E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus (HIV) infection |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the tolerability, adherence and efficacy of single tablet dolutegravir/abacavir/lamivudine antiretroviral therapy in people living with HIV with a history of injection drug use switching from existing ART or starting treatment after discontinuation of ART |
|
E.2.2 | Secondary objectives of the trial |
-To assess tolerability through self-reported adverse effect and directed symptoms questionnaire -To determine change in number and severity of reported ART-related adverse effects -To determine change in health-related quality of life (HRQOL) -To determine change in frailty score -To determine the percentage of subject with unscheduled ART discontinuations/interruptions -To determine the estimated number of weeks of missed ART -To determine change of medication possession ratio (MPR) or adherence score -To determine the percentage of subjects with HIV RNA<40 copies/mL -To determine change in genotypic resistance profiles in subjects experiencing virological failure -To determine change in CD4+ T-cell counts -To determine change in bone mineral density -To determine the number of subjects with any adverse and any serious adverse events (SAE) -To determine the number of subject with Grade 1 to 4 laboratory abnormalities
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•HIV-infected adults (≥18 years of age) with a history of IDU as the principal HIV transmission risk factor or with current or recent (past 12 months) history of IDU •Either ART-naïve or currently receiving an antiretroviral regimen but experiencing adherence or tolerability issues on current ART or restarting ART after an unscheduled treatment interruption •Willing to switch current ART regimen •No documented viral resistance to currently licensed HIV-1 integrase inhibitors, abacavir and lamivudine (with the exception of M184V) based either on previous HIV-1 genotypic resistance testing or in the judgment of the study investigators •Integrase inhibitor naïve (defined as no-prior exposure to any INSTI) •Documented negative HLAB*5701 allele
|
|
E.4 | Principal exclusion criteria |
•Anticipated need for hepatitis C treatment during the first 24 weeks of the study •Subjects with active hepatitis B infection (defined as hepatitis B surface antigen (sAg) positive) •Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification; •Chronic renal failure estimated by eGFR <60mls/min/1.73m2 at screening using the abbreviated Modification of Diet in Renal Disease (MDRD) equation •Any active illness (including AIDS-defining illness) which in the opinion of the investigator would prevent the subject from completing all study assessments •Female subjects who are pregnant, breastfeeding or planning future pregnancies or unwilling to take measures to avoid pregnancy for the study duration •Any grade 4 laboratory abnormalities •Subjects with moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification; •Subjects weighing less than 40 kilograms and those are likely to require a Triumeq dose adjustment •History or presence of allergy to the study drug or their components •A diagnosis of cancer under current active chemotherapy or radiotherapy or having received chemotherapy or radiotherapy for a diagnosis of cancer within the previous 21 days prior to screening •Subjects with a documented HLAB*5701 positive test on archived or screening bloods •Concurrent use of any contraindicated medication |
|
E.5 End points |
E.5.1 | Primary end point(s) |
•Tolerability through self-reported adverse effects and directed symptom questionnaire •Percentage of subject with unscheduled ART discontinuations/interruptions over 96 weeks •Change from baseline of medication possession ratio (MPR) at 48 weeks or adherence score as measured by an antiretroviral therapy medication self-report form •Percentage of subjects with HIV RNA<40 copies/mL at 48 weeks
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
•Change in number and severity of reported ART-related adverse effects from baseline to week 48 and 96 •Change in health-related quality of life (HRQOL) from baseline to week 48 and 96 •Change in frailty score from baseline to week 48 and 96 •Estimated number of weeks of missed ART over 48 and 96 weeks of follow-up •Change from baseline of medication possession ratio (MPR) at 48 and 96 weeks or adherence score as measured by an antiretroviral therapy medication self-report form at the same time points •Percentage of subjects with HIV RNA<40 copies/mL at 96 weeks •Change in genotypic resistance profiles in subjects experiencing virological failure •Change in CD4+ T-cell counts over 96 weeks •Change in bone mineral density over 96 weeks •Number of subjects with any adverse and any serious adverse events (SAE) from baseline to week 96 •Number of subject with Grade 1 to 4 laboratory abnormalities from baseline to week 96
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, week 48 and week 96 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |