HIV-1-infectionPhase 3DORDOLNCT04892654
Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch
A Phase 3 study testing Doravirine, Dolutegravir and Triple cART regimen in people with HIV-1-infection, run by Chelsea and Westminster NHS Foundation Trust at 3 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Doravirine, Dolutegravir and Triple cART regimen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 17 Aug 2022to 30 Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Depot injection
- Intra-uterine device or system
- Oral hormonal contraception
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom3 sites, 3 recruiting
- Recruiting
Mortimer Market Centre
London, NW1 0PE
Rubina Choudhry, contact.noclor@nhs.net
- Recruiting
Chelsea & Westminster Hospital NHS Foundation Trust
London, SW10 9NH
Research Regulatory Compliance Manager, 02033158209, chelwest.research@nhs.net
020 3315 6825
- Recruiting
Imperial College Healthcare NHS Trust
London
Tara Tamang, tara.tamang@nhs.net
About this study
Official title: Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch (DORDOL)
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.
Read the 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.
- Conditions
- HIV-1-infection
- Being tested
- Doravirine, Dolutegravir, Triple cART regimen
- Keywords
- HIV, Doravirine, Dolutegravir, cART
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoravirineDrug
Also called Pifeltro
Antiretroviral, Non-nucleoside Reverse Transcriptase Inhibitor
DolutegravirDrug
Also called Tivicay
Antiretroviral, Integrase strand transfer inhibitors
Triple cART regimenOther
Participant standard triple cART regimen
| Study group | Role | What they receive |
|---|---|---|
| Immediate Switch | Experimental | Two-pill regimen, doravirine (100 mg) + dolutegravir (50 mg) tablets taken orally once daily for 96 weeks. Receives: Drug: Doravirine; Drug: Dolutegravir |
| Delayed Switch | Other | Participants will continue their current triple cART regimen for 48 weeks. Patients will then be switched to two-pill regimen, doravirine (100 mg) + dolutegravir (50 mg) tablets taken orally once daily for 48 weeks. Receives: Drug: Doravirine; Drug: Dolutegravir; Other: Triple cART regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with undetectable plasma HIV RNA levels at Week 48
Undetectable will be defined as plasma HIV RNA levels of <50 copies/ml. Any patient with HIV RNA levels >50 copies/ml at analysis time points will have a repeat test
Measured: 48 weeks from randomisation (+/- 7 days)
Secondary outcomes (6)
Proportion of patients treated on each treatment arm with HIV viral load less than 50 copies/ml to determine absolute efficacy of study treatments
Proportion of patients treated on each treatment arm with HIV viral load less than 50 copies/ml at weeks and 24, 72 and 96.
Measured: 96 weeks from randomisation (+/- 7 days)
Frequency and severity of adverse events to determine safety and tolerability of study treatments
Occurrence of adverse events (including laboratory results), severity of adverse events and occurrence of treatment discontinuations measured through adverse event reporting by sites.
