Clinical trial NCT04892654: Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch
Official title: Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch (DORDOL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: HIV-1-infection
Keywords: HIV
Doravirine
Dolutegravir
cART
Lead sponsor: Chelsea and Westminster NHS Foundation Trust
Sponsor class: OTHER
First posted: 2021-05-19
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Combination antiretroviral therapy (cART) HIV treatments are associated with increased quality of life, and a normalisation of life expectancy in people living with HIV. However, long-term use of cART can lead to side-effects through exposure to drug-related toxicity.

For this reason researchers are interested in looking at alternative therapies that might expose patients to fewer and less severe side effects while providing the same quality of care as antiretroviral therapies most often used to treat HIV.

The purpose of this study is to investigate if the study drug combination that is being tested (doravirine + dolutegravir) is safe compared with other triple cART regimens.

Detailed description: A randomised, open label study to assess the efficacy of switching from suppressive triple cART to doravirine + dolutegravir dual cART in people living with HIV (PLWH) with an undetectable viral load

A computer-based software will randomise participants 2:1 to either the (1) experimental arm (early switch group) to take two-pill regimen for 96 weeks, or (2) control arm (delayed switch group) where participants continue their current triple cART regimen for 48 weeks, then switch to the two-pill regimen for another 48 weeks.

Viral load will be measured at each study visit to determine the percentage of participants in each treatment arm with undetectable plasma HIV RNA levels at week 48.

Additional research urine and bloods will be taken, as well as questionnaires completed at baseline and every 24 weeks to further investigate safety, tolerability, and quality of life from switch of suppressive triple cART to doravirine + dolutegravir dual cART.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infected, 18 years or older
* On stable \& suppressive triple cART for at least 6 months
* No evidence of resistance to DOR or DTG
* No laboratory abnormalities, medical/psychiatric conditions or alcohol/drug use considered a barrier to participation by investigators
* Women who are pre-menopausal and sexually active should be on one of the following methods of contraception:

  * Implant
  * Depot injection
  * Intra-uterine device or system
  * Oral hormonal contraception

Exclusion Criteria:

* History of virological failure on an NNRTI in absence of a post-failure genotypic resistance test proving absence of resistance to DOR
* 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)
* Concomitant medication contra-indicated with DTG or DOR
* Haemoglobin \<9 g/dL
* Platelets \<80,000/mm3
* Creatinine clearance \<30 mL/min
* AST or ALT ≥5N
* Acute Hepatitis A infection.
* Concomitant DAA for anti-HCV therapy
* Known acute or chronic viral hepatitis B or C.

  * Individuals testing positive for HBcAb, but negative HBsAg/HBeAg, may be included on the trial.
  * Individuals with positive anti-HCV results, but with HCV RNA not detected may be included on the trial.
* Pregnant or breastfeeding women

Primary outcomes:
measure: Percentage of Participants with undetectable plasma HIV RNA levels at Week 48
timeFrame: 48 weeks from randomisation (+/- 7 days)
Secondary outcomes:
measure: Proportion of patients treated on each treatment arm with HIV viral load less than 50 copies/ml to determine absolute efficacy of study treatments
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Frequency and severity of adverse events to determine safety and tolerability of study treatments
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Changes in CD4 count and CD4:CD8 ratio to determine safety and tolerability of study treatments
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Scores from participant-recorded outcome measures on quality of life to determine safety and tolerability of study treatments
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Scores from participant-recorded outcome measures on patient treatment satisfaction to determine safety and tolerability of study treatments
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Scores from participant-recorded outcome measures on sleep quality to determine safety and tolerability of study treatments
timeFrame: 96 weeks from randomisation (+/- 7 days)
Other outcomes:
measure: Serum Neurofilament light chains (sNFL) comparison
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Telomerase length comparison
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Digit span tests comparison
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Trail making tests comparison
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Verbal fluency tests comparison
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Groove pegboard tests comparison
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Bisyllabic words tests comparison
timeFrame: 96 weeks from randomisation (+/- 7 days)
measure: Metabolomics comparison
timeFrame: 96 weeks from randomisation (+/- 7 days)
Locations:
city: London
country: United Kingdom
facility: Mortimer Market Centre
city: London
country: United Kingdom
facility: Chelsea & Westminster Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Chelsea and Westminster NHS Foundation Trust
name: Marta Boffito, MD PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References: