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Safety and Immune Response to Vicriviroc in Combination Regimens in HIV-Infected ART Experienced Children and Adolescents

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ClinicalTrials.gov Identifier: NCT00766597
Recruitment Status : Completed
First Posted : October 6, 2008
Results First Posted : February 1, 2016
Last Update Posted : February 1, 2016
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV Infections
Intervention Drug: Vicriviroc
Enrollment 9
Recruitment Details Nine participants were recruited in 9 US sites between Sept 21, 2009 to June 16, 2010 prior to the early study closure on August 10, 2010.
Pre-assignment Details In Step I, 9 participants under Cohort I were screened for evaluation for co-receptor tropism. Five participants did not have the required tropism and were discontinued from the study. Only 4 participants had the CCR-5-tropic virus tropism, and thus were eligible to go to Step II and were assigned to receive the study drug.
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml)
Hide Arm/Group Description

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Period Title: Overall Study
Started 9 [1]
With CCR5-tropic Virus 4 [2]
Without CCR5-tropic Virus 5 [3]
Completed Week 24 1 [4]
Completed Week 48 0 [5]
Completed 0 [6]
Not Completed 9
Reason Not Completed
Unexpected closure of study             4
Without CCR5-tropic virus             5
[1]
Screened participants who were evaluated for co-receptor tropism
[2]
Evaluable participants, received the study drug
[3]
Not evaluable participants, did not receive the study drug
[4]
Week 24 is the first primary time point of analysis
[5]
Week 48 is the second primary time point of analysis
[6]
Treatment duration is 48 weeks plus 5 years of follow-up
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml)
Hide Arm/Group Description

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Overall Number of Baseline Participants 4
Hide Baseline Analysis Population Description
The HIV-1 infected antiretroviral therapy experienced participants With CCR5-tropic virus who started treatment in Step II
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants
15  (2.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
Female
2
  50.0%
Male
2
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
Hispanic or Latino
2
  50.0%
Not Hispanic or Latino
2
  50.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
  50.0%
White
1
  25.0%
More than one race
0
   0.0%
Unknown or Not Reported
1
  25.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants
4
1.Primary Outcome
Title Number of Participants With Suspected Adverse Drug Reaction Leading to Treatment Termination
Hide Description The protocol required reporting of signs and symptoms and laboratory abnormalities of >=Grade 2 and all grades of fever. The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs. Expedited adverse event reporting followed Version 2.0 of the DAIDS Expedited Adverse Event Manual.The attribution of relationship of serious adverse events to study drug for the purposes of employing the start, stop and pause rules is to be determined by the Study Team. Gradation of relationship will use the following terminology: Not related, Probably not related, Possibly related, Probably related or Definitely related.
Time Frame From study entry to Week 24 or the early study termination whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
The HIV-1 infected antiretroviral therapy experienced participants with CCR5-tropic virus who started treatment in Step II.
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1mg/ml)
Hide Arm/Group Description:
HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic virus
Overall Number of Participants Analyzed 4
Measure Type: Number
Unit of Measure: participants
0
2.Primary Outcome
Title Number of Participants With Adverse Events of Grade 3 or Higher Severity
Hide Description Adverse events were graded using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004, Clarification August 2009, which is available on the RCC website at (http://rcc.tech-res.com/). All grade 3 and higher signs, symptoms, and laboratory toxicities were included.
Time Frame From study entry to Week 24 or the early study termination whichever occurred earlier
Hide Outcome Measure Data
Hide Analysis Population Description
The HIV-1 infected antiretroviral therapy experienced participants with CCR-5 tropic virus who started treatment in Step II
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1mg/ml)
Hide Arm/Group Description:

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Overall Number of Participants Analyzed 4
Measure Type: Number
Unit of Measure: participants
1
3.Primary Outcome
Title Number of Participants Who Failed to Meet PK Targets
Hide Description For Stage I subjects who are enrolled in Step II, the average of the pre-dose and 24 hour post dose sample from the intensive PK evaluations of said subjects will be used as the estimate of Cmin. The whole cohort will fail the PK targets if the population target (median vicriviroc Cmin should be =>200 ng/mL) is not met, and that nearly all of subjects’ Cmin failed to be > 100 ng/mL.
Time Frame At Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The HIV-1 infected antiretroviral therapy experienced participants with CCR-5 tropic virus who started treatment in Step II and who failed the PK targets. Outcome measure not analyzed since the PK targets were for the whole cohort, but the lone cohort opened was not fully enrolled due to early study termination.
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1mg/ml)
Hide Arm/Group Description:

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Number of Participants Who Failed to Achieve =>1-log Drop From Baseline in HIV-1 Viral Load and HIV-1 Viral Load of =>400 Copies/mL (Virologic Failures)
Hide Description Plasma HIV RNA (RNA) concentrations were determined at entry and at regular intervals using the HIV-1 MONITOR Test, version 1.5 (Roche Molecular Diagnostics) or RealTime HIV-1 (Abbott Molecular). The primary definition of virologic success will require subjects to have achieved and maintained 1-log drops from baseline of HIV-1 RNA or HIV-1 RNA <400 copies/mL.
Time Frame At Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
HIV-1 infected ART-experienced participants with CCR5-tropic virus who started treatment in Step II and have reached Week 24. Measure was not analyzed since only one participant reached Week 24, no aggregate results were available for posting, and the individual participant-level data were not posted due to being potentially identifiable.
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1mg/ml)
Hide Arm/Group Description:

