Evaluating the Safety, Tolerance, and Pharmacokinetics of a Raltegravir-Containing Antiretroviral Therapy (ART) Regimen in Children Infected With HIV and TB
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Dose-Finding, Safety, Tolerance, and Pharmacokinetics Study of a Raltegravir-Containing Antiretroviral Therapy (ART) Regimen in HIV-Infected and TB Co-Infected Children ≥ 2 Years to < 12 Years of Age|
- Termination from treatment due to adverse events of greater than or equal to Grade 3 deemed at least possibly related to raltegravir [ Time Frame: Measured through a participant's last study visit, at approximately Month 4 to 9 ]
- Death, Grade 4 life-threatening adverse events deemed at least possibly related to raltegravir [ Time Frame: Measured through a participant's last study visit, at approximately Month 4 to 9 ]
- Adverse events of greater than or equal to Grade 3 deemed at least possibly related to raltegravir [ Time Frame: Measured through a participant's last study visit, at approximately Month 4 to 9 ]
- Early termination of TB therapy if there is multi-drug-resistant (MDR)/extensively drug-resistant (XDR) TB detected subsequent to starting ARV treatment or if due to toxicity attributable to TB medication [ Time Frame: Measured through a participant's last study visit, at approximately Month 4 to 9 ]
- Failure to respond at Week 8, which includes HIV RNA (copies/mL) greater than 400 copies/mL AND less than 1-log10 drop from baseline [ Time Frame: Measured at Week 8 ]
- Development of new opportunistic infections (OIs) [ Time Frame: Measured through a participant's last study visit, at approximately Month 4 to 9 ]
|Study Start Date:||May 2014|
|Estimated Primary Completion Date:||May 2019 (Final data collection date for primary outcome measure)|
Experimental: 2 to Less than 12 Years of Age
Participants will receive chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) twice daily, in addition to two NRTIs to treat HIV and a rifampicin-containing regimen to treat TB. Participants will be enrolled into the study into two cohorts: Cohort I: 2 years of age to less than 6 years of age and Cohort II: 6 years of age to less than 12 years of age. After a study visit at Day 5 to 8, a fourth ARV medication will be added to the regimen.
Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) twice daily.
People who are infected with HIV are also at risk for becoming infected with TB, particularly in many resource-limited settings, including Sub-Saharan Africa. Rifampicin is a medication commonly used to treat TB. There is a need for HIV treatment regimens that contain newer ARV medications that are well-tolerated and have minimal interactions with rifampicin-containing TB medication regimens. This study will enroll HIV-infected children who have never taken any ARV medications or who have not received ARVs for at least 30 days prior to study entry and who are infected with TB and are taking or will be starting a TB medication regimen that includes rifampicin. The purpose of this study is to evaluate the safety and tolerance of raltegravir-containing ARV regimens to treat HIV when administered with a rifampicin-containing regimen to treat TB in children. Study researchers will also evaluate the pharmacokinetics of the medications (i.e., how medication is absorbed and processed in the body) and determine the most effective dose of raltegravir when it is administered with a TB regimen that contains rifampicin.
During the study, researchers will continuously monitor participant data for safety and other factors. Researchers may adjust the dose of raltegravir given to participants prior to enrolling additional participants.
At study entry, participants will undergo a medical and medication history review, physical examination, medication adherence assessment, blood collection, and urine collection. Participants will receive chewable raltegravir tablets twice daily, and they will also take their TB medications, including rifampicin, and two nucleoside reverse transcriptase inhibitor (NRTI) ARV medications that will be chosen by participants' doctors. This study will provide raltegravir to participants; all other medications will be prescribed by participants' own doctors.
At a study visit at Days 5 to 8, participants will remain in the clinic for about 12 hours. They will take part in the same study procedures that occurred at the entry visit, but they will also have small amounts of blood collected several times throughout the 12 hours to measure the amount of medication in the blood. After the Day 5 to 8 visit, participants will begin receiving a fourth ARV medication chosen by their doctor, in addition to the other medications. Participants will continue receiving raltegravir until they stop taking their TB medications. They will continue to take the third ARV medication and the other two ARV medications for 3 months after they stop receiving raltegravir and the TB medications.
Additional study visits will occur at Day 14, Weeks 4 and 8, every 4 weeks until the participant stops receiving raltegravir and the TB medications, and 4 and 12 weeks after stopping raltegravir and the TB medications. These study visits will include the same study procedures that occurred at study entry. Participants will be enrolled in the study for a total of about 4 to 9 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01751568
|Soweto IMPAACT CRS||Recruiting|
|Johannesburg, Gauteng, South Africa, 1862|
|Contact: Nasreen Abrahams, M.B.A., B.Tech 27-11-9899700 email@example.com|
|Shandukani Research CRS||Recruiting|
|Johannesburg, Gauteng, South Africa, 2001|
|Contact: Hermien Gous, Pharm.D. 27-11-3585500 ext 5502 firstname.lastname@example.org|
|Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS||Recruiting|
|Cape Town, Western Cape Province, South Africa, 7505|
|Contact: Frieda A. Verheye-Dua 27-21-9389772 Frieda@sun.ac.za|
|Tygerberg, Western Cape Province, South Africa, 7505|
|Contact: Joan Coetzee 27-21-9384157 email@example.com|
|Study Chair:||Tammy Meyers, MD||Bamboo Grove, Wan Chai, Hong Kong, People's Republic of China|
|Study Chair:||Paul Krogstad, MD||University of California, Los Angeles|