Trial Outcomes & Findings for Safety and Immune Response to Vicriviroc in Combination Regimens in HIV-Infected ART Experienced Children and Adolescents (NCT NCT00766597)

Last Updated: 2021-11-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

9 participants

Primary outcome timeframe

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

Results posted on

2021-11-05

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml) 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 Study STARTED	9
Overall Study With CCR5-tropic Virus	4
Overall Study Without CCR5-tropic Virus	5
Overall Study Completed Week 24	1
Overall Study Completed Week 48	0
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml) 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 Study Unexpected closure of study	4
Overall Study Without CCR5-tropic virus	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1 mg/ml) n=4 Participants 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
Age, Continuous	15 years STANDARD_DEVIATION 2.2 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants

PRIMARY outcome

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

Population: The HIV-1 infected antiretroviral therapy experienced participants with CCR5-tropic virus who started treatment in Step II.

Outcome measures

Outcome measures
Measure	Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1mg/ml) n=4 Participants HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic virus
Number of Participants With Suspected Adverse Drug Reaction Leading to Treatment Termination	0 participants

PRIMARY outcome

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

Population: The HIV-1 infected antiretroviral therapy experienced participants with CCR-5 tropic virus who started treatment in Step II

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.

Outcome measures

Outcome measures
Measure	Vicriviroc in Tablet Form (20/30 mg) or Liquid Form (1mg/ml) n=4 Participants HIV-1 Infected Antiretroviral Therapy Experienced Participants with CCR5-tropic virus
Number of Participants With Adverse Events of Grade 3 or Higher Severity	1 participants

PRIMARY outcome

Timeframe: At Week 24

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Baseline, Week 24

Vicriviroc in Tablet Form (20/30mg) or Liquid Form (1mg/ml)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Vicriviroc in Tablet Form (20/30mg) or Liquid Form (1mg/ml) n=4 participants at risk 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
Blood and lymphatic system disorders Lymphadenopathy	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Eye disorders Eyelid oedema	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Gastrointestinal disorders Diarrhoea	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Gastrointestinal disorders Nausea	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Hepatobiliary disorders Hepatomegaly	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Infections and infestations Acarodermatitis	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Infections and infestations Tinea cruris	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Injury, poisoning and procedural complications Arthropod bite	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Investigations Blood bicarbonate abnormal	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Investigations Blood bilirubin increased	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Investigations Blood glucose decreased	75.0% 3/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Investigations Blood glucose increased	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Investigations Blood potassium decreased	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Investigations Blood sodium decreased	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Investigations Neutrophil count decreased	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Reproductive system and breast disorders Genital rash	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Respiratory, thoracic and mediastinal disorders Rales	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Respiratory, thoracic and mediastinal disorders Rhonchi	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.
Skin and subcutaneous tissue disorders Rash generalised	25.0% 1/4 • From study entry to the very early study discontinuation Adverse event summary pertains to the 4 participants accrued into Step I and then into Step II and treated with the study medication.

Additional Information

Melissa Allen, Director, IMPAACT Operations Center

Family Health International (FHI 360)

Phone: (919) 405-1429

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER