HIV-1Phase 2NCT00665847
TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents
A Phase 2 study testing Etravirine (TMC125) and Optimized background regimen (OBR) in people with HIV-1, run by Tibotec Pharmaceuticals, Ireland at 42 sites in 13 countries.
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. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- HIV-1
- What is being tested?
- Etravirine (TMC125) and Optimized background regimen (OBR)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 42 sitesin 13 countries
- Study dates
- Nov 2008to Aug 2011
- Phase
- Phase 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 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
42 sites in 13 countries.
42 sites in 13 countries
United States13 sites
Study site
Dallas, Texas
Study site
Fort Worth, Texas
Study site
Los Angeles, California
Study site
Memphis, Tennessee
Study site
Mobile, Alabama
Study site
New Brunswick, New Jersey
Study site
New Orleans, Louisiana
Study site
New York, New York
Study site
Philadelphia, Pennsylvania
Study site
St Louis, Missouri
Study site
Syracuse, New York
Study site
The Bronx, New York
Study site
Washington D.C., District of Columbia
France4 sites
Study site
Lyon
Study site
Nantes
Study site
Paris
Study site
Toulouse Cedex 3 N/A
Spain4 sites
Study site
Barcelona
Study site
Esplugues de Llobregat
Study site
Madrid
Study site
Seville
Brazil3 sites
Study site
Belo Horizonte
Study site
Ribeirão Preto
Study site
Rio de Janeiro
Canada3 sites
Study site
Montreal, Quebec
Study site
Ottawa, Ontario
Study site
Toronto, Ontario
South Africa3 sites
Study site
Dundee
Study site
Durban
Study site
Port Elizabeth
About this study
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
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.
Read the detailed 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.
- Conditions
- HIV-1
- Being tested
- Etravirine (TMC125), Optimized background regimen (OBR)
- Keywords
- HIV-1, TMC125-TiDP35-C213, TMC125-C213
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Etravirine (TMC125)Drug
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)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Etravirine (TMC125) | Experimental | Not described Receives: Drug: Etravirine (TMC125); Drug: Optimized background regimen (OBR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 48 weeks
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
Measured: 48 weeks
Secondary outcomes (7)
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.
Measured: Weeks 4-48
Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Trough Plasma Concentration (C0h)
Measured: Week 48
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.
Measured: Week 4
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.
Measured: Week 24
Change From Baseline in Human Immunodeficiency Virus - Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma Over Time
Measured: Baseline, Week 48
The Change From Baseline in CD4 Cell Counts Over Time
Measured: Baseline, Week 48
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).
Measured: Baseline and Endpoint (up to Week 48)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2008 (estimated)
- Study startNov 2008
- Primary completionMay 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tibotec Pharmaceuticals, Ireland Clinical Trial, Study director, Tibotec Pharmaceuticals, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00665847
- Sponsor's protocol ID
- CR002746
- Other IDs
- TMC125-TiDP35-C213, 2007-007086-21
- Status last verified
- Apr 2015
- First submitted
- 22 Apr 2008
- Last updated
- 23 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tambuyzer L, Thys K, Hoogstoel A, Nijs S, Tomaka F, Opsomer M, De Meyer S, Vingerhoets J. Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing: final results of the PIANO study. Antivir Ther. 2016;21(4):317-27. doi: 10.3851/IMP3011. Epub 2015 Nov 13.
PubMed 26566161
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00665847
- Acronym / sponsor ID
- CR002746
- Conditions
- HIV-1
- Keywords
- HIV-1, TMC125-TiDP35-C213, TMC125-C213
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Nov 2008
- Primary completion
- May 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 24 Apr 2008 (estimated)
- Results
- Posted 21 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Etravirine (TMC125) | Experimental | Drug: Etravirine (TMC125), Drug: Optimized background regimen (OBR) |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Etravirine (TMC125) |
| 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. | Drug | Etravirine (TMC125) |
Primary outcome
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Time frame: 48 weeks
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
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
Time frame: 48 weeks
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
7 secondary outcomes
Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Area Under the Plasma Concentration-time Curve Over 12 Hours at Steady-state (AUC12h)
Time frame: Weeks 4-48
Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Trough Plasma Concentration (C0h)
Time frame: Week 48
Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Maximum Plasma Concentration (Cmax)
Time frame: Week 4
Percentage of Patients With Virologic Response at Week 24
Time frame: Week 24
Change From Baseline in Human Immunodeficiency Virus - Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma Over Time
Time frame: Baseline, Week 48
The Change From Baseline in CD4 Cell Counts Over Time
Time frame: Baseline, Week 48
The Emergence of Non-nucleoside Reverse Transcriptase Inhibitor Resistance-associated Mutations (NNRTI RAMs) in Patients Classified as Virologic Failures
Time frame: Baseline and Endpoint (up to Week 48)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26566161Tambuyzer L, Thys K, Hoogstoel A, Nijs S, Tomaka F, Opsomer M, De Meyer S, Vingerhoets J. Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing: final results of the PIANO study. Antivir Ther. 2016;21(4):317-27. doi: 10.3851/IMP3011. Epub 2015 Nov 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tibotec Pharmaceuticals, Ireland Clinical Trial study director
Tibotec Pharmaceuticals, Ireland
42 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etravirine (TMC125) and Optimized background regimen (OBR) in people with HIV-1, run by Tibotec Pharmaceuticals, Ireland at 42 sites in 13 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 5 inclusion and 7 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 23 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 42 sites in United States, France, Spain, Brazil, Canada and 8 more countries. 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 phase mean?
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 21 Dec 2012). 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?
The Number of Patients With Treatment-emergent Adverse Events (TEAEs) (time frame: 48 weeks). The study lists 2 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 NCT00665847, which also lists 1 linked publication.
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 23 Apr 2015.