Doravirine for HIV

Not currently recruiting at 3 trial locations

Overseen By Theodoros Kelesidis, MD PHD

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: University of Texas Southwestern Medical Center

Must be taking: Antiretrovirals

Must not be taking: CYP3A inducers, CYP3A cleared

Disqualifiers: Pregnancy, Hepatitis, Renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new HIV treatment called doravirine, combined with other common HIV medications. The goal is to determine if this combination can reduce the side effects of current treatments, particularly those affecting cholesterol and heart health. The trial seeks individuals who have maintained stable HIV treatment with controlled viral levels for over six months and have cholesterol issues. Participants will help researchers assess whether switching medications can improve heart health and metabolism. As an Early Phase 1 trial, participants will be among the first to help researchers understand how this new treatment works in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must be on stable antiretroviral therapy for more than 6 months with specific medications like Genvoya or Biktarvy. You cannot take certain medications that affect liver enzymes, like phenobarbital or rifampin, as they may interfere with the trial drugs.

Is there any evidence suggesting that doravirine is likely to be safe for humans?

Research has shown that the combination of doravirine, emtricitabine, and tenofovir alafenamide is generally safe and well-tolerated. In several studies, patients who switched to this combination maintained control over their HIV and experienced few side effects. Doravirine, in particular, has a strong safety record, causing few serious side effects. It also benefits blood fat levels, which are linked to heart health, making it helpful for people with HIV concerned about heart disease. Overall, this combination appears to be a reliable option for managing HIV without adding extra health risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about doravirine for HIV because it offers a different approach compared to many standard treatments like efavirenz or ritonavir-boosted protease inhibitors. Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that is known for having fewer side effects, particularly related to the central nervous system, which can improve the quality of life for patients. Additionally, when combined with emtricitabine and tenofovir alafenamide fumarate, it forms a potent regimen that could potentially enhance treatment adherence due to its simpler dosing schedule of just one pill a day. This combination is designed to be effective while minimizing the risk of resistance development.

What evidence suggests that doravirine might be an effective treatment for HIV?

Research has shown that doravirine effectively treats HIV. One study found it to work well over time, comparing favorably to treatments like darunavir. Another study demonstrated that doravirine kept the virus under control in 91.5% of participants after 48 weeks, a strong result. Additionally, it is considered safe and may benefit cholesterol levels and heart health. In this trial, participants will receive doravirine combined with emtricitabine and tenofovir alafenamide fumarate. Doravirine's promising results make it an attractive option for managing HIV effectively. ^{1 4 6 7 8}

Who Is on the Research Team?

Theodoros Kelesidis, MD PHD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

Adults over 18 with chronic, treated HIV and suppressed viremia for at least 3 months can join. They must have dyslipidemia (abnormal lipids or on lipid-lowering meds) and good kidney function. Participants should be on a stable antiretroviral therapy regimen with Genvoya or Biktarvy for more than six months.

Inclusion Criteria

I have been on stable HIV treatment with Genvoya or Biktarvy for over 6 months.

I've been on stable HIV treatment with Genvoya or Biktarvy for over 6 months.

I have been on HIV treatment with low virus levels for at least 3 months.

Exclusion Criteria

Anemia precluding safe donation of blood (For men, anemia is typically defined as hemoglobin level of less than 13.5 gram/100 ml and in women as hemoglobin of less than 12.0 gram/100 ml).

I have had a serious heart problem recently.

My kidney function is severely impaired.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Doravirine plus emtricitabine and tenofovir alafenamide fumarate for 3 months

12 weeks

Regular visits as per trial protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Doravirine

Trial Overview The trial is testing Doravirine's effects on cholesterol levels and molecular factors linked to heart disease in people with HIV. It compares the switch from an integrase inhibitor-based regimen to one including Doravirine, alongside standard HIV medications TAF/FTC.

How Is the Trial Designed?

Group I: Doravirine plus emtricitabine and tenofovir alafenamide fumarate Experimental Treatment 1 Intervention

PIFELTRO (doravirine) 100 mg tablet one daily for 3 months Descovy (200 mg emtricitabine + 10 mg tenofovir alafenamide fumarate) tablet one daily for 3 months

Doravirine is already approved in United States, European Union for the following indications:

Approved in United States as Pifeltro for:

• HIV-1 infection

Approved in United States as Delstrigo for:

• HIV-1 infection

Approved in European Union as Delstrigo for:

• HIV-1 infection

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Doravirine shows promise as a treatment option for multidrug-resistant HIV-1, with 23% of cases demonstrating full susceptibility, compared to only 18% for etravirine and 5% for rilpivirine, based on a study of 22 participants with a long history of HIV treatment.

The study found that higher numbers of NNRTI mutations in the virus correlated with increased resistance to doravirine, but doravirine's effectiveness can still be predicted accurately using the Stanford HIVdb algorithm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Residual phenotypic susceptibility to doravirine in multidrug-resistant HIV-1 from subjects enrolled in the PRESTIGIO Registry. Saladini, F., Giammarino, F., Maggiolo, F., et al.[2023]

Doravirine is a safe and effective part of antiretroviral therapy for both treatment-naive and treatment-experienced adults with HIV-1, showing no resistance after 48 weeks in virologically suppressed individuals switching to a regimen including doravirine.

