This study is a Phase II, non-randomized, open label trial to evaluate Safety and Antiviral activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents.
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective is long-term safety and tolerability of TMC125 in
combination with other HIV drugs [ Time Frame: 24 weeks ]
Secondary outcome
The secondary objectives are pharmacokinetic parameters throughout the study,
HIV viral load, CD4 count and percentage, Genotypic and phenotypic resistance
measures [ Time Frame: 48 week ]
Background summary
Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). In
adults, etravirine has shown significant antiretroviral activity in clinical
trials and is generally safe and well tolerated. However, there is no data on
the drug's long-term safety and antiviral activity in children and adolescents.
HIV-1 infection in the pediatric population follows a similar course as seen in
adult HIV-1
infection. However, pediatric HIV infection presents considerable challenges
due to the
differences in epidemiology and transmission, diagnostic challenges, clinical
manifestations, and
management. Control of HIV replication is the goal of treatment in both
children and adults.
Recent trials of antiretroviral combination therapy in infants and children
have provided an
improved understanding of the pathogenesis of pediatric human immunodeficiency
virus-type 1
(HIV-1) infection. Currently, highly active combination regimens including at
least 3 drugs are
recommended. Such regimens have been associated with enhanced survival,
reduction in
opportunistic infections and other complications of HIV infection, and improved
quality of life in
children.
Not all ARVs approved in adults are available for children.
Of the 4 NNRTIs currently available, 2 (nevirapine [NVP] and efavirenz [EFV])
have an approved pediatric indication. Development of new, potent
antiretroviral (ARV)
compounds with different and improved resistance and safety profiles remains a
high unmet need
especially in treatment experienced HIV-1 infected pediatric population. In
addition to the need
for new ARVs, the treatment of HIV-1 infected pediatric subjects has to take
into account
clinical care issues that are unique to this population such as age-related
differences in virologic,
immunologic, and pharmacokinetic parameters and obstacles associated with
adherence to
complex regimens.
Study objective
This study is a Phase II, non-randomized, open label trial to evaluate Safety
and Antiviral activity of Etravirine (TMC125) in Treatment-Experienced, HIV
Infected Children and Adolescents.
Study design
This study will last for a maximum of 48 weeks and will enroll participants
aged 6 to 17 years. A total of 100 participants will receive etravirine tablets
based on body weight and an investigator selected 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.
The TMC125 dose will be based on body weight. TMC125 tablets will be provided
as 25mg and 100mg.
Intervention
The OBR will be composed at the discretion of the investigator and should
consist of a regimen of at least 2 ARV drugs (not counting low dose ritonavir),
including a boosted PI in combination with N(t)RTI(s). Additional use of ENF is
optional. All ARVs for which pediatric dosing guidelines have been established
with adequate safety information and for which co-administration with TMC125 is
allowed can be used. ATV/rtv may be used after discussion with the Sponsor.
However, the OBR may not contain an NNRTI, or any disallowed ARVs. ARVs that
are not yet labeled for use in the pediatric population but
where dosing recommendations are available based on clinical data may be used
after discussion with the Sponsor.
For all subjects entering the trial, results of the screening resistance test
(virco®TYPE HIV-1) should be used together with the treatment history to select
the OBR. The OBR should contain at least 2 active ARV drugs. In case of ENF
use, ENF is considered sensitive if it has not previously been used.
Sensitivity for TMC125 will be determined using the most recent resistance
algorithm. An up to date resistance interpretation will be provided to the
investigator and can be used to determine eligibility in the trial.
On the baseline visit (Day 1), all subjects will be treated with TMC125, in
combination with the OBR. The TMC125 dose will be based on body weight.
Study burden and risks
Burden is the visit frequency per protocol and blood sampling procedures, over
a period of 58 weeks in total.
Risks are the risks associated with the commercial OBR therapies and risks of
TMC125 (and TMC114 if applicable) described in the Informed Consent Forms.
Roderveldlaan 1
B-2600 Berchem
Belgie
Roderveldlaan 1
B-2600 Berchem
Belgie
Listed location countries
Age
Inclusion criteria
Children and adolescents aged 6 years to 17 years inclusive
Both male and female patients
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 500 copies/ml or greater at study entry
Parent or legal guardian willing to provide informed consent, if necessary
Exclusion criteria
Evidence of resistance to etravirine
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)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-007086-21-NL |
| ClinicalTrials.gov | NCT00665847 |
| CCMO | NL23759.029.08 |