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HIV InfectionsPhase 1/2NCT00766597

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

A Phase 1/2 study testing Vicriviroc in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Complications with current HIV antiretroviral therapy have left many children and adolescents with limited therapeutic options due to drug resistance. The purpose of this study is to test the effectiveness and safety of Vicriviroc (VCV), an HIV entry inhibitor and CCR5 co-receptor antagonist. Read more about this study

Who is it for?
Ages 2 to 18 years
Conditions the study is for
HIV Infections
What is being tested?
Vicriviroc
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
9 sitesin 2 countries
Study dates
Aug 2009to Aug 2010
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Confirmed HIV infection
  • Treatment experienced subjects: Children or adolescents on an unchanged therapeutic regimen for at least 12 weeks and experiencing virologic failure OR participants on no treatment for 4 weeks or more but with history of virologic failure on a prior therapeutic regimen.
  • Likely to have virus that is sensitive to at least one ritonavir boosted protease inhibitor
  • HIV viral load greater than or equal to 1,000 copies/ml within 90 days prior to Step I entry
  • Able to swallow study medication, in tablets or liquid form specific to age-assigned cohort
  • Parent, legal guardian or participant able and willing to provide signed informed consent and to have the participant followed at the clinic site
Show all 10Show fewer
  • Willing to use effective methods of contraception
  • Inclusion Criteria for Step II (In addition to the inclusion criteria for Step I):
  • Participant's plasma HIV tested at Step I must be R5 tropic
  • Genotypic sensitivity enabling the participant to take optimized background therapy (OBT) consisting of at least a ritonavir-based protease inhibitor. More information on this criterion can be found in the study protocol.

Who cannot join

  • Presence of any currently active AIDS defining illness or history of malignancy
  • History of a seizure disorder that requires current anti-seizure medication for control or at risk for seizures. Those with a history of febrile seizures alone are not excluded.
  • Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
  • Any vaccinations 14 days prior to Step I, or scheduled to occur within 14 days prior to entry into Step II, and the week 24 and 48 visits in Step II
  • Allergy or sensitivity to study drug or its ingredients
  • Taking any Step II disallowed medications (see protocol) and unable or unwilling to discontinue them at least one week prior to entering Step II
Show all 13Show fewer
  • Use of NNRTIs other than etravirine 21 days prior to Step II entry
  • Pregnancy or breastfeeding. Infants who are receiving breastmilk are allowed to enroll.
  • All exclusion criteria for Step I
  • Participants harboring dual or mixed tropic virus (R5/X4) or X4 virus or non phenotypable virus
  • Current or anticipated use of any disallowed medications
  • Use of efavirenz, nevirapine, and delavirdine for 21 days prior to Step II entry
  • Pregnant within 3 days of Step II entry

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States8 sites

  • Chicago Children's CRS

    Chicago, Illinois, 60614

  • St. Jude/UTHSC CRS

    Memphis, Tennessee, 38105

  • Metropolitan Hosp. NICHD CRS

    New York, New York, 10029

  • UCSD Mother-Child-Adolescent Program CRS

    San Diego, California

  • Jacobi Med. Ctr. Bronx NICHD CRS

    The Bronx, New York, 10461

  • Bronx-Lebanon Hosp. IMPAACT CRS

    The Bronx, New York

  • Children's National Med. Ctr. Washington DC NICHD CRS

    Washington D.C., District of Columbia, 20010

  • Howard Univ. Washington DC NICHD CRS

    Washington D.C., District of Columbia, 20060

Other trials in United States

Puerto Rico1 site

  • Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS

    San Juan, 00935

Other trials in Puerto Rico

About this study

Official title: Phase I/II Open-Label Study to Evaluate the PK, Safety, Tolerability and Antiviral Activity of Vicriviroc, a Novel CCR5 Antagonist in Combination Regimens in HIV-Infected ART Experienced Children and Adolescents

Complications with current HIV antiretroviral therapy have left many children and adolescents with limited therapeutic options due to drug resistance. The purpose of this study is to test the effectiveness and safety of Vicriviroc (VCV), an HIV entry inhibitor and CCR5 co-receptor antagonist.

Read the detailed description

Highly active antiretroviral therapy (HAART) that includes a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) has become the standard treatment of HIV-infected adults and children. When effective, HAART decreases the viral population, increases the body's immune responses, and leads to decreased disease progression and increased survival. However, several factors including poor adherence, drug toxicities, and drug resistance complicate HIV management and allow for children and adolescents to develop resistance to multiple drug classes, leaving them with very limited therapeutic options. Fortunately, drugs with new mechanisms of action, such as HIV entry inhibitors, demonstrate activity even in people with resistance to the currently available reverse transcriptase and protease inhibitors.

