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

NCT00766597 | Completed Phase 1 Results

• 3 other identifiers: P107110634IMPAACT P1071
• Study Type: interventional
• Target: 9
• Locations: 2 countries
• Sites: 9

Brief 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.

Conditions

HIV Infections

Keywords

Treatment Experienced

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

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

• 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.

  At Week 24

Secondary Outcomes (6)

• 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)

  At Baseline, Week 24

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

  At Baseline, Week 24

• Change in CD4 Counts

  At Baseline, Week 24

• Change in CD4 Percent

  At Baseline, Week 24

• Change in Polymerase Genome and Envelope Sequence

  At Baseline, Week 24

Study Arms (1)

Vicriviroc in tablet form (20/30 mg) or liquid form (1 mg/ml)

EXPERIMENTAL

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

Drug: Vicriviroc

Interventions

Vicriviroc DRUG

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

Vicriviroc in tablet form (20/30 mg) or liquid form (1 mg/ml)

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Willing to use effective methods of contraception
• 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.

You may not qualify if:

• 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
• 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.
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (9)

UCSD Mother-Child-Adolescent Program CRS

San Diego, California, United States

Location

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

Washington D.C., District of Columbia, 20010, United States

Location

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, 20060, United States

Location

Chicago Children's CRS

Chicago, Illinois, 60614, United States

Location

Metropolitan Hosp. NICHD CRS

New York, New York, 10029, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

Location

Bronx-Lebanon Hosp. IMPAACT CRS

The Bronx, New York, United States

Location

St. Jude/UTHSC CRS

Memphis, Tennessee, 38105, United States

Location

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

San Juan, 00935, Puerto Rico

Location

Related Publications (2)

• 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.

  PMID: 17933723 BACKGROUND

• 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.

  PMID: 17627557 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

vicriviroc

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)

mallen@fhi360.org

(919) 405-1429

Study Officials

• Rolando M Viani, M.D., M.T.P.

  University of California

  STUDY CHAIR

• Stephen A Spector, M.D.

  University of California, San Diego

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2008
• First Posted: October 6, 2008
• Study Start: August 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: August 1, 2010
• Last Updated: November 5, 2021
• Results First Posted: February 1, 2016

Record last verified: 2015-12

Locations

US (8); PR (1)