Evaluating the Safety, Tolerance, and Pharmacokinetics of a Raltegravir-Containing Antiretroviral Therapy (ART) Regimen in Infants and Children Infected With HIV and TB
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
First received: December 14, 2012
Last updated: December 11, 2019
Last Verified: December 2019
History of Changes
People who are infected with HIV and tuberculosis (TB) need to receive medications that treat both diseases safely and effectively. This study will enroll infants and children infected with HIV and TB and evaluate the safety and tolerance of an antiretroviral (ARV) treatment regimen for HIV that contains raltegravir when administered with a TB treatment regimen that includes rifampicin. Study researchers will also determine the most effective dose of raltegravir for infants and children when it is taken with rifampicin.
Drug : Raltegravir
Intervention Model: Single Group Assignment
Masking: None (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 Infants and Children|
Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):
Primary Outcome Measures
- 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 ]
- Grade 4 non-life threatening adverse events deemed as probably or definitely 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|
|Study Completion Date:||November 27, 2019|
|Primary Completion Date:||November 27, 2019 (Final data collection date for primary outcome measure)|
4 Weeks 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 three cohorts: Cohort I: 2 years of age to less than 6 years of age, Cohort II: 6 years of age to less than 12 years of age, and Cohort III: 4 weeks of age to less than 2 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 infants and 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 infants and 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.
|Ages Eligible for Study:||up to 11 Years|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Age greater than or equal to 4 weeks to less than 12 years at entry
- Weight greater than or equal to 3.5 kg at entry
- Confirmation of HIV-1 infection is defined as positive results from two samples collected at different time points. All samples tested must be whole blood, serum, or plasma. For studies conducted under an Investigational New Drug (IND), all test methods should be Food and Drug Administration (FDA)-approved if available. If FDA-approved methods are not available, test methods should be verified according to good clinical laboratory practice (GCLP) and approved by the IMPAACT Laboratory Center. More information on this criterion can be found in the protocol.
- ARV treatment naïve or has not received ARVs for at least 30 days prior to entry. Note: Participants with prior exposure to ARVs for prevention of mother-to-child transmission (PMTCT) or treatment - regardless of duration - are eligible provided the participant has not received ARVs for at least 30 days prior to entry. The reasons for interruption could include drug toxicity, poor adherence, or treatment failure that preceded enrollment and has not been imposed by study staff. ARVs should not be withheld for the purposes of enrollment into the study and against the participant's best interest.
- ARV treatment eligible as defined by:
- Country-specific guidelines OR
- World Health Organization (WHO) pediatric treatment algorithm (http://apps.who.int/iris/bitstream/10665/208825/1/9789241549684_eng.pdf?ua=1)
- Diagnosis of pulmonary TB or TB adenitis. More information on this criterion can be found in the protocol.
- Participant has initiated at least a 2-drug TB regimen containing rifampicin, and has tolerated at least 1 week of the TB drug regimen prior to initiation of raltegravir. Note: TB treatment may be started after being diagnosed by the site investigator. Treatment regimens may include isoniazid, pyrazinamide, ethambutol and streptomycin in addition to rifampicin. ART should ideally be started within 2 weeks of starting TB treatment. A patient who has started therapy for TB elsewhere but has not yet been started on ART is eligible for enrollment provided they have not had greater than 20 weeks of TB therapy. Delay between starting TB treatment and ART is not encouraged, and local or international guidelines should be followed for managing TB and HIV coinfection in infants and children.
- Female participant who is of child bearing potential and sexually active has agreed to use two reliable methods of contraception, including a medically accepted barrier method of contraception (e.g., female/male condoms, diaphragm or cervical cap with a cream or gel that kills sperm (excluding nonoxydyl-9), intrauterine device [IUD], others) together with another reliable form of contraception while on study and for 4 weeks after stopping RAL
- Parent, legal guardian, or designated guardian according to country-specific guidelines able and willing to provide signed informed consent and to have the participant followed at the clinical site
- Greater than or equal to Grade 2 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at screening, which must be within 30 days of entry. Note: Participants can be re-screened provided that they will have at least 4 weeks of TB treatment remaining at the time of entry.
- Any greater than or equal to Grade 4 clinical toxicity or laboratory result at screening except fever, chills, fatigue or malaise, unintentional weight loss, and dyspnea or respiratory distress that could be associated with TB
- Acute, serious infections other than TB requiring active treatment (e.g., Pneumocystis jirovecii [previously Pneumocystis carinii] pneumonia [PCP], cryptococcal meningitis, etc.). Infants and children diagnosed with acute bacterial pneumonia at time of diagnosis of TB may be included. Prophylaxis against opportunistic infections will be allowed.
- Diagnosis of Kwashiorkor (less than 80% expected weight-for-age with the presence of edema and hypoalbuminemia)
- Current chemotherapy for active malignancy and history of chemotherapy discontinued within 1 year of entry
- Rifampicin therapy of greater than 20 weeks duration immediately prior to enrollment
- Known or suspected MDR or XDR TB, including contact with a documented MDR or XDR TB source case, as these may require longer duration of therapy or non-rifampicin containing regimen. Note: Participants found to have MDR or XDR TB before or during the study will be informed of their illness and referred for appropriate care as determined by local guidelines.
- Current TB regimen containing rifabutin, macrolides, and any other anti-mycobacterial agents with known interactions with raltegravir
- Any clinically significant diseases (other than HIV and TB infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study
- Participant is pregnant or breastfeeding
- Participant is unlikely to adhere to the study procedures or keep appointments
- Participant is planning to relocate during the study to a non-IMPAACT study site
- Participant is taking any disallowed medications. More information on this criterion
Contacts and LocationsChoosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01751568
Locations Show More
|Soweto IMPAACT CRS|
|Johannesburg, Gauteng, South Africa, 1862|
|Wits RHI Shandukani Research Centre CRS|
|Johannesburg, Gauteng, South Africa, 2001|
|Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS|
|Cape Town, Western Cape Province, South Africa, 7505|
|Tygerberg, Western Cape Province, South Africa, 7505|
Sponsors and CollaboratorsNational Institute of Allergy and Infectious Diseases (NIAID)
|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|
|Responsible Party:||National Institute of Allergy and Infectious Diseases (NIAID)|
|ClinicalTrials.gov Identifier:||NCT01751568 History of Changes|
|Other Study ID Numbers:||P1101|
|Study First Received:||December 14, 2012|
|Last Updated:||December 11, 2019|
Additional relevant MeSH terms:
ClinicalTrials.gov processed this data on March 27, 2020
This information is provided by ClinicalTrials.gov.