 100.0%      8 100.0%      70 100.0%      34 100.0%      544  99.8% 
Previously      1   0.3%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      1   0.2% 
Hepatitis B Surface Antigen Result, categorical 
[Units: Participants]
Count of Participants
             
Positive      14   4.9%      0   0.0%      0   0.0%      8 100.0%      3   4.3%      4  11.8%      29   5.3% 
Negative      273  95.1%      74 100.0%      72 100.0%      0   0.0%      66  94.3%      30  88.2%      515  94.5% 
Indeterminate      0   0.0%      0   0.0%      0   0.0%      0   0.0%      1   1.4%      0   0.0%      1   0.2% 


  Outcome Measures

1.  Primary:   Proportion of Participants With Plasma HIV-1 RNA ≤200 Copies/mL at 48 Weeks   [ Time Frame: 48 weeks after the date of entry ]

2.  Secondary:   Suppression Rate of Plasma HIV-1 RNA to ≤200 Copies/mL at Week 24 and 72   [ Time Frame: Baseline to week 24 and 72 ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

3.  Secondary:   Time to Confirmed VF Defined as First HIV-1 RNA >1000 Copies/mL at or After 24 Weeks.   [ Time Frame: Throughout study; participants are expected to be followed for an average of 84 weeks ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

4.  Secondary:   Time to Confirmed VF Defined as First HIV-1 RNA >1000 Copies/mL at or After 24 Weeks With a New Resistance-associated Mutation Detected in Population-based Sequencing.   [ Time Frame: Throughout study; participants are expected to be followed for an average of 84 weeks ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

5.  Secondary:   Change in CD4+ T-cell Count From Baseline at Week 24, 48, and 72.   [ Time Frame: Baseline to week 24, 48, and 72 ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

6.  Secondary:   Time From Randomization to Death.   [ Time Frame: Throughout study; participants are expected to be followed for an average of 84 weeks ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

7.  Secondary:   Time From Randomization to the First of Death, an AIDS-defining Event or a Non-AIDS-defining Event.   [ Time Frame: Throughout study; participants are expected to be followed for an average of 84 weeks ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

8.  Secondary:   Time From Randomization to the First of Death or Hospitalization.   [ Time Frame: Throughout study; participants are expected to be followed for an average of 84 weeks ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

9.  Secondary:   Time From Randomization to Treatment Modification or Discontinuation.   [ Time Frame: Throughout study; participants are expected to be followed for an average of 84 weeks ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

10.  Secondary:   Time From Randomization to Treatment Modification or Discontinuation Due to Toxicity.   [ Time Frame: Throughout study; participants are expected to be followed for an average of 84 weeks ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

11.  Secondary:   Change From Baseline in Fasting Values of Total Cholesterol at Week 24, 48 and 72.   [ Time Frame: Baseline to week 24, 48 and 72 ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

12.  Secondary:   Change From Baseline in Fasting Values of HDL-C at Week 24, 48 and 72.   [ Time Frame: Baseline to week 24, 48 and 72 ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

13.  Secondary:   Change From Baseline in Fasting Values of Calculated LDL-C at Week 24, 48 and 72.   [ Time Frame: Baseline to week 24, 48 and 72 ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

14.  Secondary:   Change From Baseline in Fasting Values of Triglycerides at Week 24, 48 and 72.   [ Time Frame: Baseline to week 24, 48 and 72 ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

15.  Secondary:   Change From Baseline in Fasting Values of Glucose at Week 24, 48 and 72.   [ Time Frame: Baseline to week 24, 48 and 72 ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

16.  Secondary:   Time From Randomization to the Development of IRIS.   [ Time Frame: Throughout study; participants are expected to be followed for an average of 84 weeks ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  

17.  Secondary:   Time to First Dose Modification Due to Grade 3 or 4 Toxicity.   [ Time Frame: Throughout study; participants are expected to be followed for an average of 84 weeks ]
Results not yet reported.   Anticipated Reporting Date:   12/2018  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
phone: (301) 628-3313
e-mail: ACTGCT.Gov@s-3.com



Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01641367     History of Changes
Other Study ID Numbers: ACTG A5288
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: June 28, 2012
First Posted: July 16, 2012
Results First Submitted: November 20, 2017
Results First Posted: February 20, 2018
Last Update Posted: February 20, 2018