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Number of Participants With Changes in Co-receptor Tropism From Baseline
Hide Description Among all patients enrolled in Step I, the prevalence of detectable coreceptor phenotype, R5 tropic, R5/X4 mixed and X4 tropic viruses will be evaluated. The extent to which coreceptor phenotype in Step I is associated with Step I CD4 cell count, HIV RNA, and age will be evaluated. The association of Step I coreceptor phenotype and nadir CD4, HIV subtype, number of ART regimens, and years of ART will be evaluated. At the time of virologic failure, the extent of change from Step I and/or baseline R5 tropic virus to R5/X4 mixed or to X4 tropic virus as detected by the TrofileTM assay will be evaluated.
Time Frame At Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
HIV-1 infected ART-experienced participants with CCR5-tropic virus who started treatment in Step II and have reached Week 24. Measure was not analyzed since only one participant reached Week 24, no aggregate results were available for posting, and the individual participant-level data were not posted due to being potentially identifiable.
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml)
Hide Arm/Group Description:

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Change in CD4 Counts
Hide Description Change in CD4 count from baseline to weeks 24 will be presented both in the aggregate and broken down by age cohort.
Time Frame At Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
HIV-1 infected ART-experienced participants with CCR5-tropic virus who started treatment in Step II and have reached Week 24. Measure was not analyzed since only one participant reached Week 24, no aggregate results were available for posting, and the individual participant-level data were not posted due to being potentially identifiable.
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml)
Hide Arm/Group Description:

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Change in CD4 Percent
Hide Description Change in CD4 percent from baseline to weeks 24 will be presented both in the aggregate and broken down by age cohort.
Time Frame At Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
HIV-1 infected ART-experienced participants with CCR5-tropic virus who started treatment in Step II and have reached Week 24. Measure was not analyzed since only one participant reached Week 24, no aggregate results were available for posting, and the individual participant-level data were not posted due to being potentially identifiable.
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml)
Hide Arm/Group Description:

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Change in Polymerase Genome and Envelope Sequence
Hide Description Number of subjects with changes in genotypic and phenotypic drug resistance to the OBT and to vicriviroc (envelope sequence) from baseline to Week 24 and/or virologic failure will be presented both in the aggregate and broken down by age cohort.
Time Frame At Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
HIV-1 infected ART-experienced participants with CCR5-tropic virus who started treatment in Step II and have reached Week 24. Measure was not analyzed since only one participant reached Week 24, no aggregate results were available for posting, and the individual participant-level data were not posted due to being potentially identifiable.
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml)
Hide Arm/Group Description:

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Change in Plasma HIV RNA PCR
Hide Description Changes in HIV RNA (copies/mL) from baseline to Week 24 will be presented both in the aggregate and broken down by age cohort.
Time Frame At Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
HIV-1 infected ART-experienced participants with CCR5-tropic virus who started treatment in Step II and have reached Week 24. Measure was not analyzed since only one participant reached Week 24, no aggregate results were available for posting, and the individual participant-level data were not posted due to being potentially identifiable.
Arm/Group Title Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml)
Hide Arm/Group Description:

HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus

Vicriviroc: Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame From study entry to the very early study discontinuation
Adverse Event Reporting Description Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
 
Arm/Group Title Vicriviroc in Tablet Form (20/30mg) or Liquid Form (1mg/ml)
Hide Arm/Group Description Drug: Vicriviroc Administered orally in either tablet or liquid form at a dosage of approximately 0.8/mg/kg every 24 hours, with a ritonavir boosted protease inhibitor containing background regimen
All-Cause Mortality
Vicriviroc in Tablet Form (20/30mg) or Liquid Form (1mg/ml)
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vicriviroc in Tablet Form (20/30mg) or Liquid Form (1mg/ml)
Affected / at Risk (%)
Total   0/4 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vicriviroc in Tablet Form (20/30mg) or Liquid Form (1mg/ml)
Affected / at Risk (%)
Total   4/4 (100.00%) 
Blood and lymphatic system disorders   
Lymphadenopathy  1  1/4 (25.00%) 
Eye disorders   
Eyelid oedema  1  1/4 (25.00%) 
Gastrointestinal disorders   
Diarrhoea  1  1/4 (25.00%) 
Nausea  1  1/4 (25.00%) 
Hepatobiliary disorders   
Hepatomegaly  1  1/4 (25.00%) 
Infections and infestations   
Acarodermatitis  1  1/4 (25.00%) 
Tinea cruris  1  1/4 (25.00%) 
Injury, poisoning and procedural complications   
Arthropod bite  1  1/4 (25.00%) 
Investigations   
Blood bicarbonate abnormal  1  1/4 (25.00%) 
Blood bilirubin increased  1  1/4 (25.00%) 
Blood glucose decreased  1  3/4 (75.00%) 
Blood glucose increased  1  1/4 (25.00%) 
Blood potassium decreased  1  1/4 (25.00%) 
Blood sodium decreased  1  1/4 (25.00%) 
Neutrophil count decreased  1  1/4 (25.00%) 
Reproductive system and breast disorders   
Genital rash  1  1/4 (25.00%) 
Respiratory, thoracic and mediastinal disorders   
Rales  1  1/4 (25.00%) 
Rhonchi  1  1/4 (25.00%) 
Skin and subcutaneous tissue disorders   
Rash generalised  1  1/4 (25.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Study was terminated early with Merck's announcement on July 15, 2010 on the discontinuation of the development of Vicriviroc, with 4 participants given study drug and only 1 participant reached Week 24.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
In accordance with the Clinical Trial Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Results Point of Contact
Name/Title: Melissa Allen, Director, IMPAACT Operations Center
Organization: Family Health International (FHI 360)
Phone: (919) 405-1429
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00766597     History of Changes
Other Study ID Numbers: P1071
10634 ( Registry Identifier: DAIDS ES )
IMPAACT P1071
First Submitted: October 3, 2008
First Posted: October 6, 2008
Results First Submitted: November 12, 2015
Results First Posted: February 1, 2016
Last Update Posted: February 1, 2016