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Dual Therapy With Boosted Darunavir + Dolutegravir (Dualis)

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ClinicalTrials.gov Identifier: NCT02486133
Recruitment Status : Completed
First Posted : July 1, 2015
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Technische Universität München

Brief Summary:
A switch strategy to investigate whether a dual therapy with Ritonavir-boosted (RTV) Darunavir (DRV) + Dolutegravir (DTG) over 48 weeks is non-inferior to a continuous standard of care therapy with RTV-boosted DRV in combination with 2 Nucleosidic Reverse Transcriptase Inhibitors (NRTIs) in HIV patients, who are on a stable antiretroviral therapy (ART) with RTV-boosted DRV in combination with 2 NRTIs.

Condition or disease Intervention/treatment Phase
HIV-Infection Drug: Prezista Drug: Norvir Drug: Tivicay Drug: Truvada Drug: Kivexa Phase 3

Detailed Description:

Modern combination antiretroviral therapy (cART) leads to well-controlled HIV infection with a potentially normal life expectancy. Nucleosidic reverse transcriptase inhibitors (NRTIs) play a major role as "ART backbone" and are essential antiretroviral agents according to current European and WHO HIV treatment guidelines. However, NRTI use can be associated with substantial side effects, e.g. bone and kidney toxicity, lipotoxicity and mitochondrial toxicity and can put patients at serious risk. Especially long-term NRTI-exposure is a risk factor for these often cumulative side effects, since the standard of care (SOC) therapy with the different NRTIs consists of the combination of multiple substances. Furthermore NRTI resistances may emerge over time and limit treatment options for pre-treated HIV patients.

As a consequence, alternative NRTI free (so called "nuke sparing") therapy options have been evaluated in different studies but were associated with less virologic therapeutic success and higher rates of therapy induced resistance compared to standard regimens in ART naïve patients. This is particularly true for patients with a high baseline viral load.

As an alternative to NRTI-based therapy options, Ritonavir-boosted protease inhibitor (PI/r)-based nuke-sparing dual therapies have been studied widely, mostly in combination with the integrase inhibitor (INI) Raltegravir (RAL). In this setting, the PI was not fully capable to prevent the development of INI resistant viruses.

The HIV protease inhibitor Darunavir (DRV) and the novel INI Dolutegravir (DTG) are both very potent anchor drugs with a high barrier to resistance. Due to a favourable side-effect profile, a once-daily (QD) formulation and its virological potency, DRV is currently one of the most frequently used PIs in Europe and the USA. In addition, the new, once-daily administrable integrase inhibitor DTG showed an excellent tolerability profile as well as a high resistance barrier.

The nuke-free combination of DTG (50 mg) with the Ritonavir (/r)- or Cobicistat-boosted protease inhibitor DRV (800 mg) may offer a favorable safety and efficacy profile with the advantage of QD-dosing.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 269 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Randomized, Open-label Trial to Assess the Safety, Tolerability and Efficacy of Dual Therapy With Boosted Darunavir + Dolutegravir When Switching From Standard of Care ART in HIV-patients With Sustained Virological Suppression: The DUALIS Study
Actual Study Start Date : July 2015
Actual Primary Completion Date : May 31, 2018
Actual Study Completion Date : May 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: A
Prezista & Norvir & Tivicay
Drug: Prezista
once daily
Other Name: Darunavir

Drug: Norvir
once daily
Other Name: Ritonavir

Drug: Tivicay
once daily
Other Name: Dolutegravir

Active Comparator: B
Prezista & Norvir & Truvada or Prezista & Norvir & Kivexa
Drug: Prezista
once daily
Other Name: Darunavir

Drug: Norvir
once daily
Other Name: Ritonavir

Drug: Truvada
once daily
Other Name: Tenofovir disaproxil fumarat/emtricitabine

Drug: Kivexa
once daily
Other Name: Abacavir/Lamivudine




Primary Outcome Measures :
  1. number (%) of patients with fully suppressed HIV RNA < 50 cps/ml at week 48 [ Time Frame: 48 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • HIV-1 infection with HIV-1 RNA < 50 cps/ml at screening and within a period of 24 weeks prior to screening with one accepted blip of HIV-1 RNA < 200 cps/ml and well-tolerated antiretroviral therapy of 2 NRTI in combination with DRV/r.
  • No known genotypic DRV- or integrase inhibitor-related HIV resistance
  • Signed written informed consent
  • Documented negative HLA B*57:01 (only in case of Abacavir-containing ART)
  • A female subject may be eligible to enter and participate in the study if she:

    • is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or
    • is of child-bearing potential with a negative pregnancy test at both screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
  • Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IMP, throughout the study, and for at least 2 weeks after discontinuation of all study medications
  • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide)
  • Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject
  • Approved hormonal contraception without DRV/r interactions and a barrier method
  • Any other method with published data showing that the expected failure rate is <1% per year. Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of IMP.

Exclusion Criteria:

  • Pregnant women and nursing mothers
  • Chronic HBV infection (HBsAg and/or HBV DNA positive)
  • Any evidence of a Center for Disease Control and Prevention (CDC) Category C disease at screening, except cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts < 200 cells/mm3 or historic CDC C diseases are not exclusionary
  • History or presence of allergy to the study drugs or their components
  • Subject has creatinine clearance of <50 mL/min by MDRD eGFR calculation
  • Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (ULN), OR ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin)
  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Subjects with severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification
  • Anticipated need for interferon-based Hepatitis C virus (HCV) therapy during the study
  • Participation in other interventional clinical trials at the same time
  • Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
  • Persons held in an institution by legal or official order
  • Imprisoned people, people requiring in-house treatment for psychiatric disorders or people who are unable to give informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02486133


Locations
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Germany
Klinikum rechts der Isar
Munich, Germany, 81675
Sponsors and Collaborators
Technische Universität München

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Responsible Party: Technische Universität München
ClinicalTrials.gov Identifier: NCT02486133     History of Changes
Other Study ID Numbers: DUA-1463-SPI-0320-I
First Posted: July 1, 2015    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019

Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Emtricitabine
Darunavir
Dolutegravir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Ritonavir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors