DOLUTEGRAVIR SODIUM for HIV-1 infection

Inclusion criteria

• {"criterion_text":"- HIV-1 infected, 18 years or older"}
• {"criterion_text":"- On stable & suppressive triple cART for at least 6 months (this can include DOR and/or DTG)"}
• {"criterion_text":"- No evidence of resistance to DOR or DTG (INSTI mutations that will lead to the need of administering DTG twice-daily are considered as resistance to DTG)"}
• {"criterion_text":"- No laboratory abnormalities, medical/psychiatric conditions or alcohol/drug use considered a barrier to participation by investigators"}
• {"criterion_text":"- Women who are of childbearing potential (WOCBP) and sexually active need to use the hormonal contraceptive methods, associated with inhibition of ovulation: 1. Implant 2. Progesterone injection 3. Intra-uterine device or system 4. Oral hormonal contraception"}
• {"criterion_text":"- Men who are sexually active and have partners who are women of childbearing potential must be using an adequate method of contraception to avoid pregnancy (male condom or sterilisation confirmed prior to the subject’s entry into the study)"}

Exclusion criteria

• {"criterion_text":"- History of virological failure on an NNRTI in absence of a post-failure genotypic resistance test proving absence of resistance to DOR"}
• {"criterion_text":"- Known acute or chronic viral hepatitis B or C. Exceptions: 1. Individuals testing positive for HBcAb, but negative HBsAg/HBeAg, may be included on the trial. 2. Individuals with positive anti-HCV results, but with HCV RNA not detected may be included on the trial."}
• {"criterion_text":"- Pregnant or breastfeeding women"}
• {"criterion_text":"- Hypersensitivity to the active substance or to any of the excipients in the dolutegravir and/or doravirine formulations"}
• {"criterion_text":"- Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption."}
• {"criterion_text":"- History of virological failure on an INSTI in absence of a post-failure genotypic resistance test proving absence of resistance to DTG (INSTI mutations that will lead to the need of administering DTG twice-daily are considered as resistance to DTG – and the subject will be considered NOT eligible)"}
• {"criterion_text":"- Concomitant medication contra-indicated with DTG or DOR"}
• {"criterion_text":"- Haemoglobin <9 g/dL"}
• {"criterion_text":"- Platelets <80,000/mm3"}
• {"criterion_text":"- Creatinine clearance <30 mL/min"}
• {"criterion_text":"- AST or ALT ≥5N"}
• {"criterion_text":"- Acute Hepatitis A infection"}
• {"criterion_text":"- Concomitant DAA for anti-HCV therapy"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint will be a comparison of the percentage of participants in each treatment arm with undetectable plasma HIV RNA levels at week 48. Undetectable will be defined as plasma RNA levels of <50 copies/ml. Any patient with HIV RNA levels >50 copies/ml at analysis time points will have a repeat test. If the result from the repeat test is below 50 copies/ml the participant will be classified as a responder.","definition_or_measurement_approach":"Undetectable defined as plasma RNA levels of <50 copies/ml. Any patient with HIV RNA levels >50 copies/ml at analysis time points will have a repeat test. If the repeat test is <50 copies/ml the participant will be classified as a responder."}

Secondary endpoints

• {"endpoint_text":"- Absolute efficacy of study treatments: Proportion of patients treated on each arm with HIV viral load <50 copies/ml at weeks 24,72,96.","definition_or_measurement_approach":"Proportion with HIV viral load <50 copies/ml measured at weeks 24, 72, and 96."}
• {"endpoint_text":"- Safety and tolerability: 1 Occurrence of adverse events (including laboratory results), severity of adverse events and occurrence of treatment discontinuations due to tolerability of treatments.","definition_or_measurement_approach":"Occurrence and severity of adverse events and treatment discontinuations captured throughout study; includes laboratory assessments."}
• {"endpoint_text":"- Safety and tolerability- 2. Changes in CD4 count and CD4:CD8 ratio at screening, weeks 24, 48, 72 and 96","definition_or_measurement_approach":"Change from baseline in CD4 count and CD4:CD8 ratio assessed at screening and weeks 24, 48, 72, 96."}
• {"endpoint_text":"- Safety and tolerability - 3. Occurrences and details of viral resistance in study participants","definition_or_measurement_approach":"Recording and analysis of occurrences and details of viral resistance in participants as they occur."}
• {"endpoint_text":"- Safety and tolerability- 4. Scores from participant-recorded outcome measures at weeks 0, 24, 48, 72 and 96: • EuroQoL Questionnaire • Patient Treatment Satisfaction Questionnaire • Pittsburgh Sleep Questionnaire","definition_or_measurement_approach":"Participant-reported outcome measures (EuroQoL, Patient Treatment Satisfaction Questionnaire, Pittsburgh Sleep Questionnaire) administered at weeks 0, 24, 48, 72, 96; scores recorded and analysed."}

Italy

Earliest CTIS Part Ii Submission Date

08-10-2024

Latest Decision Or Authorization Date

14-10-2025

Processing Time Days

371

Number Of Sites

1

Number Of Participants

50

Primary sponsor

Full Name

Chelsea And Westminster Hospital NHS Foundation Trust

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

United Kingdom