The purpose of this study is to test the effectiveness and safety of Vicriviroc (VCV), an HIV entry inhibitor. Vicriviroc targets the CCR5 chemokine receptor, which HIV uses to bind and enter CD4+ cells.

This study is a two-stage, age-stratified, non-comparative study to explore the safety, tolerability, pharmacokinetic profile and antiviral activity of the investigational CCR5 inhibitor Vicriviroc in HIV-infected treatment experienced children and adolescents.

In Step I participants will be screened for the co-receptor CCR5 to assess whether they can enter Step II. Only participants with CCR5-tropic virus are eligible for Step II - the main portion of the study to evaluate the study outcome measures. Those participants who continue to Step II will be assigned to one of four age-stratifies cohorts which will receive varying forms, either liquid or tablet, of Vicriviroc:

Cohort I: 12 years to less than 19 years of age, to receive tablet formulation of VCV

Cohort II: 6 years to less than 12 years of age, to receive tablet formulation of VCV

Cohort III: 6 years to less than 12 years of age, to receive liquid formulation of VCV

Cohort IV: 2 years to less than 6 years of age, to receive liquid formulation of VCV

Dose strengths of 20 mg and 30 mg will be used, or in liquid formulation at a concentration of 1mg/mL.

Step II is composed of Stage I and Stage II. Stage I is a dose ranging study designed to explore how the body responds to different doses of vicriviroc, including safety factors associated with dosage. After optimal dosage information and safety measures have been assessed for the different cohorts in Stage I, Stage II will open. Stage II will evaluate the long term safety, tolerability and effectiveness of vicriviroc.

The study, including Steps I and II will last for approximately 48 weeks. Follow-up for all subjects exposed to vicriviroc will last for 5 years after initial exposure. Visits will be every 3 months for subjects on study provided vicriviroc and every 6 months for subjects who discontinue vicriviroc.

The study was terminated shortly after the initiation, when the drug company decided to discontinue development of the study drug. As of study termination, nine participants had enrolled under Cohort I in Step I, but only 4 participants had CCR5 tropism and received the study medication under Step II. All 4 participants had limited post-baseline data.

Conditions
HIV Infections
Being tested
Vicriviroc
Keywords
Treatment Experienced
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VicrivirocDrug

    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

Study groups in NCT00766597
Study groupRoleWhat they receive
Vicriviroc in tablet form (20/30 mg) or liquid form (1 mg/ml)ExperimentalHIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic Virus
Receives: Drug: Vicriviroc

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Suspected Adverse Drug Reaction Leading to Treatment Termination

    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.

    Measured: From study entry to Week 24 or the early study termination whichever occurred earlier

  2. Number of Participants With Adverse Events of Grade 3 or Higher Severity

    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.

    Measured: From study entry to Week 24 or the early study termination whichever occurred earlier

  3. Number of Participants Who Failed to Meet PK Targets

    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.

    Measured: At Week 24

Secondary outcomes (6)

  1. 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)

    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.

    Measured: At Baseline, Week 24

  2. Number of Participants With Changes in Co-receptor Tropism From Baseline

    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.

    Measured: At Baseline, Week 24

  3. Change in CD4 Counts

    Change in CD4 count from baseline to weeks 24 will be presented both in the aggregate and broken down by age cohort.

    Measured: At Baseline, Week 24

  4. Change in CD4 Percent

    Change in CD4 percent from baseline to weeks 24 will be presented both in the aggregate and broken down by age cohort.

    Measured: At Baseline, Week 24

  5. Change in Polymerase Genome and Envelope Sequence

    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.

    Measured: At Baseline, Week 24

  6. Change in Plasma HIV RNA PCR

    Changes in HIV RNA (copies/mL) from baseline to Week 24 will be presented both in the aggregate and broken down by age cohort.

    Measured: At Baseline, Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2008 (estimated)
  2. Study startAug 2009
  3. Primary completionJul 2010
  4. Study completionAug 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00766597
Sponsor's protocol ID
P1071
Other IDs
10634, IMPAACT P1071
Status last verified
Dec 2015
First submitted
3 Oct 2008
Last updated
5 Nov 2021

Publications

  • Lorenzen T, Stoehr A, Walther I, Plettenberg A. CCR5 antagonists in the treatment of treatment-experienced patients infected with CCR5 tropic HIV-1. Eur J Med Res. 2007 Oct 15;12(9):419-25.

    PubMed 17933723

  • Rusconi S, Scozzafava A, Mastrolorenzo A, Supuran CT. An update in the development of HIV entry inhibitors. Curr Top Med Chem. 2007;7(13):1273-89. doi: 10.2174/156802607781212239.

    PubMed 17627557

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Vicriviroc in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Suspected Adverse Drug Reaction Leading to Treatment Termination (time frame: From study entry to Week 24 or the early study termination whichever occurred earlier). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00766597, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2021.

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