TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents

HIV-1 Clinical Trial

Official title:

A Phase II, Open-label Trial, to Evaluate the Safety, Tolerability and Antiviral Activity of TMC125 in Antiretroviral Experienced HIV-1 Infected Children and Adolescents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00665847
• Other study ID #: CR002746
• Secondary ID: TMC125-TiDP35-C2
• Status: Completed
• Phase: Phase 2
• First received: April 22, 2008
• Last updated: April 2, 2015
• Start date: November 2008
• Est. completion date: August 2011

Study information

• Verified date: April 2015
• Source: Tibotec Pharmaceuticals, Ireland
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIreland: Irish Agriculture and Food Development AuthorityGreat Britain: Medicines and Healthcare Products Regulatory AgencyUnited States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and antiviral activity of etravirine in treatment-experienced human immunodeficiency virus (HIV) infected children and adolescents.

Description:

The study design is a single arm treatment (all patients assigned to receive etravirine), open label (patients will know the identity of the treatments they are receiving) safety and antiviral activity of Etravirine (TMC125) in treatment-experienced, HIV infected children and adolescents 6 to 17 years of age. Etravirine is a new drug belonging to the NNRTI (a non-nucleoside reverse transcriptase inhibitor) drug class that slows down the growth of the human immunodeficiency virus (HIV). This drug has been tested for safety and effectiveness in adults, however, there is no data on the drug's long-term safety and antiviral activity in children and adolescents. This study will last for a maximum of 48 weeks. A total of 100 ptients will receive etravirine tablets based on body weight and an investigator selected optimized background regimen (OBR) of at least 2 antiretrovirals (ARVs), consisting of a boosted protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor(s) (NRTI[s]). Use of enfuvirtide is optional. Safety will be monitored throughout the study.

Other known NCT identifiers

• NCT00750542

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: August 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

• HIV-1 infected

• Body weight according to age within the 10-90th percentile of CDC growth chart

• On steady antiretroviral therapy regimen for at least 8 weeks at screening and willing to remain on that regimen until baseline

• HIV viral load of 1,000 copies/ml or greater at study entry

• Parent or legal guardian willing to provide informed consent, if necessary

Exclusion Criteria:

• The Key Exclusion Criteria are: Evidence of resistance to etravirinel Any grade 3 or 4 toxicity (More information available in the protocol)

• Use of disallowed concomitant therapy (specified in the protocol)

• Currently active AIDS defining illness (category C)

• Active hepatitis A, B or C virus infection

• Any clinically significant diseases or findings that, in the opinion of the investigator, would interfere with the study

• Receipt of any ARV or non-ARV investigational medication or investigational vaccine within 30 days prior to screening

• History of clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication (TMC125)

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1

Intervention

Drug:
• Etravirine (TMC125)
Patients will be dosed by body weight , i.e. 5.2 mg/kg twice daily (b.i.d.) up to a maximum of 200 mg b.i.d. for 48 weeks.
• Optimized background regimen (OBR)
An investigator-selected optimized background regimen (OBR) comprising of a low-dose ritonavir (rtv)-boosted protease inhibitor (PI) (either lopinavir [LPV], darunavir [DRV], atazanavir [ATV] or saquinavir [SQV]) in combination with nucleos(t)ide reverse transcriptase inhibitor(s) (N[t]RTIs) to be dosed according to the drugs individual package inserts for 48 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tibotec Pharmaceuticals, Ireland

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  France,  Netherlands,  Portugal,  Puerto Rico,  Romania,  South Africa,  Spain,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Number of Patients With Treatment-emergent Adverse Events (TEAEs)	A treatment-emergent adverse event (TEAE) was defined as an event that occurred in the 48-week treatment period during which it emerged (i.e. started or worsened in severity, relation, or other attribute), and not in the subsequent study periods, even if the event continued to be present. Adverse events were graded from 1 to 4 in severity using the Division of Acquired Immunodeficiency Syndrome severity scale (grade 1 being less severe and grade 4 being more severe). ETR=etravirine/TMC125; OBR=optimized background regimen	48 weeks	Yes
Primary	The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)	The percentage of patients with a treatment-emergent adverse event (TEAE) (defined as an event that occurred in the 48-week treatment period during which it emerged [i.e. started or worsened in severity, relation, or other attribute], and not in the subsequent study periods, even if the event continued to be present] are provided below. Adverse events were graded from 1 to 4 in severity using the Division of Acquired Immunodeficiency Syndrome severity scale (grade 1 being less severe and grade 4 being more severe). ETR=etravirine/TMC125; OBR=optimized background regimen	48 weeks	Yes
Secondary	Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Area Under the Plasma Concentration-time Curve Over 12 Hours at Steady-state (AUC12h)	The AUC12h is a Bayesian estimation based on a population pharmacokinetic model and sparse samples collected at each visit over the duration of trial. For each sparse sample taken, the time blood sample was recorded as well as the time of etravirine intake just prior to the time of blood sample.	Weeks 4-48	No
Secondary	Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Trough Plasma Concentration (C0h)		Week 48	No
Secondary	Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Maximum Plasma Concentration (Cmax)	Etravirine/TMC125 (ETR) Cmax was approximated for each individual using the median value of plasma ETR concentrations taken 4 hours postdose (± 1 hour), when available, on the day of the Week 4 visit as shown in the table below.	Week 4	No
Secondary	Percentage of Patients With Virologic Response at Week 24	Virologic response was defined as the percentage of patients with plasma viral load < 50 copies/mL at Week 24 calculated according to the non-completer=failure (NC=F) imputation method.	Week 24	No
Secondary	Change From Baseline in Human Immunodeficiency Virus - Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma Over Time		Baseline, Week 48	No
Secondary	The Change From Baseline in CD4 Cell Counts Over Time		Baseline, Week 48	No
Secondary	The Emergence of Non-nucleoside Reverse Transcriptase Inhibitor Resistance-associated Mutations (NNRTI RAMs) in Patients Classified as Virologic Failures	Virologic failure (lack of response) was defined as: plasma viral load decline of < 0.5 log10 from Baseline by Week 8 and/or plasma viral load decline of <1.0 log10 from Baseline by Week 12. Virologic failure (loss of response) was defined as 2 consecutive measurements of plasma viral load > 0.5 log10 above the nadir after a minimum of 12 weeks of treatment. The table below provides data for 41 viologic failures of which 30 had mutation data available. In the table below, only the 4 most frequently emerging mutations are presented (emerging in at least 3 patients).	Baseline and Endpoint (up to Week 48)	No