Emergent drug resistance to doravirine is rare (<2%) in treatment-naive patients, and it remains effective against the common K103N resistance mutation, suggesting that resistance to doravirine-based therapies is expected to be uncommon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical, clinical, and resistance information on doravirine, a novel non-nucleoside reverse transcriptase inhibitor for the treatment of HIV-1 infection. Pham, HT., Xiao, MA., Principe, MA., et al.[2020]

In a study involving 769 adults with treatment-naive HIV-1, doravirine demonstrated superior efficacy compared to ritonavir-boosted darunavir, with 73% of participants achieving an HIV-1 RNA concentration of less than 50 copies per mL at 96 weeks, compared to 66% in the darunavir group.

Doravirine also showed a better safety profile, with significant reductions in LDL and non-HDL cholesterol levels, and similar rates of adverse events compared to darunavir, indicating it may be a preferable long-term treatment option for HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial. Molina, JM., Squires, K., Sax, PE., et al.[2020]

Doravirine is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI) for treating HIV-1 infection, available as both a single-agent tablet and a fixed-dose combination with other antiretroviral drugs.

It is specifically indicated for adults with no prior antiretroviral treatment and has received positive regulatory opinions in the USA and EU, highlighting its safety and efficacy for treatment-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine: First Global Approval. Deeks, ED.[2021]

In a Phase IIb trial involving 342 participants, doravirine 100 mg showed similar effectiveness to efavirenz 600 mg in reducing HIV-1 RNA levels, with 72.9% of doravirine recipients achieving viral suppression compared to 73.1% for efavirenz.

Doravirine was associated with significantly fewer central nervous system adverse events (26.9%) compared to efavirenz (47.2%), indicating a better safety profile for doravirine in this regard.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial. Gatell, JM., Morales-Ramirez, JO., Hagins, DP., et al.[2020]

Doravirine, a new treatment for HIV-1, is taken once daily and shows a favorable pharmacokinetic profile, with no significant impact from age, gender, or mild to moderate renal and hepatic impairments, making it suitable for diverse patient populations.

The drug has a low potential for drug-drug interactions, allowing it to be safely combined with other antiretroviral medications, although it should not be used with strong CYP3A inducers like rifampin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of the Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor Doravirine: An Assessment of the Effect of Patient Characteristics and Drug-Drug Interactions. Khalilieh, S., Yee, KL., Sanchez, R., et al.[2023]

Doravirine, particularly at a dose of 100 mg, demonstrated the highest efficacy in treating HIV-1 among various treatment options, based on a meta-analysis of six randomized controlled trials.

While doravirine showed a good safety profile, the placebo group had the least adverse events, indicating that doravirine is a safe and well-tolerated option for initial HIV-1 therapy, comparable to other standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of doravirine in treatment-naive HIV-1-infected adults: a systematic review and meta-analysis. Afify, MA., Ahmed, IGG., Alkahtani, TA., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02275780

Safety and Efficacy of Doravirine (MK-1439) in Participants ... Safety and Efficacy of Doravirine (MK-1439) in Participants With Human Immunodeficiency Virus 1 (HIV-1) (MK-1439-018) (DRIVE-FORWARD). ClinicalTrials.gov ID ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11302240/

Long-term effectiveness, safety, and tolerability of doravirine in ... The combination of DOR plus ABV/3TC has shown even better safety and effectiveness than TFV/FTC. DOR plus two NRTI offers cost benefits compared ...

3. merckconnect.com merckconnect.com/doravirine/pifeltro-clinical-efficacy/

Clinical Efficacy Data for PIFELTRO® (doravirine) Tablets In a 96-week clinical trial, PIFELTRO demonstrated: Durable efficacy compared to boosted DRV in treatment-naïve adults.

4. merck.com merck.com/news/merck-announces-positive-data-from-phase-3-trials-that-show-the-investigational-once-daily-oral-two-drug-regimen-of-doravirine-islatravir-dor-isl-maintained-hiv-1-viral-suppression-at-week-48/

Merck Announces Positive Data from Phase 3 Trials that ... At Week 48, 91.5% of participants who switched to DOR/ISL maintained viral suppression (HIV-1 RNA <50 copies/mL) compared to 94.2% of ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352301823002588

Safety and efficacy of doravirine as first-line therapy in ... Doravirine showed non-inferior efficacy, a favourable safety profile, and a superior lipid profile to darunavir and efavirenz through to 48 and 96 weeks.

6. merck.com merck.com/news/merck-announces-new-data-from-phase-3-trials-evaluating-the-investigational-once-daily-oral-two-drug-regimen-of-doravirine-islatravir-dor-isl-in-adults-with-virologically-suppressed-hiv-1-infecti/

Merck Announces New Data from Phase 3 Trials ... In trial MK-8591A-052, adults living with virally suppressed HIV-1 infection who switched to DOR/ISL from BIC/FTC/TAF showed minimal changes in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04820933?intr=Doravirine%20Tenofovir%20Alafenamide&rank=2

Doravirine Versus Integrase Inhibitors on Backbone of ... A Switch Clinical Trial of Antiretrovirals to Compare the Impact of Doravirine Versus Integrase Inhibitors With Backbone of Emtricitabine and Tenofovir ...

8. natap.org natap.org/2023/HIV/PIIS2352301823002588.pdf

Safety and efficacy of doravirine as first-line therapy in ... Switching to doravirine/ lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintains HIV-1 virologic suppression through 48 weeks: results ...