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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: HIV-1

Treatments: Drug: Ritonavir; Drug: TRUVADA™ or EPZICOM™/KIVEXA™; Drug: Doravirine; Drug: Darunavir

Study type: Interventional

Funder types: Industry

Identifiers

NCT02275780

MK-1439-018 (Other Identifier)

1439-018

2014-001127-69 (EudraCT Number)

Details and patient eligibility

About

To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy and safety of doravirine will be determined relative to a protease inhibitor (PI). Participants will receive double-blind treatment during the 96-week Base Study. Eligible participants in either of the Base Study groups will continue to receive the doravirine-containing regimen open label for an additional 96 weeks in the Study Extension 1. Eligible participants who are deriving benefit will continue in Study Extension 2 to receive the doravirine-containing regimen open label until doravirine becomes locally available or for an additional 96 weeks, whichever comes first. The primary hypothesis is that doravirine 100 mg once a day (q.d.) is non-inferior to darunavir/ritonavir (800 mg/100 mg) q.d., each in combination with TRUVADA™ or EPZICOM™/KIVEXA™, as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48. If non-inferiority is established, then the superiority of doravirine 100 mg q.d. compared to darunavir/ ritonavir (800 mg/100 mg) q.d. will be assessed.

Full description

Participants in Australia, Russia, and South Africa who are deriving benefit from MK-1439A are also eligible to continue receiving study drug during Study Extension 3, which will last for 2 years or until drug is available locally, whichever comes first.

Enrollment: 769 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is HIV-1 positive and has HIV treatment indicated based on physician assessment.
• Has received no (0 days of) antiretroviral therapy (ART), including investigational antiretroviral agents.
• Is considered clinically stable with no signs or symptoms of active infection for at least 2 weeks prior to the start of treatment.
• Female is highly unlikely to become pregnant, or male is highly unlikely to impregnate a partner because they are not of reproductive potential, or agree to practice abstinence or use acceptable contraception for up to 14 days after the last dose of study drug.
• Eligibility for the Study Extension 1 at the Week 96 visit: 1) completed the Week 96 visit, 2) derived benefit from participation through Week 96 in the opinion of the investigator, 3) is a clinically-appropriate candidate for an additional 96 weeks of treatment with the Study Extension regimen.
• Eligibility for the Study Extension 2 at the Week 192 visit: 1) completed the Week 192 visit, 2) derived benefit from participation through Week 192 in the opinion of the investigator, 3) is a clinically-appropriate candidate for 96 weeks of treatment with the Study Extension regimen.

Exclusion criteria

• Uses or has had a recent history of using recreational or illicit drugs.
• Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1.
• Has documented or known resistance to study drugs including doravirine, darunavir, ritonavir, emtricitabine, tenofovir, abacavir and/or lamivudine.
• Has participated in a study with an investigational compound/device within the prior month, or anticipates doing so during this study.
• Has used systemic immunosuppressive therapy or immune modulators within the prior 30 days, or anticipates doing so during this study.
• Has significant hypersensitivity or other contraindication to any of the components of the study drugs.
• Has a current (active) diagnosis of acute hepatitis due to any cause.
• Is pregnant, breastfeeding or expecting to conceive at any time during the study.
• Female who expects to donate eggs, or male who expects to donate sperm at any time during the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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769 participants in 2 patient groups

Doravirine 100 mg

Experimental group

Description:

Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.

Treatment:

Drug: Doravirine

Drug: TRUVADA™ or EPZICOM™/KIVEXA™

Darunavir 800 mg and Ritonavir 100 mg

Active Comparator group

Description:

Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.

Treatment:

Drug: Darunavir

Drug: Doravirine

Drug: TRUVADA™ or EPZICOM™/KIVEXA™

Drug: Ritonavir