Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch

NCT04892654 | Recruiting Phase 3 DMC

• 2 other identifiers: CW0042020-003928-17
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 3

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.

Conditions

HIV-1-infection

Keywords

HIV; Doravirine; Dolutegravir; cART

Outcome Measures

Primary Outcomes (1)

• 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

  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

  96 weeks from randomisation (+/- 7 days)

• Frequency and severity of adverse events to determine safety and tolerability of study treatments

  96 weeks from randomisation (+/- 7 days)

• Changes in CD4 count and CD4:CD8 ratio to determine safety and tolerability of study treatments

  96 weeks from randomisation (+/- 7 days)

• Scores from participant-recorded outcome measures on quality of life to determine safety and tolerability of study treatments

  96 weeks from randomisation (+/- 7 days)

• Scores from participant-recorded outcome measures on patient treatment satisfaction to determine safety and tolerability of study treatments

  96 weeks from randomisation (+/- 7 days)

Other Outcomes (8)

• Serum Neurofilament light chains (sNFL) comparison

  96 weeks from randomisation (+/- 7 days)

• Telomerase length comparison

  96 weeks from randomisation (+/- 7 days)

• Digit span tests comparison

  96 weeks from randomisation (+/- 7 days)

Study Arms (2)

Immediate Switch

EXPERIMENTAL

Two-pill regimen, doravirine (100 mg) + dolutegravir (50 mg) tablets taken orally once daily for 96 weeks.

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.

Drug: Doravirine; Drug: Dolutegravir; Other: Triple cART regimen

Interventions

Doravirine DRUG

Antiretroviral, Non-nucleoside Reverse Transcriptase Inhibitor

Also known as: Pifeltro

Delayed Switch; Immediate Switch

Dolutegravir DRUG

Antiretroviral, Integrase strand transfer inhibitors

Also known as: Tivicay

Delayed Switch; Immediate Switch

Triple cART regimen OTHER

Participant standard triple cART regimen

Delayed Switch

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chelsea and Westminster NHS Foundation Trust: lead

Study Sites (3)

Mortimer Market Centre

London, NW1 0PE, United Kingdom

RECRUITING

Chelsea & Westminster Hospital NHS Foundation Trust

London, SW10 9NH, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, United Kingdom

RECRUITING

MeSH Terms

Interventions

doravirine; dolutegravir

Study Officials

• Marta Boffito, MD PhD FRCP

  Chelsea and Westminster NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Regulatory Compliance Manager

CONTACT

020 3315 6825; chelwest.research@nhs.net

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: May 19, 2021
• Study Start: August 17, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: October 25, 2023

Record last verified: 2023-10

Locations

GB (3)