A PHASE IIIB, RANDOMIZED, OPEN-LABEL STUDY OF THE SAFETY AND EFFICACY OF DOLUTEGRAVIR OR EFAVIRENZ EACH ADMINISTERED WITH TWO NRTIS IN HIV-1-INFECTED ANTIRETROVIRAL THERAPY-NAÏVE ADULTS STARTING TREATMENT FOR RIFAMPICIN-SENSITIVE TUBERCULOSIS
- Conditions
- -B200 HIV disease resulting in mycobacterial infectionHIV disease resulting in mycobacterial infectionB200
- Registration Number
- PER-069-14
- Lead Sponsor
- ViiV Healthcare UK Limited,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 14
1. Subject or the subjects legal representative is willing and able to understand and provide signed and dated written informed consent prior to Screening;
2. Subject has HIV-1 RNA (Human immunodeficiency virus type 1, Ribonucleic Acid) ≥1000 copies/mL at Screening;
3. CD4+ cell count is ≥50 cells/mm3 at Screening;
4. Subject is ≥18 years of age;
5. HIV-1-infected, Antiretroviral therapy (ART)-naïve; (≤10 days of prior therapy with any antiretroviral drug
following a diagnosis of HIV-1 infection);
6. A female subject may be eligible to enter and participate in the study if she: a) is of non-childbearing potential defined as either postmenopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, b) is of childbearing potential, with a negative pregnancy test at both Screening and Day 1, and agrees to use one of the methods of contraception, allowed in the study, to avoid pregnancy. All subjects participating in the study should be counseled on safer sexual practices including the use of effective barrier methods (e.g. male condom/ spermicide).
7. New diagnosis of pulmonary, pleural, or LN tuberculosis based on identification of Mycobacterium tuberculosis using culture methods or GeneXpert on sputum or on samples collected by needle aspirate of pleural fluid or an affected Lymph node;
8. Rifampicin sensitivity of Mycobacterium tuberculosis either by culture or Gene Xpert (or other validated nucleic acid amplification test);
9. Rifampicin-containing first-line Tuberculosis treatment or an alternate Rifampicin-containing Tuberculosis treatment started up to a maximum of 8 weeks before randomization and no later than the screening date;
10. Karnofsky score ≥70% before randomization.
•Exclusionary Medical Conditions:
1. Any previous Tuberculosis (TB) treatment (not including treatment for latent disease);
2. Evidence of Rifampicin resistance of Mycobacterium tuberculosis either by culture or Gene
Xpert (or other validated nucleic acid amplification test);
3. Expected requirement for Tuberculosis treatment >9 months;
4. Concomitant disorders or conditions for which isoniazid, Rifampicin (RIF), pyrazinamide, or ethambutol are contraindicated;
5. Central nervous system, miliary, or pericardial Tuberculosis (TB);
6. Women who are pregnant or breastfeeding;
7. Any evidence of an active Acquired immunodeficiency syndrome (AIDS)-defining disease (CDC Category C). Exceptions include TB, cutaneous Kaposi’s sarcoma not requiring systemic therapy, and historic CD4+ cell counts of <200 cells/mm3;
8. Subjects with moderate to severe hepatic impairment (Class B or C) as determined by Child-Pugh classification; unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, or known biliary abnormalities (with the exception of Gilbert´s syndrome or asymptomatic gallstones);
9. Subjects positive for hepatitis B surface antigen (HBsAg) at screening;
10. Anticipated need for hepatitis C virus (HCV) therapy during the Randomized Phase of the study;
11. History or presence of allergy or intolerance to the study drugs or their components or drugs of their class;
12. Ongoing malignancy other than cutaneous Kaposi´s sarcoma, basal cell carcinoma, resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the study medical monitor for inclusion of the subject;
13. Subjects who, in the investigator’s judgment, pose a significant suicidality risk.
Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk.
•Exclusionary Treatments Prior to Screening or Day 1:
14. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening;
15. Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any immunomodulators that alter immune response;
16. Treatment with any agent, other than licensed ART as allowed above (inclusion criterion 5), with documented activity against HIV-1 in vitro/vivo within 28 days of first dose of the investigational product (IP);
17. Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of IP;
•Exclusionary Laboratory Values or Clinical Assessments at Screening:
18. Any evidence of primary viral resistance to Nucleoside reverse transcriptase inhibitor (NRTIs), Non-nucleoside reverse transcriptase inhibitor (NNRTIs), or Protease Inhibitor (PI)s based on the presence of any major resistance-associated mutation [IAS USA, 2013] in the Screening result or, if known, any historical resistance test result. Retests of Screening genotypes are not allowed;
19. Any verified Grade 4 laboratory abnormality;
20. Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method