HIV/TB Coinfection Clinical Trial
Official title:
Efficacy, Safety and Pharmacokinetics of Dolutegravir 50 mg Once Daily With Food Versus Dolutegravir 50 mg Twice Daily in HIV/TB Co-infected Patients Receiving Rifampin-based Antituberculosis Therapy
The overall aim of the project is to evaluate optimal DTG dose for the combined treatment of TB and HIV infections with RIF based anti-TB therapy. This Stage II trial will determine precisely the PK parameters of DTG in combination with RIF regimen in Thai HIV/TB co-infected patients. After the optimal dose of DTG has been found, it will be further tested in a larger Stage III trial to assess its safety, tolerability and efficacy when used with RIF based regimen.
| Status | Recruiting |
| Enrollment | 200 |
| Est. completion date | June 30, 2024 |
| Est. primary completion date | June 30, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: 1. documented HIV positive 2. Aged >18 years 3. ARV naïve (previous exposure to ARV for < 2 weeks) 4. Any CD4 cell count 5. ALT <5 times ULN 6. estimated GFR>60 ml/min/1.73m2 7. Hemoglobin >7 mg/L 8. TB is diagnosed and there is a plan to receive stable doses of RIF containing anti-TB therapy for at least another 4 week period after initiation of ART 9. No other active OI (CDC class C event) except oral candidiasis or disseminated MAC 10. Body weight >40kg 11. Able to provide written informed consent Exclusion Criteria: 1. Have documented history of HIV treatment failure or HIV mutation to NRTI, NNRTI, and/or INIs 2. Have previously treated for tuberculosis 3. Currently using immunosuppressive agents. 4. Currently using any prohibited medications that can affect the pharmacokinetics of the study drug such as phenobarbital, and carbamazepine 5. Currently using alcohol or illicit substances that may affect the conduct of the trial as per the opinion of the site Principal Investigator 6. Unlikely to be able to remain in the follow-up period as defined by the protocol 7. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN. 8. Have Karnofsky performance score <30% 9. Have TB meningitis, bone/joints (due to prolonged use of anti-TB drug) 10. Pregnant or breastfeeding |
| Country | Name | City | State |
|---|---|---|---|
| Thailand | Bhumibol Adulyadej Hospital | Bangkok | |
| Thailand | Chest Division, Faculty of Medicine, Chulalongkorn University | Bangkok | |
| Thailand | HIV-NAT, Thai Red Cross - AIDS Research Centre | Bangkok | |
| Thailand | Infectious Disease Taksin Hospital | Bangkok | |
| Thailand | Infectious Disease, Chulalongkorn University | Bangkok | |
| Thailand | Klang Hospital | Bangkok | |
| Thailand | Infectious Disease Chiangrai Prachanukroh Hospital | Chiang Rai | Chiangrai |
| Thailand | Infectious Disease Chonburi Hospital | Chon Buri | |
| Thailand | Bamrasnaradura Infectious Diseases Institute | Nonthaburi | |
| Thailand | Infectious Disease Buddhachinaraj Phitsanulok Hospital | Phitsanulok |
| Lead Sponsor | Collaborator |
|---|---|
| The HIV Netherlands Australia Thailand Research Collaboration | Bamrasnaradura Infectious Diseases Institute, Bhumibol Adulyadej Hospital, Chest Division, Chulalongkorn University, Department of Disease Control, Ministry of Public Health (MOPH), Thailand, Infectious Disease Buddhachinaraj Phitsanulok Hospital, Infectious Disease Chiangrai Prachanukroh Hospital, Infectious Disease Chonburi Hospital, Infectious Disease Taksin Hospital, Infectious Disease, Chulalongkorn University, Klang Hospital, Radboud University Medical Center |
Thailand,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | proportion of subjects from the ITT analysis population with plasma HIV-1 RNA <50 c/mL at Week 24 | The primary efficacy endpoint is the proportion of subjects from the ITT analysis population with plasma HIV-1 RNA <50 c/mL at Week 24. | Week 24 | |
| Secondary | AUC of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID | AUC of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID | Week 4 | |
| Secondary | Cmax of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID | Cmax of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID | Week 4 | |
| Secondary | Cmin of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID | Cmin of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID | Week 4 | |
| Secondary | Oral clearance of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID | Oral clearance of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID | Week 4 | |
| Secondary | Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 24 | Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 24 | Week 24 | |
| Secondary | Changes in CD4+ counts from baseline to Week 24 and Week 48 | Changes in CD4+ counts from baseline to Week 24 and Week 48 | Weeks 24 and 48 | |
| Secondary | Incidence of disease progression | Incidence of disease progression (HIV-associated conditions, new AIDS diagnoses, and death) | Week 48 | |
| Secondary | Proportion of subjects that have completed TB treatment | Proportion of subjects that have completed TB treatment | Week 48 | |
| Secondary | Proportion of subjects that are cured from TB | Proportion of subjects that are cured from TB | Week 48 | |
| Secondary | Proportion of subjects that have relapsed | Proportion of subjects that have relapsed | Week 48 | |
| Secondary | Proportion of subjects that have defaulted | Proportion of subjects that have defaulted | Week 48 | |
| Secondary | TB outcome in terms of cure | Number of participants that have been cured of TB | Week 48 | |
| Secondary | TB outcome in terms of relapse | Number of participants with relapse | Week 48 | |
| Secondary | TB outcome in terms of treatment failure due to TB resistance | Number of participants with treatment failure due to TB resistance | Week 48 | |
| Secondary | TB outcome in terms of incidence | Incidence of all AEs, SAEs, and laboratory abnormalities | Week 48 | |
| Secondary | TB outcome in terms of severity | Severity of all AEs, SAEs, and laboratory abnormalities | Week 48 | |
| Secondary | discontinuation from the study | Proportion of subjects who permanently discontinued randomization arm due to AEs or death | Week 48 | |
| Secondary | discontinuation from the study drugs | Proportion of subjects who temporarily discontinued the study drugs and/or TB therapy due to AEs | Week 48 | |
| Secondary | Proportion of subjects with TB-associated IRIS | Proportion of subjects with TB-associated IRIS | Week 48 | |
| Secondary | AUC of DTG at Weeks 4 (with RIF) and 48 (without RIF) | AUC of DTG at Weeks 4 (with RIF) and 48 (without RIF) will be analyzed using population PK modeling approach to estimate AUC | Weeks 4 and 48 | |
| Secondary | Cmax of DTG at Weeks 4 (with RIF) and 48 (without RIF) | Cmax of DTG at Weeks 4 (with RIF) and 48 (without RIF) will be analyzed using population PK modeling approach to estimate Cmax | Weeks 4 and 48 | |
| Secondary | Ctrough of DTG at Weeks 4 (with RIF) and 48 (without RIF) | Ctrough of DTG at Weeks 4 (with RIF) and 48 (without RIF) will be analyzed using population PK modeling approach to estimate Ctrough | Weeks 4 and 48 | |
| Secondary | proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 48 | proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 48 (viral suppression) | Week 48 |