Measured: 96 weeks from randomisation (+/- 7 days)
Changes in CD4 count and CD4:CD8 ratio to determine safety and tolerability of study treatments
CD4 count and CD4:CD8 ratio will be measured at screening and compared to measurements in both arms weeks 24, 48, 72 and 96
Measured: 96 weeks from randomisation (+/- 7 days)
Scores from participant-recorded outcome measures on quality of life to determine safety and tolerability of study treatments
Scores from participant-recorded outcome measures at weeks 0, 24, 48, 72 and 96:
EuroQoL EQ-5D-3L Questionnaire Score from 0 to 100 (with 100 as best outcome)
Measured: 96 weeks from randomisation (+/- 7 days)
Scores from participant-recorded outcome measures on patient treatment satisfaction to determine safety and tolerability of study treatments
Scores from participant-recorded outcome measures at weeks 0, 24, 48, 72 and 96:
Patient Treatment Satisfaction Questionnaire At week 0: Score from 0 to 6 (with 6 as best outcome) All other visits: Score -3 to +3 compared to week previous (with higher score best outcome)
Measured: 96 weeks from randomisation (+/- 7 days)
Scores from participant-recorded outcome measures on sleep quality to determine safety and tolerability of study treatments
Scores from participant-recorded outcome measures at weeks 0, 24, 48, 72 and 96:
Pittsburgh Sleep Quality Index (PSQI) Score range for each PSQI evaluation ranges from 0 to 21 (with 0 as best outcome)
Measured: 96 weeks from randomisation (+/- 7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2021
- Study start17 Aug 2022
- Primary completion30 Nov 2026 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chelsea and Westminster NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marta Boffito, MD PhD FRCP, Principal investigator, Chelsea and Westminster NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04892654
- Sponsor's protocol ID
- CW004
- Other IDs
- 2020-003928-17
- Acronym
- DORDOL
- Status last verified
- Oct 2023
- First submitted
- 11 Aug 2020
- Last updated
- 25 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch (DORDOL)
- ClinicalTrials.gov ID
- NCT04892654
- Acronym / sponsor ID
- DORDOL / CW004
- Conditions
- HIV-1-infection
- Keywords
- HIV, Doravirine, Dolutegravir, cART
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Chelsea and Westminster NHS Foundation TrustUniversity, hospital or other
- Study start
- 17 Aug 2022 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 Nov 2027 (estimated)
- First posted
- 19 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immediate Switch | Experimental | Drug: Doravirine, Drug: DolutegravirTwo-pill regimen, doravirine (100 mg) + dolutegravir (50 mg) tablets taken orally once daily for 96 weeks. |
| Delayed Switch | Other | Drug: Doravirine, Drug: Dolutegravir, Other: Triple cART regimenParticipants will continue their current triple cART regimen for 48 weeks. Patients will then be switched to two-pill regimen, doravirine (100 mg) + dolutegravir (50 mg) tablets taken orally once daily for 48 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoravirineAlso: PifeltroAntiretroviral, Non-nucleoside Reverse Transcriptase Inhibitor | Drug | Delayed Switch, Immediate Switch |
| DolutegravirAlso: TivicayAntiretroviral, Integrase strand transfer inhibitors | Drug | Delayed Switch, Immediate Switch |
| Triple cART regimenParticipant standard triple cART regimen | Other | Delayed Switch |
Primary outcome
Percentage of Participants with undetectable plasma HIV RNA levels at Week 48
Time frame: 48 weeks from randomisation (+/- 7 days)
Undetectable will be defined as plasma HIV RNA levels of <50 copies/ml. Any patient with HIV RNA levels >50 copies/ml at analysis time points will have a repeat test
6 secondary outcomes
Proportion of patients treated on each treatment arm with HIV viral load less than 50 copies/ml to determine absolute efficacy of study treatments
Time frame: 96 weeks from randomisation (+/- 7 days)
Frequency and severity of adverse events to determine safety and tolerability of study treatments
Time frame: 96 weeks from randomisation (+/- 7 days)
Changes in CD4 count and CD4:CD8 ratio to determine safety and tolerability of study treatments
Time frame: 96 weeks from randomisation (+/- 7 days)
Scores from participant-recorded outcome measures on quality of life to determine safety and tolerability of study treatments
Time frame: 96 weeks from randomisation (+/- 7 days)
Scores from participant-recorded outcome measures on patient treatment satisfaction to determine safety and tolerability of study treatments
Time frame: 96 weeks from randomisation (+/- 7 days)
Scores from participant-recorded outcome measures on sleep quality to determine safety and tolerability of study treatments
Time frame: 96 weeks from randomisation (+/- 7 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marta Boffito, MD PhD FRCP principal investigator
Chelsea and Westminster NHS Foundation Trust
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Doravirine, Dolutegravir and Triple cART regimen in people with HIV-1-infection, run by Chelsea and Westminster NHS Foundation Trust at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Research Regulatory Compliance Manager (020 3315 6825, chelwest.research@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants with undetectable plasma HIV RNA levels at Week 48 (time frame: 48 weeks from randomisation (+/- 7 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2023.